TY - CONF AB - Multispectral optoacoustic tomography (MSOT) has been utilized to non-invasively resolve morphological changes like angiogenesis and metabolic parameters like hemoglobin concentration and oxygenation in breast tumors. Compared to other optical methods, MSOT provides higher spatial resolution, higher penetration depth and does not require the use of contrast agents. Thus, MSOT could aid the non-invasive diagnosis and treatment monitoring of breast cancer. Because MSOT illuminates tissue at multiple wavelengths, the acquired data contains spectral information about the chromophores contained in tissue. This spectral data may serve as additional dimension to infer cancer biomarkers. Recent advances in data processing and image reconstruction enable the spectroscopic analysis of MSOT data. However, effects like fluence attenuation and spectral coloring alter the spectral data hampering the identification of chromophores. Hence, it is necessary to analyze and understand spectral MSOT data—"MSOT spectra”—to not draw wrong conclusions. In this work, we showcase MSOT spectra of healthy and cancerous breast tissue in four patients between 680 nm and 1100 nm for the first time. We investigate trends and variations in MSOT spectra of tumor, tumor core, tumor rim, tumor perimeter and healthy background tissue with respect to different regions of interest and with respect to the tumors’ molecular subtypes. Moreover, we showcase effects of spectral coloring which are observed in the in-vivo MSOT spectra. Our work provides a new perspective on MSOT imaging of breast cancer. We lay the foundation to derive novel, spectral MSOT biomarkers of breast cancer aiding the clinical translation. AU - Bader, M. AU - Mc Larney, B.E.* AU - Pinker, K.* AU - Grimm, J.* AU - Jüstel, D. AU - Ntziachristos, V. C1 - 74694 C2 - 57563 TI - Deciphering the spectra of breast cancer in multispectral optoacoustic tomography. JO - Proc. SPIE VL - 13319 PY - 2025 SN - 0277-786X ER - TY - CONF AB - Fluorescence molecular imaging (FMI) and endoscopy (FME) are technologies with great potential for image-guided surgical or diagnostic interventions. However, FMI and FME still present challenges that can confound real-time decision making for disease management and/or treatment. Importantly, the markedly different systems hurdle the repeatability of measurements, the unbiased readout interpretation, and the wide clinical acceptability of FMI and FME. Herein we present different multi-parametric standards to perform quality control and performance assessment of FMI and FME systems. Moreover, we discuss examples illustrating how data analysis and the design of fluorescence standards influence performance assessment outcomes, potentially affecting comparisons between systems or studies. We, also, show the first standard tailored to the requirements of FME and demonstrate its use for quality control of a fiberscope-based FME system. The discussed performance assessment and quality control framework can accelerate the clinical translation of fluorescence molecular imaging and endoscopy and steer further developments in the field. AU - Gorpas, D. AU - Ntziachristos, V. C1 - 74556 C2 - 57507 CY - 1000 20th St, Po Box 10, Bellingham, Wa 98227-0010 Usa TI - Multi-parametric standards for performance assessment and quality control of fluorescence molecular imaging and endoscopy systems. JO - Proc. SPIE VL - 13308 PB - Spie-int Soc Optical Engineering PY - 2025 SN - 0277-786X ER - TY - CONF AB - Artificial I ntelligence (AI) h as e merged a s a v aluable t ool f or a ssisting r adiologists i n b reast c ancer detection and diagnosis. However, the success of AI applications in this domain is restricted by the quantity and quality of available data, posing challenges due to limited and costly data annotation procedures that often lead to annotation shifts. This study simulates, analyses and mitigates annotation shifts in cancer classification in the breast mammography domain. First, a high-accuracy cancer risk prediction model is developed, which effectively d istinguishes b enign f rom m alignant l esions. N ext, m odel p erformance i s u sed t o q uantify t he impact of annotation shift. We uncover a substantial impact of annotation shift on multiclass classification performance particularly for malignant lesions. We thus propose a training data augmentation approach based on single-image generative models for the affected c lass, r equiring a s f ew a s f our i n-domain a nnotations t o c onsiderably mitigate annotation shift, while also addressing dataset imbalance. Lastly, we further increase performance by proposing and validating an ensemble architecture based on multiple models trained under different d ata augmentation regimes. Our study offers k ey i nsights i nto a nnotation s hift i n d eep l earning b reast c ancer c lassification and explores the potential of single-image generative models to overcome domain shift challenges. All code used for this study is made publicly available at https://github.com/MartaBuetas/EnhancingBreastCancerDiagnosis. AU - Arcas, M.B.* AU - Osuala, R. AU - Lekadir, K.* AU - Diaz, O.* C1 - 70855 C2 - 55894 CY - 1000 20th St, Po Box 10, Bellingham, Wa 98227-0010 Usa TI - Mitigating annotation shift in cancer classification using single-image generative models. JO - Proc. SPIE VL - 13174 PB - Spie-int Soc Optical Engineering PY - 2024 SN - 0277-786X ER - TY - CONF AB - Multispectral optoacoustic tomography requires real-time image feedback during clinical use. Herein, we present DeepMB, a deep learning framework to express the model-based reconstruction operator with a deep neural network and reconstruct high-quality optoacoustic images from arbitrary experimental input data at speeds that enable live imaging (31ms per image). AU - Dehner, C. AU - Ntziachristos, V. AU - Jüstel, D. AU - Zahnd, G. C1 - 70798 C2 - 55660 CY - 1000 20th St, Po Box 10, Bellingham, Wa 98227-0010 Usa TI - Deep model-based optoacoustic image reconstruction (DeepMB). JO - Proc. SPIE VL - 12842 PB - Spie-int Soc Optical Engineering PY - 2024 SN - 0277-786X ER - TY - CONF AB - Breast density has demonstrated to be an important risk factor for the development of breast cancer and, therefore, different fully automated density assessment tools have been introduced to obtain quantitative glandular tissue measures. Density maps (DMs) provide local tissue information, representing the amount of glandular tissue between the image receptor and the x-ray source at every pixel in the image. Usually, DMs are obtained from for processing, i.e. raw, mammograms. This fact could become a tricky problem because this type of images are not preserved in the clinical setting. The aim of this work is to introduce a deep learning based framework to synthesize glandular tissue DMs from for presentation mammograms. First, the breast region is located using a dedicated object detector network. Next, a generative adversarial network is used to obtain synthetic density maps, that are useful to evaluate not only the glandular tissue distribution but also the total glandular tissue volume within the breast. Results show that synthetic DMs obtain a structural similarity index of SSIM = 0.93 ± 0.06 with respect to real images. Similarly, shared information between the real and synthetic images, computed using the histogram intersection, corresponds to HI = 0.84 ± 0.10, while the average pixel difference represents only 3.85 ± 2.78 % of breast thickness. Furthermore, glandular tissue volume (GTV) obtained from synthetic density map show a strong correlation with the value provided by the real one (ρ = 0.89 [C.I 0.87 − 0.91]). In conclusion, generative deep learning models can be useful to evaluate breast composition, from local to global tissue distribution. AU - Garcia, E.B.G.* AU - Lladó, X.* AU - Mann, R.M.* AU - Osuala, R. AU - Martí, R.* C1 - 70853 C2 - 55966 CY - 1000 20th St, Po Box 10, Bellingham, Wa 98227-0010 Usa TI - Breast composition measurements from Full-Field Digital Mammograms using generative adversarial networks. JO - Proc. SPIE VL - 13174 PB - Spie-int Soc Optical Engineering PY - 2024 SN - 0277-786X ER - TY - CONF AB - Imaging peripheral nerve morphology, function, and vascular supply is important in clinical medicine and research. In this work, we evaluate the imaging capabilities of multispectral optoacoustic tomography (MSOT) for peripheral nerves. We demonstrate how recent advances in MSOT data processing combined with data-driven unmixing overcome adverse effects of measurement noise and light fluence attenuation and provide detailed insights into the vasa nervorum and the internal structure of peripheral nerves. AU - Jüstel, D. AU - Irl, H.* AU - Hinterwimmer, F.* AU - Dehner, C. AU - Simson, W.* AU - Navab, N.* AU - Schneider, G.* AU - Ntziachristos, V. C1 - 70800 C2 - 55657 CY - 1000 20th St, Po Box 10, Bellingham, Wa 98227-0010 Usa TI - Multispectral optoacoustic imaging of peripheral nerve vascularization and morphology. JO - Proc. SPIE VL - 12842 PB - Spie-int Soc Optical Engineering PY - 2024 SN - 0277-786X ER - TY - CONF AB - We investigated gastric tissue biopsies using a liquid crystal-based Mueller microscope and a machine-learning approach to examine the degree of inflammation. Machine learning and statistical analysis were performed with the multidimensional dataset including the polarimetric properties (linear retardance and dichroism, and circular depolarization) and total transmitted intensity images of the unstained thin sections of gastric tissue to identify and quantify the microstructural differences between healthy control, chronic gastritis, and gastric cancer. AU - Kim, M. AU - Lee, H.R.* AU - Ossikovski, R.* AU - Jobart-Malfait, A.* AU - Lamarque, D.* AU - Novikova, T.* C1 - 71435 C2 - 56111 CY - 1000 20th St, Po Box 10, Bellingham, Wa 98227-0010 Usa TI - Digital histology of gastric tissue biopsies with liquid crystal-based Mueller microscope and machine learning approach. JO - Proc. SPIE VL - 13016 PB - Spie-int Soc Optical Engineering PY - 2024 SN - 0277-786X ER - TY - CONF AB - Despite its benefits for tumour detection and treatment, the administration of contrast agents in dynamic contrast-enhanced MRI (DCE-MRI) is associated with a range of issues, including their invasiveness, bioaccumulation, and a risk of nephrogenic systemic fibrosis. This study explores the feasibility of producing synthetic contrast enhancements by translating pre-contrast T1-weighted fat-saturated breast MRI to their corresponding first DCE-MRI sequence leveraging the capabilities of a generative adversarial network (GAN). Additionally, we introduce a Scaled Aggregate Measure (SAMe) designed for quantitatively evaluating the quality of synthetic data in a principled manner and serving as a basis for selecting the optimal generative model. We assess the generated DCE-MRI data using quantitative image quality metrics and apply them to the downstream task of 3D breast tumour segmentation. Our results highlight the potential of post-contrast DCE-MRI synthesis in enhancing the robustness of breast tumour segmentation models via data augmentation. Our code is available at https://github.com/RichardObi/pre_post_synthesis. AU - Osuala, R. AU - Joshi, S.* AU - Tsirikoglou, A.* AU - Garrucho, L.* AU - Pinaya, W.H.L.* AU - Diaz, O.* AU - Lekadir, K.* C1 - 70986 C2 - 55970 CY - 1000 20th St, Po Box 10, Bellingham, Wa 98227-0010 Usa TI - Pre- to post-contrast breast MRI synthesis for enhanced tumour segmentation. JO - Proc. SPIE VL - 12926 PB - Spie-int Soc Optical Engineering PY - 2024 SN - 0277-786X ER - TY - CONF AB - In histology, the widely used staining agents are hematoxylin and eosin (H&E), with hematoxylin marking cell nuclei and eosin staining the cytoplasm. By this, the color-coded information enables the early identification of histopathological changes using optical microscopy. However, the traditional histological process has significant drawbacks: the irreversible nature of tissue preparation often results in sample damage during dehydration, embedding, and sectioning, which can lead to the loss of crucial information. Moreover, standard microscopy techniques are limited to two-dimensional (2D) imaging, neglecting volumetric data crucial for detailed tissue analysis. X-ray imaging offers a non-destructive alternative, using contrast agents to enhance soft tissue visibility and allowing further investigations without compromising the sample. However, recently developed modified Xray stains require adjustment for specific tissues, presenting a new challenge. Hematein can be chemically modified through the incorporation of high atomic number metals to enhance contrast in X-ray Imaging, whereas eosin staining can be augmented by increasing its concentration and acidifying the samples tissue. In this study, we aimed to demonstrate the feasibility of applying both modified hematoxylin and eosin stains to the same specimen sequentially, using a washing step with ethylenediaminetetraacetic acid (EDTA) to remove the hematein stain between scans. This novel approach preserves the distinct information provided by each stain, enabling comprehensive visualization in two separate micro-computed tomography (microCT) scans. The method was applied to biological samples from a rat strain spontaneously developing multiple endocrine tumors (MENX), provided by the Division of Neuroendocrinology at the Helmholtz Centre Munich. Specifically, the pituitary and adrenal glands of wild-type and MENX-affected rats were stained and imaged using the microCT system versaXRM-500 (ZEISS/xradia, Oberkochen Germany). The results revealed promising differentiation between healthy and affected tissues, with high-resolution imaging showing visible tumor formations, blood pools, and tissue degradation in diseased samples. This study highlights the potential of combining sequential H&E staining with microCT for enhanced tissue analysis and visualization of disease progression. AU - Petzold, L.M.* AU - Busse, M.* AU - Mohr, H. AU - Pellegata, N.S. AU - Pfeiffer, F.* AU - Herzen, J.* C1 - 72900 C2 - 56779 CY - 1000 20th St, Po Box 10, Bellingham, Wa 98227-0010 Usa TI - Development of a H&E multi-agent-staining method for laboratory-microCT applied to endocrine glands of MENX rats. JO - Proc. SPIE VL - 13152 PB - Spie-int Soc Optical Engineering PY - 2024 SN - 0277-786X ER - TY - CONF AB - Medical image registration aims to identify the spatial deformation between images of the same anatomical region and is fundamental to image-based diagnostics and therapy. To date, the majority of the deep learning-based registration methods employ regularizers that enforce global spatial smoothness, e.g., the diffusion regularizer. However, such regularizers are not tailored to the data and might not be capable of reflecting the complex underlying deformation. In contrast, physics-inspired regularizers promote physically plausible deformations. One such regularizer is the linear elastic regularizer, which models the deformation of elastic material. These regularizers are driven by parameters that define the material’s physical properties. For biological tissue, a wide range of estimations of such parameters can be found in the literature, and it remains an open challenge to identify suitable parameter values for successful registration. To overcome this problem and to incorporate physical properties into learning-based registration, we propose to use a hypernetwork that learns the effect of the physical parameters of a physics-inspired regularizer on the resulting spatial deformation field. In particular, we adapt the HyperMorph framework to learn the effect of the two elasticity parameters of the linear elastic regularizer. Our approach enables the efficient discovery of suitable, data-specific physical parameters at test time. To the best of our knowledge, we are the first to use a hypernetwork to learn physics-inspired regularization for medical image registration. We evaluate our approach on 3D intra-patient lung CT images. The results show that the linear elastic regularizer can yield comparable results to the diffusion regularizer in unsupervised learning-based registration while predicting deformations with fewer foldings. With our method, the adaptation of the physical parameters to the data can successfully be performed at test time. Our code is available at https://github.com/annareithmeir/elastic-regularization-hypermorph. AU - Reithmeir, A.* AU - Schnabel, J.A. AU - Zimmer, V.A. C1 - 70988 C2 - 55854 CY - 1000 20th St, Po Box 10, Bellingham, Wa 98227-0010 Usa TI - Learning physics-inspired regularization for medical image registration with hypernetworks. JO - Proc. SPIE VL - 12926 PB - Spie-int Soc Optical Engineering PY - 2024 SN - 0277-786X ER - TY - JOUR AB - The viscoelastic properties of cells are an essential physical parameter in many biological processes. A crucial example is the softening of cancer cells during the metastatic cascade. The drivers behind the change in cell mechanics are still not fully understood and the mechanical properties of the substrate, the ECM, and crosstalk with other cells often influence measurements of cell mechanics.We used the optical stretcher (OS), a dual laser beam trap, to measure the active and passive viscoelastic properties of cancer cells in suspension. We compare cancerous cells with and without co-culturing them with adipose tissue cells. With this assay, we can investigate the impact of the cellular crosstalk between the cancerous and adipose tissue cells on the physical properties of cells, thereby disentangling it from any substrate effects. Our goal is to understand how cancer cells are able to migrate through soft fatty tissue and what mechanical properties are essential during this process. AU - Blauth, E.* AU - Kubitschke, H.* AU - Wolf, B.* AU - Kovacs, P.* AU - Blüher, M. AU - Dornhöfer, N.* AU - Aktas, B.* AU - Käs, J.A.* C1 - 68809 C2 - 53717 TI - Fatty tissue as a modulator of cancer cell mechanics. JO - Proc. SPIE VL - 12649 PY - 2023 SN - 0277-786X ER - TY - CONF AB - Hyperspectral imaging (HSI) is an optical technique that processes the electromagnetic spectrum at a multitude of monochromatic, adjacent frequency bands. The wide-bandwidth spectral signature of a target object's reflectance allows fingerprinting its physical, biochemical, and physiological properties. HSI has been applied for various applications, such as remote sensing and biological tissue analysis. Recently, HSI was also used to differentiate between healthy and pathological tissue under operative conditions in a surgery room on patients diagnosed with brain tumors. In this article, we perform a statistical analysis of the brain tumor patients' HSI scans from the HELICoiD dataset with the aim of identifying the correlation between reflectance spectra and absorption spectra of tissue chromophores. By using the principal component analysis (PCA), we determine the most relevant spectral features for intra- and inter-tissue class differentiation. Furthermore, we demonstrate that such spectral features are correlated with the spectra of cytochrome, i.e., the chromophore highly involved in (hyper) metabolic processes. Identifying such fingerprints of chromophores in reflectance spectra is a key step for automated molecular profiling and, eventually, expert-free biomarker discovery. AU - Ezhov, I.* AU - Giannoni, L.* AU - Shit, S.* AU - Lange, F.* AU - Kofler, F. AU - Menze, B.* AU - Tachtsidis, I.* AU - Rueckert, D.* C1 - 68210 C2 - 53619 TI - Identifying chromophore fingerprints of brain tumor tissue on hyperspectral imaging using principal component analysis. JO - Proc. SPIE VL - 12628 PY - 2023 SN - 0277-786X ER - TY - JOUR AB - Mid-infrared (mid-IR) spectroscopy and optoacoustic/optothermal (OA/OT) imaging are perfectly complementary technologies to each other. Vibrational molecular excitations by mid-IR absorption are utterly de-excited in the form of heat while efficient OA/OT signal generation primarily depends on heat deposition. This synergy allows overcoming the (otherwise) persistent limitations of traditional mid-IR spectroscopy and imaging in live-cell/fresh-tissue applications—i.e., sample opacity due to water absorption. Combination of mid-IR excitation and OA/OT detection has resulted in new tools for label-free live-cell, tissues, and in vivo metabolic research. Here we discuss basic principles on mid-IR detection for spectroscopy and imaging as well as the most recent developments on mid-IR OA and OT microscopy that overcome the limitations of conventional vibrational spectroscopy for biosensing and label-free metabolic microscopy. AU - Yuan, T. AU - Gasparin, F. AU - Uluc, N. AU - Ntziachristos, V. AU - Pleitez, M.A. C1 - 68555 C2 - 53672 TI - Functional live-cell mid-infrared microscopy and spectroscopy by optoacoustic and optothermal detection. JO - Proc. SPIE VL - 12392 PY - 2023 SN - 0277-786X ER - TY - JOUR AB - The inability to directly visualize large-scale neural dynamics across the entire mammalian brain in the millisecond temporal resolution regime is among the main limitations of existing neuroimaging methods. Recent advances in optoacoustic imaging systems have led to the establishment of this technology as an alternative method for real-time deep-tissue observations. Particularly, functional optoacoustic neurotomography (FONT) has recently been suggested for three-dimensional imaging of both direct calcium activity and cerebral hemodynamic parameters in rodents. However, the lack of suitable calcium indicators featuring optical absorption peaks within the so-called near-infrared window has hampered the applicability of FONT for imaging neuronal activity deep within the mammalian brain. To surmount this challenge, we developed and validated an intracardially perfused murine brain model labelled with genetically encoded calcium indicator GCaMP6f that closely simulates in vivo conditions. Penetration of light through skull and skin is greatly facilitated after blood is substituted by artificial cerebrospinal fluid (ACSF). The new preparation enabled here the observation of stimulus-evoked calcium dynamics within the mouse brain at penetration depths and spatio-temporal resolution scales not attainable with other neuroimaging techniques. AU - Degtyaruk, O. AU - Mc Larney, B. AU - Deán-Ben, X.L.* AU - Shoham, S.* AU - Razansky, D. C1 - 62383 C2 - 50935 TI - Optoacoustic visualization of GCaMP6f labeled deep brain activity in a murine intracardiac perfusion model. JO - Proc. SPIE VL - 11629 PY - 2021 SN - 0277-786X ER - TY - JOUR AB - Visualizing whole-body dynamics across entire living organisms is crucial for understanding complex biology, disease progression as well as evaluating efficacy of new drugs and therapies. Existing small animal functional and molecular imaging modalities either suffer from low spatial and temporal resolution, limited penetration depth or poor contrast. In this work, we present flash scanning volumetric optoacoustic tomography (fSVOT) imaging system that enables the acquisition speeds required for visualizing fast kinetics and biodistribution of optical contrast agents across whole mice. fSVOT can render images of intricate vascular and organ anatomy with rich contrast by capitalizing on the large angular coverage of a spherical matrix array transducer rapidly scanned around the mouse. Volumetric (three-dimensional) images with 200 μm resolution can be acquired within 45 seconds, which corresponds to an imaging speed gain of an order of magnitude with respect to existing state-of-the-art modalities offering comparable resolution performance. We demonstrate volumetric tracking and quantification of gold nanorod kinetics and their differential uptake across the spleen, liver and kidneys. Overall, fSVOT offers unprecedented capabilities for multi-scale imaging of pharmacokinetics and bio-distribution of agents with high contrast, resolution and image acquisition speed. AU - Kalva, S.K.* AU - Ron, A. AU - Periyasamy, V. AU - Reiss, M.* AU - Deán-Ben, X.L.* AU - Razansky, D. C1 - 62505 C2 - 50790 TI - Whole-body visualization of nanoagent kinetics in mice with flash scanning volumetric optoacoustic tomography. JO - Proc. SPIE VL - 11642 PY - 2021 SN - 0277-786X ER - TY - JOUR AB - Ultrasound (US) and optoacoustic (OA) imaging provide complementary information for quantitative analysis of the tumor microenvironment. Herein, we demonstrate the unique capabilities of transmission-reflection optoacoustic ultrasound (TROPUS) for characterizing breast cancer in tumor-bearing mice. For this, 4 different mice featuring orthotopic tumor of different sizes were scanned with a full-ring ultrasound transducer array to simultaneously render pulse-echo US images, speed of sound (SoS) maps and OA images. The tumor size, vascular density and its elastic parameters were further quantified in the images. Our results pave the way toward clinical translation of the hybrid TROPUS imaging for tumor detection and characterization. AU - Lafci, B.* AU - Mercep, E. AU - Herraiz, J.L.* AU - Deán-Ben, X.L.* AU - Razansky, D. C1 - 62506 C2 - 50789 TI - Transmission-reflection optoacoustic ultrasound (TROPUS) imaging of mammary tumors. JO - Proc. SPIE VL - 11642 PY - 2021 SN - 0277-786X ER - TY - JOUR AB - Laser ablation (LA) is gaining acceptance for the treatment of tumors as a viable alternative to surgical resection. In parallel, optoacoustic tomography (OAT) has enabled defining new regimes for diagnosis and characterization of malignant neoplastic lesions with high sensitivity and specificity. Even though pulsed nanosecond lasers are commonly used for both imaging and therapeutic purposes, real-time thermal treatment monitoring with a single laser source has not been previously attempted. Herein, we demonstrate the feasibility of combined OAT and LA by percutaneous irradiation of subcutaneous tumors with a 100 mJ short-pulsed (∼5 ns) laser operating at 1064 nm and 100 Hz pulse repetition frequency. The OAT images rendered with a spherical ultrasound transducer array enabled real-time monitoring of the LA lesion progression, which is essential for determining the optimal treatment end-point. Local changes in the optoacoustic signal intensity associated with the induced temperature changes as well as structural alterations in the tumor vasculature could clearly be observed. The optoacoustic volumetric projections further correlated with crosssections extracted from the excised tumors. This newly enabled capability anticipates new theranostic approaches in cancer research and treatment with potential applicability in a clinical setting. AU - Özsoy, Ç.* AU - Periyasamy, V. AU - Reiss, M.* AU - Deán-Ben, X.L.* AU - Razansky, D. C1 - 62504 C2 - 50788 TI - Concurrent in vivo tumor ablation and real-time optoacoustic monitoring with a pulsed 1064 nm laser source. JO - Proc. SPIE VL - 11642 PY - 2021 SN - 0277-786X ER - TY - JOUR AB - Particles with sizes in the order of a few micrometers can significantly enhance the capabilities of optoacoustic imaging systems by improving visualization of arbitrarily oriented vascular structures and achieving resolution beyond the acoustic diffraction barrier. Particle tracking may also be used for mapping the blood flow in two and three dimensions. However, a trade-off exists between the particle absorption properties and size, whereas large sized microparticles also tend to arrest in the capillary network. We analyzed the flow of microparticles in an intracardiac perfusion mouse model in which blood is effectively substituted by artificial cerebrospinal fluid (ACSF). This enables mitigating the strong blood absorption background in the optoacoustic images thus facilitating the visualization of microparticles. A sequence of three-dimensional optoacoustic images of the mouse brain is then acquired at a high frame rate of 100 Hz after injection of the particles in the left heart ventricle. By visualizing the flow of particles of different sizes in microvascular structures it is possible to establish optimal trade-offs between the particle size, their optoacoustic signal and perfusion properties. AU - Deán-Ben, X.L.* AU - Degtyaruk, O. AU - Razansky, D. C1 - 58831 C2 - 48625 TI - Visualization of microparticle flow in the mouse brain in an intracardiac perfusion model. JO - Proc. SPIE VL - 11240 PY - 2020 SN - 0277-786X ER - TY - JOUR AB - Understanding the mechanisms of cardiac disorders largely depends on availability of multi-dimensional and multiparametric imaging methods capable of quantitative assessment of cardiac morphology and function. The imaging modalities commonly employed in cardiac research, such as ultrasonography and magnetic resonance imaging, are lacking sufficient contrast and/or spatio-temporal resolution in 3D in order to reveal the multi-scale nature of rapid electromechanical activity in a beating heart. Our recently developed volumetric optoacoustic tomography (VOT) platform offers versatile observations of the heart function with rich optical contrast at otherwise unattainable temporal and spatial resolutions. Herein, we further advance the imaging performance by developing compressed acquisition scheme to boost the temporal resolution of VOT into the kilohertz range, thus enabling 3D mapping of electromechanical wave propagation in the heart. Experiments in isolated mouse hearts were performed by exciting the entire imaged tissue volume with nanosecond-duration laser pulses at 1 kHz repetition rate pulse operating at 532 nm and sparse tomographic signal sampling using a custom-made 512-element spherical matrix ultrasound array. By analyzing the strain maps obtained from the rapid VOT image sequence, it was possible to quantify the phase velocity of the electromechanical cardiac waves, in good agreement with previously reported values. AU - Özsoy, Ç.* AU - Özbek, A. AU - Dean-Ben, X.L.* AU - Razansky, D. C1 - 58830 C2 - 48624 TI - Ultrafast imaging of cardiac electromechanical wave propagation with volumetric optoacoustic tomography. JO - Proc. SPIE VL - 11240 PY - 2020 SN - 0277-786X ER - TY - JOUR AB - Changes in the structure of the nasal mucosa can be a morphological biomarker and therefore helpful for diagnosis and follow-up of various pulmonary diseases such as asthma, cystic fibrosis and primary ciliary dyskinesia. In order to verify that microscopic optical coherence tomography (mOCT) is a valuable instrument for the investigation of those changes, an endoscopic OCT system with microscopic resolution (emOCT) was developed and built for clinical testing. The endoscope is based on a graded-index (GRIN) lens optic and provides a calculated lateral resolution of 0.7 µm and an axial resolution of 1.25 µm. The imaging depth was up to 500 µm in tissue; axially, a lateral range of approximate 250 µm could be covered. B-scans were acquired at 80 Hz with 512 pixels in lateral and 1024 pixels in depth-direction. The diameter of the endoscope decreases over a length of 8 cm from 8 mm at the beginning to 1.4 mm at the end and is small enough to observe the mucous membrane in the human nasal concha media and inferior down to the nasopharynx. The emOCT workstation was designed to meet German electrical, optical and biological safety standards. The applicability of the endoscope could be demonstrated in vivo. Mucus transport, glands, blood and lymphatic vessels could be visualized. AU - Ahrens, M.* AU - Idel, C.* AU - Chaker, A. AU - Wollenberg, B.* AU - König, P.* AU - Schulz-Hildebrandt, H.* AU - Hüttmann, G.* C1 - 57203 C2 - 47608 TI - An endomicroscopic OCT for clinical trials in the field of ENT. JO - Proc. SPIE VL - 11073 PY - 2019 SN - 0277-786X ER - TY - JOUR AB - Optoacoustic imaging is a highly scalable and versatile method that can be used for optical resolution (OR) microscopy applications at superficial depth yet can be adapted for tomographic imaging with ultrasonic resolution at centimeter penetration scales. However, imaging speed of the commonly employed scanning-based microscopy methods is slow as far as concerned with acquisition of volumetric data. Herein, we propose a new approach using multifocal structured illumination in conjunction with a spherical matrix ultrasonic array detection to achieve fast volumetric optoacoustic imaging in both optical and acoustic resolution modes. In our approach, the laser beam is raster scanned by an acousto-optic deflector running at hundred hertz scanning rate with the beam then split into hundreds of mini-beams by a beamsplitting grating, which are subsequently focused by a condensing lens to generate multifocal structured illumination. Phantom experimental results show that 10 x 10 x 5 cm 3 volumetric imaging can be accomplished with spatial resolution around 29 μm. We believe by further speeding up the data acquisition in the further, the system will be operated in full power, making it possible to study functional, kinetic and metabolic processes across multiple penetration scales. AU - Chen, Z. AU - Deán-Ben, X.L.* AU - Özbek, A. AU - Rebling, J.* AU - Razansky, D. C1 - 56059 C2 - 46796 TI - Multifocal structured illumination optoacoustic microscopy. JO - Proc. SPIE VL - 10878 PY - 2019 SN - 0277-786X ER - TY - JOUR AB - Biomedical optoacoustic (photoacoustic) imaging is generally performed with short laser pulses with durations in the order of a few nanoseconds. This enables maximizing the conversion efficiency of optical energy into acoustic (ultrasound) energy when light is absorbed in biological tissues. The generated ultrasound waves are generally very broadband, with typical frequency spectra ranging from tens of kHz to tens of MHz. Most ultrasound transducers used for the detection of optoacoustic signals have a finite detection bandwidth, in a way that they are not optimal for the acquisition of optoacoustic signals generated with a single pulse. In this work, we analyze a narrowband excitation approach based on a tone-burst consisting of multiple equally-delayed short pulses. We compare the power spectral density of the signals generated with a tone-burst with those generated with a single pulse having the same energy under safety exposure limits. We further analyze the performance of tone-burst excitation when non-linear effects take place. Specifically, we consider non-linearities associated to temperature increase and to optical absorption saturation. AU - Dean-Ben, X.L. AU - Razansky, D. C1 - 56061 C2 - 46798 TI - Analysis of the optoacoustic signals generated with a tone-burst of nanosecond duration pulses. JO - Proc. SPIE VL - 10878 PY - 2019 SN - 0277-786X ER - TY - JOUR AB - A myriad of optoacoustic imaging systems based on scanning focused ultrasound transducers or on tomographic acquisition of pressure signals are available. In all cases, image formation is based on the assumption that ultrasound waves undergo no distortion and propagate with constant velocity across the sample and coupling medium (typically water). Thereby, ultrasound time-of-flight readings from multiple time-resolved signals are required to form an image. Acoustic scattering is known to cause distortion in the signals and is generally to be avoided. In this work, we exploit acoustic scattering to physically encode the position of optical absorbers in the acquired time-resolved signals and hence reduce the amount of data required to reconstruct an image. This new approach was experimentally tested with an array of cylindrically-focused transducers, where a cluster of acoustic scatterers was introduced in the ultrasound propagating path between the sample and the array elements. Ultrasound transmission was calibrated by raster scanning a lightabsorbing particle across the effective field of view. The acquired calibrating signals were then used for the development of a regularized model-based iterative algorithm that enabled reconstructing an image from a relatively low number of optoacoustic signals. A relatively short acquisition time window was needed to capture the entire optoacoustic field, which demonstrates the high signal compression efficiency. The feasibility to form an image with a relatively low number of signals is expected to play a major role in the development of a new generation of optoacoustic imaging systems. AU - Dean-Ben, X.L. AU - Özbek, A. AU - Razansky, D. C1 - 56062 C2 - 46799 TI - Compressed optoacoustic data acquisition based on a cluster of acoustic scatterers. JO - Proc. SPIE VL - 10878 PY - 2019 SN - 0277-786X ER - TY - JOUR AB - Model-based reconstruction techniques have been successfully implemented in optoacoustic tomography and acoustic-resolution microscopy to retrieve improved image quality over delay-and-sum methods. In scanning optical resolution optoacoustic microscopy (OR-OAM), no reconstruction methods are employed while post- processing is usually limited to basic frequency filtering and envelope extraction with the Hilbert transform. This results in considerable deterioration of the acoustically-determined resolution in the axial (depth) direction. In addition, when OR-OAM is used for transcranial mouse brain imaging, the skull strongly attenuates high ultrasonic frequencies and induces reverberations, which need to be accounted for during the reconstruction process to avoid image distortions and further deterioration of the axial resolution. Here we show a basic implementation of a model-based reconstruction to increase the axial resolution in OR-OAM. The model matrix is calculated using Field II for free field conditions, taking into account the shape and bandwidth of the spherically focused transducer. Assuming the confinement of the optoacoustic sources within the limits of the optical focus, one may calculate the model matrix by assuming a line source of small absorbing spheres equal in size to the optical beam. In addition, a plate model used in the recently reported virtual-craniotomy deconvolution algorithm is incorporated into the model matrix to tackle the transcranial acoustic transmission problem. The free-field model-based results are compared against the plate model for transcranial brain data obtained in-vivo. AU - Estrada, H. AU - Razansky, D. C1 - 56064 C2 - 46794 TI - Model-based optical resolution optoacoustic microscopy. JO - Proc. SPIE VL - 10878 PY - 2019 SN - 0277-786X ER - TY - JOUR AB - Fluorescence-guided intervention is increasingly considered for real-time intra-operative oncological applications. Herein we propose a novel composite phantom for standardization and quality control, which could serve as a framework toward good clinical practices. AU - Gorpas, D. AU - Anastasopoulou, M. AU - Koch, M. AU - Klemm, U. AU - Nieberler, M.* AU - Ntziachristos, V. C1 - 57263 C2 - 47659 TI - Standardization phantom for intra-operative fluorescence molecular imaging. JO - Proc. SPIE VL - 11079 PY - 2019 SN - 0277-786X ER - TY - JOUR AB - Chronic hypoxia in pulmonary diseases is known to have a severe negative impact on heart function, including right heart hypertrophy, increased workload on the heart and arrhythmia. Yet, the direct effect of the chronic hypoxic environment on the cardiovascular system is still not fully understood. Usual pre-clinical analytic methods analysing this effect are limited to ex vivo histology or highly invasive approaches such as right heart catheterisation, which inevitably interfere with cardiac tissue. In this work, we propose volumetric optoacoustic tomography as a method for assessing heart function in response to chronic hypoxia non-invasively. Hypoxic and normoxic murine hearts were imaged in vivo at high temporal (100 Hz) and spatial resolution (200 μm). Analysis of the murine models on a beat-to-beat scale enabled identifying and characterizing arrhythmic events in hypoxic models. In addition, blood flow was tracked using indocyanide green (ICG) contrast agent, which revealed a clear difference in the pulmonary transit time (PTT) between the hypoxic and normoxic models. Validation for presence of hypoxia in the lungs was carried out by α-smooth muscle actin staining for muscularization of the pulmonary vasculature. We expect that the novel capabilities offered by volumetric optoacoustic tomography for analysing impaired heart function under hypoxic conditions in pre-clinical models will provide important insights into early diagnosis and treatment methods for pulmonary diseases. AU - Ivankovic, I. AU - Lin, H.-C. AU - Dean-Ben, X.L. AU - Zhang, Z.* AU - Trautz, B.* AU - Gorlach, A.* AU - Razansky, D. C1 - 56065 C2 - 46795 TI - In vivo assessment of heart function under chronic hypoxic stress with volumetric optoacoustic tomography. JO - Proc. SPIE VL - 10878 PY - 2019 SN - 0277-786X ER - TY - JOUR AB - Bright synchrotron x-ray sources enable imaging with short exposure times, and hence in a high-speed image sequence. These x-ray movies can capture not only sample structure, but also how the sample changes with time, how it functions. The use of a synchrotron x-ray source also provides high spatial coherence, which facilitates the capture of not only a conventional attenuation-based x-ray image, but also phase-contrast and dark-field signals. These signals are strongest from air/tissue interfaces, which means that they are particularly useful for examining the respiratory system. We have performed a range of x-ray imaging studies that look at lung function, airway surface function, inhaled and instilled treatment delivery, and treatment effect in live small animal models [Morgan, 2019]. These have utilized a range of optical set-ups and phase-contrast imaging methods in order to be sensitive to the relevant sample features, and be compatible with high-speed imaging. For example, we have used a grating interferometer to measure how the airsacs in the lung inflate during inhalation, via changes in the dark-field signal [Gradl, 2018], a single-exposure, single-grid set-up to capture changes in the liquid lining of the airways [Morgan, 2015] and propagation-based phase contrast to image clearance of inhaled debris [Donnelley, 2019]. Studies have also utilized a range of analysis methods to extract how the sample features change within a time-sequence of two-dimensional projections or three-dimensional volumes. While these imaging studies began in large-scale synchrotron facilities, we have recently performed these kinds of studies at an inverse-Compton-based compact synchrotron, the Munich Compact Light Source (MuCLS) [Gradl, 2018b]. 1. Morgan, Kaye, et al., "Methods for dynamic synchrotron X-ray imaging of live animals.", under review 01/2019. 2. Gradl, R., et al. "Dynamic in vivo chest x-ray dark-field imaging in mice." IEEE Transactions on Medical Imaging (2018). 3. Morgan, Kaye S., et al. "In vivo X-ray imaging reveals improved airway surface hydration after a therapy designed for cystic fibrosis." American Journal of Respiratory and Critical Care Medicine 190.4 (2014): 469-472. 4. Donnelley, Martin, et al. "Live-pig-airway surface imaging and whole-pig CT at the Australian Synchrotron Imaging and Medical Beamline." Journal of Synchrotron Radiation 26.1 (2019). 5. Gradl, Regine, et al. "In vivo Dynamic Phase-Contrast X-ray Imaging using a Compact Light Source." Scientific Reports 8.1 (2018b): 6788. AU - Morgan, K.S.* AU - Gradl, R.* AU - Dierolf, M.* AU - Jud, C.* AU - Günther, B.* AU - Werdiger, F.* AU - Gardner, M.* AU - Cmielewski, P.* AU - McCarron, A.* AU - Farrow, N.* AU - Haas, H.* AU - Kimm, M.A.* AU - Yang, L.* AU - Kutschke, D. AU - Stöger, T. AU - Schmid, O. AU - Achterhold, K.* AU - Pfeiffer, F.* AU - Parsons, D.* AU - Donnelley, M.* C1 - 57866 C2 - 47993 TI - In vivo x-ray imaging of the respiratory system using synchrotron sources and a compact light source. JO - Proc. SPIE VL - 11113 PY - 2019 SN - 0277-786X ER - TY - JOUR AB - Efficient monitoring of radiofrequency ablation procedures is essential to optimize the lesions induced to treat cancer, cardiac arrhythmias and other conditions. Recently, optoacoustic imaging and sensing methods have been suggested as a promising approach to address this challenge, offering unique advantages such as high sensitivity to temperature changes and chemical transformations in coagulated tissues, real-time operation and use of non- ionizing radiation. However, assessing how the ablation lesion boundary progresses is still challenged by changes in optical properties induced during the interventions. Herein, we suggest a new approach for dimensional characterization of the induced lesion based on detecting sharp positive variations in the time derivative of optoacoustic signals. Experiments in porcine tissue samples indicate that such variations are uniquely associated to the onset of ablation and that the method can robustly visualize the evolution of the lesion in three dimensions. AU - Oyaga Landa, F.J. AU - Özsoy, C. AU - Dean-Ben, X.L. AU - Razansky, D. C1 - 56058 C2 - 46797 TI - Optoacoustic monitoring of RF ablation lesion progression. JO - Proc. SPIE VL - 10878 PY - 2019 SN - 0277-786X ER - TY - JOUR AB - Laser ablation (LA) represents a minimally invasive intervention that is gaining acceptance for the treatment of different types of cancer, leading to important advantages such as less pain and shorter recovery time. Accurate monitoring of ablation progression is crucial to prevent damage of non-cancerous tissues and optimize the outcome of the intervention. To this end, imaging techniques such as ultrasound, computed tomography or magnetic resonance imaging have been used for monitoring LA. However, these techniques feature important drawbacks such as the need of contrast agents, poor spatio-temporal resolution or high cost. Optoacoustics (OA, photoacoustic) has recently been shown to provide unique properties to monitor thermal treatments. Herein, we demonstrate the feasibility of optoacoustic laser-ablation (OLA) monitoring in a murine breast tumor model using a single short-pulsed 1064 nm laser source. The effect of irradiation was volumetrically tracked with the OA images acquired with a 256-element spherical array. Structural damage of the tissue was clearly seen during the LA procedure. AU - Periyasamy, V. AU - Özsoy, Ç.* AU - Reiss, M.* AU - Deán-Ben, X.L.* AU - Razansky, D. C1 - 57264 C2 - 47660 TI - Tumor ablation and volumetric optoacoustic monitoring with a short-pulsed laser source. JO - Proc. SPIE VL - 11077 PY - 2019 SN - 0277-786X ER - TY - JOUR AB - Breast cancer and Glioblastoma brain cancer are aggressive malignancies with poor prognosis. In this study primary Glioblastoma and secondary breast cancer spheroids are formed and treated with the well-known Temozolomide and Doxorubicin chemotherapeutics, respectively. A custom multi-angle Light Sheet Fluorescence Microscope is employed for high resolution imaging of both cancer cell spheroids. Such a technique is successful in realizing pre-clinical drug screening, while enables the discrimination among physiologic tumor parameters. LSFM technique, parameters and method followed are also presented. AU - Psycharakis, S.E.* AU - Liapis, E. AU - Zacharopoulos, A.* AU - Oraiopoulou, M.E.* AU - Aivalioti, C.* AU - Sakkalis, V.* AU - Papamatheakis, J.* AU - Ripoll, J.* AU - Zacharakis, G.* C1 - 57261 C2 - 47658 TI - High resolution 3D imaging of primary and secondary tumor spheroids using multicolor multi-angle Light Sheet Fluorescence Microscopy (LSFM). JO - Proc. SPIE VL - 11076 PY - 2019 SN - 0277-786X ER - TY - JOUR AB - Ground-based remote sensing by three ceilometers for mixing layer height detection over Augsburg as well as a Radio-Acoustic Sounding System (RASS) for temperature and wind profile measurements at the campus of Augsburg University are applied together with UAV height profiling with low-weight meteorological sensors and particle counter to monitor the three-dimensional dynamics of the lower atmosphere. Results about meteorological influences upon spatial variation of air pollution exposure are presented on this data basis which is more than one year long. Special focus is on the information about atmospheric layering as well as mixing and transport conditions for emitted particulate matter. Better understanding of these complex processes support knowledge about quality of air, which we breath, and especially high air pollution episodes and hot spot pollution regions. AU - Redelstein, J.* AU - Budde, M.* AU - Cyrys, J. AU - Emeis, S.* AU - Gratza, T.* AU - Grimm, H.* AU - Hank, M.* AU - Holst, C.* AU - Münkel, C.* AU - Pesch, M.* AU - Petersen, E.* AU - Philipp, A.* AU - Riedel, T.* AU - Riesterer, J.* AU - Schäfer, K.* AU - Schnelle-Kreis, J. AU - Uhrner, U.* AU - Werhahn, J.* AU - Ziegler, V.* AU - Beigl, M.* C1 - 58173 C2 - 48066 TI - Assessment of three-dimensional, fine-granular measurement of particulate matter by a smart air quality network in urban area. JO - Proc. SPIE VL - 11152 PY - 2019 SN - 0277-786X ER - TY - JOUR AB - We present the investigation of in vivo small model organisms, which are well established in biological and biomedical research, using a hybrid multiphoton and optoacoustic microscope (HyMPOM). The unique capabilities of HyMPOM for multimodal and potentially label-free signal acquisition, high resolution, as well as deep and fast imaging allow extraction of detailed information across large areas of living tissue on the microscale. Applying HyMPOM to living zebrafish-like fish larvae allowed exploration of the structural composition of the entire brain, including the brain vasculature and the neuronal network. Applying HyMPOM to the ears of living mice enabled accurate imaging of vasculature, connective tissue, keratinocytes, and sebaceous glands. The hybrid microscope proposed here constitutes a novel approach to explore small model organisms in vivo in great detail by revealing the spatial distribution and interplay of various tissue compartments on the microscale. AU - Seeger, M. AU - Westmeyer, G.G. AU - Ntziachristos, V. C1 - 57265 C2 - 47661 TI - In vivo hybrid microscopy of small model organisms. JO - Proc. SPIE VL - 11077 PY - 2019 SN - 0277-786X ER - TY - CONF AB - In this work we developed a novel near-infrared two-path optoacoustic spectrometer (NiR-TAOS) that could sense OA intensity changes due to metabolite concentration changes in-vivo. The main aim of dividing the optical path in two is 1) perform real time correction of the laser emission profile of the laser source at different wavelengths and, 2) perform pulse to pulse correction to remove laser beam fluctuation and instability to increase signal to noise ratio. Signal to noise ratio improvement was significant not only at spectral peaks, but also at all other wavelengths. The system can be used for broad applications in biomedical measurements such as various metabolites in the SWIR. AU - Seyedebrahimi, M.M. AU - Pleitez, M.A. AU - Mohajerani, P. AU - Ntziachristos, V. C1 - 57262 C2 - 47657 TI - Non-invasive In-vivo sensing of metabolites with a novel Optoacoustic Spectroscope in the SWIR. JO - Proc. SPIE VL - 11077 PY - 2019 SN - 0277-786X ER - TY - JOUR AB - Even though the speed of sound (SoS) is non-homogeneous in biological tissue, most reconstruction algorithms for optoacoustic imaging neglect its variation. In addition, when heavy water is used as coupling medium to enable imaging of certain biological chromophores such as lipids and proteins, the SoS also differs significantly between couplant and tissue. While the assumption of uniform SoS is known to introduce visible deformations of features in single-wavelength optoacoustic images, the spectral error introduced by the assumption of uniform SoS is not fully understood. In this work, we provide an in-depth spectral analysis of multi-spectral optoacoustic imaging artifacts that result from the assumption of uniform SoS in situations where SoS changes substantially. We propose a dual-SoS model to incorporate the SoS variation between the couplant and the sample. Tissue-mimicking phantom experiments and in vivo measurements show that uniform SoS reconstruction causes spectral smearing, which dual-SoS modeling can largely eliminate. Due to this increased spectral accuracy, the method has the potential to improve clinical studies that rely on quantitative optoacoustic imaging of biomolecules like hemoglobin or lipids. AU - Yang, H. AU - Jüstel, D. AU - Prakash, J. AU - Ntziachristos, V. C1 - 55746 C2 - 46502 TI - Modeling the variation in speed of sound between couplant and tissue improves the spectral accuracy of multispectral optoacoustic tomography. JO - Proc. SPIE VL - 10890 PY - 2019 SN - 0277-786X ER - TY - JOUR AB - Fluorescence imaging is widely employed in all fields of cell and molecular biology due to its high sensitivity, high contrast and ease of implementation. However, the low spatial resolution and lack of depth information, especially in strongly-scattering samples, restrict its applicability for deep-tissue imaging applications. On the other hand, optoacoustic imaging is known to deliver a unique set of capabilities such as high spatial and temporal resolution in three dimensions, deep penetration and spectrally-enriched imaging contrast. Since fluorescent substances can generate contrast in both modalities, simultaneous fluorescence and optoacoustic readings can provide new capabilities for functional and molecular imaging of living organisms. Optoacoustic images can further serve as valuable anatomical references based on endogenous hemoglobin contrast. Herein, we propose a hybrid system for in vivo real-time planar fluorescence and volumetric optoacoustic tomography, both operating in reflection mode, which synergistically combines the advantages of stand-alone systems. Validation of the spatial resolution and sensitivity of the system were first carried out in tissue mimicking phantoms while in vivo imaging was further demonstrated by tracking perfusion of an optical contrast agent in a mouse brain in the hybrid imaging mode. Experimental results show that the proposed system effectively exploits the contrast mechanisms of both imaging modalities, making it especially useful for accurate monitoring of fluorescence-based signal dynamics in highly scattering samples. AU - Chen, Z. AU - Dean-Ben, X.L. AU - Gottschalk, S. AU - Razansky, D. C1 - 53859 C2 - 45089 TI - Hybrid system for in vivo real-time planar fluorescence and volumetric optoacoustic imaging. JO - Proc. SPIE VL - 10494 PY - 2018 SN - 0277-786X ER - TY - JOUR AB - Fluorescence imaging is widely employed in biological discovery due to its excellent molecular sensitivity and contrast. However, due to light scattering wide-field fluorescence images are blurred resulting in very low spatial resolution and low image contrast. The existing scanning optical microscopy techniques are commonly restricted to sub-millimeter field-of-view or otherwise slow imaging speeds, limiting their applicability for imaging of fast biological dynamics occurring on larger spatial scales. Herein, we developed a rapid scanning wide-field multifocal structured illumination microscopy method based on a beam-splitting grating and an acousto-optic deflector synchronized with a high speed camera. The multi-beam pattern is focused by a condensing lens and a macroscopic objective to generate multifocal structured illumination profile on the imaged sample that is rapidly scanned at kHz rates. Experimental results show that the proposed method can achieve real-time fluorescence microscopy over a centimeter-scale field of view. Owing to the low numerical aperture of the diffracted beams, the illumination has a large depth of focus and hence is generally not affected by the sample's curvature, which allowed here imaging of perfusion in the entire mouse cerebral cortex noninvasively. The new approach can be readily incorporated into traditional wide-field microscopes to attain optimal tradeoff between spatial resolution and field of view. It further establishes a bridge between conventional wide-field macroscopy and laser scanning confocal microscopy, thus anticipated to find broad applicability in a variety of applications looking at large-scale fluorescent-based biodynamics. AU - Chen, Z. AU - Mc Larney, B. AU - Rebling, J. AU - Dean-Ben, X.L. AU - Gottschalk, S. AU - Razansky, D. C1 - 54868 C2 - 45866 TI - Multifocal structured illumination fluorescence microscopy with large field-of-view and high spatio-temporal resolution. JO - Proc. SPIE VL - 10816 PY - 2018 SN - 0277-786X ER - TY - JOUR AB - Downloading of the abstract is permitted for personal use only. Optical microscopy remains a major workhorse in biological discovery despite the fact that light scattering limits its applicability to depths of ∼ 1 mm in scattering tissues. Optoacoustic imaging has been shown to overcome this barrier by resolving optical absorption with microscopic resolution in significantly deeper regions. Yet, the time domain is paramount for the observation of biological dynamics in living systems that exhibit fast motion. Commonly, acquisition of microscopy data involves raster scanning across the imaged volume, which significantly limits temporal resolution in 3D. To overcome these limitations, we have devised a fast optoacoustic micro-tomography (OMT) approach based on simultaneous acquisition of 3D image data with a high-density hemispherical ultrasound array having effective detection bandwidth around 25 MHz. We performed experiments by imaging tissue-mimicking phantoms and zebrafish larvae, demonstrating that OMT can provide nearly cellular resolution and imaging speed of 100 volumetric frames per second. As opposed to other optical microscopy techniques, OMT is a hybrid method that resolves optical absorption contrast acoustically using unfocused light excitation. Thus, no penetration barriers are imposed by light scattering in deep tissues, suggesting it as a powerful approach for multi-scale functional and molecular imaging applications. AU - Dean-Ben, X.L. AU - López-Schier, H. AU - Razansky, D. C1 - 53854 C2 - 45078 TI - High-frame-rate imaging of biological samples with optoacoustic micro-tomography. JO - Proc. SPIE VL - 10494 PY - 2018 SN - 0277-786X ER - TY - JOUR AB - Diffraction causes blurring of high-resolution features in images and has been traditionally associated to the resolution limit in light microscopy and other imaging modalities. The resolution of an imaging system can be generally assessed via its point spread function, corresponding to the image acquired from a point source. However, the precision in determining the position of an isolated source can greatly exceed the diffraction limit. By combining the estimated positions of multiple sources, localization-based imaging has resulted in groundbreaking methods such as super-resolution fluorescence optical microscopy and has also enabled ultrasound imaging of microvascular structures with unprecedented spatial resolution in deep tissues. Herein, we introduce localization optoacoustic tomography (LOT) and discuss on the prospects of using localization imaging principles in optoacoustic imaging. LOT was experimentally implemented by real-time imaging of flowing particles in 3D with a recently-developed volumetric optoacoustic tomography system. Provided the particles were separated by a distance larger than the diffraction-limited resolution, their individual locations could be accurately determined in each frame of the acquired image sequence and the localization image was formed by superimposing a set of points corresponding to the localized positions of the absorbers. The presented results demonstrate that LOT can significantly enhance the well-established advantages of optoacoustic imaging by breaking the acoustic diffraction barrier in deep tissues and mitigating artifacts due to limited-view tomographic acquisitions. AU - Dean-Ben, X.L. AU - Razansky, D. C1 - 53861 C2 - 45088 TI - Breaking the acoustic diffraction barrier with localization optoacoustic tomography. JO - Proc. SPIE VL - 10494 PY - 2018 SN - 0277-786X ER - TY - JOUR AB - A critical issue associated with the clinical translation of fluorescence molecular imaging relates to the reproducibility of the collected measurements. In particular, images acquired from the same target using different fluorescence cameras may vary considerably when the employed systems have markedly different specifications. Methods that standardize fluorescence imaging are therefore becoming necessary for assessing the performance of fluorescence systems and agents and for providing a reference to the data collected. In the work presented herein we propose a composite phantom for integrating multiple targets within the field of view of a fluorescence camera. Each quadrant of this phantom resolves different fluorescence features: (1) sensitivity as a function of the optical properties; (2) sensitivity as a function of the depth from the top surface; (3) resolution of the fluorescence and optical imaging; and (4) cross-talk from the excitation light. In addition, there exist structures in the phantom for assessing homogeneity of the incident illumination. In order to validate our main hypothesis that standardization of fluorescence imaging systems is feasible through imaging such a phantom, we employed two systems of different specifications and quantified all relevant performance metrics. The derived results showcase the feasibility of fluorescence cameras calibration. Additionally, we demonstrate a methodology of comparing fluorescence cameras by means of benchmarking scoring. We expect that such approaches will boost the clinical translation of fluorescence molecular imaging and will allow for the investigation of novel fluorescence agents. AU - Gorpas, D. AU - Koch, M. AU - Anastasopoulou, M. AU - Klemm, U. AU - Ntziachristos, V. C1 - 54226 C2 - 45449 TI - Phantom and methodology for fluorescence molecular imaging systems benchmarking. JO - Proc. SPIE VL - 10677 PY - 2018 SN - 0277-786X ER - TY - JOUR AB - A novel fourth generation micro-CT (WATCH-CT) with a unique scanning geometry, that collects parallel projections from a standard x-ray source without the requirement to interpolate or rebin the data, is studied and evaluated for its imaging qualities and performance characteristics. For a comparative analysis of the WATCH micro-CT system and the conventional CT geometry, the local noise power spectrum and the modulation transfer function is derived from the same initial parameters. The spatial resolution (MTF), characterized by the response of the system, is determined by the MTF derived by the oversampling method. The calculations involve varying the parameters like the region of evaluation (ROE) position, FOV magnification, angular sampling, pixel size, filtration and reconstruction algorithm to provide an extensive analogy between these systems. The spatial resolution of the scanning geometries is evaluated and compared. The MTF curves illustrate a higher relative resolving capacity for the WATCH micro-CT compared to the conventional geometries which is due to the characteristics of this unique geometry. The WATCH system exhibits higher resolutions explicitly at the regions away from the center. The NPS curves of WATCH geometry shows higher noise content in comparison to the conventional geometry. AU - Kumar, K.G.* AU - Saeid Nezhad, N.* AU - Mueller, B.H.* AU - Tischenko, O. AU - Hoeschen, C.* C1 - 53913 C2 - 45147 TI - Assessment of image quality parameters of a novel micro-CT system compared to a conventional CT geometry. JO - Proc. SPIE VL - 10573 PY - 2018 SN - 0277-786X ER - TY - JOUR AB - Photoacoustic mesoscopy (PAMe), offering high-resolution (sub-100-μm) and high optical contrast imaging at the depth of 1-10 mm, generally obtains massive collection data using a high-frequency focused ultrasonic transducer. The spatial impulse response (SIR) of this focused transducer causes the distortion of measured signals in both duration and amplitude. Thus, the reconstruction method considering the SIR needs to be investigated in the computation-economic way for PAMe. Here, we present a modified back-projection algorithm, by introducing a SIR-dependent calibration process using a non-satationary convolution method. The proposed method is performed on numerical simulations and phantom experiments of microspheres with diameter of both 50 μm and 100 μm, and the improvement of image fidelity of this method is proved to be evident by methodology parameters. The results demonstrate that, the images reconstructed when the SIR of transducer is accounted for have higher contrast-to-noise ratio and more reasonable spatial resolution, compared to the common back-projection algorithm. AU - Lu, T.* AU - Wang, Y.* AU - Gao, F.* AU - Zhao, H.* AU - Ntziachristos, V. AU - Li, J.* C1 - 53860 C2 - 45090 TI - Spatial-impulse-response-dependent back-projection using the non-stationary convolution in optoacoustic mesoscopy. JO - Proc. SPIE VL - 10494 PY - 2018 SN - 0277-786X ER - TY - JOUR AB - Downloading of the abstract is permitted for personal use only. Medium intensity focused ultrasound (MIFU) holds promise in important clinical applications. Generally, the aim in MIFU is to stimulate physiological mechanisms that reinforce healing responses, avoiding reaching temperatures that can cause permanent tissue damage. The outcome of interventions is then strongly affected by the temperature distribution in the treated region, and accurate monitoring represents a significant clinical need. In this work, we showcase the capacities of 4D optoacoustic imaging to monitor tissue heating during MIFU. The proposed method allows localizing the ultrasound focus, estimating the peak temperature and measuring the size of the heat-affected volume. Calibration experiments in a tissue-mimicking phantom demonstrate that the optoacoustically-estimated temperature accurately matches thermocouple readings. The good performance of the suggested approach in real tissues is further showcased in experiments with bovine muscle samples. AU - Oyaga Landa, F.J. AU - Ronda Penacoba, S.* AU - Dean-Ben, X.L. AU - Montero de Espinosa, F.* AU - Razansky, D. C1 - 53855 C2 - 45077 TI - Monitoring of tissue heating with medium intensity focused ultrasound via four dimensional optoacoustic tomography. JO - Proc. SPIE VL - 10494 PY - 2018 SN - 0277-786X ER - TY - JOUR AB - Downloading of the abstract is permitted for personal use only. Photoablative laser therapy is in common use for selective destruction of malignant masses, vascular and brain abnormalities. Tissue ablation and coagulation are irreversible processes occurring shortly after crossing a certain thermal exposure threshold. As a result, accurate mapping of the temperature field is essential for optimizing the outcome of these clinical interventions. Here we demonstrate four-dimensional optoacoustic temperature mapping of the entire photoablated region. Accuracy of the method is investigated in tissue-mimicking phantom experiments. Deviations of the volumetric optoacoustic temperature readings provided at 40ms intervals remained below 10% for temperature elevations above 3°C, as validated by simultaneous thermocouple measurements. The excellent spatio-temporal resolution of the new temperature monitoring approach aims at improving safety and efficacy of laser-based photothermal procedures. AU - Oyaga Landa, F.J. AU - Dean-Ben, X.L. AU - Sroka, R.* AU - Razansky, D. C1 - 53857 C2 - 45076 TI - Four-dimensional optoacoustic temperature mapping in laser-induced thermotherapy. JO - Proc. SPIE VL - 10494 PY - 2018 SN - 0277-786X ER - TY - JOUR AB - Electrosurgery, i.e. the application of radiofrequency current for tissue ablation, is a frequently used treatment for many cardiac arrhythmias. Electrophysiological and anatomic mapping, as well as careful radiofrequency power control typically guide the radiofrequency ablation procedure. Despite its widespread application, accurate monitoring of the lesion formation with sufficient spatio-temporal resolution remains challenging with the existing imaging techniques. We present a novel integrated catheter for simultaneous radiofrequency ablation and optoacoustic monitoring of the lesion formation in real time and 3D. The design combines the delivery of both electric current and optoacoustic excitation beam in a single catheter consisting of copper-coated multimode light-guides and its manufacturing is described in detail. The electrical current causes coagulation and desiccation while the excitation light is locally absorbed, generating OA responses from the entire treated volume. The combined ablation-monitoring capabilities were verified using ex-vivo bovine tissue. The formed ablation lesions showed a homogenous coagulation while the ablation was monitored in realtime with a volumetric frame rate of 10 Hz over 150 seconds. AU - Rebling, J. AU - Oyaga Landa, F.J. AU - Dean-Ben, X.L. AU - Razansky, D. C1 - 53881 C2 - 45115 TI - A new catheter design for combined radiofrequency ablation and optoacoustic treatment monitoring using copper-coated light-guides. JO - Proc. SPIE VL - 10488 PY - 2018 SN - 0277-786X ER - TY - JOUR AB - A pragmatic, data driven approach, which for the first time combines existing in situ and remote sensing data sets with a networked mobile air pollutant measurement strategy in the urban space is an objective of the Smart Air Quality Network (SmartAQnet) project. It aims to implement an intelligent, reproducible, finely-tuned (spatial, temporal), yet cost-effective air quality measuring network, initially in the model region of Augsburg, Germany. Central to this is the development and utilization of partial, already existing (but not yet combined) data on the one hand and the collection and integration of relevant missing data on the other hand. Unmanned aerial vehicles (UAV) with low-weight meteorological sensors and particle counter are used to monitor the three-dimensional dynamics of the lower atmosphere. Ground-based remote sensing by ceilometer for mixing layer height detection as well as a Radio-Acoustic Sounding System (RASS) for temperature and wind profile measurements at the University campus complete the new network architecture and UAV height profiling of atmospheric parameters. The SmartAQnet research initiative focuses on the subject of data access and data-based applications. Such complex monitoring provides the basis of deeper process understanding of air pollution exposure. The network architecture is shown and first results about spatial variation of meteorological influences upon air pollution exposure is presented using ceilometer, UAV and the existing monitoring network data. AU - Redelstein, J.* AU - Budde, M.* AU - Cyrys, J. AU - Emeis, S.* AU - Gratza, T.* AU - Grimm, H.* AU - Hank, M.* AU - Hinterreiter, S.* AU - Münkel, C.* AU - Pesch, M.* AU - Petersen, E.* AU - Philipp, A.* AU - Riedel, T.* AU - Riesterer, J.* AU - Schäfer, K.* AU - Schnelle-Kreis, J. AU - Uhrner, U.* AU - Werhahn, J.* AU - Ziegler, V.* AU - Beigl, M.* C1 - 55028 C2 - 46023 TI - Smart air quality network for spatial high-resolution monitoring in urban area. JO - Proc. SPIE VL - 10786 PY - 2018 SN - 0277-786X ER - TY - JOUR AB - Downloading of the abstract is permitted for personal use only. Optoacoustic microscopy (OAM) has enabled high-resolution, label-free imaging of tissues at depths not achievable with purely optical microscopy. However, widespread implementation of OAM into existing epi-illumination microscopy setups is often constrained by the performance and size of the commonly used piezoelectric ultrasound detectors. In this work, we introduce a novel acoustic detector based on a π-phase-shifted fiber Bragg grating (π-FBG) interferometer embedded inside an ellipsoidal acoustic cavity. The cavity enables seamless integration of epi-illumination OAM into existing microscopy setups by decoupling the acoustic and optical paths between the microscope objective and the sample. The cavity also acts as an acoustic condenser, boosting the sensitivity of the π-FBG and enabling cost effective CW-laser interrogation technique. We characterize the sensor's sensitivity and bandwidth and demonstrate hybrid OAM and second-harmonic imaging of phantoms and mouse tissue in vivo. AU - Shnaiderman, R. AU - Wissmeyer, G. AU - Seeger, M. AU - Estrada, H. AU - Ntziachristos, V. C1 - 53858 C2 - 45075 TI - Intravital hybrid optical-optoacoustic microscopy based on fiber-Bragg interferometry. JO - Proc. SPIE VL - 10494 PY - 2018 SN - 0277-786X ER - TY - JOUR AB - his study aimed to model virtual human lung phantoms including both non-parenchymal and parenchymal structures. Initial branches of the non-parenchymal structures (airways, arteries, and veins) were segmented from anatomical data in each lobe separately. A volume-filling branching algorithm was utilized to grow the higher generations of the airways and vessels to the level of terminal branches. The diameters of the airways and vessels were estimated using established relationships between flow rates and diameters. The parenchyma was modeled based on secondary pulmonary lobule units. Polyhedral shapes with variable sizes were modeled, and the borders were assigned to interlobular septa. A heterogeneous background was added inside these units using a non-parametric texture synthesis algorithm which was informed by a high-resolution CT lung specimen dataset. A voxelized based CT simulator was developed to create synthetic helical CT images of the phantom with different pitch values. Results showed the progressive degradation in depiction of lung details with increased pitch. Overall, the enhanced lung models combined with the XCAT phantoms prove to provide a powerful toolset to perform virtual clinical trials in the context of thoracic imaging. Such trials, not practical using clinical datasets or simplistic phantoms, can quantitatively evaluate and optimize advanced imaging techniques towards patient-based care. AU - Abadi, E.* AU - Sturgeon, G.M.* AU - Agasthya, G.* AU - Harrawood, B.* AU - Hoeschen, C. AU - Kapadia, A.* AU - Segars, W.P.* AU - Samei, E.* C1 - 50734 C2 - 42480 TI - Airways, vasculature, and interstitial tissue: Anatomically informed computational modeling of human lungs for virtual clinical trials. JO - Proc. SPIE VL - 10132 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - Despite recent advances in fluorescence imaging, standardization of systems remains an unmet need. We developed a new comprehensive phantom that resolves multiple system parameters simultaneously and could be used for system performance comparison. AU - Anastasopoulou, M. AU - Gorpas, D. AU - Koch, M. AU - Garcia-Allende, P. AU - Klemm, U. AU - Karlas, A. AU - Ntziachristos, V. C1 - 51811 C2 - 43356 TI - Multiparameter solid phantom for fluorescence imaging standardization. JO - Proc. SPIE VL - 10411 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - To extend sensitivity field for effective optoacoustic imaging, a novel concept of a non-mechanical point spread function (PSF) adjustment is proposed. Method was validated on phantoms and showed to be useful for distance-adaptive imaging. AU - Bozhko, D. AU - Gorpas, D. AU - Jaffer, F.A.* AU - Ntziachristos, V. C1 - 51810 C2 - 43355 TI - Intravascular optoacoustic catheter with extended sensitivity field. JO - Proc. SPIE VL - 10415 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - Air quality and the associated subjective and health-related quality of life are among the important topics of urban life in our time. However, it is very difficult for many cities to take measures to accommodate today's needs concerning e.g. mobility, housing and work, because a consistent fine-granular data and information on causal chains is largely missing. This has the potential to change, as today, both large-scale basic data as well as new promising measuring approaches are becoming available. The project "SmartAQnet", funded by the German Federal Ministry of Transport and Digital Infrastructure (BMVI), is based on a pragmatic, data driven approach, which for the first time combines existing data sets with a networked mobile measurement strategy in the urban space. By connecting open data, such as weather data or development plans, remote sensing of influencing factors, and new mobile measurement approaches, such as participatory sensing with low-cost sensor technology, "scientific scouts" (autonomous, mobile smart dust measurement device that is auto-calibrated to a high-quality reference instrument within an intelligent monitoring network) and demand-oriented measurements by light-weight UAVs, a novel measuring and analysis concept is created within the model region of Augsburg, Germany. In addition to novel analytics, a prototypical technology stack is planned which, through modern analytics methods and Big Data and IoT technologies, enables application in a scalable way. AU - Budde, M.* AU - Riedel, T.* AU - Beigl, M.* AU - Schäfer, K.* AU - Emeis, S.* AU - Cyrys, J. AU - Schnelle-Kreis, J. AU - Philipp, A.* AU - Ziegler, V.* AU - Grimm, H.* AU - Gratza, T.* C1 - 52865 C2 - 44205 TI - SmartAQnet: Remote and in-situ sensing of urban air quality. JO - Proc. SPIE VL - 10424 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - Imaging dynamics in living organisms is essential for the understanding of biological complexity. While multiple imaging modalities are often required to cover both microscopic and macroscopic spatial scales, dynamic phenomena may also extend over different temporal scales, necessitating the use of different imaging technologies based on the trade-off between temporal resolution and effective field of view. Optoacoustic (photoacoustic) imaging has been shown to offer the exclusive capability to link multiple spatial scales ranging from organelles to entire organs of small animals. Yet, efficient visualization of multi-scale dynamics remained difficult with state-of-the-art systems due to inefficient trade-offs between image acquisition and effective field of view. Herein, we introduce a spiral volumetric optoacoustic tomography (SVOT) technique that provides spectrally-enriched high-resolution optical absorption contrast across multiple spatio-temporal scales. We demonstrate that SVOT can be used to monitor various in vivo dynamics, from video-rate volumetric visualization of cardiac-associated motion in whole organs to high-resolution imaging of pharmacokinetics in larger regions. The multi-scale dynamic imaging capability thus emerges as a powerful and unique feature of the optoacoustic technology that adds to the multiple advantages of this technology for structural, functional and molecular imaging. AU - Dean-Ben, X.L. AU - Fehm, T. AU - Ford, S.J. AU - Gottschalk, S. AU - Razansky, D. C1 - 55501 C2 - 46194 TI - Imaging multi-scale dynamics in vivo with spiral volumetric optoacoustic tomography. JO - Proc. SPIE VL - 10064 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - Limited-view artefacts affect most optoacoustic (photoacoustic) imaging systems due to geometrical constraints that impede achieving full tomographic coverage as well as limited light penetration into scattering and absorbing objects. Indeed, it has been theoretically established and experimentally verified that accurate optoacoustic images can only be obtained if the imaged sample is fully enclosed (< π angular coverage) by the measuring locations. Since in many cases full angular coverage cannot be achieved, the visibility of structures along certain orientations is hampered. These effects are of particular relevance in the case of hand-held scanners with the imaged volume only accessible from one side. Herein, a new approach termed dynamic particle-enhanced optoacoustic tomography (DPOT) is described for accurate structural imaging in limited-view scenarios. The method is based on the non-linear combination of a sequence of tomographic reconstructions representing sparsely distributed moving particles. Good performance of the method is demonstrated in experiments consisting of dynamic visualization of flow of suspended microspheres in three-dimensions. The method is expected to be applicable for improving accuracy of angiographic optoacoustic imaging in living organisms. AU - Dean-Ben, X.L. AU - Ding, L AU - Razansky, D. C1 - 55502 C2 - 46195 TI - Improving visibility in limited-view scenarios with dynamic particle-enhanced optoacoustic tomography. JO - Proc. SPIE VL - 10064 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - Due to modeling and experimental imperfections, multispectral optoacoustic tomography images are often afflicted with negative values, which are further amplified when propagating into the spectrally unmixed images of chromophore concentrations. Since negative values have no physical meaning, accuracy can potentially be improved by imposing non-negativity constraints on the initial reconstructions and the unmixing steps. Herein, we compare several non-negative constrained approaches with reconstruction and spectral unmixing performed separately or combined in a single inverse step. The quantitative performance and sensitivity of the different approaches in detecting small amounts of spectrally-distinct chromophores are studied in tissue-mimicking phantoms and mouse experiments. AU - Ding, L AU - Dean-Ben, X.L. AU - Burton, N.C.B.* AU - Sobol, R.W.* AU - Ntziachristos, V. AU - Razansky, D. C1 - 50737 C2 - 42484 TI - Non-negative constrained inversion approaches for unmixing chromophores in multispectral optoacoustic tomography. JO - Proc. SPIE VL - 10064 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - Scanning optoacoustic microscopy operates in two distinct regimes optical resolution microscopy relies on a focused illumination and acoustic resolution microscopy that forms images by focusing the received acoustic field. Recently, a number of approaches have been proposed that combine those two modes of operation to create a highly scalable technique that can image at multiple penetration scales by gradually exchanging microscopic optical resolution in superficial tissues with ultrasonic resolution at diffuse (macroscopic) depths. However, scanning microscopy schemes commonly employ acquisition geometries that impede the use of synthetic aperture techniques to achieve meaningful images due to non-stationary illumination patterns and strong non-uniformity of the excitation light field. Here we present a Weighted Synthetic Aperture Focusing Technique (W-SAFT) as a universal framework that effectively accounts for the non-uniform distribution of both the excitation light field and spatial sensitivity field of the detector. As a result, W-SAFT maintains optical resolution performance at superficial depths while improving the acoustic resolving capacity for deeper tissues. The dynamic range of the optoacoustic data is compressed using a general fluence decay term applied to the W-SAFT operator, allowing a more uniform visualization of the entire imaged volume. Our three-dimensional algorithm makes use of the sample's surface to account for the heterogeneity produced when scanning a finite-size light beam. We tested a GPU implementation of W-SAFT with numerical simulations and showcase its performance on experimental data acquired from targets embedded in tissue mimicking phantoms. AU - Estrada, H. AU - Turner, J.E. AU - Kneipp, M. AU - Razansky, D. C1 - 51185 C2 - 42795 TI - Weighted synthetic aperture focusing for optoacoustic microscopy with scanning illumination and detection. JO - Proc. SPIE VL - 10064 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - The skull bone, a curved solid multilayered plate protecting the brain, constitutes a big challenge for the use of ultrasound-mediated techniques in neuroscience. Ultrasound waves incident from water or soft biological tissue are mostly reflected when impinging on the skull. To this end, skull properties have been characterized for both high-intensity focused ultrasound (HIFU) operating in the narrowband far-field regime and optoacoustic imaging applications. Yet, no study has been conducted to characterize the near-field of water immersed skulls. We used the thermoelastic effect with a 532 nm pulsed laser to trigger a wide range of broad-band ultrasound modes in a mouse skull. In order to capture the waves propagating in the near-field, a thin hydrophone was scanned in close proximity to the skull's surface. While Leaky pseudo-Lamb waves and grazing-angle bulk water waves are clearly visible in the spatio-temporal data, we were only able to identify skull-guided acoustic waves after dispersion analysis in the wavenumber-frequency space. The experimental data was found to be in a reasonable agreement with a flat multilayered plate model. AU - Estrada, H. AU - Rebling, J. AU - Razansky, D. C1 - 51360 C2 - 43011 TI - Observation of skull-guided acoustic waves in a water-immersed murine skull using optoacoustic excitation. JO - Proc. SPIE VL - 10067 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - Lack of standardization in fluorescence imaging challenges its clinical translation. We investigate the use of a composite phantom to perform standardization, which could serve as a framework toward the benchmarking of fluorescence imaging systems. AU - Gorpas, D. AU - Koch, M. AU - Anastasopoulou, M. AU - Klemm, U. AU - Ntziachristos, V. C1 - 51812 C2 - 43357 TI - Standardization of fluorescence molecular imaging systems. JO - Proc. SPIE VL - 10413 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - Purpose: The purpose of the present study was to evaluate if x-ray dark-field imaging can help to visualize lung cancer in mice. Materials and Methods: The experiments were performed using mutant mice with high-grade adenocarcinomas. Eight animals with pulmonary carcinoma and eight control animals were imaged in radiography mode using a prototype small-animal x-ray dark-field scanner and three of the cancerous ones additionally in CT mode. After imaging, the lungs were harvested for histological analysis. To determine their diagnostic value, x-ray dark-field and conventional attenuation images were analyzed by three experienced readers in a blind assessment. Results radiographic imaging: The lung nodules were much clearer visualized on the dark-field radiographs compared to conventional radiographs. The loss of air-tissue interfaces in the tumor leads to a significant loss of x-ray scattering, reflected in a strong dark-field signal change. The difference between tumor and healthy tissue in terms of x-ray attenuation is significantly less pronounced. Furthermore, the signal from the overlaying structures on conventional radiographs complicates the detection of pulmonary carcinoma. Results CT imaging: The very first in-vivo CT-imaging results are quite promising as smaller tumors are often better visible in the dark-field images. However the imaging quality is still quite low, especially in the attenuation images due to un-optimized scanning parameters. Conclusion: We found a superior diagnostic performance of dark-field imaging compared to conventional attenuation based imaging, especially when it comes to the detection of small lung nodules. These results support the motivation to further develop this technique and translate it towards a clinical environment. AU - Gromann, L.B.* AU - Scherer, K.* AU - Yaroshenko, A.* AU - Bölükbas, D.A. AU - Hellbach, K.* AU - Meinel, F.G.* AU - Braunagel, M.* AU - Eickelberg, O. AU - Reiser, M.F.* AU - Pfeiffer, F.* AU - Meiners, S. AU - Herzen, J.* C1 - 51380 C2 - 42991 TI - First experiences with in-vivo x-ray dark-field imaging of lung cancer in mice. JO - Proc. SPIE VL - 10132 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - A hybrid optical and acoustic resolution optoacoustic endoscopy is proposed. Laser light is transmitted to tissue by two types of illumination for optical and acoustic resolution imaging respectively. An unfocused ultrasound detector is used for recording optoacoustic signals. The endoscopy probe attains 3.6 mm diameter and is fully encapsulated into a catheter system. We examine the performance of the hybrid endoscope with phantoms and tissue sample, which shows that the hybrid endoscopy can obtain optical resolution in superficial microscopic imaging and ultrasonic tomography reconstruction resolution when imaging at greater depths. © (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only. AU - He, H. AU - Wissmeyer, G. AU - Ovsepian, S.V. AU - Bühler, A. AU - Ntziachristos, V. C1 - 50740 C2 - 42487 TI - Optoacoustic endoscopy with optical and acoustic resolution. JO - Proc. SPIE VL - 10064 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - Sparse recovery algorithms have shown great potential to reconstruct images with limited view datasets in optoacoustic tomography, with a disadvantage of being computational expensive. In this paper, we improve the fast convergent Split Augmented Lagrangian Shrinkage Algorithm (SALSA) method based on least square QR (LSQR) formulation for performing accelerated reconstructions. Further, coherence factor is calculated to weight the final reconstruction result, which can further reduce artifacts arising in limited-view scenarios and acoustically heterogeneous mediums. Several phantom and biological experiments indicate that the accelerated SALSA method with coherence factor (ASALSA-CF) can provide improved reconstructions and much faster convergence compared to existing sparse recovery methods. AU - He, H. AU - Prakash, J. AU - Bühler, A. AU - Ntziachristos, V. C1 - 51183 C2 - 42799 TI - Fast sparse recovery and coherence factor weighting in optoacoustic tomography. JO - Proc. SPIE VL - 10064 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - In-vivo fluorescently labelled drug (bevacizumab) breast cancer specimen where obtained from patients. We propose a new structured method to determine the optimal classification threshold in targeted fluorescence intra-operative imaging. AU - Koch, M. AU - de Jong, J.S.* AU - Glatz, J. AU - Symvoulidis, P. AU - Lamberts, L.E.* AU - Adams, A.L.L.* AU - Kranendonk, M.E.G.* AU - van Scheltinga, A.T.* AU - Aichler, M. AU - Jansen, L.* AU - de Vries, J.* AU - Lub-de Hooge, M.* AU - Schröder, C.P.* AU - Jorritsma-Smit, A.* AU - Linssen, M.D.* AU - de Boer, E.* AU - van der Vegt, B.* AU - Nagengast, W.B.* AU - Elias, S.G.* AU - Oliveira, S.* AU - Witkamp, A.J.* AU - Mali, W.P.Th.M.* AU - van der Wall, E.* AU - Garcia-Allende, P. AU - van Diest, P.J.* AU - de Vries, E.G.* AU - Walch, A.K. AU - van Dam, G.M.* AU - Ntziachristos, V. C1 - 51813 C2 - 43358 TI - Fluorescently labeled bevacizumab in human breast cancer: Defining the classification threshold. JO - Proc. SPIE VL - 10411 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - Multispectral optoacoustic mesoscopy (MSOM) has been recently introduced for cancer imaging, it has the potential for high resolution imaging of cancer development in vivo, at depths beyond the diffusion limit. Based on spectral features, optoacoustic imaging is capable of visualizing angiogenesis and imaging cancer heterogeneity of malignant tumors through endogenous hemoglobin. However, high-resolution structural and functional imaging of whole tumor mass is limited by modest penetration and image quality, due to the insufficient capability of ultrasound detectors and the twodimensional scan geometry. In this study, we introduce a novel multi-spectral optoacoustic mesoscopy (MSOM) for imaging subcutaneous or orthotopic tumors implanted in lab mice, with the high-frequency ultrasound linear array and a conical scanning geometry. Detailed volumetric images of vasculature and oxygen saturation of tissue in the entire tumors are obtained in vivo, at depths up to 10 mm with the desirable spatial resolutions approaching 70μm. This unprecedented performance enables the visualization of vasculature morphology and hypoxia conditions has been verified with ex vivo studies. These findings demonstrate the potential of MSOM for preclinical oncological studies in deep solid tumors to facilitate the characterization of tumor’s angiogenesis and the evaluation of treatment strategies. AU - Li, J.* AU - Zhang, S.* AU - Chekkoury, A. AU - Glasl, S. AU - Vetschera, P. AU - Koberstein-Schwarz, B. AU - Omar, M. AU - Ntziachristos, V. C1 - 50738 C2 - 42485 TI - Three-dimensional optoacoustic mesoscopy of the tumor heterogeneity in vivo using high depth-to-resolution multispectral optoacoustic tomography. JO - Proc. SPIE VL - 10064 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - Determination of ovarian status and follicle monitoring are common methods of diagnosing female infertility. We evaluated the suitability of selective plane illumination microscopy (SPIM) for the study of ovarian follicles. Owing to the large field of view and fast acquisition speed of our newly developed SPIM system, volumetric image stacks from entire intact samples of pig ovaries have been rendered demonstrating clearly discernible follicular features like follicle diameters (70 μm-2.5 mm), size of developing Cumulus oophorus complexes (COC) (40 μm-110 μm), and follicular wall thicknesses (90 μm-120 μm). The observation of clearly distinguishable COCs protruding into the follicular antrum was also shown possible, and correlation with the developmental stage of the follicles was determined. Follicles of all developmental stages were identified, and even the small primordial follicle clusters forming the egg nest could be observed. The ability of the system to non-destructively generate sub-cellular resolution 3D images of developing follicles, with excellent image contrast and high throughput capacity compared to conventional histology, suggests that it can be used to monitor follicular development and identify structural abnormalities indicative of ovarian ailments. Accurate folliculometric measurements provided by SPIM images can immensely help the understanding of ovarian physiology and provide important information for the proper management of ovarian diseases. AU - Lin, H.-C. AU - Dutta, R.* AU - Mandal, S. AU - Kind, A.* AU - Schnieke, A.* AU - Razansky, D. C1 - 51169 C2 - 42800 TI - Light-sheet microscopy for quantitative ovarian folliculometry. JO - Proc. SPIE VL - 10043 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - Extraction of murine cardiac functional parameters on a beat-by-beat basis remains challenging with the existing imaging modalities. Novel methods enabling in vivo characterization of functional parameters at a high temporal resolution are poised to advance cardiovascular research and provide a better understanding of the mechanisms underlying cardiac diseases. We present a new approach based on analyzing contrast-enhanced optoacoustic (OA) images acquired at high volumetric frame rate without using cardiac gating or other approaches for motion correction. Acute myocardial infarction was surgically induced in murine models, and the method was modified to optimize for acquisition of artifact-free optoacoustic data. Infarcted hearts could be differentiated from healthy controls based on a significantly higher pulmonary transit time (PTT: infarct 2.07 s vs. healthy 1.34 s), while no statistically significant difference was observed in the heart rate (318 bpm vs. 309 bpm). In combination with the proven ability of optoacoustics to track targeted probes within the injured myocardium, our method is capable of depicting cardiac anatomy, function, and molecular signatures on a beat-by-beat basis, both with high spatial and temporal resolution, thus providing new insights into the study of myocardial ischemia. AU - Lin, H.-C. AU - Dean-Ben, X.L. AU - Kimm, M.* AU - Kosanke, K.* AU - Haas, H.* AU - Meier, R.* AU - Lohöfer, F.* AU - Wildgruber, M.* AU - Razansky, D. C1 - 51186 C2 - 42796 TI - Non-invasive volumetric optoacoustic imaging of cardiac cycles in acute myocardial infarction model in real-time. JO - Proc. SPIE VL - 10064 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - Model organisms such as zebrafish play an important role for developmental biologists and experimental geneticists. Still, as they grow into their post-embryonic stage of development it becomes more and more difficult to image them because of high light scattering inside biological tissue. Optoacoustic mesoscopy based on spherically focused, high frequency, ultrasound detectors offers an alternative, where it relies on the focusing capabilities of the ultrasound detectors in generating the image rather than on the focusing of light. Nonetheless, because of the limited numerical aperture the resolution is not isotropic, and many structures, especially elongated ones, such as blood vessels and other organs, are either invisible, or not clearly identifiable on the final image. Herein, based on high frequency ultrasound detectors at 100 MHz and 50 MHz we introduce multi orientation (view) optoacoustic mesoscopy. We collect a rich amount of signals from multiple directions and combine them using a weighted sum in the Fourier domain and a Wiener deconvolution into a single high resolution three-dimensional image. The new system achieves isotropic resolutions on the order of 10 μm in-plane, 40 μm axially, and SNR enhancement of 15 dB compared to the single orientation case. To showcase the system we imaged a juvenile zebrafish ex vivo, which is too large to image using optical microscopic techniques, the reconstructed images show unprecedented performance in terms of SNR, resolution, and clarity of the observed structures. Using the system we see the inner organs of the zebrafish, the pigmentation, and the vessels with unprecedented clarity. AU - Omar, M. AU - Rebling, J. AU - Wicker, K. AU - Schmitt-Manderbach, T. AU - Schwarz, M. AU - Gateau, J.* AU - López-Schier, H. AU - Mappes, T.* AU - Ntziachristos, V. C1 - 50739 C2 - 42486 TI - Imaging of post-embryonic stage model-organisms at high resolution using multi orientation optoacoustic mesoscopy. JO - Proc. SPIE VL - 10064 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - Lack of haptic feedback during laser surgery hampers controlling the incision depth, leading to a high risk of undesired tissue damage. Here we present a new feedback sensing method that accomplishes non-contact realtime monitoring of laser ablation procedures by detecting shock waves emanating from the ablation spot with air-coupled transducers. Experiments in soft and hard tissue samples attained high reproducibity in real-time depth estimation of the laser-induced cuts. The advantages derived from the non-contact nature of the suggested monitoring approach are expected to greatly promote the general applicability of laser-based surgeries. AU - Oyaga Landa, F.J. AU - Dean-Ben, X.L. AU - Montero de Espinosa, F.* AU - Razansky, D. C1 - 51188 C2 - 42798 TI - Non-contact monitoring during laser surgery by measuring the incision depth with air-coupled transducers. JO - Proc. SPIE VL - 10064 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - Ablation and photothermal therapy are widely employed medical protocols where the selective destruction of tissue is a necessity as in cancerous tissue removal or vascular and brain abnormalities. Tissue denaturation takes place when the temperature reaches a threshold value while the time of exposure determines the lesion size. Therefore, the spatio-temporal distribution of temperature plays a crucial role in the outcome of these clinical interventions. We demonstrate fast volumetric temperature mapping with optoacoustic tomography based on real-time optoacoustic readings from the treated region. The performance of the method was investigated in tissue-mimicking phantom experiments. The new ability to non-invasively measure temperature volumetrically in an entire treated region with high spatial and temporal resolutions holds potential for improving safety and efficacy of thermal ablation and to advance the general applicability of laser-based therapy. AU - Oyaga Landa, F.J. AU - Dean-Ben, X.L. AU - Montero de Espinosa, F.* AU - Razansky, D. C1 - 51852 C2 - 43533 TI - Real-time three-dimensional temperature mapping in photothermal therapy with optoacoustic tomography. JO - Proc. SPIE VL - 10415 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - Many neurological disorders are linked to abnormal activation or pathological alterations of the vasculature in the affected brain region. Obtaining simultaneous morphological and physiological information of neurovasculature is very challenging due to the acoustic distortions and intense light scattering by the skull and brain. In addition, the size of cerebral vasculature in murine brains spans an extended range from just a few microns up to about a millimeter, all to be recorded in 3D and over an area of several dozens of mm2. Numerous imaging techniques exist that excel at characterizing certain aspects of this complex network but are only capable of providing information on a limited spatiotemporal scale. We present a hybrid ultrasound and dual-wavelength optoacoustic microscope, capable of rapid imaging of murine neurovasculature in-vivo, with high spatial resolution down to 12 μm over a large field of view exceeding 50mm2. The dual wavelength imaging capability allows for the visualization of functional blood parameters through an intact skull while pulse-echo ultrasound biomicroscopy images are captured simultaneously by the same scan head. The flexible hybrid design in combination with fast high-resolution imaging in 3D holds promise for generating better insights into the architecture and function of the neurovascular system. AU - Rebling, J. AU - Estrada, H. AU - Zwack, M.K.* AU - Sela, G. AU - Gottschalk, S. AU - Razansky, D. C1 - 51187 C2 - 42797 TI - Hybrid ultrasound and dual-wavelength optoacoustic biomicroscopy for functional neuroimaging. JO - Proc. SPIE VL - 10064 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - Optoacoustic imaging is a rapidly developing area of biomedical imaging due its combination of rich optical contrast and ultrasound depth penetration. Just like conventional pulse-echo ultrasound imaging, optoacoustic tomography relies on the use of ultrasound detector arrays with a large number of elements. The precise knowledge of the transducer's sensitivity is crucial for the prediction of its performance for a given imaging task. Sensitivity characteristics such as the central frequency and bandwidth are routinely characterized. However, this characterization is typically performed solely under normal incidence since the measurement of the angle and frequency depended sensitivity (directivity) is difficult and time consuming with existing ultrasound characterization methods. We present a simple and fast characterization method for broadband directivity measurements of the angular transducer sensitivity based on the optoacoustic effect. The method utilizes a thin absorbing suture in order to generate omnidirectional and broadband optoacoustic signals, which are calibrated using a needle hydrophone. We applied this method to characterize and compare the directivity of a conventional piezoelectric (PZT) transducer to the directivity of a capacitive micromachined ultrasonic (cMUT) transducer. Both technologies showed a similar broadband response at normal incidence and the PZT transducer displayed a more than two times larger signal to noise ratio at normal incidence. However, the cMUT transducer's sensitivity was significantly less angle-depended and outperformed the PZT's sensitivity for angles larger than 20°. AU - Rebling, J. AU - Warshavski, O.* AU - Meynier, C.* AU - Razansky, D. C1 - 51441 C2 - 43144 TI - Broadband optoacoustic characterization of cMUT and PZT transducer directivity in receive mode. JO - Proc. SPIE VL - 10139 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - SPIE-OSA. We present an optoacoustic microscope, combining structural and functional opticalresolution optoacoustic and ultrasound pulse-echo imaging. The system was applied to image Zebrafish larvae and complex vascular networks in the murine brain and ear. AU - Rebling, J. AU - Estrada, H. AU - Gottschalk, S. AU - Razansky, D. C1 - 52260 C2 - 43839 TI - Structural and functional small animal imaging using hybrid-focus optoacoustic biomicroscopy. JO - Proc. SPIE VL - 10415 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - Imaging x-ray fluorescence generally generates a conflict between the best image quality or highest sensitivity and lowest possible radiation dose. Consequently many experimental studies investigating the feasibility of this molecular imaging method, deal with either monochromatic x-ray sources that are not practical in clinical environment or accept high x-ray doses in order to maintain the advantage of high sensitivity and producing high quality images. In this work we present a x-ray fluorescence imaging setup using a HOPG crystal fan construction consisting of a Bragg reflecting analyzer array together with a scatter reducing radial collimator. This method allows for the use of polychromatic x-ray tubes that are in general easily accessible in contrast to monochromatic x-ray sources such as synchrotron facilities. Moreover this energy-selecting device minimizes the amount of Compton scattered photons while simultaneously increasing the fluorescence signal yield, thus significantly reducing the signal to noise ratio. The aim is to show the feasibility of this approach by measuring the Bragg reflected Kα fluorescence signal of an object containing an iodine solution using a large area detector with moderate energy resolution. Contemplating the anisotropic energy distribution of background scattered x-rays we compare the detection sensitivity, applying two different detector angular configurations. Our results show that even for large area detectors with limited energy resolution, iodine concentrations of 0.12 % can be detected. However, the potentially large scan times and therefore high radiation dose need to be decreased in further investigations. AU - Rosentreter, T. AU - Müller, B.* AU - Schlattl, H. AU - Hoeschen, C. C1 - 50741 C2 - 42488 TI - Experimental investigation of a HOPG crystal fan for x-ray fluorescence molecular imaging. JO - Proc. SPIE VL - 10132 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - Due to the increasing number of cone-beam CT (CBCT) devices on the market, reliable estimates of patient doses for these imaging modality is desired. Cone-beam CT devices differ from conventional CT not only by a larger collimation but also by different recording modes. In this work, it has been investigated whether reliable patient doses can be obtained for CBCT devices in partial-fan mode using pre-computed slices. As an exemplary case, chest CBCT scans for the ICRP reference adult models has been examined. By normalizing organ doses to CTDI100w , the resulting dose conversion coefficients for CBCT could be well reproduced by precomputed slices, with a relative difference in the effective dose conversion coefficients of less than 10%. AU - Schlattl, H. C1 - 50742 C2 - 42489 TI - Dose conversion coefficients for partial-fan CBCT scans. JO - Proc. SPIE VL - 10132 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - Carotid atheromatosis is causally related to stroke, a leading cause of disability and death. We present the analysis of a human carotid atheroma using a novel hybrid microscopy system that combines optical-resolution optoacoustic (photoacoustic) microscopy and several non-linear optical microscopy modalities (second and third harmonic generation, as well as, two-photon excitation fluorescence) to achieve a multimodal examination of the extracted tissue within the same imaging framework. Our system enables the label-free investigation of atheromatous human carotid tissue with a resolution of about 1 μm and allows for the congruent interrogation of plaque morphology and clinically relevant constituents such as red blood cells, collagen, and elastin. Our data reveal mutual interactions between blood embeddings and connective tissue within the atheroma, offering comprehensive insights into its stage of evolution and severity, and potentially facilitating the further development of diagnostic tools, as well as treatment strategies. AU - Seeger, M. AU - Karlas, A. AU - Soliman, D. AU - Pelisek, J.* AU - Ntziachristos, V. C1 - 50735 C2 - 42481 TI - Hybrid microscopy of human carotid atheroma by means of optical-resolution optoacoustic and non-linear optical microscopy. JO - Proc. SPIE VL - 10064 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - A new and simple object for calibrating tomographic scanners has been proposed. Instead of a conventional high-density ball as an object for calibration, we propose a high-density conic body. The cone is advantageous compare to the ball both because of its easy availability (uncomplicated manufacturing) and the straightforward and less error-prone analysis necessary for the identification of a space point (ball’s center vs. cone apex). Applying the conic body instead of a ball as a calibration object enables to reduce calibration errors substantially. Additionally we propose an efficient way to determine the discrepancy between ideal and misaligned positions of the detector that may be crucial for the quality of the reconstruction. AU - Tischenko, O. AU - Saeednejad, N.* AU - Hoeschen, C.* C1 - 50743 C2 - 42490 TI - Novel method to calibrate CT scanners with a conic probe body. JO - Proc. SPIE VL - 10132 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - We present an optoacoustic (photoacoustic) microscopy (OAM) imaging system that uses a pi-shifted Fiber Bragg Grating (pi-FBG) as ultrasound (US) sensor. The sensor has an ultra-small footprint and hence allows for the detection of optoacoustic signals in close proximity to their origin. The interrogation of the pi-FBG is performed by a broadband pulsed laser, enabling a high sensitivity of the sensor as well as the elimination of ambient noise. We characterize the pi-FBG in terms of axial and lateral resolution as well as its bandwidth and find that its performance is comparable to US sensors that are based on the piezoelectric effect. We demonstrate the system’s capabilities by images taken from ex vivo zebrafish and mouse ear samples. The results presented herein highlight that pi-FBGs are a promising tool for the comprehensive label-free optoacoustic imaging of biomedical samples. AU - Wissmeyer, G. AU - Shnaiderman, R. AU - Soliman, D. AU - Ntziachristos, V. C1 - 50736 C2 - 42482 TI - Optoacoustic microscopy based on pi-FBG ultrasound sensors. JO - Proc. SPIE VL - 10064 PY - 2017 SN - 0277-786X ER - TY - JOUR AB - Optoacoustic techniques rely on ultrasound transmission between optical absorbers within tissues and the measurement location. Much like in echography, commonly used piezoelectric transducers require either direct contact with the tissue or through a liquid coupling medium. The contact nature of this detection approach then represents a disadvantage of standard optoacoustic systems with respect to other imaging modalities (including optical techniques) in applications where non-contact imaging is needed, e.g. in open surgeries or when burns or other lesions are present in the skin. Herein, non-contact optoacoustic imaging using raster-scanning of a spherically-focused piezoelectric air-coupled ultrasound transducer is demonstrated. When employing laser fluence levels not exceeding the maximal permissible human exposure, it is shown possible to attain detectable signals from objects as small as 1 mm having absorption properties representative of blood at near-infrared wavelengths with a relatively low number of averages. Optoacoustic images from vessel-mimicking tubes embedded in an agar phantom are further showcased. The initial results indicate that the air-coupled ultrasound detection approach can be potentially made suitable for non-contact biomedical imaging with optoacoustics. AU - Dean-Ben, X.L. AU - Pang, G.A. AU - de Espinosa, F.M.* AU - Razansky, D. C1 - 48910 C2 - 41464 TI - Non-contact optoacoustic imaging by raster scanning a piezoelectric air-coupled transducer. JO - Proc. SPIE VL - 9708 PY - 2016 SN - 0277-786X ER - TY - JOUR AB - Synthetic and genetically encoded chromo- and fluorophores have become indispensable tools for biomedical research enabling a myriad of applications in imaging modalities based on biomedical optics. The versatility offered by the optoacoustic (photoacoustic) contrast mechanism enables to detect signals from any substance absorbing light, and hence these probes can be used as optoacoustic contrast agents. While contrast versatility generally represents an advantage of optoacoustics, the strong background signal generated by light absorption in endogeneous chromophores hampers the optoacoustic capacity to detect a photo-absorbing agent of interest. Increasing the optoacoustic sensitivity is then determined by the capability to differentiate specific features of such agent. For example, multispectral optoacoustic tomography (MSOT) exploits illuminating the tissue at multiple optical wavelengths to spectrally resolve (unmix) the contribution of different chromophores. Herein, we present an alternative approach to enhance the sensitivity and specificity in the detection of optoacoustic contrast agents. This is achieved with photoswitchable probes that change optical absorption upon illumination with specific optical wavelengths. Thereby, temporally unmixed MSOT (tuMSOT) is based on photoswitching the compounds according to defined schedules to elicit specific time-varying optoacoustic signals, and then use temporal unmixing algorithms to locate the contrast agent based on their particular temporal profile. The photoswitching kinetics is further affected by light intensity, so that tuMSOT can be employed to estimate the light fluence distribution in a biological sample. The performance of the method is demonstrated herein with the reversibly switchable fluorescent protein Dronpa and its fast-switching fatigue resistant variant Dronpa-M159T. AU - Dean-Ben, X.L. AU - Stiel, A.-C. AU - Jiang, Y. AU - Ntziachristos, V. AU - Westmeyer, G.G. AU - Razansky, D. C1 - 48913 C2 - 41467 TI - Imaging the distribution of photoswitchable probes with temporally-unmixed multispectral optoacoustic tomography. JO - Proc. SPIE VL - 9708 PY - 2016 SN - 0277-786X ER - TY - JOUR AB - Wavefront shaping based on optoacoustic (photoacoustic) feedback has recently emerged as a promising tool to control the light distribution in optically-scattering media. In this approach, the phase of a short-pulsed light beam is spatially-modulated to create constructive light interference (focusing) at specific locations in the speckle pattern of the scattered wavefield. The optoacoustic signals generated by light absorption provide a convenient feedback mechanism to optimize the phase mask of the spatial light modulator in order to achieve the desired light intensity distribution. The optimization procedure can be done by directly considering the acquired signals or the reconstructed images of the light absorption distribution. Recently, our group has introduced a volumetric (three-dimensional) optoacoustic wavefront shaping platform that enables monitoring the distribution of light absorption in an entire volume with frame rates of tens of Hz. With this approach, it is possible to simultaneously control the volumetric light distribution through turbid media. Experiments performed with absorbing microparticles distributed in a three-dimensional region showcase the feasibility of enhancing the light intensity at specific points, where the size of particles is also essential to maximize the signal enhancement. The advantages provided by optoacoustic imaging in terms of spatial and temporal resolution anticipate new capabilities of wavefront shaping techniques in biomedical optics. AU - Dean-Ben, X.L. AU - Estrada, H. AU - Özbek, A. AU - Razansky, D. C1 - 49824 C2 - 40944 TI - Controlling the light distribution through turbid media with wavefront shaping based on volumetric optoacoustic feedback. JO - Proc. SPIE VL - 9717 PY - 2016 SN - 0277-786X ER - TY - JOUR AB - maging plays an increasingly important role in clinical management and preclinical studies of cancer. Application of optical molecular imaging technologies, in combination with highly specific contrast agent approaches, eminently contributed to understanding of functional and histological properties of tumors and anticancer therapies. Yet, optical imaging exhibits deterioration in spatial resolution and other performance metrics due to light scattering in deep living tissues. High resolution molecular imaging at the whole-organ or whole-body scale may therefore bring additional understanding of vascular networks, blood perfusion and microenvironment gradients of malignancies. In this work, we constructed a volumetric multispectral optoacoustic tomography (vMSOT) scanner for cancer imaging in preclinical models and explored its capacity for real-time 3D intravital imaging of whole breast cancer allografts in mice. Intrinsic tissue properties, such as blood oxygenation gradients, along with the distribution of externally administered liposomes carrying clinically-approved indocyanine green dye (lipo-ICG) were visualized in order to study vascularization, probe penetration and extravasation kinetics in different regions of interest within solid tumors. The use of v-MSOT along with the application of volumetric image analysis and perfusion tracking tools for studies of pathophysiological processes within microenvironment gradients of solid tumors demonstrated superior volumetric imaging system performance with sustained competitive resolution and imaging depth suitable for investigations in preclinical cancer models. AU - Dean-Ben, X.L. AU - Ermolayev, V. AU - Mandal, S. AU - Ntziachristos, V. AU - Razansky, D. C1 - 49826 C2 - 40946 TI - Four dimensional optoacoustic imaging of perfusion in preclinical breast tumor model in vivo. JO - Proc. SPIE VL - 9708 PY - 2016 SN - 0277-786X ER - TY - JOUR AB - The acoustically-mismatched skull bone poses significant challenges for the application of ultrasonic and optical techniques in neuroimaging, still typically requiring invasive approaches using craniotomy or skull thinning. Optoacoustic imaging partially circumvents the acoustic distortions due to the skull because the induced wave is transmitted only once as opposed to the round trip in pulse-echo ultrasonography. To this end, the mouse brain has been successfully imaged transcranially by optoacoustic scanning microscopy. Yet, the skull may adversely affect the lateral and axial resolution of transcranial brain images. In order to accurately characterize the complex behavior of the optoacoustic signal as it traverses through the skull, one needs to consider the ultrawideband nature of the optoacoustic signals. Here the insertion loss of murine skull has been measured by means of a hybrid optoacoustic-ultrasound scanning microscope having a spherically focused PVDF transducer and pulsed laser excitation at 532 nm of a 20 μm diameter absorbing microsphere acting as an optoacoustic point source. Accurate modeling of the acoustic transmission through the skull is further performed using a Fourier-domain expansion of a solid-plate model, based on the simultaneously acquired pulse-echo ultrasound image providing precise information about the skull's position and its orientation relative to the optoacoustic source. Good qualitative agreement has been found between the a solid-plate model and experimental measurements. The presented strategy might pave the way for modeling skull effects and deriving efficient correction schemes to account for acoustic distortions introduced by an adult murine skull, thus improving the spatial resolution, effective penetration depth and overall image quality of transcranial optoacoustic brain microscopy. AU - Estrada, H. AU - Rebling, J. AU - Turner, J.E. AU - Kneipp, M. AU - Shoham, S.* AU - Razansky, D. C1 - 48912 C2 - 41466 TI - Estimation of the skull insertion loss using an optoacoustic point source. JO - Proc. SPIE VL - 9708 PY - 2016 SN - 0277-786X ER - TY - JOUR AB - Chronic venous insufficiency (CVI) is one of the most common medical conditions with reported prevalence estimates as high as 30% in the adult population. Although conservative management with compression therapy may improve the symptoms associated with CVI, healing often demands invasive procedures. Besides established surgical methods like vein stripping or bypassing, endovenous laser therapy (ELT) emerged as a promising novel treatment option during the last 15 years offering multiple advantages such as less pain and faster recovery. Much of the treatment success hereby depends on monitoring of the treatment progression using clinical imaging modalities such as Doppler ultrasound. The latter however do not provide sufficient contrast, spatial resolution and three-dimensional imaging capacity which is necessary for accurate online lesion assessment during treatment. As a consequence, incidence of recanalization, lack of vessel occlusion and collateral damage remains highly variable among patients. In this study, we examined the capacity of volumetric optoacoustic tomography (VOT) for real-time monitoring of ELT using an ex-vivo ox foot model. ELT was performed on subcutaneous veins while optoacoustic signals were acquired and reconstructed in real-time and at a spatial resolution in the order of 200μm. VOT images showed spatio-temporal maps of the lesion progression, characteristics of the vessel wall, and position of the ablation fiber’s tip during the pull back. It was also possible to correlate the images with the temperature elevation measured in the area adjacent to the ablation spot. We conclude that VOT is a promising tool for providing online feedback during endovenous laser therapy. AU - Fehm, T. AU - Dean-Ben, X.L. AU - Schaur, P.* AU - Sroka, R.* AU - Razansky, D. C1 - 48911 C2 - 41465 TI - Volumetric optoacoustic monitoring of endovenous laser treatments. JO - Proc. SPIE VL - 9708 PY - 2016 SN - 0277-786X ER - TY - JOUR AB - In optoacoustic imaging, the resolution and image quality in a certain imaging position usually cannot be enhanced without changing the imaging configuration. Post-reconstruction image processing methods offer a new possibility to improve image quality and resolution. We have developed a geometrical super-resolution (GSR) method which uses information from spatially separated frames to enhance resolution and contrast in optoacoustic images. The proposed method acquires several low resolution images from the same object located at different positions inside the imaging plane. Thereafter, it applies an iterative registration algorithm to integrate the information in the acquired set of images to generate a single high resolution image. Herein, we present the method and evaluate its performance in simulation and phantom experiments, and results show that geometrical super-resolution techniques can be a promising alternative to enhance resolution in optoacoustic imaging. AU - He, H. AU - Mandal, S. AU - Bühler, A. AU - Dean-Ben, X.L. AU - Razansky, D. AU - Ntziachristos, V. C1 - 48890 C2 - 41491 TI - Optoacoustic imaging quality enhancement based on geometrical super-resolution method. JO - Proc. SPIE VL - 9708 PY - 2016 SN - 0277-786X ER - TY - JOUR AB - Optoacoustic technique has been shown to resolve anatomical, functional and molecular features at depths that go beyond the reach of epi-illumination optical microscopy offering new opportunities for endoscopic imaging. Herein, we interrogate the merits of optoacoustic endoscopy implemented by translating a sound detector in linear or curved geometries. The linear and curved detection geometries are achieved by employing an intravascular ultrasound transducer (IVUS) within a plastic guide shaped to a line or a curve. This concept could be used together with optical endoscopes to yield hybrid optical and optoacoustic imaging. AU - He, H. AU - Bühler, A. AU - Ntziachristos, V. C1 - 48893 C2 - 41490 TI - Optoacoustic endoscopy in curved scanning mode. JO - Proc. SPIE VL - 9708 PY - 2016 SN - 0277-786X ER - TY - JOUR AB - Imaging depth is one of the most prominent limitations in light microscopy. The depth in which we are still able to resolve biological structures is limited by the scattering of light within the sample. We have developed an algorithm to compensate for the influence of scattering. The potential of algorithm is demonstrated on a 3D image stack of a zebrafish embryo captured with a selective plane illumination microscope (SPIM). With our algorithm we were able shift the point in depth, where scattering starts to blur the imaging and effect the image quality by around 30 µm. For the reconstruction the algorithm only uses information from within the image stack. Therefore the algorithm can be applied on the image data from every SPIM system without further hardware adaption. Also there is no need for multiple scans from different views to perform the reconstruction. The underlying model estimates the recorded image as a convolution between the distribution of fluorophores and a point spread function, which describes the blur due to scattering. Our algorithm performs a space-variant blind deconvolution on the image. To account for the increasing amount of scattering in deeper tissue, we introduce a new regularizer which models the increasing width of the point spread function in order to improve the image quality in the depth of the sample. Since the assumptions the algorithm is based on are not limited to SPIM images the algorithm should also be able to work on other imaging techniques which provide a 3D image volume. AU - Koberstein-Schwarz, B. AU - Omlor, L.* AU - Schmitt-Manderbach, T.* AU - Mappes, T.* AU - Ntziachristos, V. C1 - 49825 C2 - 40945 TI - Increasing the imaging depth through computational scattering correction. JO - Proc. SPIE VL - 9713 PY - 2016 SN - 0277-786X ER - TY - JOUR AB - We used raster-scan optoacoustic mesoscopy (RSOM) at 50 MHz, and at 100 MHz, to monitor tumor growth, and tumor angiogenesis, which is a central hallmark of cancer, in-vivo. In this study we compared the performance, and the effect of the 50 MHz, and the 100 MHz frequencies on the quality of the final image. The system is based on a reflection-mode implementation of RSOM. The detectors used are custom made, ultrawideband, and spherically focused. The use of such detectors enables light coupling from the same side as the detector, thus reflection-mode. Light is in turn coupled using a fiber bundle, and the detector is raster scanned in the xy-plane. Subsequently, to retrieve small features, the raw data are reconstructed using a multi-bandwidth, beamforming reconstruction algorithm. Comparison of the system performance at the different frequencies shows as expected a higher resolution in case of the 100 MHz detector compared to the 50 MHz. On the other hand the 50 MHz has a better SNR, can detect features from deeper layers, and has higher angular acceptance. Based on these characteristics the 50 MHz detector was mostly used. After comparing the performance we monitored the growth of B16F10 cells, melanin tumor, over the course of 9 days. We see correspondence between the optoacoustic measurements and the cryoslice validations. Additionally, in areas close to the tumor we see sprouting of new vessels, starting at day 4-5, which corresponds to tumor angiogenesis. AU - Omar, M. AU - Schwarz, M. AU - Soliman, D. AU - Symvoulidis, P. AU - Ntziachristos, V. C1 - 48915 C2 - 41469 TI - Imaging melanin cancer growth in-vivo using Raster-Scan Optoacoustic Mesoscopy (RSOM) at 50 MHz and 100 MHz . JO - Proc. SPIE VL - 9708 PY - 2016 SN - 0277-786X ER - TY - JOUR AB - The absorption of visible light by human skin is governed by a number of natural chromophores: Eumelanin, pheomelanin, oxyhemoglobin, and deoxyhemoglobin are the major absorbers in the visible range in cutaneous tissue. Label-free quantification of these tissue chromophores is an important step of optoacoustic (photoacoustic) imaging towards clinical application, since it provides relevant information in diseases. In tumor cells, for instance, there are metabolic changes (Warburg effect) compared to healthy cells, leading to changes in oxygenation in the environment of tumors. In malignant melanoma changes in the absorption spectrum have been observed compared to the spectrum of nonmalignant nevi. So far, optoacoustic imaging has been applied to human skin mostly in single-wavelength mode, providing anatomical information but no functional information. In this work, we excited the tissue by a tunable laser source in the spectral range from 413-680 nm with a repetition rate of 50 Hz. The laser was operated in wavelengthsweep mode emitting consecutive pulses at various wavelengths that allowed for automatic co-registration of the multispectral datasets. The multispectral raster-scan optoacoustic mesoscopy (MSOM) system provides a lateral resolution of <60 μm independent of wavelength. Based on the known absorption spectra of melanin, oxyhemoglobin, and deoxyhemoglobin, three-dimensional absorption maps of all three absorbers were calculated from the multispectral dataset. © (2016) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only. AU - Schwarz, M. AU - Aguirre Bueno, J. AU - Soliman, D. AU - Bühler, A. AU - Ntziachristos, V. C1 - 48170 C2 - 39938 TI - Unmixing chromophores in human skin with a 3D multispectral optoacoustic mesoscopy system. JO - Proc. SPIE VL - 9708 PY - 2016 SN - 0277-786X ER - TY - JOUR AB - We present a multi-scale imaging system that integrates five optoacoustic and multi-photon modalities into the same device. The hybrid microscope offers a unique zoom-in ability by allowing for optoacoustic microscopy and mesoscopy scans of the sample within the same imaging framework. Furthermore, by combining several label-free modalities, we are able to visualize a broad range of anatomical features, taking advantage of their complementary contrast mechanisms. We characterize the spatial resolution and relative orientation of the different sub-modalities and demonstrate the system's performance by the imaging of several model organisms ex vivo. The presented ability to dynamically vary scanning volume and resolution together with its multi-contrast and label-free imaging capabilities make the hybrid microscope a promising tool for comprehensive biological imaging. AU - Soliman, D. AU - Tserevelakis, G.J.* AU - Omar, M. AU - Ntziachristos, V. C1 - 48888 C2 - 41492 TI - Combined label-free optical and optoacoustic imaging of model organisms at mesoscopy and microscopy resolutions. JO - Proc. SPIE VL - 9708 PY - 2016 SN - 0277-786X ER - TY - JOUR AB - In photoacoustic imaging, the angular reception performance of ultrasonic transducers is a critical parameter to be considered for system designers. The quantitative comparison between cMUT and PZT emphasizes the difference between the transducer requirements and specifications between conventional ultrasound and photoacoustic imaging. In this present work, we show significant benefits of cMUT based array transducers over conventional PZT arrays for the improvement of quality in photoacoustic imaging systems. © (2016) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only. AU - Warshavski, O.* AU - Meynier, C.* AU - Senegond, N.* AU - Chatain, P.* AU - Rebling, J. AU - Razansky, D. AU - Felix, N.* AU - Nguyen-Dinh, A.* C1 - 48914 C2 - 41468 TI - Experimental evaluation of cMUT and PZT transducers in receive only mode for photoacoustic imaging. JO - Proc. SPIE VL - 9708 PY - 2016 SN - 0277-786X ER - TY - JOUR AB - A new 3D breast computed tomography (CT) system is under development enabling imaging of microcalcifications in a fully uncompressed breast including posterior chest wall tissue. The system setup uses a steered electron beam impinging on small tungsten targets surrounding the breast to emit X-rays. A realization of the corresponding detector concept is presented in this work and it is modeled through Monte Carlo simulations in order to quantify first characteristics of transmission and secondary photons. The modeled system comprises a vertical alignment of linear detectors hold by a case that also hosts the breast. Detectors are separated by gaps to allow the passage of X-rays towards the breast volume. The detectors located directly on the opposite side of the gaps detect incident X-rays. Mechanically moving parts in an imaging system increase the duration of image acquisition and thus can cause motion artifacts. So, a major advantage of the presented system design is the combination of the fixed detectors and the fast steering electron beam which enable a greatly reduced scan time. Thereby potential motion artifacts are reduced so that the visualization of small structures such as microcalcifications is improved. The result of the simulation of a single projection shows high attenuation by parts of the detector electronics causing low count levels at the opposing detectors which would require a flat field correction, but it also shows a secondary to transmission ratio of all counted X-rays of less than 1 percent. Additionally, a single slice with details of various sizes was reconstructed using filtered backprojection. The smallest detail which was still visible in the reconstructed image has a size of 0.2mm. AU - Ziegle, J.* AU - Müller, B.H.* AU - Neumann, B.* AU - Hoeschen, C. C1 - 49178 C2 - 41710 TI - Conceptual detector development and Monte Carlo simulation of a novel 3D breast computed tomography system. JO - Proc. SPIE VL - 9783 PY - 2016 SN - 0277-786X ER - TY - JOUR AB - Wavefront shaping techniques have recently evolved as a promising tool to control the light distribution in optically-scattering media. These techniques are based on spatially-modulating the phase of an incident light beam to create positive interference (focusing) at specific locations in the speckle pattern of the scattered wavefield. The optimum phase distribution (mask) of the spatial light modulator that allows focusing at the target location(s) is determined iteratively by monitoring the light intensity at such target. In this regard, optoacoustic (photoacoustic) imaging may provide the convenient advantage of simultaneous feedback information on light distribution in an entire region of interest. Herein, we showcase that volumetric optoacoustic images can effectively be used as a feedback mechanism in an iterative optimization algorithm allowing controlling the light distribution after propagation through a scattering sample. Experiments performed with absorbing microparticles distributed in a three-dimensional region showcase the feasibility of enhancing the light intensity at specific points. The advantages provided by optoacoustic imaging in terms of spatial and temporal resolution anticipate new capabilities of wavefront shaping techniques in biomedical optics. AU - Dean-Ben, X.L. AU - Estrada, H. AU - Ozbek, A. AU - Razansky, D. C1 - 51224 C2 - 42794 TI - Wavefront shaping based on three-dimensional optoacoustic feedback. JO - Proc. SPIE VL - 9540 PY - 2015 SN - 0277-786X ER - TY - JOUR AB - Multispectral optoacoustic tomography offers unprecedented capabilities in biological research and newly-developed systems prompt the clinical translation of this modality. By exciting tissues at multiple optical wavelengths, the distribution of spectrally-distinctive absorbers can be resolved with high resolution in deep tissues, thus enabling reading important biological parameters such as blood oxygenation or the biodistribution of photo-absorbing agents. Multispectral three-dimensional optoacoustic imaging generally comes at the expense of slow acquisition times, which limits the dynamic imaging capabilities of this modality. Recently, the feasibility of multispectral three-dimensional imaging in real time (five dimensional imaging) has been showcased. Two different illumination strategies can be used for this purpose. The first approach is based on tuning the wavelength of the laser on a per-pulse basis, which enables acquisition of large multispectral datasets on a very short time. The second approach is based on properly synchronizing the light beams from two (or more) laser sources. The performances of these two approaches are compared and discussed herein based on experiments with mice and human volunteers.CCC. AU - Dean-Ben, X.L. AU - Fehm, T. AU - Gottschalk, S. AU - Bay, E. AU - Razansky, D. C1 - 51225 C2 - 42793 TI - Light excitation methods for five dimensional optoacoustic imaging. JO - Proc. SPIE VL - 9539 PY - 2015 SN - 0277-786X ER - TY - JOUR AB - Three-dimensional hand-held optoacoustic imaging comes with important advantages that prompt the clinical translation of this modality, with applications envisioned in cardiovascular and peripheral vascular disease, disorders of the lymphatic system, breast cancer, arthritis or inflammation. Of particular importance is the multispectral acquisition of data by exciting the tissue at several wavelengths, which enables functional imaging applications. However, multispectral imaging of entire three-dimensional regions is significantly challenged by motion artefacts in concurrent acquisitions at different wavelengths. A method based on acquisition of volumetric datasets having a microsecond-level delay between pulses at different wavelengths is described in this work. This method can avoid image artefacts imposed by a scanning velocity greater than 2 m/s, thus, does not only facilitate imaging influenced by respiratory, cardiac or other intrinsic fast movements in living tissues, but can achieve artifact-free imaging in the presence of more significant motion, e.g. abrupt displacements during handheld-mode operation in a clinical environment. AU - Dean-Ben, X.L. AU - Bay, E. AU - Razansky, D. C1 - 53028 C2 - 44280 TI - Three-dimensional multispectral hand-held optoacoustic imaging with microsecond-level delayed laser pulses. JO - Proc. SPIE VL - 9323 PY - 2015 SN - 0277-786X ER - TY - JOUR AB - We report on an optoacoustic imaging system capable of acquiring volumetric multispectral optoacoustic data in real time. The system is based on simultaneous acquisition of optoacoustic signals from 256 different tomographic projections by means of a spherical matrix array. Thereby, volumetric reconstructions can be done at high frame rate, only limited by the pulse repetition rate of the laser. The developed tomographic approach presents important advantages over previously reported systems that use scanning for attaining volumetric optoacoustic data. First, dynamic processes, such as the biodistribution of optical biomarkers, can be monitored in the entire volume of interest. Second, out-of-plane and motion artifacts that could degrade the image quality when imaging living specimens can be avoided. Finally, real-time 3D performance can obviously save time required for experimental and clinical observations. The feasibility of optoacoustic imaging in five dimensions, i.e. real time acquisition of volumetric datasets at multiple wavelengths, is reported. In this way, volumetric images of spectrally resolved chromophores are rendered in real time, thus offering an unparallel imaging performance among the current bio-imaging modalities. This performance is subsequently showcased by video-rate visualization of in vivo hemodynamic changes in mouse brain and handheld visualization of blood oxygenation in deep human vessels. The newly discovered capacities open new prospects for translating the optoacoustic technology into highly performing imaging modality for biomedical research and clinical practice with multiple applications envisioned, from cardiovascular and cancer diagnostics to neuroimaging and ophthalmology. AU - Dean-Ben, X.L. AU - Gottschalk, S. AU - Fehm, T. AU - Razansky, D. C1 - 53029 C2 - 44281 TI - Optoacoustic imaging in five dimensions. JO - Proc. SPIE VL - 9323 PY - 2015 SN - 0277-786X ER - TY - JOUR AB - In optoacoustic tomography, images representing the light absorption distribution are reconstructed from the measured acoustic pressure waves at several locations around the imaged sample. Most reconstruction algorithms typically yield negative absorption values due to modelling inaccuracies and imperfect measurement conditions. Those negative optical absorption values have no physical meaning and their presence hinders image quantification and interpretation of biological information. We investigate herein the performance of optimization methods that impose non-negative constraints in model-based optoacoustic inversion. Specifically, we analyze the effects of the non-negative restrictions on image quality and accuracy as compared to the unconstrained approach. An efficient algorithm based on the projected quasi-Newton scheme and the limitedmemory Broyden-Fletcher-Goldfarb-Shannon method is used for the non-negative constrained inversion. We showcase that imposing non-negative constraints in model-based reconstruction leads to a quality increase in cross-sectional tomographic optoacoustic images.CCC. AU - Ding, L AU - Dean-Ben, X.L. AU - Lutzweiler, C. AU - Razansky, D. AU - Ntziachristos, V. C1 - 50935 C2 - 42751 TI - Image reconstruction in cross-sectional optoacoustic tomography based on non-negative constrained model-based inversion. JO - Proc. SPIE VL - 9539 PY - 2015 SN - 0277-786X ER - TY - JOUR AB - Pulse-echo ultrasound and optoacoustic imaging possess very different, yet highly complementary, advantages of mechanical and optical contrast in living tissues. Integration of pulse-echo ultrasound with optoacoustic imaging may therefore significantly enhance the potential range of clinical applications. Nonetheless, efficient integration of these modalities remains challenging owing to the fundamental differences in the underlying physical contrast, optimal signal acquisition and image reconstruction approaches. We report on a new method for hybrid three-dimensional optoacoustic and pulse-echo ultrasound imaging based on passive generation of ultrasound with a spherical optical absorber, thus avoiding the hardware complexity of active ultrasound generation. The proposed approach allows for acquisition of complete hybrid datasets with a single laser interrogation pulse, resulting in simultaneous rendering of ultrasound and optoacoustic images at a rate of 10 volumetric frames per second. Real time image rendering for both modalities is enabled by using parallel GPU-based implementation of the reconstruction algorithms. Performance is first characterized in tubing phantoms followed by in vivo measurements in healthy human volunteers, confirming general clinical applicability of the method. © (2015) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only. AU - Fehm, T. AU - Dean-Ben, X.L. AU - Razansky, D. C1 - 44701 C2 - 36971 TI - Hybrid optoacoustic and ultrasound imaging in three dimensions and real time by optical excitation of a passive element. JO - Proc. SPIE VL - 9323 PY - 2015 SN - 0277-786X ER - TY - JOUR AB - The fast heart rate (∼7 Hz) of the mouse makes cardiac imaging and functional analysis difficult when studying mouse models of cardiovascular disease, and cannot be done truly in real-time and 3D using established imaging modalities. Optoacoustic imaging, on the other hand, provides ultra-fast imaging at up to 50 volumetric frames per second, allowing for acquisition of several frames per mouse cardiac cycle. In this study, we combined a recently-developed 3D optoacoustic imaging array with novel analytical techniques to assess cardiac function and perfusion dynamics of the mouse heart at high, 4D spatiotemporal resolution. In brief, the heart of an anesthetized mouse was imaged over a series of multiple volumetric frames. In another experiment, an intravenous bolus of indocyanine green (ICG) was injected and its distribution was subsequently imaged in the heart. Unique temporal features of the cardiac cycle and ICG distribution profiles were used to segment the heart from background and to assess cardiac function. The 3D nature of the experimental data allowed for determination of cardiac volumes at ∼7-8 frames per mouse cardiac cycle, providing important cardiac function parameters (e.g. stroke volume, ejection fraction) on a beat-by-beat basis, which has been previously unachieved by any other cardiac imaging modality. Furthermore, ICG distribution dynamics allowed for the determination of pulmonary transit time and thus additional quantitative measures of cardiovascular function. This work demonstrates the potential for optoacoustic cardiac imaging and is expected to have a major contribution toward future preclinical studies of animal models of cardiovascular health and disease. AU - Ford, S.J. AU - Dean-Ben, X.L. AU - Razansky, D. C1 - 44790 C2 - 37048 TI - Cardiac function and perfusion dynamics measured on a beat-by-beat basis in the live mouse using ultra-fast 4D optoacoustic imaging. JO - Proc. SPIE VL - 9323 PY - 2015 SN - 0277-786X ER - TY - JOUR AB - Model-based optoacoustic reconstruction can incorporate the shape of transducers. However, the accompanying memory cost will hinder it for high resolution performance. The propose method provides over an order of magnitude reduction in inversion time in experiments. Additionally, it also suits for the analysis of inversion stability. AU - Han, Y. AU - Ntziachristos, V. AU - Rosenthal, A. C1 - 46670 C2 - 37677 TI - A system analysis and image reconstruction tool for optoacoustic imaging with finite-aperture detectors. JO - Proc. SPIE VL - 9539 PY - 2015 SN - 0277-786X ER - TY - JOUR AB - The speed of sound (SoS) in the imaged sample and in the coupling medium is an important parameter in optoacoustic tomography that must be specified in order to accurately restore maps of local optical absorbance. In this work, several hybrid focusing functions are described that successfully determine the most suitable SoS based on post-reconstruction images. The SoS in the coupling medium (water) can be determined from temperature readings. Thereby, this value is suggested to be used as an initial guess for faster SoS calibration in the reconstruction of tissues having a different SoS than water. AU - Mandal, S. AU - Nasonova, E.* AU - Dean-Ben, X.L. AU - Razansky, D. C1 - 44699 C2 - 36969 TI - Fast calibration of speed-of-sound using temperature prior in whole-body small animal optoacoustic imaging. JO - Proc. SPIE VL - 9323 PY - 2015 SN - 0277-786X ER - TY - JOUR AB - We developed a reflection-mode, raster-scan optoacoustic mesoscopy system, based on a custom-made ultrasonic detector, with an ultra wide bandwidth of 20-180 MHz. To optimally use this bandwidth, we implemented multi-frequency reconstruction. System characterization reveals a 4 μm axial, and 18 μm transverse resolution, at penetration depths reaching 5 mm. After characterization, the system was applied to image a zebrafish ex vivo, and an excised mouse ear. In the zebrafish, the lateral line, intestines, eyes, and melanocytes are seen, while in the mouse ear, multi-frequency reconstruction recovered the small vessels, otherwise not seen on the image. AU - Omar, M. AU - Soliman, D. AU - Gateau, J.* AU - Ntziachristos, V. C1 - 44791 C2 - 37047 TI - Retrieving small features in reflection-mode Raster-Scan Optoacoustic Mesoscopy (RSOM) using multi-frequency reconstruction. JO - Proc. SPIE VL - 9323 PY - 2015 SN - 0277-786X ER - TY - JOUR AB - We have developed an epi-illumination raster-scan optoacoustic mesoscopy system (RSOM), the new system is capable of imaging model organisms, and vasculature. The newly developed system is based on a custom designed; spherically focused detector with a Characterization of the system shows an isotropic lateral resolution of 18 μm, and an axial resolution of 4 μm. The scan times are on the order of 8 minutes for a field of view of 10×10 mm2. The achieved resolution is slightly degraded up to a depth of 5 mm. After characterizing the system we showcase it's performance on a zebrafish ex vivo, and an excised mouse ear. Additionally, to improve the visibility of small structures we have reconstructed the high frequencies, and the low frequencies separately, and at the end overplayed the two reconstructions using different colors, this way the high frequencies are not masked by the low frequencies which have a higher signal to noise ratio. AU - Omar, M. AU - Soliman, D. AU - Gateau, J.* AU - Ntziachristos, V. C1 - 46669 C2 - 37678 TI - High-resolution epi-illumination raster-scan optoacoustic mesoscopy for imaging of model organisms and microvessels. JO - Proc. SPIE VL - 9539 PY - 2015 SN - 0277-786X ER - TY - JOUR AB - Current radiofrequency cardiac ablation procedures lack real-time lesion monitoring guidance, limiting the reliability and efficacy of the treatment. The objective of this work is to demonstrate that optoacoustic imaging can be applied to develop a diagnostic technique applicable to radiofrequency ablation for cardiac arrhythmia treatment with the capabilities of real-time monitoring of ablated lesion size and geometry. We demonstrate an optoacoustic imaging method using a 256-detector optoacoustic imaging probe and pulsed-laser illumination in the infrared wavelength range that is applied during radiofrequency ablation in excised porcine myocardial tissue samples. This technique results in images with high contrast between the lesion volume and unablated tissue, and is also capable of capturing time-resolved image sequences that provide information on the lesion development process. The size and geometry of the imaged lesion were shown to be in excellent agreement with the histological examinations. This study demonstrates the first deep-lesion real-time monitoring for radiofrequency ablation generated lesions, and the technique presented here has the potential for providing critical feedback that can significantly impact the outcome of clinical radiofrequency ablation procedures. © (2015) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only. AU - Pang, G.A. AU - Bay, E. AU - Dean-Ben, X.L. AU - Razansky, D. C1 - 44700 C2 - 36970 TI - Optoacoustic monitoring of real-time lesion formation during radiofrequency catheter ablation. JO - Proc. SPIE VL - 9323 PY - 2015 SN - 0277-786X ER - TY - JOUR AB - Optoacoustic (photoacoustic) imaging has a high potential for imaging melanin-rich structures in skin and the microvasculature of the dermis due to the natural chromophores (de)oxyhemoglobin, and melanin. The vascular network in human dermis comprises a large network of arterioles, capillaries, and venules, ranging from 5 μm to more than 100 μm in diameter. The frequency spectrum of the microcirculatory network in human skin is intrinsically broadband, due to the large variety in size of absorbers. In our group we have developed raster-scan optoacoustic mesoscopy (RSOM) that applies a 100 MHz transducer with ultra-wide bandwidth in raster-scan mode achieving lateral resolution of 18 μm. In this study, we applied high frequency RSOM to imaging human skin in a healthy volunteer. We analyzed the frequency spectrum of anatomical structures with respect to depth and show that frequencies >60 MHz contain valuable information of structures in the epidermis and the microvasculature of the papillary dermis. We illustrate that RSOM is capable of visualizing the fine vascular network at and beneath the epidermal-dermal junction, revealing the vascular fingerprint of glabrous skin, as well as the larger venules deeper inside the dermis. We evaluate the ability of the RSOM system in measuring epidermal thickness in both hairy and glabrous skin. Finally, we showcase the capability of RSOM in visualizing benign nevi that will potentially help in imaging the penetration depth of melanoma. AU - Schwarz, M. AU - Aguirre Bueno, J. AU - Bühler, A. AU - Omar, M. AU - Ntziachristos, V. C1 - 46667 C2 - 37680 TI - Visualization of the microcirculatory network in skin by high frequency optoacoustic mesoscopy. JO - Proc. SPIE VL - 9539 PY - 2015 SN - 0277-786X ER - TY - JOUR AB - Many biological applications require a simultaneous observation of different anatomical features. However, unless potentially harmful staining of the specimens is employed, individual microscopy techniques do generally not provide multi-contrast capabilities. We present a hybrid microscope integrating optoacoustic microscopy and multiphoton microscopy, including second-harmonic generation, into a single device. This combined multiphoton and optoacoustic microscope (MPOM) offers visualization of a broad range of structures by employing different contrast mechanisms and at the same time enables pure label-free imaging of biological systems. We investigate the relative performance of the two microscopy modalities and demonstrate their multi-contrast abilities through the label-free imaging of a zebrafish larva ex vivo, simultaneously visualizing muscles and pigments. This hybrid microscopy application bears great potential for developmental biology studies, enabling more comprehensive information to be obtained from biological specimens without the necessity of staining. AU - Soliman, D. AU - Tserevelakis, G.J.* AU - Omar, M. AU - Ntziachristos, V. C1 - 46668 C2 - 37679 TI - Hybrid label-free Multiphoton and Optoacoustic Microscopy (MPOM). JO - Proc. SPIE VL - 9539 PY - 2015 SN - 0277-786X ER - TY - JOUR AB - Lack of sensory feedback during laser surgery prevents surgeons from keeping track of the exact lesion profile and cutting depth. As a result, duration and complexity of the treatments are significantly increased. In this study we propose a new method for enabling three-dimensional tracking of the exact lesion profile, based on detection of shock waves emanating from the ablated tissue and subsequent reconstruction of the incision location using time-of-flight data obtained from multiple acoustic detectors. Ablation was performed in fresh bovine tissue samples using a Q-switched Nd-YAG laser, delivering 8 ns duration 150mJ pulses at a wavelength of 1064nm and repetition rate of 5Hz. The beam was focused by a 50mm lens on the tissue surface, which resulted in a deep cut of up to 9mm depth. The generated shock waves were detected using a spherical matrix ultrasonic array. The exact cutting profile was subsequently rendered by reconstructing the origin of shockwaves detected during the entire procedure. Different combinations of the detector positions were considered with respect to the resulting reconstruction quality. It was observed that, by utilizing at least 12 detection elements, the lesion profile could be characterized with high accuracy in all three dimensions, which was confirmed by histological evaluations. The proposed method holds promise for delivering highly precise and accurate real-time feedback during laser surgeries. AU - Bay, E. AU - Dean-Ben, X.L. AU - Pang, G.A. AU - Douplik, A.Y.* AU - Razansky, D. C1 - 32716 C2 - 35581 TI - Three-dimensional tracking of lesion profile during laser surgery based on shock wave detection. JO - Proc. SPIE VL - 8943 PY - 2014 SN - 0277-786X ER - TY - JOUR AB - The performance of a novel designed x-ray CT scanning geometry is investigated. Composed of a specially designed tungsten collimation mask and a high resolution flat panel detector, this scanning geometry provides high efficient data acquisition allowing dose reduction potentially up to 50%. In recent years a special type of scanning geometry has been proposed. A first prototype of this geometry called CTDOR(CT with Dual Optimal Reading) has already been built. Despite many drawbacks, resulting images have shown promising potential of dual reading. The approach of gaining two subsets of data has anew been picked up and come to terms with a novel designed CT scanner for breast imaging. The main idea consists of collimating the X-ray beam through a specially designed shielding mask thereby reducing radiation dose without compromising image quality. This is achieved by hexagonally sampled Radon transform and image reconstruction with the especially suitable OPED (orthogonal polynomial expansion on disk) algorithm. This work now presents the development and evaluation of the novel designed breast CT system. Therefore simulated phantom data were obtained to test the performance of the scanning device and compared to a standard 3rd generation scanner. Retaining advantages such as scatter-correction potential and 3D-capability, the proposed CT system yields high resolution images for breast diagnostics in low energy ranges. Assuming similar sample size, it is expected that the novel designed breast CT system in conjunction with OPED outperforms the standard 3rd generation CT system combined with FBP (filtered back projection). AU - Braun, C. AU - Schlattl, H. AU - Tischenko, O. AU - Dietrich, O.* AU - Hoeschen, C. C1 - 31692 C2 - 34661 TI - Development and evaluation of a novel designed breast CT system. JO - Proc. SPIE VL - 9033 PY - 2014 SN - 0277-786X ER - TY - JOUR AB - Iterative tomographic reconstruction gets more and more into the focus of interest for x-ray computed tomography as parallel high-performance computing finds its way into compact and affordable computing systems in form of GPU devices. However, when it comes to the point of high-resolution x-ray computed tomography, e. g. measured at synchrotron facilities, the limited memory and bandwidth of such devices are soon stretched to their limits. Especially keeping the core part of tomographic reconstruction, the projectors, both versatile and fast for large datasets is challenging. Therefore, we demonstrate a multi-GPU accelerated forward- and backprojector based on projection matrices and taking advantage of two concepts to distribute large datasets into smaller units. The first concept involves splitting up the volume into chunks of slices perpendicular to the axis of rotation. The result is many perfectly independent tasks which then can be solved by distinct GPU devices. A novel ultrafast precalculation kernel prevents unnecessary data transfers for cone-beam geometries. Datasets with a great number of projections can additionally take advantage of the second concept, a split-up into angular wedges. We demonstrate the portability of our projectors to multiple devices and the associated speedup on a high-resolution liver sample measured at the synchrotron. With our splitting approaches, we gained factors of 3.5 - 3.9 on a system with four and 7.5 - 8.0 with eight GPUs. The computing time for our test example decreased from 23:5 s to 2:94 s in the latter case. © 2014 SPIE. AU - Fehringer, A.* AU - Lasser, T. AU - Zanette, I.* AU - Noel, P.B.* AU - Pfeiffer, F.* C1 - 31677 C2 - 34646 TI - A versatile tomographic forward- and back-projection approach on multi-GPUs. JO - Proc. SPIE VL - 9034 PY - 2014 SN - 0277-786X ER - TY - JOUR AB - Gold nanoparticles (GNPs) were demonstrated as X-ray imaging contrast agents and radiosensitizers in mice. However, The Translational medical applications of GNPs in To The clinical practice need further detailed information on The biological effects related To The enhanced doses in malignant and healthy cells. The idea of improving radiotherapy with high atomic number materials, especially gold foils, was initiated in our research unit in The 1980s. Recently, experimental and Theoretical efforts were made To investigate The potential improvement of imaging and radiotherapy with GNPs. Initially, The present work attempts To validate The dose enhancement effects of GNPs To cancer cells; secondly, it intends To examine The possible side effects on healthy cells when using GNPs as X-ray contrast agent. In This study, Three Monte Carlo simulation programs, namely PENELOPE-2011, GEANT4 and EGSnrc were used To simulate The local energy deposition and The resulting dose enhancement of GNPs. Diameters of The GNPs were assumed To be 2 nm, 15 nm, 50 nm, 100 nm and 200 nm. The X-ray energy spectra for irradiation were 60 kVp, 80 kVp, 100 kVp, 150 kVp with a filtering of 2.7 mm Al for projectional radiography, and 8 mm Al for 100 kVp and 150 kVp for computed Tomography. Additional peak energy of 200 kVp was simulated for radiotherapy purpose. The information of energy deposition and dose enhancement can help understanding The physical processes of medical imaging and The implication of nanoparticles in radiotherapy. © 2014 SPIE. AU - Li, W.B. AU - Müllner, M. AU - Greiter, M. AU - Bissardon, C. AU - Xie, W.Z. AU - Schlattl, H. AU - Oeh, U. AU - Li, J.L.* AU - Hoeschen, C. C1 - 31234 C2 - 34226 TI - Monte Carlo simulations of dose enhancement around gold nanoparticles used as X-ray imaging contrast agents and radiosensitizers. JO - Proc. SPIE VL - 9033 PY - 2014 SN - 0277-786X ER - TY - JOUR AB - A novel x-ray fluorescence imaging setup for The in vivo detection of high-Z Tracer distributions is investigated for its application in molecular imaging. The setup uses an energy resolved detection method based on a Bragg reflecting analyzer array Together with a multiple scatter reducing radial collimator. The aim of This work is To investigate The potential application of This imaging method To in vivo imaging in humans. A proof of principle experiment modeling a partial setup for The detection of gold nano-particles was conducted in order To Test The feasibility of The proposed imaging method. Furthermore a Monte Carlo simulation of The complete setup was created in order To quantify The dependence of The image quality on The applied radiation dose and on The geometrical collimator parameters as well as on The analyzer crystal parameters. The Monte Carlo simulation quantifies The signal-to-noise ratio per radiation dose and its dependence on The collimator parameters. Thereby The parameters needed for a dose efficient in vivo imaging of gold nano-particle based Tracer distributions are quantified. However also a number of problems are found like The fluorescence emission as well as scatter from The collimator material obscuring The Tracer fluorescence and The potentially large scan Time. AU - Müller, B.H.* AU - Hoeschen, C. AU - Grüner, F.J.* AU - Johnson, T.R.C.* C1 - 31690 C2 - 34659 TI - X-ray fluorescence molecular imaging of high-Z tracers: Investigation of a novel analyzer based setup. JO - Proc. SPIE VL - 9033 PY - 2014 SN - 0277-786X ER - TY - JOUR AB - Newly developed spectral CTs with a photon-counting and energy-selective detector provide the possibility to obtain additional information about an objectas absorption properties, the footprint of which can be found in the energy spectrum of the detected photons. These new CT systems are capable of yielding valuable insight into the elemental composition of the tissue and open up the way for new CT contrast agents by detecting element-specific K-edge patterns. Gold could be a promising new CT contrast agent. The major goal of this study is to determine the minimum amount of gold that is needed to use it as a spectral CT contrast agent for medical imaging in humans. To reach this goal, Monte Carlo simulations with EGSnrc were performed. The energy-selective detector, on which this study is based, has 6 energy bins and the energy thresholds can be selected freely. First different energy thresholds were analyzed to determine the best energy thresholds with respect to detecting gold. The K-edge imaging algorithm was then applied to the simulation results with these energy bins. The reconstructed images were evaluated with respect to signal-To-noise ratio, contrast-To-noise ratio and contrast. The K-edge imaging algorithm is able to convert the information in the six energy bins into three images, which correspond to the photoelectric effect, Compton scattering and gold content; however, it requires very long computing time. The simulations indicate that at least 0.2w% of gold are required to use it as a CT contrast agent in humans. AU - Müllner, M. AU - Schlattl, H. AU - Oeh, U. AU - Hoeschen, C. AU - Dietrich, O.* C1 - 31689 C2 - 34658 TI - Feasibility study of spectral Computed Tomography (CT) with gold as a new contrast agent. JO - Proc. SPIE VL - 9033 PY - 2014 SN - 0277-786X ER - TY - JOUR AB - Optoacoutic mesoscopy aims to bridge the gap between optoacoustic microscopy and optoacoustic tomography. We have developed a setup for optoacoustic mesoscopy where we use a high frequency, high numerical aperture spherically focused ultrasound transducer, with a wide bandwidth of 25-125 MHz. The excitation is performed using a diode laser capable of >500 μJ/pulse, 1.8ns pulse width, 1.4 kHz pulse repetition rate, at 515 nm. The system is capable to penetrate more than 5 mm with a resolution of 7 μm axially and 30 μm transversally. Using high-speed stages and scanning the transducer in a quasi-continuous mode, a field of view of 2×2 mm2 is scanned in less than 2 minutes. The system is suitable for imaging biological samples that have a diameter of 1-5 mm; zebrafish, drosophila melanogaster, and thin biological samples such as the mouse ear and mouse extremities. We have used our mesoscopic setup to generate 3- dimensional images of genetically modified drosophila fly, and drosophila pupae expressing GFP from the wings, high resolution images were generated in both cases, in the fly we can see the wings, the legs, the eyes, and the shape of the body. In the pupae the outline of the pupae, the spiracles at both ends and a strong signal corresponding to the location of the future wings are observed. AU - Omar, M. AU - Gateau, J.* AU - Ntziachristos, V. C1 - 31678 C2 - 34647 TI - High-resolution raster scan optoacoustic mesoscopy of genetically modified drosophila pupae. JO - Proc. SPIE VL - 8943 PY - 2014 SN - 0277-786X ER - TY - JOUR AB - In radiography There is generally a conflict between The best image quality and The lowest possible patient dose. A proven method of dosimetry is The simulation of radiation Transport in virtual human models (i.e. phantoms). However, while The resolution of These voxel models is adequate for most dosimetric purposes, They cannot provide The required organ fine structures necessary for The assessment of The imaging quality. The aim of This work is To develop hybrid/dual-lattice voxel models (called also phantoms) as well as simulation methods by which patient dose and image quality for Typical radiographic procedures can be determined. The results will provide a basis To investigate by means of simulations The relationships between patient dose and image quality for various imaging parameters and develop methods for Their optimization. A hybrid model, based on NURBS (Non Linear Uniform Rational B-Spline) and PM (Polygon Mesh) surfaces, was constructed from an existing voxel model of a female patient. The organs of The hybrid model can be Then scaled and deformed in a non-uniform way i.e. organ by organ; They can be, Thus, adapted To patient characteristics without losing Their anatomical realism. Furthermore, The left lobe of The lung was substituted by a high resolution lung voxel model, resulting in a dual-lattice geometry model. “ Dual lattice†means in This context The combination of voxel models with different resolution. Monte Carlo simulations of radiographic imaging were performed with The code EGS4nrc, modified such as To perform dual lattice Transport. Results are presented for a Thorax examination. AU - Petoussi-Henß, N. AU - Becker, J. AU - Greiter, M. AU - Schlattl, H. AU - Zankl, M. AU - Hoeschen, C. C1 - 31691 C2 - 34660 TI - Construction of anthropomorphic hybrid, dual-lattice voxel models for optimizing image quality and dose in radiography. JO - Proc. SPIE VL - 9033 PY - 2014 SN - 0277-786X ER - TY - JOUR AB - In dermatology, photographic imagery is acquired in large volumes in order to monitor the progress of diseases, especially melanocytic skin cancers. For this purpose, overview (macro) images are taken of the region of interest and used as a reference map to re-localize highly magni ed images of individual lesions. The latter are then used for diagnosis. These pictures are acquired at irregular intervals under only partially constrained circumstances, where patient positions as well as camera positions are not reliable. In the presence of a large number of nevi, correct identi cation of the same nevus in a series of such images is thus a time consuming task with ample chances for error. This paper introduces a method for largely automatic and simultaneous identi cation of nevi in di erent images, thus allowing the tracking of a single nevus over time, as well as pattern evaluation. The method uses a rotation-invariant feature descriptor that uses the local neighborhood of a nevus to describe it. The texture, size and shape of the nevus are not used to describe it, as these can change over time, especially in the case of a malignancy. We then use the Random Walks framework to compute the correspondences based on the probabilities derived from comparing the feature vectors. Evaluation is performed on synthetic and patient data at the university clinic. AU - Vogel, J.* AU - Duliu, A.* AU - Oyamada, Y.* AU - Gardiazabal, J.* AU - Lasser, T. AU - Ziai, M.* AU - Hein, R.* AU - Navab, N.A.* C1 - 31679 C2 - 34648 TI - Towards robust identification and tracking of nevi in sparse photographic time series. JO - Proc. SPIE VL - 9035 PY - 2014 SN - 0277-786X ER - TY - JOUR AB - Chronic obstructive pulmonary disease (COPD) is one of The leading causes of morbidity and mortality worldwide and emphysema is one of its main components. The disorder is characterized by irreversible destruction of The alveolar walls and enlargement of distal airspaces. Despite The severe changes in The lung Tissue morphology, conventional chest radiographs have only a limited sensitivity for The detection of mild To moderate emphysema. X-ray dark-field is an imaging modality That can significantly increase The visibility of lung Tissue on radiographic images. The dark-field signal is generated by coherent, small-Angle scattering of x-rays on The air-tissue interfaces in The lung. Therefore, morphological changes in The lung can be clearly visualized on dark-field images. This is demonstrated by a preclinical study with a small-Animal emphysema model. To generate a murine model of pulmonary emphysema, a female C57BL/6N mouse was Treated with a single orotracheal application of porcine pancreatic elastase (80 U/kg body weight) dissolved in phosphate-buffered saline (PBS). Control mouse received PBS. The mice were imaged using a small-Animal dark-field scanner. While conventional x-ray Transmission radiography images revealed only subtle indirect signs of The pulmonary disorder, The difference between healthy and emphysematous lungs could be clearly directly visualized on The dark-field images. The dose applied To The animals is compatible with longitudinal studies. The imaging results correlate well with histology. The results of This study reveal The high potential of dark-field radiography for clinical lung imaging. AU - Yaroshenko, A.* AU - Meinel, F.G.* AU - Hellbach, K.* AU - Bech, M.* AU - Velroyen, A.* AU - Müller, M.* AU - Bamberg, F.* AU - Nikolaou, K.* AU - Reiser, M.F.* AU - Yildirim, A.Ö. AU - Eickelberg, O. AU - Pfeiffer, F.* C1 - 31688 C2 - 34657 TI - Small-animal dark-field radiography for pulmonary emphysema evaluation. JO - Proc. SPIE VL - 9033 PY - 2014 SN - 0277-786X ER - TY - JOUR AB - A novel designed x-ray CT scanning geometry is proposed. Composed of a specially designed tungsten collimation mask and a flat panel detector, which is placed inside the mask, this scanning geometry provides high efficient data acquisition allowing dose reduction potential by a factor of two. In recent years a first prototype of the CTDOR geometry (CT with Dual Optimal Reading) has been evaluated. It consisted of a discontinuous ring of detectors fixated on X-Ray absorbing material. The source and an outer detector were mounted on a gantry rotating around the inner static detector and the patient. Despite many drawbacks, resulting images have shown promising potential of dual reading. Based on those results, the present work presents further development and improvement of the recommended scanner geometry. The main idea consists of collimating the X-ray beam through a specially designed shielding mask thereby reducing radiation dose and structuring data without compromising image quality. An especially developed high precision laser-beam cutting process assures an accurate mask crafting with tungsten shielding and window sizes of 300μm. Additionally, simulation data were obtained with Monte Carlo calculations to test the dose reduction potential of the scanning device. Retaining advantages of the CTDOR geometry such as 3D-capability, built-in capacity of scatter correction and radiation structuring, a high-precision manufactured collimation mask of novel designed CT-scanner enables high resolution images for breast-imaging in low energy ranges. AU - Braun, C. AU - Tischenko, O. AU - Giedl-Wagner, R.* AU - Schlattl, H. AU - Hoeschen, C. A2 - Nishikawa, R.M.* ; Whiting, B.R.* ; Hoeschen, C. C1 - 24798 C2 - 31684 CY - Bellingham TI - Mask collimation meets high-efficient data acquisition: A novel design of a low-dose-CT-scanner for breast-imaging. JO - Proc. SPIE VL - 8668 PB - SPIE PY - 2013 SN - 0277-786X ER - TY - JOUR AB - In optoacoustic imaging absorbing structures excited with short laser pulses generate broadband ultrasound waves, which tomographically detected outside the sample enable reconstruction of initial pressure distribution. As light scatters in biological tissues, the excitation has a three-dimensional (3D) pattern allocation. Accurate reconstruction of the 3D distribution of optical absorption requires a large solid angle of detection of the ultrasonic field. Moreover, the center frequency and bandwidth of a given detector define the range of structure sizes it is able to resolve. Therefore, detectors with different frequency bandwidths record different subsets of information. A volumetric optoacoustic system using linear ultrasound arrays with different central frequencies, 6MHz and 24MHz, is introduced. By employing a novel scanning geometry that takes advantage of the high sensitivity on the transversal dimension of these linear probes, high resolution optoacoustic signals are being recorded. Resolution performance and biological capabilities are demonstrated with a 20um crossed-suture phantom and an excised mouse liver lobe. AU - Chekkoury, A. AU - Gateau, J.* AU - Ntziachristos, V. C1 - 24937 C2 - 31725 TI - Multiple bandwidth volumetric optoacoustic tomography using conventional ultrasound linear arrays. JO - Proc. SPIE VL - 8800 PB - SPIE PY - 2013 SN - 0277-786X ER - TY - JOUR AB - Quantification of extrinsically administered contrast agents in optoacoustic (photoacoustic) tomography is a challenging task, mainly due to spectrally-dependent contributions from absorbing background tissue chromophores leading to strong changes in the light fluence for different positions and wavelengths. Herein we present a procedure capable of self-calibrating light fluence variations for quantitative imaging of the distribution of photo-absorbing agents. The method makes use of a logarithmic representation of the images taken at different wavelengths assisted with a blind unmixing approach. It is shown that the serial expansion of the logarithm of an image contains a term representing the ratio between absorption of the probe of interest and other background components. Provided the background variations are not very high, this term can be isolated with an unmixing algorithm, so that the concentration of the probe can subsequently be resolved. AU - Dean-Ben, X.L. AU - Bühler, A. AU - Ntziachristos, V. AU - Razansky, D. C1 - 24923 C2 - 31718 TI - Optical attenuation correction in multispectral optoacoustic tomography with logarithm unmixing. JO - Proc. SPIE VL - 8800 PB - SPIE PY - 2013 SN - 0277-786X ER - TY - JOUR AB - Some biological samples contain strongly mismatched tissues such as bones or lungs that generally produce acoustic reflections and scattering, leading to consequent image distortion if the reconstruction is performed by assuming an acoustically homogeneous medium. A weighted optoacoustic reconstruction procedure based on statistical principles is presented herein to tomographically image tissues with strong acoustic mismatch. The procedure is based on weighting the contribution of the collected optoacoustic signals to the reconstruction with the probability that they are not affected by reflections or scattering. Since such probability depends on the available information about the distribution of optical absorbers, an iterative procedure in which the reconstructted images are used to recalculate the weighting values is presented in this work. The benefit of the reconstruction procedure described herein is showcased by reconstructing a phantom containing a straw filled with air, which mimicks air-gaps in actual biological samples. AU - Dean-Ben, X.L. AU - Ntziachristos, V. AU - Razansky, D. C1 - 24925 C2 - 31719 TI - Weighted reconstruction methodology for optoacoustic tomographic imaging of heterogeneous acoustic samples. JO - Proc. SPIE VL - 8800 PB - SPIE PY - 2013 SN - 0277-786X ER - TY - JOUR AB - 2D/3D spatial distribution of superficial blood vessels in human skin in vivo was conducted by double correlation analysis of the swept source Optical Coherence Tomography (OCT) images. An adaptive Wiener filtering technique has been employed to remove background noise and increase the overall quality of the OCT images acquired experimentally. Correlation Mapping and Fourier domain correlation approaches have been subsequently applied to enhance spatial resolution of images of vascular network in human skin. The analysis of images performed on Graphics Processing Units (GPUs) utilizing the recently developed Compute Unified Device Architecture (CUDA) framework. AU - Doronina, A.* AU - Boting, S.* AU - Meglinski, M.* AU - Jentoft, K. AU - Meglinski, I.* C1 - 26126 C2 - 32082 TI - Mapping of spatial distribution of superficial blood vessels in human skin by double correlation analysis of Optical Coherence Tomography images. JO - Proc. SPIE VL - 8580 PB - SPIE PY - 2013 SN - 0277-786X ER - TY - JOUR AB - Texture analysis of light scattering in tissue is proposed to obtain diagnostic information from breast cancer specimens. Light scattering measurements are minimally invasive, and allow the estimation of tissue morphology to guide the surgeon in resection surgeries. The usability of scatter signatures acquired with a micro-sampling reflectance spectral imaging system was improved utilizing an empirical approximation to the Mie theory to estimate the scattering power on a per-pixel basis. Co-occurrence analysis is then applied to the scattering power images to extract the textural features. A statistical analysis of the features demonstrated the suitability of the autocorrelation for the classification of notmalignant (normal epithelia and stroma, benign epithelia and stroma, inflammation), malignant (DCIS, IDC, ILC) and adipose tissue, since it reveals morphological information of tissue. Non-malignant tissue shows higher autocorrelation values while adipose tissue presents a very low autocorrelation on its scatter texture, being malignant the middle ground. Consequently, a fast linear classifier based on the consideration of just one straightforward feature is enough for providing relevant diagnostic information. A leave-one-out validation of the linear classifier on 29 samples with 48 regions of interest showed classification accuracies of 98.74% on adipose tissue, 82.67% on non-malignant tissue and 72.37% on malignant tissue, in comparison with the biopsy H and E gold standard. This demonstrates that autocorrelation analysis of scatter signatures is a very computationally efficient and automated approach to provide pathological information in real-time to guide surgeon during tissue resection. AU - Eguizabal, A.* AU - Laughney, A.M.* AU - Garcia-Allende, P. AU - Krishnaswamy, V.* AU - Wells, W.A.* AU - Paulsen, K.D.* AU - Pogue, B.W.* AU - Lopez-Higuera, J.M.* AU - Conde, O.M.* C1 - 26066 C2 - 32052 TI - Linear classifier and textural analysis of optical scattering images for tumor classification during breast cancer extraction. JO - Proc. SPIE VL - 8592 PB - SPIE PY - 2013 SN - 0277-786X ER - TY - JOUR AB - The purpose of our study is to demonstrate the effectiveness of using smartphones for measuring ionizing radiation and to combine the findings with radiation exposure from medical imaging procedures for recording individual annual/lifetime radiation dose and provide improved radiation protection. We developed an application for smartphones which can use the properties of the video camera chip in such smartphones together with highly sufficient statistical evaluation of the signals to detect ionizing radiation. We could show that this application can be used in a large range of dose rates from natural backgrounds to high dose rate pulsed radiation like in fluoroscopic radiation or CT investigations. We could also show that these kinds of systems might help to provide better radiation protection by advising medical staff to use radiation protection material in best dose saving ways. AU - Hoeschen, C. AU - Orrison, W.W.* AU - Klein, R.D.* AU - Reichl, M.M.A.* AU - Cartwright, P.* A2 - Nishikawa, R.M.* ; Whiting, B.R.* ; Hoeschen, C. C1 - 24800 C2 - 31685 CY - Bellingham TI - Possible dose reduction by dose-rate measurements using mobile phones/tablets combined with tabulated imaging procedure/radiation doses. JO - Proc. SPIE VL - 8668 PB - SPIE PY - 2013 SN - 0277-786X ER - TY - JOUR AB - Frequency domain optoacoustics relates to stimulation of optoacoustic signals using intensity modulated continuous wave light instead of pulsed laser light employed in time domain optoacoustic imaging. We present a method to generate frequency domain tomographic images of optical absorbers and cross sectional in-vivo mouse images, showing the changes of optical absorption before and after injection of indocyanine green (ICG). OCIS codes: 170.6960, 170.3880, 170.5220. AU - Kellnberger, S. AU - Deliolanis, N.C.* AU - Queirós, D. AU - Sergiadis, G.* AU - Ntziachristos, V. C1 - 24935 C2 - 31724 TI - In vivo mouse imaging using frequency domain optoacoustic tomography. JO - Proc. SPIE VL - 8800 PB - SPIE PY - 2013 SN - 0277-786X ER - TY - JOUR AB - Reconstruction in multispectral optoacoustic tomography has become an critical area of importance, given the development of real-time imaging and visualization techniques. Speed of sound calibration is an intrinsic problem associated with the reconstruction process. Traditionally, the calibration has been user mediated, making it a tedious and offline affair. In this manuscript, we aim to introduce autofocusing and wavelet based measures to automatically calibrate the speed of sound. Further, it is observed that the temperature of the coupling medium (water) often drift during the signal acquisition, severely straining the image quality. The measures address these problems by iteratively determining the speeds with the changing boundary conditions with time. AU - Mandal, S. AU - Dean-Ben, X.L. AU - Razansky, D. C1 - 24929 C2 - 31721 TI - Automated calibration of temporal changes in the speed of sound in optoacoustic tomography. JO - Proc. SPIE VL - 8800 PB - SPIE PY - 2013 SN - 0277-786X ER - TY - JOUR AB - We have generated high resolution images of RF-Contrast in small animals using nearfield thermoacoustic system. This enables us to see some anatomical features of a mouse such as the heart, the spine and the boundary. OCIS codes: (000.0000) General; (000.0000) General [8-pt. type. For codes, see www.opticsinfobase.org/submit/ocis.] AU - Omar, M. AU - Kellnberger, S. AU - Sergiadis, G.* AU - Razansky, D. AU - Ntziachristos, V. C1 - 24933 C2 - 31723 TI - Transmission line based thermoacoustic imaging of small animals. JO - Proc. SPIE VL - 8800 PB - SPIE PY - 2013 SN - 0277-786X ER - TY - JOUR AB - Back-projection algorithms are probably the fastest approach to reconstruct an image from a set of optoacoustic (photoacoustic) data set. However, standard implementations of back-projection formulae are still not adequate for real-time (greater than 5 frames per second) visualization of three-dimensional structures. This is due to the fact that the number of voxels one needs to reconstruct in three-dimensions is orders of magnitude larger than the number of pixels in two dimensions. Herein we describe a parallel implementation of optoacoustic signal processing and back-projection reconstruction in an attempt to achieve real-time visualization of structures with three-dimensional optoacoustic tomographic systems. For this purpose, the parallel computation power of a graphics processing unit (GPU) is utilized. The GPU is programmed with OpenCL, a programming language for heterogenous platforms. We showcase that with the implementation suggested in this work imaging at frame rates up to 50 high-resolution three-dimensional images per second is achievable. AU - Ozbek, A.* AU - Dean-Ben, X.L. AU - Razansky, D. C1 - 27503 C2 - 32702 TI - Realtime parallel back-projection algorithm for three-dimensional optoacoustic imaging devices. JO - Proc. SPIE VL - 8800 PB - SPIE PY - 2013 SN - 0277-786X ER - TY - JOUR AB - The discrepancy between optoacoustic reconstruction algorithms assuming point-like and realistic finite-size transducers causes severe artifacts. Two model-based algorithms accounting for finite-size of cylindrically focused detectors are presented and its performance tested in simulations and experiments. AU - Queirós, D. AU - Dean-Ben, X.L. AU - Bühler, A. AU - Razansky, D. AU - Rosenthal, A. AU - Ntziachristos, V. C1 - 24927 C2 - 31720 TI - Incorporating geometric detector properties into three-dimensional optoacoustic tomography. JO - Proc. SPIE VL - 880 PB - SPIE PY - 2013 SN - 0277-786X ER - TY - JOUR AU - Rosenthal, A. AU - Razansky, D. AU - Ntziachristos, V. C1 - 28001 C2 - 32896 SP - 23 TI - Resonator interrogation using pulse interferometry. JO - Proc. SPIE VL - 8600 PB - SPIE PY - 2013 SN - 0277-786X ER - TY - JOUR AB - The paper discusses the design of charged-particle detectors commissioned and developed at the Institute of Electron Technology (ITE) in collaboration with foreign partners, used in international research on transactinide elements and to build personal radiation protection devices in Germany. Properties of these detectors and the results obtained using the devices are also presented. The design of the following epiplanar detector structures is discussed: ◆ 64-element chromatographic arrays for the COMPACT (Cryo On-line Multidetector for Physics And Chemistry of Transactinides) detection system used at the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt (GSI) for research on Hassium, Copernicium and Flerovium, as well as elements 119 and 120, ◆ 2-element flow detectors for the COLD (Cryo On-Line Detector) system used for research on Copernicium and Flerovium at the Joint Institute for Nuclear Research, Dubna, ◆ detectors for a radon exposimeter and sensors for a neutron dosimeter developed at the Institut für Strahlenschutz, Helmholtz Zentrum München. The design of planar detectors - single-sided and double-sided strip detectors for the Focal Plane Detector Box used at GSI for research on Flerovium and elements 119 and 120 is also discussed. AU - Wegrzecki, M.* AU - Bar, J.* AU - Budzynski, T.* AU - Ciez, M.* AU - Grabiec, P.* AU - Kozlowski, R.* AU - Kulawik, J.* AU - Panas, A.* AU - Sarnecki, J.* AU - Slysz, W.* AU - Szmigiel, D.* AU - Wegrzecka, I.* AU - Wielunski, M. AU - Witek, K.* AU - Yakushev, A.* AU - Zaborovski, M.* C1 - 27461 C2 - 32681 TI - Design and properties of silicon charged-particle detectors developed at the Institute of Electron Technology (ITE). JO - Proc. SPIE VL - 8902 PB - SPIE PY - 2013 SN - 0277-786X ER - TY - CONF AB - In order to decrease the patient’s radiation exposure from Computed Tomography, the new CT geometry CTDOR has been invented. It consists of two data sets: A conventional arc or flat panel detector and a mask ring with shieldings on the outside and detectors on the inside separated by windows. Combined with the reconstruction algorithm OPED, it has the theoretical potential to decrease the dose about 50% while providing the same image quality as conventional systems. First steps to evaluate this theory were done with a mask ring demonstrator combined with a conventional C-arm device. Although the quality of the demonstrator is limited, this set-up was supposed to demonstrate how the combination of the two data sets works in principle. Preliminary results from earlier studies, however, provided images of rather poor quality. This work presents better images obtained with an optimized data treatment. We showed that most artifacts are eliminated and that we get sharper images with higher contrast compared to the images reconstructed from the single data sets and compared to the earlier study. Regarding the limitations of the set-up, the resulting images were remarkably good. CTDOR is therefore a promising method, which is worth to perform further studies. AU - Brunner, C.C. AU - Tischenko, O. AU - de las Heras, H. AU - Renger, B.* AU - Schlattl, H. AU - Hoeschen, C. A2 - Pelc, N.J.* ; Nishikawa, R.M.* ; Whiting, B.R.* C1 - 10526 C2 - 30293 CY - Bellingham, USA TI - The CTDOR geometry: An optimized data treatment to demonstrate its potential. JO - Proc. SPIE VL - 8313 IS - 1 PB - International Soc. for Optics and Photonics PY - 2012 SN - 0277-786X ER - TY - JOUR AB - A blind separation technique based on Independent Component Analysis (ICA) is proposed for breast tumor delineation and pathologic diagnosis. Tissue morphology is determined by fitting local measures of tissue reflectance to a Mie theory approximation, parameterizing the scattering power, scattering amplitude and average scattering irradiance. ICA is applied on the scattering parameters by spatial analysis using the Fast ICA method to extract more determinant features for an accurate diagnostic. Neither training, nor comparisons with reference parameters are required. Tissue diagnosis is provided directly following ICA application to the scattering parameter images. Surgically resected breast tissues were imaged and identified by a pathologist. Three different tissue pathologies were identified in 29 samples and classified as not-malignant, malignant and adipose. Scatter plot analysis of both ICA results and optical parameters where obtained. ICA subtle ameliorates those cases where optical parameter's scatter plots were not linearly separable. Furthermore, observing the mixing matrix of the ICA, it can be decided when the optical parameters themselves are diagnostically powerful. Moreover, contrast maps provided by ICA correlate with the pathologic diagnosis. The time response of the diagnostic strategy is therefore enhanced comparing with complex classifiers, enabling near real-time assessment of pathology during breast-conserving surgery. AU - Eguizabal, A.* AU - Laughney, A.M.* AU - Garcia-Allende, P. AU - Krishnaswamy, V.* AU - Wells, W.A.* AU - Paulsen, K.D.* AU - Pogue, B.W.* AU - Lopez-Higuera, J.M.* AU - Conde, O.M.* C1 - 26328 C2 - 32176 TI - Blind breast tissue diagnosis using independent component analysis of localized backscattering response. JO - Proc. SPIE VL - 8230 PB - SPIE PY - 2012 SN - 0277-786X ER - TY - JOUR AB - A spectral analysis technique to enhance tumor contrast during breast conserving surgery is proposed. A set of 29 surgically-excised breast tissues have been imaged in local reflectance geometry. Measures of broadband reflectance are directly analyzed using Principle Component Analysis (PCA), on a per sample basis, to extract areas of maximal spectral variation. A dynamic selection threshold has been applied to obtain the final number of principal components, accounting for inter-patient variability. A blind separation technique based on Independent Component Analysis (ICA) is then applied to extract diagnostically powerful results. ICA application reveals that the behavior of one independent component highly correlates with the pathologic diagnosis and it surpasses the contrast obtained using empirical models. Moreover, blind detection characteristics (no training, no comparisons with training reference data) and no need for parameterization makes the automated diagnosis simple and time efficient, favoring its translation to the clinical practice. Correlation coefficient with model-based results up to 0.91 has been achieved. AU - Eguizabal, A.* AU - Laughney, A.M.* AU - Garcia-Allende, P. AU - Krishnaswamy, V.* AU - Wells, W.A.* AU - Paulsen, K.D.* AU - Pogue, B.W.* AU - Lopez-Higuera, J.M.* AU - Conde, O.M.* C1 - 26340 C2 - 32182 TI - Enhanced tumor contrast during breast lumpectomy provided by independent component analysis of localized reflectance measures. JO - Proc. SPIE VL - 8230 PB - SPIE PY - 2012 SN - 0277-786X ER - TY - JOUR AB - Computer-aided diagnosis of ophthalmic diseases using optical coherence tomography (OCT) relies on the extraction of thickness and size measures from the OCT images, but such defined layers are usually not observed in emerging OCT applications aimed at "optical biopsy" such as pulmonology or gastroenterology. Mathematical methods such as Principal Component Analysis (PCA) or textural analyses including both spatial textural analysis derived from the two-dimensional discrete Fourier transform (DFT) and statistical texture analysis obtained independently from center-symmetric auto-correlation (CSAC) and spatial grey-level dependency matrices (SGLDM), as well as, quantitative measurements of the attenuation coefficient have been previously proposed to overcome this problem. We recently proposed an alternative approach consisting of a region segmentation according to the intensity variation along the vertical axis and a pure statistical technology for feature quantification. OCT images were first segmented in the axial direction in an automated manner according to intensity. Afterwards, a morphological analysis of the segmented OCT images was employed for quantifying the features that served for tissue classification. In this study, a PCA processing of the extracted features is accomplished to combine their discriminative power in a lower number of dimensions. Ready discrimination of gastrointestinal surgical specimens is attained demonstrating that the approach further surpasses the algorithms previously reported and is feasible for tissue classification in the clinical setting. AU - Garcia-Allende, P. AU - Amygdalos, I.* AU - Dhanapala, H.* AU - Goldin, R.D.F.* AU - Hanna, G.B.* AU - Elson, D.S.* C1 - 31224 C2 - 34229 TI - Morphological image analysis for classification of gastrointestinal tissues using optical coherence tomography. JO - Proc. SPIE VL - 8213 PY - 2012 SN - 0277-786X ER - TY - JOUR AB - The signal curves in perfusion dynamic contrast enhanced MRI (DCE-MRI) of cancerous breast tissue reveal valuable information about tumor angiogenesis. Pathological studies have illustrated that breast tumors consist of different subregions, especially with more homogeneous properties during their growth. Differences should be identifiable in DCEMRI signal curves if the characteristics of these sub-regions are related to the perfusion and angiogenesis. We introduce a stepwise clustering method which in a first step uses a new similarity measure. The new similarity measure (PM) compares how parallel washout phases of two curves are. To distinguish the starting point of the washout phase, a linear regression method is partially fitted to the curves. In the next step, the minimum signal value of the washout phase is normalized to zero. Finally, PM is calculated according to maximal variation among the point wise differences during washout phases. In the second step of clustering the groups of signal curves with parallel washout are clustered using Euclidean distance. The introduced method is evaluated on 15 DCE-MRI breast datasets with different types of breast tumors. The use of our new heterogeneity analysis is feasible in single patient examination and improves breast MR diagnostics. AU - Mohajer, M. AU - Schmid, V.J.* AU - Engels, N. A.* AU - Noel, P. B.* AU - Rummeny, E.* AU - Englmeier, K.-H. A2 - Molthen, R.C.* ; Waver, J.B.* C1 - 7917 C2 - 29917 CY - Bellingham, USA TI - Stepwise heterogeneity analysis of breast tumors in perfusion DCE-MRI datasets. JO - Proc. SPIE VL - 8317 PB - International Soc. for Optics and Photonics PY - 2012 SN - 0277-786X ER - TY - JOUR AB - Multi-Spectral Optoacoustic Tomography (MSOT) offers real time imaging that simultaneously exploits high ultrasound resolutions and strong optical contrast. It allows visualizing absorbers in tissue by using their distinct spectral absorption profiles. This work presents a non-invasive in vivo study of kinetics involved in the clearance of carboxylated dye in mouse kidneys AU - Morscher, S.* AU - Burton, N.C. AU - Taruttis, A. AU - Deliolanis, N.C. AU - Razansky, D. AU - Ntziachristos, V. C1 - 11334 C2 - 30616 CY - Bellingham, USA TI - Real-time imaging of renal clearance using multispectral optoacoustic tomography. JO - Proc. SPIE VL - 8223 PB - International Soc. for Optics and Photonics PY - 2012 SN - 0277-786X ER - TY - JOUR AB - Near-field Radio-frequency Thermoacoustic Imaging (NRTI) is an imaging modality that was recently introduced to generate thermoacoustic signals using ultra-short high energy impulses. Because it allows for a higher energy coupling within an ultra-short time, it can achieve higher resolutions and higher signal to noise ratio, compared to traditional thermoacoustic tomography based on radiating sources at single frequencies. As for traditional thermoacoustic imaging the contrast comes from the conductivity and the dielectric properties of the tissues, while the resolution depends on the measured acoustic waves. Since NRTI depends on the efficient generation of high energy short impulses, the ability to control their time width and pulse shape is of high importance. We present here a methodology for generating such impulses based on transmission lines. The ability of such generators to generate impulses in the range of tens of nanoseconds enables high resolution images in the range of tens of microns to hundreds of microns without compromising the amount of the energy coupled. Finally the pulser is used to generate high resolution images of small absorbing insertions, of phantoms with different conductivities and of ex-vivo mouse images. From the phantoms it is possible to see both the capabilities of the system to accurately image small insertions as well as the high quality images generated from imaging phantoms, from ex-vivo mouse images it is possible to see several anatomical characteristics, such as the mouse boundary, the spine and some other characteristics in the mouse abdomens. AU - Omar, M. AU - Kellnberger, S. AU - Sergiadis, G.* AU - Razansky, D. AU - Ntziachristos, V. A2 - Oraevsky, A.A.* ; Wang, L.V.* C1 - 11336 C2 - 30617 CY - Bellingham, USA TI - Near-field radio-frequency thermo-acoustic imaging based on transmission lines for optimized performance. JO - Proc. SPIE VL - 8223 PB - International Soc. for Optics and Photonics PY - 2012 SN - 0277-786X ER - TY - CONF AB - Previously the Orthogonal Polynomial Expansion on the Disk (OPED) algorithm was presented. Further, in prototype experiments in combination with the CT D`or geometry feasibility was demonstrated. In this study we implemented OPED with a clinical Scanner, and evaluated the potential using phantom studies. All studies were acquired on a Siemens Somatom 64 (Erlangen, Germany) scanner, where raw projection data were reconstructed with the conventional FBP reconstruction and the OPED algorithm. OPED allows one to use fan beam geometry directly without any additional procedures such as interpolation or rebinning if using the CT D`or geometry. In particular, OPED describes an approximation of the image function as a sum of polynomials using Chebychev polynomials. For performance evaluation, the Catphan phantom 600 was imaged. OPED Images where reconstructed using C++ and MATLAB® .We measured uniformity, MTF and CNR for different dose levels and compared these to standard FBP images reconstructions with different filter kernels. The integration and interpretation of the MDCT projection data for the OPED algorithm was accomplished. Reconstruction time is about 6 s on Quad-Core 3 GHz Intel Xeon processor. Typical artifacts are reduced when applying OPED. Using OPED the MTF maintains constant over the whole FOV. Uniformity and CNR are equal compared to FBP. Advantages of OPED were demonstrated by applying the algorithm to projections images from a clinical MDCT scanner. In the future, we see OPED applications for low-dose or limited angle geometries to reduce the radiation dose while improving diagnostic quality of the reconstructed slices. AU - Rieger, B. AU - Noel, P.B.* AU - Tischenko, O. AU - Rummeny, E.J.* AU - Hoeschen, C. A2 - Pelc, N.J.* ; Nishikawa, R.M.* ; Whiting, B.R.* C1 - 10681 C2 - 30331 CY - Bellingham, USA TI - Comparison between a new reconstruction algorithm (OPED) and filtered backprojection (FBP) for MDCT data. JO - Proc. SPIE VL - 8313 PB - International Soc. for Optics and Photonics PY - 2012 SN - 0277-786X ER - TY - CONF AB - Reliable estimates for patient doses for CT examinations are desirable for the patients themselves as well as for new epidemiological studies. It has been shown that dose conversion coefficients normalized to CTDIvol provide rather scanner independent quantities. In this work, it is demonstrated that this normalization provides also tube voltage independent values by simulating axial CT scans of a seven-year old infant and an adult. The differences in the effective dose conversion coefficients per CTDIvol between 80 and 120 kV is for most body heights below 5%. Only at the height of the testes and the thyroid the difference can be as large as 15%. This results in differences of the effective dose conversion coefficient per CTDIvol between 80 and 120 kV of less than 6-7% for typical CT examinations. AU - Schlattl, H. AU - Zankl, M. AU - Hoeschen, C. A2 - Pelc, N.J.* ; Nishikawa, R.M.* ; Whiting, B.R.* C1 - 10680 C2 - 30332 CY - Bellingham, USA TI - CTDIvol: A suitable normalization for CT dose conversion coefficients at different tube voltages? JO - Proc. SPIE VL - 8313 PB - International Soc. for Optics and Photonics PY - 2012 SN - 0277-786X ER - TY - CONF AB - Optoacoustic imaging has enabled the visualization of optical contrast at high resolutions in deep tissue. Our Multispectral optoacoustic tomography (MSOT) imaging results reveal internal tissue heterogeneity, where the underlying distribution of specific endogenous and exogenous sources of absorption can be resolved in detail. Technical advances in cardiac imaging allow motion-resolved multispectral measurements of the heart, opening the way for studies of cardiovascular disease. We further demonstrate the fast characterization of the pharmacokinetic profiles of lightabsorbing agents. Overall, our MSOT findings indicate new possibilities in high resolution imaging of functional and molecular parameters. AU - Taruttis, A. AU - Razansky, D. AU - Ntziachristos, V. A2 - Oraevsky, A.A.* ; Wang, L.V.* C1 - 11338 C2 - 30618 CY - Bellingham, USA TI - Fast deep-tissue multispectral optoacoustic tomography (MSOT) for preclinical imaging of cancer and cardiovascular disease. JO - Proc. SPIE VL - 8223 PB - International Soc. for Optics and Photonics PY - 2012 SN - 0277-786X ER - TY - JOUR AB - The current IEC standard method for characterizing noise in CT scanners is based on the pixel standard deviation of the CT image of a water-equivalent uniform phantom. However, the standard deviation does not account for correlations in the noise, potentially generating misleading results about image quality. With this paper we investigate a method for estimating the Fourier based noise power spectrum (NPS) for the characterization of noise in CT, for CT scanners with linear, non-adaptive reconstruction algorithms. The IEC currently evaluates the deterministic properties of CT scanners with the Fourier based modulation transfer function (MTF). By accounting for the spatial correlations in both the stochastic and deterministic description of an imaging system, the system signal-to-noise ratio (SNR) can be determined more accurately. In this paper we investigate a method for estimating the MTF and the NPS of a CT scanner in the axial plane. Furthermore, we present examples of the Fourier SNR calculated from the MTF and the NPS in order to demonstrate that it gives more reasonable results than the pixel SNR. The MTF was estimated by following methods available in current literature. For the characterization of noise we used a standard water phantom, while for the point spread function (PSF) we used a tungsten wire phantom in air. Images were taken at four different source current settings and reconstructed with four different lters. We showed that the pixel SNR ranks the reconstruction lters differently from the Fourier SNR. AU - Brunner, C.C. AU - Renger, B.* AU - Hoeschen, C. AU - Kyprianou, I.S.* A2 - Pelc, N.J* ; Samei, E.* ; Nishikawa, R.M.* C1 - 4437 C2 - 28589 CY - Bellingham, WA TI - Investigation of a method to estimate the MTF and NPS of CT towards creating an international standard. JO - Proc. SPIE VL - 7961 PB - SPIE PY - 2011 SN - 0277-786X ER - TY - JOUR AB - Optoacoustic tomography can visualize optical contrast in tissues while capitalizing on the advantages of ultrasound, such as high spatial resolution and fast imaging capabilities. We report herein on a novel multi-spectral optoacoustic tomography system capable of resolving dynamic contrast at video rate and showcase its performance by monitoring kidney perfusion after injection of Indocyaningreen (ICG). AU - Bühler, A. AU - Herzog, E. AU - Razansky, D. AU - Ntziachristos, V. C1 - 30950 C2 - 34027 TI - Visualization of mouse kidney perfusion with multispectral optoacoustic tomography (MSOT) at video rate. JO - Proc. SPIE VL - 7899 PB - SPIE PY - 2011 SN - 0277-786X ER - TY - JOUR AB - A modified quantitative inversion algorithm is presented that minimizes the effects of internal acoustic reflections or scattering in tomographic optoacoustic images. The inversion procedure in our model-based algorithm consists in solving a linear system of equations in which each individual equation corresponds to a given position of the acoustic transducer and to a given time instant. Thus, the modification that we propose in this work consists in weighting each equation of the linear system with the probability that the measured wave is not distorted by reflection or scattering phenomena. We show that the probability that a reflected or scattered wave is detected at a given position and at a given instant is approximately proportional to the size of the area in which the original wave could have been generated, which is dependent on the position of the transducer and on the time instant, so that such probability can be used to weight each equation of the linear system. Thereby, the contribution of the waves that propagate directly to the transducer to the reconstructed images is emphasized. We experimentally test the proposed inversion algorithm with tissue-mimicking agar phantoms in which air-gaps are included to cause reflections of the acoustic waves. The tomographic reconstructions obtained with the modification proposed herein show a clear reduction of the artefacts due to these acoustic phenomena with respect to the reconstructions yielded with the original algorithm. This performance is directly related to in-vivo small animal imaging applications involving imaging in the presence of bones, lungs, and other highly mismatched organs. AU - Dean-Ben, X.L. AU - Razansky, D. AU - Ntziachristos, V. C1 - 30952 C2 - 34031 TI - Statistical weighting of model-based optoacoustic reconstruction for minimizing artefacts caused by strong acoustic mismatch. JO - Proc. SPIE VL - 7899 PY - 2011 SN - 0277-786X ER - TY - JOUR AB - An analysis of the time-shifting correction in optoacoustic tomographic reconstructions for media with an a priori known speed of sound distribution is presented. We describe a modification of the filtered back-projection algorithm, for which the absorbed optical energy at a given point is estimated from the value of the measured signals at the instant corresponding to the time-of-flight between such point and the measuring points. In the case that a non-uniform speed of sound distribution does exist, we estimate the time-of-flight with the straight acoustic rays model, for which acoustic waves are assumed not to change direction as they propagate. The validity of this model is analysed for small speed of sound variations by comparing the predicted values of the time-of-flight with the ones estimated considering the refraction of the waves. Experimental results with tissue-mimicking agar phantoms with a higher speed of sound than water showcase the effects of the time-shifting of the optoacoustic signals caused by the acoustic mismatch. The performance of the time-shifting correction relates to the optoacoustic imaging of biological tissues, for which the speed of sound variations are usually lower than 10%. AU - Dean-Ben, X.L. AU - Ntziachristos, V. AU - Razansky, D. C1 - 30951 C2 - 34028 TI - Time-shifting correction in optoacoustic tomographic imaging for media with non-uniform speed of sound. JO - Proc. SPIE VL - 8090 PY - 2011 SN - 0277-786X ER - TY - JOUR AB - The feasibility of correcting for the effects of acoustic attenuation in optoacoustic tomographic reconstructions obtained with model-based inversion is shown in this work. Acoustic attenuation is a physical phenomenon that takes place inevitably in actual acoustic media and becomes significant at high ultrasonic frequencies. The frequency dependence of acoustic attenuation and the associated dispersion lead to reduction of amplitude and broadening of the optoacoustic signals, which in turn cause, respectively, quantification errors and loss of resolution in the reconstructed images. In this work we imaged an agar phantom with embedded microparticles in three different scenarios, namely with the signals acquired with no attenuation, with the signals collected by placing an attenuating sample in between the phantom and the ultrasonic transducer and with the signals corrected for the effects of acoustic attenuation. The results obtained show that the quantification inaccuracies and the loss of resolution of the images can be partially corrected at the expense of introducing noise at high spatial frequencies due to the amplification of the high frequency components of the noise in the signals. AU - Dean-Ben, X.L. AU - Razansky, D. AU - Ntziachristos, V. C1 - 30953 C2 - 34032 TI - Correction for acoustic attenuation effects in optoacoustic tomographic reconstructions. JO - Proc. SPIE VL - 8090 PY - 2011 SN - 0277-786X ER - TY - JOUR AB - We present in this work a method to estimate the distribution of acoustic scatterers within the imaged sample in an optoacoustic tomographic setup and, subsequently, to reduce the artefacts in the tomographic reconstructions due to reflection or scattering events. The procedure to determine the position of the scatterers consists of measuring the scattered waves generated at a point light absorber located in between the transducer and the imaged sample. Such absorber is positioned in a way that the acoustic waves generated at this absorber and scattered within the sample arrive at the position of the transducer after the waves generated within the sample that propagate directly until the measuring point. Then, the signals captured by the acoustic transducer can be used to reconstruct the distribution of acoustic scatterers and to perform the optoacoustic reconstruction itself. Also, the information retrived on the distribution of acoustic scatterers can be used to improve the optoacoustic tomographic reconstructions. For this, we use a modification of the filtered back-projection algorithm based on weighting the signals with the probability that they are not affected by scattered or reflected waves, so that the artefacts in the images due to these acoustic phenomena are reduced. The experimental results obtained with a tissue-mimicking phantom in which a straw filled with air was included in order to cause scattering of the acoustic waves indicate a good performance of the method proposed. AU - Dean-Ben, X.L. AU - Razansky, D. AU - Ntziachristos, V. C1 - 30954 C2 - 34033 TI - Measurement of the acoustic scatterers distribution within the imaged sample in an optoacoustic tomographic setup. JO - Proc. SPIE VL - 8090 PY - 2011 SN - 0277-786X ER - TY - JOUR AB - Radiation exposure due to medical imaging is a topic of emerging importance. In Europe this topic has been dealt with for a long time and in other countries it is getting more and more important and it gets an aspect of public interest in the latest years. This is mainly true due to the fact that the average dose per person in developed countries is increasing rapidly since threedimensional imaging is getting more and more available and useful for diagnosis. This paper introduces the most common dose quantities used in medical radiation exposure characterization, discusses usual ways for determination of such quantities as well as some considerations how these values are linked to radiation risk estimation. For this last aspect the paper will refer to the linear non threshold theory for an imaging application. AU - Hoeschen, C. AU - Regulla, D.F. AU - Schlattl, H. AU - Petoussi-Henß, N. AU - Li, W.B. AU - Zankl, M. A2 - Pelc, N.J* ; Samei, E.* ; Nishikawa, R.M.* C1 - 4436 C2 - 28588 CY - Bellingham, WA TI - How do we measure dose and estimate risk? JO - Proc. SPIE VL - 7961 PB - SPIE PY - 2011 SN - 0277-786X ER - TY - JOUR AB - Obtaining quantified optoacoustic reconstructions is an important and longstanding challenge, mainly caused by the complex heterogeneous structure of biological tissues as well as the lack of accurate and robust reconstruction algorithms. The recently introduced model-based inversion approaches were shown to eliminate some of reconstruction artifacts associated with the commonly used back-projection schemes, while providing an excellent platform for obtaining quantified maps of optical energy deposition in experimental configurations of various complexity. In this work, we introduce a weighted model-based approach, capable of overcoming reconstruction challenges caused by perprojection variations of object's illumination and other partial illumination effects. The universal weighting procedure is equally shown to reduce reconstruction artifacts associated with other experimental imperfections, such as non-uniform transducer sensitivity fields. Significant improvements in image fidelity and quantification are showcased both numerically and experimentally on tissue phantoms. AU - Jetzfellner, T. AU - Rosenthal, A. AU - Bühler, A. AU - Dima, A. AU - Englmeier, K.-H. AU - Ntziachristos, V. AU - Razansky, D. A2 - Oraevsky, A.A.* ; Wang, L.V.* C1 - 6189 C2 - 28427 CY - Bellingham, WA TI - Tomographic optoacoustic inversion in dynamic illumination scenarios. JO - Proc. SPIE VL - 7899 PB - SPIE PY - 2011 SN - 0277-786X ER - TY - JOUR AB - Existing imaging modalities like microwave- or radiofrequency (RF) induced thermoacoustic tomography systems show the potential for resolving structures deep inside tissue due to the high penetration properties of RF. However, one of the major drawbacks of existing thermoacoustic tomography systems with pulse modulated carrier frequency excitation is the compromise between efficient signal generation and attainable spatial resolution. In order to overcome limitations of conventional thermoacoustic imaging methods, we herein present and experimentally validate our novel approach towards high resolution thermoacoustic tomography. Instead of carrier-frequency amplification, we utilize ultrahigh-energy electromagnetic impulses at nanosecond duration with near-field energy coupling, thus maintaining thermoacoustic signal strength without compromising spatial resolution. Preliminary experiments on highly absorbing objects, consisting of copper wires with characteristic sizes of ~100 μm, reveal the resolution performance which yields 160 μm. Furthermore, benefits like its cost effectiveness, simplicity and compactness with the potential application in small animal imaging as well as human body imaging show that thermoacoustic tomography with impulse excitation is a promising imaging modality which has a broad range of applications. AU - Kellnberger, S. AU - Hajiaboli, A. AU - Sergiadis, G. AU - Razansky, D. AU - Ntziachristos, V. C1 - 30955 C2 - 34034 TI - High resolution imaging with impulse based thermoacoustic tomography. JO - Proc. SPIE VL - 8089 PY - 2011 SN - 0277-786X ER - TY - JOUR AB - Radiation doses of radiopharmaceuticals to patients in nuclear medicine are, as the standard method, estimated by the administered activity, medical imaging (e.g. PET imaging), compartmental modeling and Monte Carlo simulation of radiation with reference digital human phantoms. However, in each of the contributing terms, individual uncertainty due to measurement techniques, patient variability and computation methods may propagate to the uncertainties of the calculated organ doses to the individual patient. To evaluate the overall uncertainties and the quality assurance of internal absorbed doses, a method was developed within the framework of the MADEIRA Project (Minimizing Activity and Dose with Enhanced Image quality by Radiopharmaceutical Administrations) to quantitatively analyze the uncertainties in each component of the organ absorbed doses after administration of 18F-choline to prostate cancer patients undergoing nuclear medicine diagnostics. First, on the basis of the organ PET and CT images of the patients as well as blood and urine samples, a model structure of 18F-choline was developed and the uncertainties of the model parameters were determined. Second, the model parameter values were sampled and biokinetic modeling using these sampled parameter values were performed. Third, the uncertainties of the new specific absorbed fraction (SAF) values derived with different phantoms representing individual patients were presented. Finally, the uncertainties of absorbed doses to the patients were calculated by applying the ICRP/ICRU adult male reference computational phantom. In addition to the uncertainty analysis, the sensitivity of the model parameters on the organ PET images and absorbed doses was indicated by coupling the model input and output using regression and partial correlation analysis. The results showed that the uncertainty factors of absorbed dose to patients are in most cases less than a factor of 2 without taking into account the uncertainties caused by the variability and uncertainty of individual human phantoms. The sensitivity study showed that the metabolic transfer parameter from the blood to soft tissues has a strong influence on blood sample collection from the beginning until 500 min. post administration; the transfer pathways between blood and liver impact strongly the liver imaging during the time course. The results of this study suggest that organ image acquisition of liver and kidneys after 100 min. as well as blood and urine sample collection are necessary for the reduction of uncertainties of absorbed dose estimates to patients. AU - Li, W.B. AU - Janzen, T. AU - Zankl, M. AU - Giussani, A. AU - Hoeschen, C. A2 - Pelc, N. J.* ; Samei, E.* ; Nishikawa, R.M.* C1 - 3852 C2 - 28554 CY - Bellingham, WA SP - 796129 TI - Uncertainties of organ-absorbed doses to patients from ¹⁸F-choline. JO - Proc. SPIE VL - 7961 PB - SPIE PY - 2011 SN - 0277-786X ER - TY - JOUR AB - The dramatic increase of diagnostic imaging capabilities over the past decade has contributed to increased radiation exposure to patient populations. Several factors have contributed to the increase in imaging procedures: wider availability of imaging modalities, increase in technical capabilities, rise in demand by patients and clinicians, favorable reimbursement, and lack of guidelines to control utilization. The primary focus of this research is to provide in depth information about radiation doses that patients receive as a result of CT exams, with the initial investigation involving abdominal CT exams. Current dose measurement methods (i.e. CTDIvol Computed Tomography Dose Index) do not provide direct information about a patient's organ dose. We have developed a method to determine CTDIvol normalized organ doses using a set of organ specific exponential regression equations. These exponential equations along with measured CTDIvol are used to calculate organ dose estimates from abdominal CT scans for eight different patient models. For each patient, organ dose and CTDIvol were estimated for an abdominal CT scan. We then modified the DICOM Radiation Dose Structured Report (RDSR) to store the pertinent patient information on radiation dose to their abdominal organs. AU - Morioka, C.* AU - Turner, A.* AU - McNitt-Gray, M.* AU - Zankl, M. AU - Meng, F.* AU - El-Saden, S.* A2 - Boonn, W.W.* ; Liu, B.J.* C1 - 6024 C2 - 28592 CY - Bellingham, WA TI - DICOM structured report to track patient's radiation dose to organs from abdominal CT exam. JO - Proc. SPIE VL - 7967 PB - SPIE PY - 2011 SN - 0277-786X ER - TY - JOUR AB - Multispectral optoacoustic (photoacoustic) tomography (MSOT) exploits the high resolutions provided by ultrasound imaging technology in combination with the more biologically relevant optical absorption contrast. Traces of molecules with different spectral absorption profiles, such as blood (oxy- and de-oxygenated) and biomarkers can be recovered using multiple wavelengths excitation and a set of methods described in this work. Three unmixing methods are examined for their performance in decomposing images into components in order to locate fluorescent contrast agents in deep tissue in mice. Following earlier works we find Independent Component Analysis (ICA), which relies on the strong criterion of statistical independence of components, as the most promising approach, being able to clearly identify concentrations that other approaches fail to see. The results are verified by cryosectioning and fluorescence imaging. AU - Morscher, S. AU - Glatz, J. AU - Deliolanis, N. AU - Bühler, A. AU - Razansky, D. AU - Ntziachristos, V. C1 - 30956 C2 - 34035 TI - Blind spectral unmixing to identify molecular signatures of absorbers in multispectral optoacoustic tomography. JO - Proc. SPIE VL - 7899 PY - 2011 SN - 0277-786X ER - TY - JOUR AB - In this work, we show, for the first time to our knowledge, that multispectral optoacoustic tomography (MSOT) can deliver high resolution images of activatable molecular probe's distribution, sensitive to matrix metalloproteinases (MMP), deep within optically scattering human carotid specimen. It is further demonstrated that this method can be used in order to provide accurate maps of vulnerable plaque formations in atherosclerotic disease. Moreover, optoacoustic images can simultaneously show the underlining plaque morphology for accurate localization of MMP activity in three dimensions. This performance directly relates to small animal screening applications and to clinical potential as well. AU - Morscher, S. AU - Glatz, J. AU - Deliolanis, N.C. AU - Bühler, A. AU - Sarantopoulos, A. AU - Razansky, D. AU - Ntziachristos, V. C1 - 30957 C2 - 34036 TI - Spectral unmixing using component analysis in multispectral optoacoustic tomography. JO - Proc. SPIE VL - 8089 PY - 2011 SN - 0277-786X ER - TY - JOUR AB - Since overcoming some of the inherent limitations of x-ray tubes becomes increasingly harder, it is important to consider new ways of x-ray generation and to study their applications in the field of medical imaging. In the present work we investigate a novel table-top-sized x-ray source, developed in a joint project within the Cluster of Excellence "Munich Center for Advanced Photonics". It uses laser-accelerated electrons emitting x-ray radiation in a short period undulator. This source has the potential to deliver tunable x-rays with a very narrow spectral bandwidth. The main purpose of this contribution is to investigate the performance of this source in the field of mammography and to compare it to that of conventional x-ray tubes. We simulated the whole imaging process from the electron beam dynamics through the generation of the synchrotron radiation in the undulator up to the x-ray-matter interaction and detection in the mammographic setting. A Monte Carlo simulation of the absorption and scattering processes based on the Geant4 software toolkit has been developed that uses a high-resolution voxel phantom of the female breast for the accurate simulation of mammography. We present simulated mammograms generated by using quasi-monochromatic undulator radiation and by using the polychromatic spectrum of a conventional x-ray tube. AU - Müller, B. AU - Schlattl, H. AU - Grüner, F.* AU - Hoeschen, C. A2 - Pelc, N.J* ; Samei, E.* ; Nishikawa, R.M.* C1 - 4761 C2 - 28591 CY - Bellingham, WA TI - A laser-driven undulator X-ray source: Simulation of image formation and dose deposition in mammography. JO - Proc. SPIE VL - 7961 PB - SPIE PY - 2011 SN - 0277-786X ER - TY - JOUR AB - Advances in high-throughput measurements of biological specimens necessitate the development of biologically driven computational techniques. To understand the molecular level of many human diseases, such as cancer, lipid quantifications have been shown to offer an excellent opportunity to reveal disease-specific regulations. The data analysis of the cell lipidome, however, remains a challenging task and cannot be accomplished solely based on intuitive reasoning. We have developed a method to identify a lipid correlation network which is entirely disease-specific. A powerful method to correlate experimentally measured lipid levels across the various samples is a Gaussian Graphical Model (GGM), which is based on partial correlation coefficients. In contrast to regular Pearson correlations, partial correlations aim to identify only direct correlations while eliminating indirect associations. Conventional GGM calculations on the entire dataset can, however, not provide information on whether a correlation is truly disease-specific with respect to the disease samples and not a correlation of control samples. Thus, we implemented a novel differential GGM approach unraveling only the disease-specific correlations, and applied it to the lipidome of immortal Glioblastoma tumor cells. A large set of lipid species were measured by mass spectrometry in order to evaluate lipid remodeling as a result to a combination of perturbation of cells inducing programmed cell death, while the other perturbations served solely as biological controls. With the differential GGM, we were able to reveal Glioblastoma-specific lipid correlations to advance biomedical research on novel gene therapies. AU - Müller, N.S.* AU - Krumsiek, J. AU - Theis, F.J. AU - Böhm, C.* AU - Meyer-Bäse, A.* C1 - 6772 C2 - 29260 CY - Bellingham, WA TI - Gaussian graphical modeling reveals specific lipid correlations in glioblastoma cells. JO - Proc. SPIE VL - 8058 PB - SPIE PY - 2011 SN - 0277-786X ER - TY - JOUR AB - Optoacoustic imaging can noninvasively provide visualization of vasculature structures with optical contrast well below the skin surface. For meaningful biological investigations, high-resolution at mesoscopic penetration depths and therefore thorough adaption of the systematic arrangement to the object of interest is required. A suitable modular optoacoustic tomography system is presented here and its performance is demonstrated in three exemplary studies on imaging agar phantoms, mouse head vasculature and mouse tumor vasculature ex-vivo. AU - Oancea, A. AU - Razansky, D. AU - Ntziachristos, V. C1 - 30958 C2 - 34037 TI - High-resolution imaging of mouse anatomy with a multi-purpose optoacoustic tomography system. JO - Proc. SPIE VL - 8089 PY - 2011 SN - 0277-786X ER - TY - JOUR AB - In this work, we show, for the first time to our knowledge, that multispectral optoacoustic tomography (MSOT) can deliver high resolution images of activatable molecular probe's distribution, sensitive to matrix metalloproteinases (MMP), deep within optically scattering human carotid specimen. It is further demonstrated that this method can be used in order to provide accurate maps of vulnerable plaque formations in atherosclerotic disease. Moreover, optoacoustic images can simultaneously show the underlining plaque morphology for accurate localization of MMP activity in three dimensions. This performance directly relates to small animal screening applications and to clinical potential as well. AU - Razansky, D. AU - Harlaar, N.J. AU - Hillebrands, J.-L.* AU - Taruttis, A. AU - Herzog, E. AU - Zeebregts, C.J.* AU - van Dam, G.M.* AU - Ntziachristos, V. C1 - 30959 C2 - 34038 TI - Multispectral optoacoustic tomography resolves smart probe activation in vulnerable plaques. JO - Proc. SPIE VL - 7899 PY - 2011 SN - 0277-786X ER - TY - JOUR AB - Herein we suggest and experimentally validate a novel thermoacoustic imaging method that relies on near-field exposure of the object to ultrashort impulses of safe radiofrequency energies. The physical rationale behind the Near-field Radiofrequency Tomography (NRT) is the well known ability of biological tissues to absorb a very significant portion of energy when closely coupled to radiofrequency and microwave sources. Compared to existing thermoacoustic imaging implementations, NRT offers a significantly simpler and cost-effective technology that uses high energy impulses instead of expensive and inefficient carrier-frequency amplification methods, making it possible to achieve significantly better imaging resolution without compromising thermoacoustic signal strength. AU - Razansky, D. AU - Kellnberger, S. AU - Ntziachristos, V. C1 - 30964 C2 - 34046 TI - Impulse-driven near-field radiofrequency thermoacoustic (NRT) tomography. JO - Proc. SPIE VL - 7899 PY - 2011 SN - 0277-786X ER - TY - JOUR AB - Early detection of high-risk coronary atherosclerosis remains an unmet clinical challenge. We have previously demonstrated a near-infrared fluorescence catheter system for two-dimensional intravascular detection of fluorescence molecular probes [1]. In this work we improve the system performance by introducing a novel high resolution sensor. The main challenge of the intravascular sensor is to provide a highly focused spot at an application relevant distance on one hand and a highly efficient collection of emitted light on the other. We suggest employing a double cladding optical fiber (DCF) in combination with focusing optics to provide a sensor with both highly focused excitation light and highly efficient fluorescent light collection. The excitation laser is coupled into the single mode core of DCF and guided through a focusing element and a right angle prism. The resulting side-fired beam exhibits a small spot diameter (50 μm) throughout a distance of up to 2 mm from the sensor. This is the distance of interest for intravascular coronary imaging application, determined by an average human coronary artery diameter. At the blood vessel wall, an activatable fluorescence molecular probe is excited in the diseased lesions. Next light of slightly shifted wavelength emits only in the places of the inflammations, associated with dangerous plaques [2]. The emitted light is collected by the cladding of the DCF, with a large collection angle (NA=0.4). The doublecladding acts as multimodal fiber and guides the collected light to the photo detection elements. The sensor automatically rotates and pulled-back, while each scanned point is mapped according to the amount of detected fluorescent emission. The resulting map of fluorescence activity helps to associate the atherosclerotic plaques with the inflammation process. The presented detection system is a valuable tool in the intravascular plaque detection and can help to differentiate the atherosclerotic plaques based on their biological activity, identify the ones that prone to rupture and therefore require more medical attention. AU - Razansky, D. AU - Rozental, A.* AU - Müller, M.S.* AU - Deliolanis, N. AU - Jaffer, F.A.* AU - Koch, A.W.* AU - Ntziachristos, V. C1 - 30965 C2 - 34047 TI - Double-cladding-fiber-based detection system for intravascular mapping of fluorescent molecular probes. JO - Proc. SPIE VL - 7894 PY - 2011 SN - 0277-786X ER - TY - JOUR AB - Computer tomography (CT) is vital and currently irreplaceable in diagnostic radiology. But CT operates with ionizing radiation which may cause cancer or non-cancer diseases in humans. The degree of radiation impact depends on the dose administered by an investigation. And this is the core issue: Even CT exams executed lege artis, administer doses to patients which by magnitude are far beyond the level of hitherto known doses of conventional film-screen techniques. Patients undergoing one or multiple CT examinations, digital angiographies or interventions will be exposed to effective doses between roughly several mSv and several 100 mSv depending on type and frequency of the diagnostic investigations. From the radiation protection point of view, there is therefore the worldwide problem of formulating firm rules for the control of these high-dose investigations, as dose limits can not be established for reasons of the medical benefit. This makes the difference compared with radiation protection for occupationally exposed persons. What remains is "software", namely "justification" and "optimization". Justification requires balancing the interests between the health benefit and the potential harm of an exam which has to be responsibly executed by the physician himself; therefore the radiologists' associations are in the duty to prepare practicable rules for justification. Optimization again needs a cooperative solution, and that is the establishment of reference doses for diagnostic examinations, to be checked by the technical service of the producers' companies. Experts and authorities have been aware of the high-dose dilemma in diagnostic imaging since long. It is time for the reflection of active solutions and their implementation into practice. AU - Regulla, D.F. A2 - Pelc, N.J* ; Samei, E.* ; Nishikawa, R.M.* C1 - 4760 C2 - 28590 CY - Bellingham, WA TI - Definitions and outlook targeting X-ray exposure of patients in diagnostic imaging. JO - Proc. SPIE VL - 7961 PB - SPIE PY - 2011 SN - 0277-786X ER - TY - JOUR AB - We present a fast inversion algorithm for quantitative two- and three-dimensional optoacoustic tomography. The algorithm is based on an accurate and efficient forward model, which eliminates the need for regularization in the inversion and can achieve real-time performance. The reconstruction speed and other algorithmic performances are demonstrated using numerical simulation studies and experimentally on tissue-mimicking optically heterogeneous phantoms and small animals. In the experimental examples, the model-based reconstructions manifested correctly the effect of light attenuation through the objects and did not suffer from the artifacts which usually afflict the commonly used filtered backprojection algorithms, such as negative absorption values. AU - Rosenthal, A. AU - Jetzfellner, T. AU - Razansky, D. AU - Ntziachristos, V. C1 - 30969 C2 - 34048 TI - Fast semi-analytical acoustic inversion for quantitative optoacoustic tomography. JO - Proc. SPIE VL - 7899 PY - 2011 SN - 0277-786X ER - TY - JOUR AB - Ultrasonic detectors are commonly calibrated by finding their response to incident plane waves. However, in optoacoustics, the response to broadband point sources is required. To induce such sources using the optoacoustic effect, the illuminated object's dimensions must be smaller than the resolution achievable by the optoacoustic system. The main difficulty in such measurements is that the magnitude of the field emitted by such sources is proportional to their dimensions, and thus may be weak compared to parasitic sources in the setup. In this work we experimentally demonstrate two methods for calibrating acoustic detectors. In both methods, acoustic sources are optoacoustically induced in large optically absorbing slabs. Despite the large dimensions of the illuminated objects, the geometry used yields wide-band acoustic fields, which are perceived by the detectors as originating from point sources. AU - Rosenthal, A. AU - Ntziachristos, V. AU - Razansky, D. C1 - 30970 C2 - 34049 TI - Calibration of ultrasonic sensors using optoacoustics. JO - Proc. SPIE VL - 7899 PY - 2011 SN - 0277-786X ER - TY - JOUR AB - One of the major challenges of optoacoustic imaging is that it involves relatively weak acoustic signals, which need to be detected with high signal-to-noise ratio (SNR). Because the SNR is generally proportional to the area of the detector's face, large detectors are commonly used. Although the use of such detectors improves the SNR, it may lead to significant signal distortion resulting in artifacts in the reconstructed optoacoustic image. In this work we developed a method for simulating the spatially dependent frequency response of acoustic detectors with arbitrary surface shapes. The frequency response is incorporated into a forward model for optoacoustic propagation. Our method can be used for designing detectors with desired properties and reducing reconstruction artifacts caused by the response of finite-size detectors. AU - Rosenthal, A. AU - Ntziachristos, V. AU - Razansky, D. C1 - 30971 C2 - 34050 TI - Simulating the spatially-dependent frequency response of arbitraryshape acoustic detectors for optoacoustic imaging. JO - Proc. SPIE VL - 7899 PY - 2011 SN - 0277-786X ER - TY - JOUR AB - Ceilometers are applied to detect layering of the lower atmosphere continuously. This is necessary because not only wind speeds and directions but also atmospheric layering and especially the mixing layer height (MLH) influence exchange processes of ground level emissions. It will be discussed how the ceilometer monitoring information can be used to determine the MLH influence upon the particle size distribution (PSD) which is detected near the ground. The information about atmospheric layering is continuously monitored by uninterrupted remote sensing measurements with the Vaisala ceilometers LD40 and CL31 which are eye-safe commercial lidar systems. Special software for these ceilometers provides routine retrievals of lower atmosphere layering from vertical profiles of laser backscatter data. The meteorological data are collected by the air pollution monitoring station of the Bavarian State Agency of Environment (LfU) at the southern edge of Augsburg and at the airport at the northern edge of Augsburg by the German National Meteorological Service (DWD). PSD are measured at the aerosol measurement station in the centre of Augsburg by the Cooperative Health Research in the Region of Augsburg (KORA). The two intensive measurement periods during the winter 2006/2007 and 2007/2008 are studied. The weather situations are characterized, the meteorological influences upon air pollutant concentrations like wind speed and wind direction are studied and the correlations of ceilometer backscatter densities and MLH with PSD are determined. AU - Schäfer, K.* AU - Emeis, S.* AU - Höß, M.* AU - Cyrys, J. AU - Pitz, M. AU - Munkel, C.* AU - Suppan, P. A2 - Kassianov, E.I.* ; Comeron, A.* ; Picard, R.H.* ; Schäfer, K.* C1 - 11749 C2 - 30804 CY - Bellingham, USA TI - On a relation between particle size distribution and mixing layer height. JO - Proc. SPIE VL - 8177 PB - SPIE PY - 2011 SN - 0277-786X ER - TY - JOUR AB - Multispectral Optoacoustic Tomography (MSOT) is an emerging technique for high resolution macroscopic imaging with optical and molecular contrast. We present cardiovascular imaging results from a multi-element real-time MSOT system recently developed for studies on small animals. Anatomical features relevant to cardiovascular disease, such as the carotid arteries, the aorta and the heart, are imaged in mice. The system's fast acquisition time, in tens of microseconds, allows images free of motion artifacts from heartbeat and respiration. Additionally, we present in-vivo detection of optical imaging agents, gold nanorods, at high spatial and temporal resolution, paving the way for molecular imaging applications. AU - Taruttis, A. AU - Herzog, E. AU - Razansky, D. AU - Ntziachristos, V. C1 - 30972 C2 - 34051 TI - Imaging the small animal cardiovascular system in real-time with multispectral optoacoustic tomography. JO - Proc. SPIE VL - 7899 PY - 2011 SN - 0277-786X ER - TY - JOUR AB - In order to compare different imaging systems, it is necessary to obtain detailed information about the system noise, its deterministic properties and task specic signal-to-noise ratio (SNR). The current standard method for characterizing noise in CT scanners is based on the pixel standard deviation of the image of a water-equivalent uniform phantom. The Fourier-based noise power spectrum (NPS)improves on the limitations of the pixel standard deviation by accounting for noise correlations. However, it has been shown that the Fourier-methods used to describe the system performance result in systematic errors as they make some limiting assumptions such as shift invariance and wide sense stationarity, which are not satised by real CT systems. For a more general characterization of the imaging system noise, a covariance matrix eigenanalysis can be performed. In this paper we present the experimental methodology for the evaluation of the noise of computed tomography systems. We used a bench-top at-panel-based cone-beam CT scanner and a cylindrical water-lled PMMA phantom. For the 3-dimensional reconstructed volume, we calculated the covariance matrix, its eigenvectors and eigenvalues for the xy-plane as well as for the yz-plane, and compared the results with the NPS. Furthermore, we analyzed the location-specic noise in the images. The evaluation of the noise is a rst step toward determining the task-specic SNR. AU - Brunner, C.C. AU - Hurowitz, S.A.* AU - Abboud, S.F.* AU - Hoeschen, C. AU - Kyprianou, I.S.* A2 - Samei, E.* ; Pelc, N.J.* C1 - 5031 C2 - 27860 CY - Bellingham, WA TI - Noise characterization of computed tomography using the covariance matrix. JO - Proc. SPIE VL - 7622 IS - PA PB - SPIE PY - 2010 SN - 0277-786X ER - TY - JOUR AB - Over the last decade fluorescent reporter technologies (both fluorescent probes and proteins) have become a very powerful imaging tool in everyday biomedical research. Multispectral optoacoustic tomography (MSOT) is an emerging imaging technology that can resolve fluorophore concentration in small animals situated in deep tissue by multispectral acquisition and processing of optoacoustic signals. In this work, we study the optimum operating conditions of MSOT in imaging fluorescence activity in small animals. The performance of various fluorochromes / fluorescent proteins is examined and it is shown that the new infrared fluorescent protein is an order of magnitude brighter than the red ones. Finally, wavelength reduction after principle component analysis shows, that accurate unmixing and 3D reconstruction of the distribution of fluorochromes is possible only with 2 or 3 wavelengths. AU - Glatz, J. AU - Deliolanis, N.C.* AU - Ding, L* AU - Taruttis, A.* AU - Rosenthal, A.* AU - Razansky, D. AU - Ntziachristos, V. A2 - Oraevsky, A.* ; Wang, L.V.* C1 - 6276 C2 - 28717 CY - Bellingham, WA TI - Multiparametric optimization of multispectral optoacoustic tomography for deep tissue imaging. JO - Proc. SPIE VL - 7564 PB - SPIE PY - 2010 SN - 0277-786X ER - TY - JOUR AB - The international standard IEC 62220-1-2 defines the measurement procedure for determination of the detective quantum efficiency (DQE) of digital x-ray imaging devices used in mammography. A mobile setup complying to this standard and adaptable to most current systems was constructed in the Helmholtz Zentrum München to allow for an objective technical comparison of current full field digital mammography units employed in mammography screening in Germany. This article demonstrates the setup's capabilities with a focus on the measurement uncertainties of all quantities contributing to DQE measurements. Evaluation of uncertainties encompasses results from measurements on a Sectra Microdose Mammography in clinical use, as well as on a prototype of a Fujifilm Amulet system at various radiation qualities. Both systems have a high spatial resolution of 50 μm × 50 μm. The modulation transfer function (MTF), noise power spectrum (NPS) and DQE of the Sectra MDM are presented in comparison to results previously published by other authors. AU - Greiter, M. AU - Hoeschen, C. A2 - Samei, E.* ; Pelc, N.J.* C1 - 5493 C2 - 27841 CY - Bellingham, WA TI - Mobile measurement setup according to IEC 62220-1-2 for DQE determination on digital mammography systems. JO - Proc. SPIE VL - 7622 PB - SPIE PY - 2010 SN - 0277-786X ER - TY - JOUR AB - The MADEIRA Project (Minimizing Activity and Dose with Enhanced Image quality by Radiopharmaceutical Administrations), aims to improve the efficacy and safety of 3D functional imaging by optimizing, among others, the knowledge of the temporal variation of the radiopharmaceuticals' uptake in and clearance from tumor and healthy tissues. With the help of compartmental modeling it is intended to optimize the time schedule for data collection and improve the evaluation of the organ doses to the patients. Administration of 18F-choline to screen for recurrence or the occurrence of metastases in prostate cancer patients is one of the diagnostic applications under consideration in the frame of the project. PET and CT images have been acquired up to four hours after injection of 18F-choline. Additionally blood and urine samples have been collected and measured in a gamma counter. The radioactivity concentration in different organs and data of plasma clearance and elimination into urine were used to set-up a compartmental model of the biokinetics of the radiopharmaceutical. It features a central compartment (blood) exchanging with organs. The structure describes explicitly liver, kidneys, spleen, plasma and bladder as separate units with a forcing function approach. The model is presented together with an evaluation of the individual and population kinetic parameters, and a revised time schedule for data collection is proposed. This optimized time schedule will be validated in a further set of patient studies. AU - Janzen, T. AU - Tavola, F.* AU - Giussani, A. AU - Cantone, M.C.* AU - Uusijärvi, H.* AU - Mattsson, S.* AU - Zankl, M. AU - Petoussi-Henß, N. AU - Hoeschen, C. A2 - Molthen, R.C.* ; Weaver, J.B.* C1 - 348 C2 - 27255 CY - Bellingham, WA TI - Compartmental model of ¹⁸F-choline. JO - Proc. SPIE VL - 7626 PB - SPIE PY - 2010 SN - 0277-786X ER - TY - JOUR AB - An essential problem dealing with three-dimensional optoacoustic imaging is the long data acquisition times associated with recording signals from multiple spatial projections, where signal averaging for each projection is applied to obtain satisfying signal-to-noise-ratio. This approach complicates acquisition and makes imaging challenging for most applications, especially for in vivo imaging and multispectral imaging. Instead we employ a herein introduced continuous data acquisition methodology that greatly shortens recording times over multiple projection angles and acquires high quality tomographic data without averaging. By this means a two dimensional image acquisition having 270 angular projections only takes about 9 seconds, while a full multispectral three dimensional image can normally take about 15 minutes to acquire with a single ultrasonic detector. The system performance is verified on tissue-mimicking phantoms containing known concentrations of fluorescent molecular agent as well as small animals. AU - Ma, R. AU - Ntziachristos, V. AU - Razansky, D. A2 - Oraevsky, A. A.* ; Wang, L.V.* C1 - 58 C2 - 27261 CY - Bellingham, WA TI - Continuous acquisition scanner for whole-body multispectral optoacoustic tomography. JO - Proc. SPIE VL - 7564 PB - SPIE PY - 2010 SN - 0277-786X ER - TY - JOUR AB - A novel approach is introduced for clustering tumor regions with similar signal-time series measured by dynamic contrast-enhanced (DCE) MRI to segment the tumor area in breast cancer. Each voxel of the DCE-MRI dataset is characterized by a signal-time curve. The clustering process uses two describer values for each pixel. The first value is L2-norm of each time series. The second value r is calculated as sum of differences between each pair of S(n-i) and S(i) for i = {0...n/2} where S is the intensity and n the number of values in a time series. We call r reverse value of a time series. Each time series is considered as a vector in an n-dimensional space and the L2-norm and reverse value of a vector are used as similarity measures. The curves with similar L2-norms and similar reverse values are clustered together. The method is tested on breast cancer DCE-MRI datasets with N = 256 x 256 spatial resolution and n = 128 temporal resolution. The quality of each cluster is described through the variance of Euclidean distances of the vectors to the mean vector of the corresponding cluster. The combination of both similarity measures improves the segmentation compared to using each measure alone. AU - Mohajer, M. AU - Brix, G. AU - Englmeier, K.-H. A2 - Molthen, R.C.* ; Weaver, J.B.* C1 - 459 C2 - 27230 CY - Bellingham, WA TI - A novel and fast method for cluster analysis of DCE-MR image series of breast tumors. JO - Proc. SPIE VL - 7626 PB - SPIE PY - 2010 SN - 0277-786X ER - TY - JOUR AB - Since optoacoustic tomography is considered a high-resolution modality, determination of the absolute detection limit, as it relates to the sensitivity of biomarker detection is not straightforward. This is due to the fact that experimental determination of the sensitivity as a function of target size remains difficult since no established technique exists so far to reproducibly create very small targets containing well-defined concentrations of markers. We combine theoretical analysis with imaging results for large amounts of the marker and place the measured value on the appropriate parameter-dependent signal intensity curve. A performance estimate of the particular experimental system and the expected signal-to-noise-ratio for smaller amounts of markers can then be made. AU - Razansky, D. AU - Baeten, J. AU - Ntziachristos, V. A2 - Oraevsky, A. A.* ; Wang, L.V.* C1 - 59 C2 - 27262 CY - Bellingham, WA TI - Prediction of sensitivity thresholds in optoacoustic tomography. JO - Proc. SPIE VL - 7564 PB - SPIE PY - 2010 SN - 0277-786X ER - TY - JOUR AB - In this work, we have developed a selective-plane illumination multispectral optoacoustic tomography (MSOT) technique for high-resolution whole-body visualization of intact optically diffusive organisms whose sizes may vary from sub-millimeter up to a centimeter range and beyond. By combining multi-wavelength illumination, the method is shown capable of resolving tissue-specific expression of fluorescent proteins and other molecular biomarkers located deep in living optically diffuse tissues. AU - Razansky, D. AU - Distel, M. AU - Vinegoni, C. AU - Ma, R. AU - Köster, R.W. AU - Ntziachristos, V. A2 - Oraevsky, A. A.* ; Wang, L.V.* C1 - 3332 C2 - 27327 CY - Bellingham, WA TI - Fluorescent protein imaging with multispectral optoacoustic tomography. JO - Proc. SPIE VL - 7564 PB - SPIE PY - 2010 SN - 0277-786X ER - TY - JOUR AB - We report on a new method for extraction of quantified optical absorption maps of scattering and absorbing media using sparse representation, a relatively recent and fast emerging technique in the field of signal processing. The tomographic reconstruction is facilitated by assuming slow spatial variations of illuminating optical field along with relatively sharp changes in optical absorption coefficient. As opposed to previous approaches that utilize photon transport equation in order to correct images for inhomogeneous light distribution within the imaged object, the method herein provides an estimate for photon fluence directly from the recorded optoacoustic signals. In this way a robust quantitative performance is achieved without prior knowledge of illumination geometry and optical properties of the object. AU - Rosenthal, A. AU - Razansky, D. AU - Ntziachristos, V. A2 - Oraevsky, A. A.* ; Wang, L.V.* C1 - 119 C2 - 27328 CY - Bellingham, WA TI - Sparse signal representation at the service of quantitative optoacoustic tomography. JO - Proc. SPIE VL - 7564 PB - SPIE PY - 2010 SN - 0277-786X ER - TY - JOUR AB - Novel geometrical designs of computed tomography (CT) scanners in combination with novel image reconstruction algorithms promise to reduce ionizing radiation exposure to the patient in CT scans. While the sampling density of the Field Of View (FOV) is retained, the image quality can even be increased in contrast to conventional CT scanners. In this study, we present first images obtained with a novel CT scanner that we developed in our working group. In this open CT system with irradiation within a fan beam, parallel Radon data are directly obtained for image reconstruction using the OPED (Orthogonal Polynomial Expansion on the Disk) algorithm. This algorithm uses Radon data directly, i.e., without any further data processing such as rebinning and interpolation. We experimentally test theoretical predictions for this system by quantifying image quality parameters in comparison with corresponding parameters that are derived from the images of a conventional scanner of the 3rd generation. The modulation transfer function (MTF) and noise power spectrum (NPS) are determined using a test phantom. The novel CT system quantitatively shows the same noise property as the conventional scanner. The resolution that is reached in the center of a reconstructed image is nearly identical for both scanner types. But we found that the resolution that is achieved in the novel CT system does not depend on the image position while the MTF of the conventional scanner decreases for radially outer regions of the image. AU - Schegerer, A.A. AU - Lingenheil, M. AU - Klaften, M. AU - Förster, T. AU - Hrabě de Angelis, M. AU - Hoeschen, C. A2 - Samei, E.* ; Pelc, N.J.* C1 - 5494 C2 - 27842 CY - Bellingham, WA TI - Development and quality characterization of a novel CT system. JO - Proc. SPIE VL - 7622 PB - SPIE PY - 2010 SN - 0277-786X ER - TY - JOUR AB - An angular parameterization of parallel Radon projections referred to in this paper as ψ-parameterization is discussed in relevance to the efficiency of reconstruction from fan data. The fact that the ψ-parameterization coincides with the equiangular fan beam parameterization allows us to develop a simple and efficient approach useful for the reconstruction from fan data. Within this approach parallel projections are approximated by groups of semi-parallel rays. The reconstruction is carried out directly, i.e. without any modification of original data, at the speed which is comparable or even higher than that of the parallel Filtered Back Projection (FBP) algorithm. AU - Tischenko, O. AU - Schegerer, A.A. AU - Xu, Y.* AU - Hoeschen, C. A2 - Samei, E.* ; Pelc, N.J.* C1 - 5030 C2 - 27839 CY - Bellingham, WA TI - Properties of a parameterization of radon projection by the reconstruction on circular disk. JO - Proc. SPIE VL - 7622 PB - SPIE PY - 2010 SN - 0277-786X ER - TY - JOUR AB - The sampling geometry of CT-scanners plays an important role in the reconstruction of images. We have previously reported a test-device that directly collects the Radon data within a special scanning geometry, whose acquired data can be efficiently treated with series expansion algorithms such as, for example, OPED (Orthogonal Polynomial Expansion on Disc). This geometry has the potential of reducing the radiation exposure of the patient by about a factor of two. However, a fourth of the data must be obtained by interpolation within the measured projections. In this contribution, we show by a Monte Carlo simulation that this interpolation has no significant influence on the quality of the reconstructions. AU - de las Heras, H.* AU - Tischenko, O. AU - Schlattl, H. AU - Xu, Y.* AU - Hoeschen, C. A2 - Samei, E.* ; Hsieh, J.* C1 - 213 C2 - 26325 CY - Bellingham, WA TI - Dose reduction potential of the scanning geometry CT D'OR: A simulation study. JO - Proc. SPIE VL - 7258 PB - SPIE PY - 2009 SN - 0277-786X ER - TY - JOUR AB - We describe an improved optoacoustic tomography method, that utilizes a diffusion-based photon propagation model in order to obtain quantified reconstruction of targets embedded deep in heterogeneous scattering and absorbing tissue. For the correction we utilize an iterative finite-element solution of the light diffusion equation to build a photon propagation model. We demonstrate image improvements achieved by this method by using tissue-mimicking phantom measurements. The particular strength of the method is its ability to achieve quantified reconstructions in non-uniform illumination configurations resembling whole-body small animal imaging scenarios. AU - Jetzfellner, T. AU - Razansky, D. AU - Rosenthal, A.* AU - Schulz, R.B.* AU - Englmeier, K.-H. AU - Ntziachristos, V. A2 - Ehsan, S.* ; Jiang, H.* C1 - 578 C2 - 26343 CY - Bellingham, WA TI - Iterative finite-element-based inversion for quantified detection of molecular targets using optoacoustic tomography. JO - Proc. SPIE VL - 7258 PB - SPIE PY - 2009 SN - 0277-786X ER - TY - JOUR AB - Noninvasive imaging of biological tissues using visible and near-infrared light may provide numerous insights into the underlying morphology or tissue function using a great variety of contrast and probing mechanisms. Nevertheless, mesoscopic-scale (i.e 1mm-1cm sized) living organisms remain largely inaccessible by current optical imaging methods. Depending on the optical properties of a particular object, light diffusion can significantly limit the resolution that can be achieved at depths beyond several hundred microns. To enable in-vivo optical contrast imaging of many important model organisms, such as insects, worms and similarly sized biological specimens, we have developed a multi-spectral optoacoustic tomography technique for high-resolution imaging of optically diffusive organisms and tissues. The method is capable of imaging at depths from sub-millimeter up to a centimeter range with a scalable spatial resolution on the order of magnitude of a few tenths of microns. Furthermore, we show for the first time that the technique is capable of resolving spatial distribution of fluorescent proteins inside intact opaque organisms, thus overcoming depth limitations of current fluorescence microscopy techniques. AU - Razansky, D. AU - Vinegoni, C.* AU - Ntziachristos, V. A2 - Alexander, A.* C1 - 710 C2 - 26306 CY - Bellingham, WA TI - Mesoscopic imaging of fluorescent proteins using multi-spectral optoacoustic tomography (MSOT). JO - Proc. SPIE VL - 7177 PB - SPIE PY - 2009 SN - 0277-786X ER - TY - JOUR AB - The ability to image polarization-selective tissue structures may provide valuable information on tissue anatomy, morphogenesis, and disease progression. So far, intensive light scattering in biological medium has limited implementation of polarization imaging to superficial tissue layers. We suggest overcoming the scattering problem using polarization-sensitive optoacoustic imaging. Due to intrinsically high spatial resolution and sensitivity of the method, it holds promise of becoming highly accurate modality for interrogation of small polarized structures deep in biological tissues. We show initial tomographic results in tissue-mimicking phantoms having polarization dichroism contrast. AU - Razansky, D. AU - Vinegoni, C.* AU - Ntziachristos, V. A2 - Alexander, A.* C1 - 1070 C2 - 26307 CY - Bellingham, WA TI - Deep tissue optoacoustic imaging of polarized structures. JO - Proc. SPIE VL - 7177 PB - SPIE PY - 2009 SN - 0277-786X ER - TY - JOUR AB - The collection, selection, amplification and detection of minimum genetic samples became a part of everyday life in medical and biological laboratories, to analyze DNA-fragments of pathogens, patient samples and traces on crime scenes. About a decade ago, a handful of researchers began discussing an intriguing idea. Could the equipment needed for everyday chemistry and biology procedures be shrunk to fit on a chip in the size of a fingernail? Miniature devices for, say, analysing DNA and proteins should be faster and cheaper than conventional versions. Lab-on-a-chip is an advanced technology that integrates a microfluidic system on a microscale chip device. The "laboratory" is created by means of channels, mixers, reservoirs, diffusion chambers, integrated electrodes, pumps, valves and more. With lab-ona- chip technology, complete laboratories on a square centimetre can be created. Here, a multifunctional programmable Lab-on-a-Chip driven by nanofluidics and controlled by surface acoustic waves (SAW) is presented. This system combines serial DNA-isolation-, amplification- and array-detection-process on a modified glass-platform. The fluid actuation is controlled via SAW by interdigital transducers implemented in the chemical modified chip surface. The chemical surface modification allows fluid handling in the sub-microliter range. Minute amount of sample material is extracted by laser-based microdissection out of e.g. histological sections at the single cell level. A few picogram of genetic material are isolated and transferred via a low-pressure transfer system (SPATS) onto the chip. Subsequently the genetic material inside single droplets, which behave like "virtual" beaker, is transported to the reaction and analysis centers on the chip surface via surface acoustic waves, mainly known as noise dumping filters in mobile phones. At these "biological reactors" the genetic material is processed, e.g. amplified via polymerase chain reaction methods, and genetically characterized. AU - Thalhammer, S. C1 - 1581 C2 - 26747 CY - Bellingham, WA TI - Programmable lab-on-a-chip system for single cell analysis. JO - Proc. SPIE VL - 7364 PB - SPIE PY - 2009 SN - 0277-786X ER - TY - JOUR AB - Refining the sampling geometry of a CT scanner is a standard approach used for reduction of aliasing artifacts in CT images. Although this leads to reduction of the artifacts, the principal problem of aliasing streaks artifacts remains unsolved. A different approach is proposed, which in some special cases can solve the problem very efficiently. It is shown that under certain specific conditions, the sum of images reconstructed from the data collected within different sampling geometries is free of aliasing. These conditions are studied and practical situations where they can be realized are discussed. AU - Tischenko, O. AU - Xu, Y.* AU - Goetzfried, T.* AU - Bogner, L.* AU - Hoeschen, C. A2 - Samei, E.* ; Hsieh, J.* C1 - 299 C2 - 26654 CY - Bellingham, WA TI - Reduction of aliasing artifacts in tomographic images. JO - Proc. SPIE VL - 7258 PB - SPIE PY - 2009 SN - 0277-786X ER - TY - JOUR AB - OPED is a reconstruction algorithm for Radon data based on orthogonal polynomial expansion on the disk. The algorithm involves a sum of N terms, which is determined by the number of view angles in the data. Evaluating on a rectangular grid of M×M pixels, the algorithm can be implemented with roughly O(N3) evaluations, if we assume M [approximate] N, and the constant is rather large. The new implementation uses a particular polar grid, so that the evaluation operation is reduced to 2N3 + O(N2 logN), a reduction of the evaluation time by a factor of more than 20 times. Linear interpolation on triangle is used to reduce our particular polar grid to the rectangular grid. Numerical experiments are presented to demonstrate the results. AU - Xu, Y.* AU - Tischenko, O. AU - Hoeschen, C. A2 - Samei, E.* ; Hsieh, J.* C1 - 1959 C2 - 26653 CY - Bellingham, WA TI - Fast implementation of the image reconstruction algorithm OPED. JO - Proc. SPIE VL - 7258 PB - SPIE PY - 2009 SN - 0277-786X ER - TY - JOUR AB - Preliminary results for a new CT scanning device with dose-reduction potential were presented at the SPIE Medical Imaging conference 2007. The new device acquires the Radon data after the X-ray beam is collimated through a special mask. This mask is combined with a new and efficient data collection geometry; thus the device has the potential of reducing the dose by a factor of two. In this work, we report the first complete proof of the idea using the same simplified mask of 197 detectors as last year, and a clinical C-arm with a flat panel detector to simulate the gantry. This addition enables the acquisition of two independent and complementary data sets for reconstruction. Moreover, this clinical set-up enables the acquisition of data for clinically relevant phantoms. Phantom data were acquired using both detector sets and were reconstructed with the robust algorithm OPED. The independent sinograms were matched to a single one, and from this a diagnostic image was reconstructed successfully. This image has improved resolution, as well as less noise and artifacts compared to each single independent reconstruction. The results obtained are highly promising, even though the current device acquires only 197 views. Dose comparisons can be carried out in the future with a more precise prototype, comparable to current clinical devices with respect to imaging performance. AU - de las Heras, H. AU - Tischenko, O. AU - Renger, B.* AU - Xu, Y.* AU - Hoeschen, C. A2 - Hsieh, J.* ; Samei, E.* C1 - 8869 C2 - 25656 CY - Bellingham WA TI - Experimental proof of an idea for a CT-scanner with dose reduction potential. JO - Proc. SPIE VL - 6913 PB - SPIE PY - 2008 SN - 0277-786X ER - TY - JOUR AB - We present the first hybrid photoacoustic fluorescence molecular tomography system, capable of three-dimensional imaging of both fluorochrome and chromophore distributions in highly scattering and absorbing tissue. Quantitative three-dimensional maps of optical absorption coefficient are acquired using photoacoustic tomography. The reconstructed absorption data is fed into the Fluorescence Molecular Tomography inversion scheme in order to improve its accuracy and quatification capabilities in the presence of strong and distributed absorbers that are expected to bias stand-alone fluorescence reconstructions. At all, having both techniques in one hybrid modality yields a system that combines high molecular specificity and targeting flexibility of fluorescent imaging and high spatial resolution functional information obtained via photo-acoustic images. AU - Razansky, D. AU - Ntziachristos, V. A2 - Oraevsky, A.A.* ; Wang, L.V.* C1 - 9559 C2 - 26010 CY - Bellingham, WA TI - Fluorescence Molecular Tomography using a-priori Photoacoustic data. JO - Proc. SPIE VL - 6856 PB - International Society for Optical Engineering PY - 2008 SN - 0277-786X ER - TY - JOUR AB - Current non-invasive imaging methods of fluorescent molecular probes in the visible and near-infrared suffer from low spatial resolution as a result of rapid light diffusion in biological tissues. We show that three-dimensional distribution of fluorochromes deep in small animals can be resolved with below 25 femtomole sensitivity and 150 microns spatial resolution by means of multi-spectral photo-acoustic molecular tomography. The low sensitivity limit of the method is enabled by using the highly resonant absorption spectrum of a commonly used near-infrared fluorescent molecular probe Alexa Fluor 750 in order to acquire differential images at multiple wavelengths with tomographic topology suitable for whole-body small animal imaging. AU - Razansky, D. AU - Vinegoni, C.* AU - Ntziachristos, V. A2 - Oraevsky, A.A.* ; Wang, L.V.* C1 - 9560 C2 - 26012 CY - Bellingham, WA TI - Multi-spectral photo-acoustic molecular tomography resolves fluorochrome distribution with high resolution and sensitivity in small animals. JO - Proc. SPIE VL - 6856 PB - International Society for Optical Engineering PY - 2008 SN - 0277-786X ER - TY - JOUR AB - The new scanner geometry CT D'OR (CT with Dual Optimal Reading"), developed at the Helmholtz Zentrum Mnchen (former GSF-National Research Center for Environment and Health), consists of a discontinuous ring of detectors facing toward the ring center, which are fixated on an x-ray absorbing material. The x-ray source and an additional outer detector are mounted on a gantry which rotates around the inner static detector and thus the patient. When the source is moving, the detectors are alternately exposed and shielded from the source. Data recorded during periods of direct exposure can be combined and are used for the reconstruction of the image. When the detectors are shielded, their signal is solely caused by scatter. Therefore, direct scatter correction is possible. This can be used to considerably improve the image quality, when scatter radiation yields a strong deterioration of the reconstructed image. The advantage of CT D'OR is thus, that information about scatter radiation is obtained without additional effort or exposure. This property of CT D'OR is investigated and its feasibility is demonstrated by the use of Monte Carlo simulations." AU - Schlattl, H. AU - Hoeschen, C. A2 - Hsieh, J.* ; Samei, E.* C1 - 8870 C2 - 25657 CY - Bellingham WA TI - The built-in capacity of CT D'OR's static ring for scatter correction. JO - Proc. SPIE VL - 6913 PB - SPIE PY - 2008 SN - 0277-786X ER - TY - JOUR AB - For optimisation in diagnostic medical imaging it is important to consider the relation between diagnostic image quality and patient dose. In the past, schematic representations of the human body were commonly used for dosimetric simulations together with Monte Carlo codes. During the last two decades, voxel models were introduced as an improvement to these body models. Studies performed by various research groups have shown that the more realistic organ topology of voxel models constructed from medical image data of real persons has an impact on calculated doses for external as well as internal exposures. As a consequence of these findings, the ICRP decided to use voxel models for the forthcoming update of organ dose conversion coefficients. These voxel models should be representative of an average population, i.e. they should resemble the ICRP reference anatomical data with respect to their external dimensions and their organ masses. To meet the ICRP requirements, our group at the Helmholtz Zentrum Mnchen (formerly known as GSF-National Research Center for Environment and Health) constructed voxel models of a male and female adult, based on the voxel models of two individuals whose body height and weight resembled those of the male and female ICRP reference adult. The organ masses of both models were adjusted to the ICRP reference anatomical data, without spoiling their realistic anatomy. The paper describes the method used for this process and the resulting voxel models. AU - Zankl, M. AU - Schlattl, H. AU - Becker, J. AU - Petoussi-Henß, N. AU - Hoeschen, C. A2 - Hsieh, J.* ; Samei, E.* C1 - 8871 C2 - 25658 CY - Bellingham WA TI - Voxel models representing the male and female ICRP reference adult: A dosimetric tool for medical imaging. JO - Proc. SPIE VL - 6913 PB - SPIE PY - 2008 SN - 0277-786X ER - TY - JOUR AU - Condat, L. AU - Forster-Heinlein, B. AU - van de Ville, D.* C1 - 8868 C2 - 25079 CY - Bellingham WA SP - 1-9 TI - A new family of rotation-covariant wavelets on the hexagonal lattice. JO - Proc. SPIE VL - 6701 PB - SPIE PY - 2007 SN - 0277-786X ER - TY - JOUR AB - A non-standard scanning device with dose-reduction potential was proposed at the SPIE Medical Imaging conference 2006. The new device obtains the Radon data after the X-ray beam is collimated through a special mask. This mask is combined with a new geometry that permits an efficient data collection, thus the device has the potential of reducing the dose by a factor of two. In this work, we report a prototype of the new device and experimental data acquisition using only the mask of the new scanning geometry. In order to obtain the optimal parameters for the scanning device, several factors have been considered, including detector elements and shielding shape, fan beam angle, speed of the source rotation and materials employed. The calibration of the detector elements needs especial attention, due to the dependence of the detector response on the energy of the X-rays. A simplified version of the device was designed and mounted. Phantom data were acquired using this prototype and were used to test the performance of the new design. The results obtained are highly promising, even though the prototype developed does not make use yet of all the potential features proposed in the theory. AU - de las Heras, H. AU - Tischenko, O. AU - Panzer, W. AU - Xu, Y.* AU - Hoeschen, C. A2 - Hsieh, J.* ; Flynn, M.J.* C1 - 8864 C2 - 24774 CY - Bellingham WA TI - Modelling and testing of a non-standard scanning device with dose reduction potential. JO - Proc. SPIE VL - 6510 PB - SPIE PY - 2007 SN - 0277-786X ER - TY - JOUR AU - Englmeier, K.-H. AU - Seemann, M.D.* A2 - Manduca, A.* C1 - 8865 C2 - 24404 CY - Bellingham WA TI - Virtual hybrid bronchoscopy using PET/CT data sets. JO - Proc. SPIE VL - 6511 PB - SPIE PY - 2007 SN - 0277-786X ER - TY - JOUR AB - We extend the notion of complex B-splines to a multivariate setting by employing the relationship between ordinary B-splines and multivariate B-splines by means of ridge functions. In order to obtain properties of complex B-splines in Rs, 1 < s [is-an-element-of] N, the Dirichlet average has to be generalized to include infinite dimensional simplices. Based on this generalization several identities of multivariate complex B-splines are exhibited. AU - Massopust, P. AU - Forster, P. C1 - 8867 C2 - 25077 CY - Bellingham WA SP - 670109 TI - Multivariate complex B-splines. JO - Proc. SPIE VL - 6701 PB - SPIE PY - 2007 SN - 0277-786X ER - TY - JOUR AB - Thoracic radiography was simulated making use of a virtual pediatric model created from tomographic data (voxelphantom) of a child eight weeks old. The dataset was scaled down to fit the dimensions of a premature newborn. The simulation allows a quantitative and spatially resolved analysis of the x-ray image generation. The transmission behavior of different anatomical regions present in the voxelphantom was compared to the output of the simulation of a step-like phantom made from aluminum and PMMA. The step like structure of the simulated model can be easily built and statements about its x-ray related behavior can be directly validated by means of experiments. A thin contrast plate was placed on each step to make the determination of dependences e.g. between the applied radiation energy and the contrast to noise ratio possible. AU - Schöfer, F.H. AU - Schneider, K.* AU - Hoeschen, C. A2 - Hsieh, J.* ; Flynn, M.J.* C1 - 8861 C2 - 24771 CY - Bellingham WA TI - Virtual adaption of physcical phantoms to datasets derived from clinical tomographic examinations. JO - Proc. SPIE VL - 6510 PB - SPIE PY - 2007 SN - 0277-786X ER - TY - JOUR AU - Schöfer, F.H. AU - Schneider, K.* AU - Hoeschen, C. A2 - Hsieh, J.* ; Flynn, M.J.* C1 - 8862 C2 - 24772 CY - Bellingham WA TI - Minimum dose calculation for different imaging tasks in digital projection radiography. JO - Proc. SPIE VL - 6510 PB - SPIE PY - 2007 SN - 0277-786X ER - TY - JOUR AB - Can time-resolved, high-resolution data as acquired by an intensified gated CCD camera (ICCD) aid in the tomographic reconstruction of fluorescence concentration? Usually it is argued that fluorescence is a linear process and thus does not require non-linear, time-dependent reconstructions algorithms, unless absorption and scattering coefficients need to be determined as well. Furthermore, the acquisition of a number of time frames is usually prohibitive for fluorescence measurements, at least in small animals, due to the increased total measurement time. On the other hand, it is obvious that diffusion is less pronounced in images at early gates, due to selective imaging of photons of lower scatter order. This will be the case also for photons emitted by fluorescent sources. Early-gated imaging might increase the contrast in acquired images and could possibly improve fluorescence localization. Herein, we present early gated fluorescence images obtained from phantoms and compare them to continuously acquired data. Increased contrast between background and signal maximum can be observed in time-gated images as compared to continuous data. To make use of the properties exhibited by early gated frames, it is necessary to use a modified reconstruction algorithm. We propose a variant of the well-known Born approximation to the diffusion equation that allows to take into account single time frames. The system matrix for the time-dependent Born approach is more complex to calculate, however the complexity of the actual inverse problem (and the acquisition times) of single-frame reconstructions remains the same as compared to continuous mode. AU - Schulz, R.B. AU - Schweiger, M.* AU - Andrea, C.D.* AU - Valentini, G.* AU - Peter, J. AU - Cubedduc, R.* AU - Arridge, S.R.* AU - Semmler, W. C1 - 31186 C2 - 34310 TI - Applying time-dependent data for fluorescence tomography. JO - Proc. SPIE VL - 6626 PY - 2007 SN - 0277-786X ER - TY - JOUR AU - Tischenko, O. AU - Xu, Y.* AU - Hoeschen, C. A2 - Hsieh, J.* ; Flynn, M.J.* C1 - 8863 C2 - 24773 CY - Bellingham WA SP - 65104I-1 - 65104I-9 TI - Improvement of OPED algorithm by means of indroducing an integration in the evaluation process. JO - Proc. SPIE VL - 6510 PB - SPIE PY - 2007 SN - 0277-786X ER - TY - JOUR AB - To support ophthalmologists in their routine and enable the quantitative assessment of vascular changes in color fundus photographs a multi-resolution approach was developed which segments the vessel tree efficiently and precisely in digital images of the retina. The algorithm starts at seed points, found in a preprocessing step and then follows the vessel, iteratively adjusting the direction of the search, and finding the center line of the vessels. As an addition, vessel branches and crossings are detected and stored in detailed lists. Every iteration of the Directional Smoothing Based (DSB) tracking process starts at a given point in the middle of a vessel. First rectangular windows for several directions in a neighborhood of this point are smoothed in the assumed direction of the vessel. The window, that results in the best contrast is then said to have the true direction of the vessel. The center point is moved into that direction 1/8th of the vessel width, and the algorithm continues with the next iteration. The vessel branch and crossing detection uses a list with unique vessel segment IDs and branch point IDs. During the tracking, when another vessel is crossed, the tracking is stopped. The newly traced vessel segment is stored in the vessel segment list, and the vessel, that had been traced before is broken up at the crossing- or branch point, and is stored as two different vessel segments. This approach has several advantages:- With directional smoothing, noise is eliminated, while the edges of the vessels are kept.- DSB works on high resolution images (3000 x 2000 pixel) as well as on low-resolution images (900 x 600 pixel), AU - Englmeier, K.-H. AU - Bichler, S. AU - Schmid, K. AU - Maurino, M.* AU - Porta, M.* AU - Bek, T.* AU - Ege, B.* AU - Larsen, O.V.* AU - Hejlesen, O.K.* A2 - Clough, A. V.* ; Chen, C.-T.* C1 - 8707 C2 - 20279 CY - Bellingham, WA SP - 230-237 TI - Multi-resolution retinal vessel tracker based on directional smoothing. JO - Proc. SPIE VL - 4683 PB - SPIE PY - 2002 SN - 0277-786X ER - TY - JOUR AB - We developed 3D MR based image processing methods for biomechanical analysis of joints. These methods provide quantitative data on the morphological distribution of the joint cartilage as well as biomechanical analysis of relative translation and rotation of joints. After image data acquisition in an open MR system, the segmentation of the different joint structures was performed by a semi automatic technique based on a gray value oriented region growing algorithm. After segmentation 3D reconstructions of cartilage and bone surfaces were performed. Principal axis decomposition is used to calculate a reproducible tibia plateau based coordinate system that allows the determination of relative rotation and translation of the condyles and menisci in relation to the tibia plateau. The analysis of the femoral movement is based on a reproducible, semi automatic calculated epicondylar axis. The analysis showed a posterior translation of the meniscus and even more of the femur condyles in healthy knees and in knees with an insufficiency of the anterior cruciate ligament (ACL). AU - Siebert, M. AU - Englmeier, K.-H. AU - v. Eisenhart-Rothe, R.* AU - Bringmann, C.* AU - Eckstein, F.* AU - Bonel, H.* AU - Reiser, M.* AU - Graichen, H.* A2 - Clough, A. V.* ; Chen, C.-T.* C1 - 9542 C2 - 20287 CY - Bellingham, WA SP - 476-483 TI - System for Three Dimensional Biomechanical Analysis of Joints. JO - Proc. SPIE VL - 4683 PB - SPIE PY - 2002 SN - 0277-786X ER - TY - JOUR AB - Purpose: To investigate the relative importance of spatial resolution and noise on the image quality of clinical radiographs. Methods: The spatial resolution and noise of fifteen digitized lumbar spine radiographs were altered with image processing. Three different MTF curves and three different Wiener spectra were combined into seven different combinations of spatial resolution and noise. These seven combinations were applied to the original data set, and the resulting images were printed on film. Seven expert radiologists evaluated the clinical image quality of the resulting images with visual grading analysis (VGA) of structures based on the European Image Criteria. Results: The results show that added noise is more deteriorating than reduced spatial resolution for the clinical image quality. For a given MTF and noise level, the worst was the one with increased noise followed by the one with both reduced MTF and added noise (mimicking a faster screen-film combination). Reduced MTF only gave the highest rating. Conclusions: It is more important to find methods for removing noise than to try to improve the MTF of a radiographic system. A noisy image can sometimes be improved by reducing the spatial resolution. AU - Tingberg, A.* AU - Herrmann, C. AU - Besjakov, J.* AU - Almen, A.* AU - Sund, P.* AU - Adliene, D.* AU - Mattsson, S.* AU - Mansson, L.G.* AU - Panzer, W. A2 - Chakraborty, D.P.* ; Krupinski, E.A.* C1 - 9011 C2 - 20288 CY - Bellingham, WA SP - 338-346 TI - What is Worse : Decreased Spatial Resolution or Increased Noise ? JO - Proc. SPIE VL - 4683 PB - SPIE PY - 2002 SN - 0277-786X ER - TY - JOUR AU - Englmeier, K.-H. AU - Siebert, M. AU - Brüning, R.* AU - Scheidler, J.* AU - Reiser, M.* C1 - 21797 C2 - 19996 SP - 155-162 TI - Gesture Analysis and Immersive Visualization for Virtual Endoscopy. JO - Proc. SPIE VL - 2 PY - 2001 SN - 0277-786X ER - TY - JOUR AU - Sund, P.* AU - Herrmann, C. AU - Tingberg, A.* AU - Kheddache, S.* AU - Mansson, L.G.* AU - Almen, A.* AU - Mattsson, S.* A2 - Krupinski, E.A.* C1 - 21395 C2 - 19513 SP - 251-257 TI - Comparison of two methods for evaluating image quality of chest radiographs. JO - Proc. SPIE VL - 1 PY - 2000 SN - 0277-786X ER - TY - JOUR AU - Tingberg, A.* AU - Herrmann, C. AU - Besjakov, J.* AU - Rodenacker, K. AU - Almen, A.* AU - Sund, P.* AU - Mattsson, S.* AU - Mansson, L.G.* A2 - Krupinski, E. A.* C1 - 21652 C2 - 19809 SP - 34-42 TI - Evaluation of lumbar spine images with added pathology. JO - Proc. SPIE VL - 1 IS - 26 PB - SPIE PY - 2000 SN - 0277-786X ER - TY - JOUR AU - Bittner, K. C1 - 21263 C2 - 19374 SP - 410-421 TI - Biorthogonal Wilson Bases. JO - Proc. SPIE VL - 3813 PY - 1999 SN - 0277-786X ER - TY - JOUR AB - A method of a three-dimensional surface reconstruction of the retina in the area of the papilla is presented. The surface reconstruction is based on a sequence of discrete gray-level images of the retina recorded by a Scanning Laser Ophthalmoscope (SLO). The underlying assumption of the developed surface reconstruction algorithm is that the depth information is also encoded in the brightness values of the single pixels beside the ordinary spatial 2D information. The brightness of an image position depends also on the degree of reflection of a confocal laser beam. Only these surface structures produce a high response of the focused laser light, which are located directly in the focus plane of the confocal laser beam. The occurring disparities between the single images of a sequence are considered to be approximately linear and are corrected by applying the cepstrum technique. The depth information is estimated out of the volumetric representation of the image sequence by searching the maximal value of the brightness within a computed depth profile at every image position. In the resulting range images disturbances which occur during the recording cause wrong local estimations of the depth information. These local disturbances are corrected by applying especially developed surface improvement processes. The work is completed by investigating several different approaches to reduce the noisy and disturbances of SLO image data. AU - Altmann, M. AU - Herpes, R. AU - Künzer, I. AU - Englmeier, K.-H. C1 - 57728 C2 - 0 SP - 335-345 TI - Three-dimensional surface reconstruction of the papilla nervi optici using scanning laser ophthalmoscopic sequences. JO - Proc. SPIE VL - 2434 PY - 1995 SN - 0277-786X ER - TY - JOUR AB - The assessment of blood flow in the gastrointestinal mucosa might be an important factor for the diagnosis and treatment of several diseases such as ulcers, gastritis, colitis or early cancer. The quantity of blood flow is roughly estimated by computing the spatial hemoglobin distribution in the mucosa. The presented method enables a practical realization by calculating approximately the hemoglobin concentration based on a spectrophotometric analysis of endoscopic true-color images, which are recorded during routine examinations. A system model based on the reflectance spectroscopic law of Kubelka-Munk is derived which enables an estimation of the hemoglobin concentration by means of the color values of the images. Additionally, a transformation of the color values is developed in order to improve the luminance independence. Applying this transformation and estimating the hemoglobin concentration for each pixel of interest, the hemoglobin distribution can be computed. The obtained results are mostly independent of luminance. An initial validation of the presented method is performed by a quantitative estimation of the reproducibility. AU - Jacoby, R.S.* AU - Herpers, R. AU - Zwiebel, F.M.* AU - Englmeier, K.-H. C1 - 57733 C2 - 0 SP - 87-98 TI - Blood flow estimation in gastroscopic true-color images. JO - Proc. SPIE VL - 2433 PY - 1995 SN - 0277-786X ER - TY - JOUR AU - Selige, T. AU - Friedrich, K.* AU - Vorderbrugge, T.* AU - Reinartz, P.* AU - Peter, M.* C1 - 57725 C2 - 0 SP - 292-299 TI - Groundwater management by monitoring water gathering areas using remote sensing and GIS. JO - Proc. SPIE VL - 2314 PY - 1995 SN - 0277-786X ER - TY - JOUR AB - In this contribution we investigate the performance of steerable functions to characterize keypoints. Steerable functions were introduced recently by Perona as an efficient method to calculate the response of a filter in a continuum of orientations, scales, and other parameters. For the analysis of points with events at multiple orientations, functions with a high orientational resolution are needed. We discuss criteria to judge the quality of a function to serve for orientation analysis. To handle line as well as edge junctions, we use a complex function with the real and imaginary part approximately in quadrature. An associated one-sided function allows to distinguish between terminating and nonterminating edges and lines. To analyze thick lines and blurred edges the function is also steered in scale. AU - Michaelis, M. AU - Sommer, G. C1 - 40034 C2 - 0 SP - 450-461 TI - Characterization of keypoints in images. JO - Proc. SPIE VL - 2093 PY - 1994 SN - 0277-786X ER - TY - JOUR AB - After clinical photodynamic therapy (PDT) and radiotherapy (RT) of the colon carcinoma acute and late damages on adjacent normal tissue were seen. Therefore it was the aim of this experimental study to investigate these damages on normal colon tissue of rats after PDT in comparison with RT. For PDT the rats got Photofrin® (5 mg/kg bw, i.v.) 24 h prior to the laser light illumination (630 nm, 100 mW/cm2, 20-100 J/cm2) at 20-50 mm proximal from the anus. In the RT-group a localized 300 kV x-irradiation with 23 Gy of a 24 mm long segment of the rat colon, 26-50 mm proximal from the anus, was performed. Within the first hours after PDT the endoscopic examination showed a severe acute damage. The histopathological examination showed that the acute ulceration depends on the energy density applied within the first three days. Animals receiving a synthetic diet before and during the PDT treatment survived the acute phase and showed no late effects. After x-irradiation the acute damage of the mucosa occurred in the second week post irradiation and could be observed by endoscopy. After 4 to 10 weeks late damage started with ulceration and colon obstruction. All animals receiving the synthetic diet after x-irradiation survived as long as the diet was maintained. When the diet was changed to the standard pellets more than 90% of the rats developed a progressive large bowel obstruction. This study indicates different progresses of acute effects after PDT and RT, respectively. Late damages were observed only by RT in contrast to PDT. Synthetic diet prevents acute damages after PDT. However, the synthetic diet after RT can prevent the late damage for the duration of the diet administration. AU - Sassy, T. AU - Breiter, N.* AU - Sroku, R. AU - Ernst, H.* C1 - 57678 C2 - 0 SP - 453-457 TI - Acute and chronic effects of rat colon after photodynamic therapy and radiotherapy - A comparative study. JO - Proc. SPIE VL - 2078 PY - 1994 SN - 0277-786X ER - TY - JOUR AB - The combination of fluorescence microscopy and time-resolved techniques opens up new possibilities in studying pharmacokinetics and localization of various drugs on a cellular scale. The fluorescence decay time of many molecules is modulated by the physical and chemical properties of the microenvironment, such as viscosity, polarity, pH-value, etc. The alternation of the decay time can also be used to pursue chemical transformations of a drug like degradation, monomerization, or protonation. This paper presents applications of this method from the field of photosensitizing dyes used in photodynamic therapy. AU - Seidlitz, H.K. AU - Wessels, J.M. C1 - 40006 C2 - 0 SP - 108-116 TI - Methods and application of time-resolved fluorescence microscopy. JO - Proc. SPIE VL - 2083 PY - 1994 SN - 0277-786X ER - TY - JOUR AB - Protoporphyrin-dimethylester (PP) is an amphiphilic porphyrin which shows a fast clearence and is therefore of interest for the photodynamic therapy. The localization of the sensitizer is one point of interest, since it has a strong influence on the photo toxic effect. Localization of PP in fibrosarcoma cells was probed by time resolved and steady state spectroscopy. Dioleoyl L- α-phosphatidylcholine (DOPC) liposomes were used as a carrier system for the amphiphilic sensitizer with a molar ratio of PP/DMSO = 1/200. Since intermembrane exchange is responsible for the uptake of PP we expected a membrane bound localization. Therefore the characterization of the microenvironment was based on the comparison of the spectroscopic properties of PP in organic solvents, artificial membranes and in cells. Cells were incubated with a concentration of 3.5·10-7 M in FCS free medium at T = 37°C for 4h. Aprotic solvents show a bathochromic shift of the Soret-band with increasing dielectric constant ∈ whereas the Q- bands exhibit no spectral shift within the instrumental resolution (Δλ=3nm). Additionally, the fluorescence decay time of the monomer (τ=(11.5±1.0)ns) remains constant. However, in aprotic solvents like dimethylsulfoxide, 1-propanol or ethylenglycol which exhibit an amphiphilic character we observed no spectral shift of the Soret-band with increasing € but an increase in the fluorescence decay time (τ=(16.8±1.2)ns). This decay time of PP is within the error margin in agreement with its monomer decay time in artificial membranes (τ=(16.8±1.0)ns) and in single cells (τ=(15.3±0.4)ns). Based on this comparison we suggest that PP is bound within the amphiphilic part of the membranes is between the polar headgroups and the fatty acyl chains of the cytoplasm membrane. AU - Wessels, J.M. AU - Beisker, W. AU - Seidlitz, H.K. C1 - 57680 C2 - 0 SP - 363-370 TI - Kinetic and localization properties of protoporphyrin dimethyl ester in fibrosarcoma cells. JO - Proc. SPIE VL - 2078 PY - 1994 SN - 0277-786X ER - TY - JOUR AB - Photodynamic diagnosis (PDD) and therapy (PDT) require light application devices which enable homogeneous illumination of tissue in hollow organs. Three techniques based on modification of the aperture of single fibers are presented mainly for use in urology and pneumology in combination with rigid and flexible endoscopes. All illumination systems allow for nearly entire illumination of the endoscope's viewing field. A microlens system is used for fluorescence diagnostic purposes in the lung. The system, consisting of two plano convex lenses in a condenser configuration, is attached directly to the fiber. The beam profile is optimized by ray tracing calculations. For fluorescence excitation of the tumormarker Photofrin II in the urinary bladder a 500 μm plastic fiber is used. The tip of the fiber is polished to a double cone with angles of 12 ° and 7°. With this modification the aperture is increased by a factor of two. Photodynamic treatment of confined superficial tumors in the lung was successfully performed with a fused silica fiber coupled to the endoscope in a special adaptive device. In this procedure laserlight at 630 nm is guided through the optics channel of rigid endoscopes. A homogeneous circular illumination pattern is obtained following exactly the deflection angle of the endoscope. AU - Baumgartner, R. AU - Beyer, W. AU - Friedsam, G. AU - Jocham, D. AU - Noack, A. AU - Sroka, R. AU - Stepp, H. AU - Unsöld, E. C1 - 19583 C2 - 12686 SP - 91-96 TI - Fiber optic probes for tissue illumination in photodynamic diagnosis and therapy. JO - Proc. SPIE VL - 1649 PY - 1992 SN - 0277-786X ER - TY - JOUR AB - On the basis of clinical protocols, phase II-studies have been started to evaluate photodynamic diagnosis for early visualization o cancer in bladder and lung. As tumor marker the fluorescent and photosensitizing polyporphyrin Photofrin II is used in a dose which has been proven to avoid photosensitization of the patients' skin. The drug is administered systemically in a concentration of mostly 0,4 mg/kg body weight. Fluorescence of Photofrin II in tissue is detected by an image-intensifying CCD camera coupled to endoscopes usually used in both medical disciplines. Video presentation of the marker fluorescence occurs with high contrast due to real-time image processing following two-wavelength excitation of the tissue with laser light. A keypoint of the new diagnostic method is the correlation of the fluorescence contrast and the histological examination of biopsies removed from these areas. As an examples, 87 biopsies have been taken from 17 patients suffering from bladder cancer. While all tumorous samples (n = 16) show strong fluorescence, about 30% of the biopsies are judged as false positive. A variety of premalignant diseases has been found in these sections. No false negative results have been obtained up to now. AU - Baumgartner, R. AU - Kriegmair, M. AU - Jocham, D. AU - Hofstetter, A.G. AU - Huber, R.M. AU - Karg, O. AU - Haeußinger, K. C1 - 40546 C2 - 0 SP - 107-112 TI - Photodynamic diagnosis of early stage malignancies: preliminary results in urology and pneumonology. JO - Proc. SPIE VL - 1641 PY - 1992 SN - 0277-786X ER - TY - JOUR AB - Chlorophyll fluorescence induction kinetics were used to assess different features of the photosynthetic system of trees affected by forest decline and of control trees. Several parameters can be derived from the kinetics: Fo and Fo′, the initial fluorescence intensity and its initial slope, the maximum intensity Fp, and the final steady- state intensity Fs. Furthermore, the ratio R(t) of the two fluorescence components at 685 nm and 730 nm shows the initial value Ro, the minimum value Rm, and the steady- state value Rs. Measurements were carried out on spruce, birch, oak, and poplar. If one considers the variation of the parameters obtained from the different tree species and the effect on the parameters due to the forest decline, the parameters Ro and Fp/Fo exhibit a maximum capability to differentiate between control trees and those affected by forest decline. AU - Ruth, B. C1 - 40597 C2 - 0 SP - 61-72 TI - Initial phase of the chlorophyll fluorescence induction kinetics as an indicator of the degree of forest decline. JO - Proc. SPIE VL - 1714 PY - 1992 SN - 0277-786X ER - TY - JOUR AU - Sassy, T. AU - Baumgartner, R. AU - Jocham, D. AU - Müller, E. AU - Unsöld, E. AU - Wessels, J. C1 - 19406 C2 - 12495 TI - Comparative Study on the Tumor Destructive Potential of Different Photosensitizers. JO - Proc. SPIE PY - 1992 SN - 0277-786X ER - TY - JOUR AU - Sroka, R. AU - Baumgartner, R. AU - Buser, A. AU - Ell, C. AU - Jocham, D. AU - Unsöld, E. C1 - 19584 C2 - 12687 TI - Laser assisted Detection of Endogenous Porphyrins in Malignant Diseases. JO - Proc. SPIE PY - 1992 SN - 0277-786X ER - TY - JOUR AB - Several substances, e.g., hematoporphyrin derivatives (HpD), dihematoporphyrin ether/ester (DHE), phthalocyanines, porphycenes, and other drugs are known to be temporarily and selectively stored in tumors after systematic application. This transient marking opens up new perspectives for diagnostic and therapeutic procedures. The marker most commonly used today is DHE intravenously injected at doses of 0.2 up to 3.0 mg/kg bodyweight for diagnosis and therapy respectively. The corresponding clearance intervals after injection of DHE range from 3 - 48 h and 25 - 75 h. The highly sensitive two-wavelength laser excitation method with computerized fluorescence imaging offers great advantages for the detection of photosensitized tumors and adds support to conventional diagnostic techniques. Photoinduced production of singlet oxygen is said to be the initial process leading to tumor destruction. Homogeneous irradiation of the area to be treated and a reliable light dosimetry are prerequisites for an effective tumor therapy. Standard instruments for a routine application so far do not exist. Integral irradiation techniques and special laser fiber modifications, however, are under development, which guarantee a uniform distribution of light on the area to be treated. Positive results are such treatments - especially in urology, pneumology, and otorhinolaryngology - indicate the future potential of photodynamic therapy of tumors. AU - Unsoeld, E. C1 - 40612 C2 - 0 SP - 138-142 TI - Photodynamic methods for fluorescence diagnosis and therapy of photosensitized tumors. JO - Proc. SPIE VL - 1524 PY - 1992 SN - 0277-786X ER - TY - JOUR AB - The influence of laser-induced temperature increase in transcutaneous PDT was examined in this study. First the subcutaneous temperature and the relative light intensity between tumor and skin were measured as a function of the applied power density in a series of studies. In a second experiment the influence of temperature on the effect of photodynamic therapy was studied. With the use of transcutaneous PDT it could be shown that the temperature and the relative light intensity between tumor and skin depended essentially on the concentration of pigmentation of the skin above the tumor. Dependent on pigmentation and cooling, temperatures of more than 42°C were established with irradiation at power densities starting at about 300 mW/cm2. In the second series of experiments a clear prolongation of the regrowth delay time, i.e. a better therapeutic effect, was achieved in uncooled irradiated tumors. Curative therapy was successful only in uncooled irradiated tumors. For this reason the synergistic influence of laser-induced hyperthermia on the therapeutical result of PDT could be shown on the tumor model used. AU - Gottschalk, W. AU - Hengst, J. AU - Sroka, R.C. AU - Unsoeld, E. C1 - 40721 C2 - 0 SP - 320-326 TI - Influence of the laser-induced temperature rise in photodynamic therapy (PDT). JO - Proc. SPIE VL - 1427 PY - 1991 SN - 0277-786X ER - TY - JOUR AU - Ruth, B. C1 - 19705 C2 - 12837 SP - 131-142 TI - The Reflectance at the Red Edge as a Sensitive Indicator of the Damage of Trees and its Correlation to the State of the Photosynthetic System. JO - Proc. SPIE PY - 1991 SN - 0277-786X ER - TY - JOUR AB - From the reflectance spectra R(λ), the absolute value R710 at 710 nm, the ratios G/R = R560/R660 and IR/R = R760/R660, the position λre of the inflection point at the red edge, and the chromaticity point are derived. The photosynthetic system (PS) is characterized by the fluorescence induction kinetics which provides the parameters Rfd and Vo for the estimate of the potential photosynthetic capacity and the chlorophyll concentration, respectively. Measurements obtained from spruce, birch, oak, and poplar of different damage class and color show correlations between the reflectance- and fluorescence-characteristics. The chromaticity points provide a two-dimensional analysis which may improve the separation between affected and healthy trees. AU - Ruth, B. C1 - 40796 C2 - 0 SP - 131-142 TI - Reflectance at the red edge as a sensitive indicator of the damage of trees and its correlation to the state of the photosynthetic system. JO - Proc. SPIE VL - 1521 PY - 1991 SN - 0277-786X ER - TY - JOUR AB - © 1991 SPIE. All rights reserved. Present techniques and new perspectives of microscopic fluorescence spectroscopy in cellular diagnosis are outlined. Recent applications include the detection of mitochondrial respiratory deficiencies and of the intracellular location and light-induced reactions of photosensitizing porphyrins. AU - Schneckenburger, H. AU - Seidlitz, H.K. AU - Wessels, J.M. AU - Strauß, W.S.L.* AU - Rück, A.C.* C1 - 19648 C2 - 12767 SP - 91-98 TI - Microscopic fluorescence spectroscopy and diagnosis. JO - Proc. SPIE VL - 1525 PY - 1991 SN - 0277-786X ER - TY - JOUR AU - Beyer, W. AU - Baumgartner, R. AU - Ell, C. AU - Heinze, A. AU - Jocham, D. AU - Sroka, R. AU - Stepp, H. AU - Unsöld, E. C1 - 18132 C2 - 10989 SP - 298-303 TI - Uniform Light Distribution in Hollow Organs by Means of Backscattering Layers. JO - Proc. SPIE VL - 1201 PY - 1990 SN - 0277-786X ER - TY - JOUR AB - The uniform distribution of light over the area to be photodynamically treated is one of the prerequisites for a successful tumor therapy. For homogenization of laser light distributions especially in hollow organs a new method has been developed. It applies fiber coupled emitters in combination with a highly backscattering layer deposited on the inner wall of the organ to be irradiated. The effect of homogenization by means of this layer has been calculated for spherical and cylindrical hollow organs and compared with experimental results. This method also seems to be applicable for organs with irregular geometry. Laser light applications for different medical fields will be described. Applying the same method, isotropic light detectors with diameters of less than 1 mm have been developed for irradiation control during photodynamic treatment or for determination of light distributions in tissue. AU - Beyer, W.F. AU - Baumgartner, R. AU - Ell, C.M.D. AU - Heinze, A. AU - Jocham, D. AU - Sroka, R.C. AU - Stepp, H.G. AU - Unsoeld, E. C1 - 42196 C2 - 0 SP - 298-303 TI - Uniform light distribution in hollow organs by means of backscattering layers. JO - Proc. SPIE VL - 1201 PY - 1990 SN - 0277-786X ER - TY - JOUR AU - Heinze, A. AU - Beyer, W. AU - Krug, M. AU - Schaarschmidt, K. AU - Sroka, R. AU - Stepp, H. AU - Unsöld, E. AU - Willital, G.H. C1 - 18131 C2 - 10988 SP - 304 TI - Modified Fiber Tips for Light Application in Hollow Organs. JO - Proc. SPIE VL - 1201 PY - 1990 SN - 0277-786X ER - TY - JOUR AB - Four ways of optimizing laser-assisted treatments in hollow organs are proposed in this paper: 1. For coagulation in axial direction at small irradiation distances fiber tips with enhanced divergence increase the coagulation volume and reduce vaporization. 2. Circumferentially complete coagulation of cylindrical organs can be achieved by using a radially radiating probe. 3. Radiators for photodynamic therapy in cylindrical organs can be constructed and optimized by means of a theoretical scattering model. 4. Isotropic radiators based on conical fiber tips improve the radiation into the rear hemisphere. AU - Heinze, A. AU - Beyer, W.F. AU - Krug, M. AU - Schaarschmidt, K. AU - Sroka, R.C. AU - Stepp, H.G. AU - Unsoeld, E. AU - Willital, G.H. C1 - 41141 C2 - 0 SP - 304-312 TI - Modified fiber tips for light application in hollow organs. JO - Proc. SPIE VL - 1201 PY - 1990 SN - 0277-786X ER - TY - BOOK AU - Ruth, B. A2 - Nielsen, H.O.* C1 - 18838 C2 - 11958 SP - 133-144 TI - A Device for Measuring the Microsecond-Component of the Induction Kinetics of the Chlorophyll- Fluorescence. JO - Proc. SPIE VL - 1269 PB - Washington, D.C. PY - 1990 SN - 0277-786X ER - TY - JOUR AU - Schneckenburger, H. AU - Seidlitz, H.K. AU - Wessels, J. AU - Rück, A. C1 - 19788 C2 - 12939 SP - 646-652 TI - Intracellular Location, Picosecond Kinetics and Light-induced Reactions of Photosensitizing Porphyrins. JO - Proc. SPIE VL - 1403 PY - 1990 SN - 0277-786X ER - TY - JOUR AB - In the medical field of laser light application detector systems are required for measuring the light power applied to the tissue and monitoring instabilities caused by the delivery system during the application of the laser light. An isotropic detector was developed consisting of a fiber tip molded to a sphere and covered with diffuse backscattering layers. The homogeneity of the isotropic detection is 85-90% in an angular field of ±160°C. Additionally a monitoring device has been developed which consists of a darkened chamber holding a part of the fiber bent to a curve. Integrated photodiodes detect the photons 'stepping' out of the fiber. Defects of the fiber, the fiber tip, changes in the medium around the fiber tip, and variations of the laser output have influences on the detector signal. Both devices could be useful in evaluating an exact dosimetry for light. AU - Sroka, R.C. AU - Baumgartner, R. AU - Beyer, W.F. AU - Ell, C.M.D. AU - Gebhard, G. AU - Heinze, A. AU - Jocham, D. AU - Unsoeld, E. C1 - 33819 C2 - 35454 SP - 320-326 TI - Light monitoring by isotropic and by integrated fiber detectors. JO - Proc. SPIE VL - 1201 PY - 1990 SN - 0277-786X ER - TY - JOUR AU - Hutzler, P.J.S. AU - Oosterlinck, A.J. C1 - 18903 C2 - 11266 TI - Image Processing II. Proceedings : ECO1, Hamburg, 19-21 September 1988. JO - Proc. SPIE VL - 1027 PY - 1989 SN - 0277-786X ER - TY - JOUR AB - A measuring system combining subnanosecond laser-induced fluorescence with microscopic signal detection was installed and used for diverse projects in the biomedical and environmental field. These projects range from tumor diagnosis and enzymatic analysis to measurements of the activity of methanogenic bacteria which effect biogas production and waste water cleaning. The advantages of this method and its practical applicability are discussed. AU - Schneckenburger, H. C1 - 42294 C2 - 36217 SP - 363-366 TI - Time-resolved microfluorescence in biomedical diagnosis. JO - Proc. SPIE VL - 491 IS - pt 1 PY - 1985 SN - 0277-786X ER - TY - JOUR AB - Image processing by linear systems has some fascinating aspects due to the theorems of the Fourier transform (FT). Those, whose FT operator is a piece of glass are quite familiar to them, thinking in object space images and FT space images by reason of visual experience. But also in digital image processing the study of FT images is advantageous, e.g. when designing linear filters. The realization of an apodized Laplacian operator is shown, using an image of G-banded chromosomes as test objects. The quality of the filters is tested by the application of a contour-algorithm onto the filtered images. AU - Hutzler, P.J.S. C1 - 57304 C2 - 0 SP - 433-437 TI - Enhancement of cell and chromosome images using optimized filter masks in Fourier transformed space. JO - Proc. SPIE VL - 515 PY - 1984 SN - 0277-786X ER -