TY  - JOUR
AB  - Model-based reconstruction provides state-of-the-art image quality for multispectral optoacoustic tomography. However, optimal regularization of in vivo data necessitates scan-specific adjustments of the regularization strength to compensate for fluctuations of the signal magnitudes between different sinograms. Magnitude fluctuations within in vivo data also pose a challenge for supervised deep learning of a model-based reconstruction operator, as training data must cover the complete range of expected signal magnitudes. In this work, we derive a scale-equivariant model-based reconstruction operator that i) automatically adjusts the regularization strength based on the L2 norm of the input sinogram, and ii) facilitates supervised deep learning of the operator using input singorams with a fixed norm. Scale-equivariant model-based reconstruction applies appropriate regularization to sinograms of arbitrary magnitude, achieves slightly better accuracy in quantifying blood oxygen saturation, and enables more accurate supervised deep learning of the operator.
AU  - Dehner, C.
AU  - Lilaj, L.*
AU  - Ntziachristos, V.
AU  - Zahnd, G.
AU  - Jüstel, D.
C1  - 74792
C2  - 57581
CY  - Hackerbrucke 6, 80335 Munich, Germany
TI  - Scale-equivariant deep model-based optoacoustic image reconstruction.
JO  - Photoacoustics
VL  - 44
PB  - Elsevier Gmbh
PY  - 2025
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Optoacoustic (photoacoustic) mesoscopy bridges the gap between optoacoustic microscopy and macroscopy and enables high-resolution visualization deeper than optical microscopy. Nevertheless, as images may be affected by motion and noise, it is critical to develop methodologies that offer standardization and quality control to ensure that high-quality datasets are reproducibly obtained from patient scans. Such development is particularly important for ensuring reliability in applying machine learning methods or for reliably measuring disease biomarkers. We propose herein a quality control scheme to assess the quality of data collected. A reference scan of a suture phantom is performed to characterize the system noise level before each raster-scan optoacoustic mesoscopy (RSOM) measurement. Using the recorded RSOM data, we develop a method that estimates the amount of motion in the raw data. These motion metrics are employed to classify the quality of raw data collected and derive a quality assessment index (QASIN) for each raw measurement. Using simulations, we propose a selection criterion of images with sufficient QASIN, leading to the compilation of RSOM datasets with consistent quality. Using 160 RSOM measurements from healthy volunteers, we show that RSOM images that were selected using QASIN were of higher quality and fidelity compared to non-selected images. We discuss how this quality control scheme can enable the standardization of RSOM images for clinical and biomedical applications.
AU  - He, H.
AU  - Fischer, C.*
AU  - Darsow, U.*
AU  - Aguirre, J.*
AU  - Ntziachristos, V.
C1  - 69744
C2  - 53864
TI  - Quality control in clinical raster-scan optoacoustic mesoscopy.
JO  - Photoacoustics
VL  - 35
PY  - 2024
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Microcirculatory dysfunction has been observed in the dermal white adipose tissue (dWAT) and subcutaneous white adipose tissue (scWAT) of obese humans and has been proposed as an early prediction marker for cardio-metabolic disease progression. In-vivo visualization and longitudinal monitoring of microvascular remodeling in these tissues remains challenging. We compare the performance of two optoacoustic imaging methods, i.e. multi-spectral optoacoustic tomography (MSOT) and raster-scanning optoacoustic mesoscopy (RSOM) in visualizing lipid and hemoglobin contrast in scWAT and dWAT in a mouse model of diet-induced obesity (DIO) undergoing voluntary wheel running intervention for 32 weeks. MSOT visualized lipid and hemoglobin contrast in murine fat depots in a quantitative manner even at early stages of DIO. We show for the first time to our knowledge that RSOM allows precise visualization of the dWAT microvasculature and provides quantitative readouts of skin layer thickness and vascular density in dWAT and dermis. Combination of MSOT and RSOM resolved exercise-induced morphological changes in microvasculature density, tissue oxygen saturation, lipid and blood volume content in dWAT and scWAT. The combination of MSOT and RSOM may allow precise monitoring of microcirculatory dysfunction and intervention response in dWAT and scWAT in a mouse model for DIO. Our findings have laid out the foundation for future clinical studies using optoacoustic-derived vascular readouts from adipose tissues as a biomarker for monitoring microcirculatory function in metabolic disease.
AU  - Huang, S.
AU  - He, H.
AU  - Tom, R.Z.
AU  - Glasl, S.
AU  - Anzenhofer,P.
AU  - Stiel, A.-C.
AU  - Hofmann, S.M.
AU  - Ntziachristos, V.
C1  - 71065
C2  - 55858
TI  - Non-invasive optoacoustic imaging of dermal microcirculatory revascularization in diet-induced obese mice undergoing exercise intervention.
JO  - Photoacoustics
VL  - 38
PY  - 2024
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Microvascular endothelial dysfunction may provide insights into systemic diseases, such as carotid artery disease. Raster-scan optoacoustic mesoscopy (RSOM) can produce images of skin microvasculature during endothelial dysfunction challenges via numerous microvascular features. Herein, RSOM was employed to image the microvasculature of 26 subjects (13 patients with single carotid artery disease, 13 healthy participants) to assess the dynamics of 18 microvascular features at three scales of detail, i.e., the micro- (<100 μm), meso- (≈100–1000 μm) and macroscale (<1000 μm), during post-occlusive reactive hyperemia challenges. The proposed analysis identified a subgroup of 9 features as the most relevant to carotid artery disease because they achieved the most efficient classification (AUC of 0.93) between the two groups in the first minute of hyperemia (sensitivity/specificity: 0.92/0.85). This approach provides a non-invasive solution to microvasculature quantification in carotid artery disease, a main form of cardiovascular disease, and further highlights the possible link between systemic disease and microvascular dysfunction.
AU  - Karlas, A.
AU  - Katsouli, N.
AU  - Fasoula, N.
AU  - Reidl, M.
AU  - Lees, R.
AU  - Zang, L.*
AU  - Carrillo, M.d.P.O.*
AU  - Saicic, S.*
AU  - Schäffer, C.*
AU  - Hadjileontiadis, L.*
AU  - Branzan, D.*
AU  - Ntziachristos, V.
AU  - Eckstein, H.H.*
AU  - Kallmayer, M.*
C1  - 72390
C2  - 56569
CY  - Hackerbrucke 6, 80335 Munich, Germany
TI  - Multiscale optoacoustic assessment of skin microvascular reactivity in carotid artery disease.
JO  - Photoacoustics
VL  - 40
PB  - Elsevier Gmbh
PY  - 2024
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Hepatic steatosis is characterized by intrahepatic lipid accumulation and may lead to irreversible liver damage if untreated. Here, we investigate whether multispectral optoacoustic tomography (MSOT) can offer label-free detection of liver lipid content to enable non-invasive characterization of hepatic steatosis by analyzing the spectral region around 930 nm, where lipids characteristically absorb. In a pilot study, we apply MSOT to measure liver and surrounding tissues in five patients with liver steatosis and five healthy volunteers, revealing significantly higher absorptions at 930 nm in the patients, while no significant difference was observed in the subcutaneous adipose tissue of the two groups. We further corroborated the human observations with corresponding MSOT measurements in high fat diet (HFD) - and regular chow diet (CD)-fed mice. This study introduces MSOT as a potential non-invasive and portable technique for detecting/monitoring hepatic steatosis in clinical settings, providing justification for larger studies.
AU  - Fasoula, N.-A.
AU  - Karlas, A.
AU  - Prokopchuk, O.*
AU  - Katsouli, N.
AU  - Bariotakis, M.
AU  - Liapis, E.
AU  - Götz, A.
AU  - Kallmayer, M.*
AU  - Reber, J.
AU  - Novotny, A.*
AU  - Friess, H.*
AU  - Ringelhan, M.*
AU  - Schmid, R.*
AU  - Eckstein, H.H.*
AU  - Hofmann, S.M.
AU  - Ntziachristos, V.
C1  - 67407
C2  - 54124
CY  - Hackerbrucke 6, 80335 Munich, Germany
TI  - Non-invasive multispectral optoacoustic tomography resolves intrahepatic lipids in patients with hepatic steatosis.
JO  - Photoacoustics
VL  - 29
PB  - Elsevier Gmbh
PY  - 2023
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Imaging skeletal muscle function and metabolism, as reported by local hemodynamics and oxygen kinetics, can elucidate muscle performance, severity of an underlying disease or outcome of a treatment. Herein, we used multispectral optoacoustic tomography (MSOT) to image hemodynamics and oxygen kinetics within muscle during exercise. Four healthy volunteers underwent three different hand-grip exercise challenges (60s isometric, 120s intermittent isometric and 60s isotonic). During isometric contraction, MSOT showed a decrease of HbO2, Hb and total blood volume (TBV), followed by a prominent increase after the end of contraction. Corresponding hemodynamic behaviors were recorded during the intermittent isometric and isotonic exercises. A more detailed analysis of MSOT readouts revealed insights into arteriovenous oxygen differences and muscle oxygen consumption during all exercise schemes. These results demonstrate an excellent capability of visualizing both circulatory function and oxygen metabolism within skeletal muscle under exercise, with great potential implications for muscle research, including relevant disease diagnostics.
AU  - Karlas, A.
AU  - Fasoula, N.-A.
AU  - Katsouli, N.
AU  - Kallmayer, M.*
AU  - Sieber, S.*
AU  - Schmidt, S.*
AU  - Liapis, E.
AU  - Halle, M.*
AU  - Eckstein, H.H.*
AU  - Ntziachristos, V.
C1  - 67696
C2  - 54003
CY  - Hackerbrucke 6, 80335 Munich, Germany
TI  - Skeletal muscle optoacoustics reveals patterns of circulatory function and oxygen metabolism during exercise.
JO  - Photoacoustics
VL  - 30
PB  - Elsevier Gmbh
PY  - 2023
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Atopic dermatitis (AD) is the most common chronic inflammatory skin disease worldwide. Its severity is assessed using scores that rely on visual observation of the affected body surface area, the morphology of the lesions and subjective symptoms, like pruritus or insomnia. Ideally, such scores should be complemented by objective and accurate measurements of disease severity to standardize disease scoring in routine care and clinical trials. Recently, it was shown that raster-scanning optoacoustic mesoscopy (RSOM) can provide detailed three-dimensional images of skin inflammation processes that capture the most relevant features of their pathology. Moreover, precise RSOM biomarkers of inflammation have been identified for psoriasis. However, the objectivity and validity of such biomarkers in repeated measurements have not yet been assessed for AD. Here, we report the results of a study on the repeatability of RSOM inflammation biomarkers in AD to estimate their precision. Optoacoustic imaging analysis revealed morphological inflammation biomarkers with precision well beyond standard clinical severity metrics. Our findings suggest that optoacoustic mesoscopy may be a good choice for quantitative evaluations of AD that are inaccessible by other methods. This could potentially enable the optimization of disease scoring and drug development.
AU  - Nau, T.
AU  - Schönmann, C.
AU  - Hindelang, B.
AU  - Riobo, L.
AU  - Doll, A.*
AU  - Schneider, S.A.
AU  - Englert, L.
AU  - He, H.
AU  - Biedermann, T.*
AU  - Darsow, U.*
AU  - Lauffer, F.*
AU  - Ntziachristos, V.
AU  - Aguirre Bueno, J.
C1  - 67849
C2  - 54327
CY  - Hackerbrucke 6, 80335 Munich, Germany
TI  - Raster-scanning optoacoustic mesoscopy biomarkers for atopic dermatitis skin lesions.
JO  - Photoacoustics
VL  - 31
PB  - Elsevier Gmbh
PY  - 2023
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Gastrointestinal (GI) endoscopy is a common medical diagnostic procedure used for esophageal cancer detection. Current emerging capsule optoacoustic endoscopes, however, suffer from low pulse repetition rates and slow scanning units limit attainable imaging frame rates. Consequently, motion artifacts result in inaccurate spatial mapping and misinterpretation of data. To overcome these limitations, we report a 360º, 50 Hz frame rate, distal scanning capsule optoacoustic endoscope. The translational capability of the instrument for human GI tract imaging was characterized with an Archimedean spiral phantom consisting of twelve 100 µm sutures, a stainless steel mesh with a pitch of 3 mm and an ex vivo pig esophagus sample. We estimated an imaging penetration depth of ~0.84 mm in vivo by immersing the mesh phantom in intralipid solution to simulate light scattering in human esophageal tissue and validated our findings ex vivo using pig esophagus. This proof-of-concept study demonstrates the translational potential of the proposed video-rate endoscope for human GI tract imaging.
AU  - Ali, Z.
AU  - Zakian Dominguez, C.M.
AU  - Li, Q.*
AU  - Gloriod, J.*
AU  - Crozat, S.*
AU  - Bouvet, F.*
AU  - Pierre, G.*
AU  - Sarantos, V.*
AU  - Di Pietro, M.*
AU  - Flisikowski, K.*
AU  - Andersen, P.M.*
AU  - Drexler, W.*
AU  - Ntziachristos, V.
C1  - 64309
C2  - 52176
CY  - Hackerbrucke 6, 80335 Munich, Germany
TI  - 360º optoacoustic capsule endoscopy at 50 Hz for esophageal imaging.
JO  - Photoacoustics
VL  - 25
PB  - Elsevier Gmbh
PY  - 2022
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Test-samples are necessary for the development of emerging imaging approaches such as optoacoustics (OA); these can be used to benchmark new labeling agents and instrumentation, or to characterize image analysis algorithms or the inversion required to form the three-dimensional reconstructions. Alginate beads (AlBes) loaded with labeled mammalian or bacterial cells provide a method of creating defined structures of controllable size and photophysical characteristics and are well-suited for both in vitro and in vivo use. Here we describe a simple and rapid method for efficient and reproducible production of AlBes with specific characteristics and show three example applications with multispectral OA tomography imaging. We show the advantage of AlBes for studying and eventually improving photo-switching OA imaging approaches. As highly defined, homogeneous, quasi point-like signal sources, AlBes might hold similar advantages for studying other agents, light-fluence models, or the impact of detection geometries on correct image formation in the near future.
AU  - Fuenzalida Werner, J.P.
AU  - Mishra, K.
AU  - Stankevych, M.
AU  - Klemm, U.
AU  - Ntziachristos, V.
AU  - Stiel, A.-C.
C1  - 63977
C2  - 51696
CY  - Hackerbrucke 6, 80335 Munich, Germany
TI  - Alginate beads as a highly versatile test-sample for optoacoustic imaging.
JO  - Photoacoustics
VL  - 25
PB  - Elsevier Gmbh
PY  - 2022
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Background: Since the initial breast transillumination almost a century ago, breast cancer imaging using light has been considered in different implementations aiming to improve diagnostics, minimize the number of available biopsies, or monitor treatment. However, due to strong photon scattering, conventional optical imaging yields low resolution images, challenging quantification and interpretation. Optoacoustic imaging addresses the scattering limitation and yields high-resolution visualization of optical contrast, offering great potential value for breast cancer imaging. Nevertheless, the image quality of experimental systems remains limited due to a number of factors, including signal attenuation with depth and partial view angle and motion effects, particularly in multi-wavelength measurements. Methods: We developed data analytics methods to improve the accuracy of handheld optoacoustic breast cancer imaging, yielding second-generation optoacoustic imaging performance operating in tandem with ultrasonography. Results: We produced the most advanced images yet with handheld optoacoustic examinations of the human breast and breast cancer, in terms of resolution and contrast. Using these advances, we examined optoacoustic markers of malignancy, including vasculature abnormalities, hypoxia, and inflammation, on images obtained from breast cancer patients. Conclusions: We achieved a new level of quality for optoacoustic images from a handheld examination of the human breast, advancing the diagnostic and theranostic potential of the hybrid optoacoustic-ultrasound (OPUS) examination over routine ultrasonography.
AU  - Kukacka, J.
AU  - Metz, S.*
AU  - Dehner, C.
AU  - Muckenhuber, A.*
AU  - Paul-Yuan, K.
AU  - Karlas, A.
AU  - Fallenberg, E.M.*
AU  - Rummeny, E.*
AU  - Jüstel, D.
AU  - Ntziachristos, V.
C1  - 64616
C2  - 52346
SP  - 100343
TI  - Image processing improvements afford second-generation handheld optoacoustic imaging of breast cancer patients.
JO  - Photoacoustics
VL  - 26
PY  - 2022
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Background and aims: Analysis of atherosclerotic plaque composition is a vital tool for unraveling the pathological metabolic processes that contribute to plaque growth. Methods: We visualize the constitution of human carotid plaques by mid-infrared optoacoustic microscopy (MiROM), a method for label-free analytic histology that requires minimal tissue preparation, rapidly yielding large field-of-view en-face images with a resolution of a few micrometers. We imaged endarterectomy specimens (n = 3, 12 sections total) at specific vibrational modes, targeting carbohydrates, lipids and proteins. Additionally, we recorded spectra at selected tissue locations. We identified correlations in the variability in this high-dimensional data set using non-negative matrix factorization (NMF). Results: We visualized high-risk plaque features with molecular assignment. Consistent NMF components relate to different dominant tissue constituents, dominated by lipids, proteins, and cholesterol and carbohydrates respectively. Conclusions: These results introduce MiROM as an innovative, stain-free, analytic histology technology for the biochemical characterization of complex human vascular pathology.
AU  - Visscher, M.*
AU  - Pleitez, M.A.
AU  - Van Gaalen, K.*
AU  - Nieuwenhuizen-Bakker, I.M.*
AU  - Ntziachristos, V.
AU  - Van Soest, G.*
C1  - 64774
C2  - 52447
TI  - Label-free analytic histology of carotid atherosclerosis by mid-infrared optoacoustic microscopy.
JO  - Photoacoustics
VL  - 26
PY  - 2022
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Oral cancer patients undergo diagnostic surgeries to detect occult lymph node metastases missed by preoperative structural imaging techniques. Reducing these invasive procedures that are associated with considerable morbidity, requires better preoperative detection. Multispectral optoacoustic tomography (MSOT) is a rapidly evolving imaging technique that may improve preoperative detection of (early-stage) lymph node metastases, enabling the identification of molecular changes that often precede structural changes in tumorigenesis. Here, we characterize the optoacoustic properties of cetuximab-800CW, a tumor-specific fluorescent tracer showing several photophysical properties that benefit optoacoustic signal generation. In this first clinical proof-of-concept study, we explore its use as optoacoustic to differentiate between malignant and benign lymph nodes. We characterize the appearance of malignant lymph nodes and show differences in the distribution of intrinsic chromophores compared to benign lymph nodes. In addition, we suggest several approaches to improve the efficiency of follow-up studies.
AU  - Vonk, J.*
AU  - Kukacka, J.
AU  - Steinkamp, P.J.*
AU  - de Wit, J.G.*
AU  - Voskuil, F.J.*
AU  - Hooghiemstra, W.T.R.*
AU  - Bader, M.
AU  - Jüstel, D.
AU  - Ntziachristos, V.
AU  - van Dam, G.M.*
AU  - Witjes, M.J.H.*
C1  - 64974
C2  - 52594
TI  - Multispectral optoacoustic tomography for in vivo detection of lymph node metastases in oral cancer patients using an EGFR-targeted contrast agent and intrinsic tissue contrast: A proof-of-concept study.
JO  - Photoacoustics
VL  - 26
PY  - 2022
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Several imaging techniques aim at identifying features of carotid plaque instability but come with limitations, such as the use of contrast agents, long examination times and poor portability. Multispectral optoacoustic tomography (MSOT) employs light and sound to resolve lipid and hemoglobin content, both features associated with plaque instability, in a label-free, fast and highly portable way. Herein, 5 patients with carotid atherosclerosis, 5 healthy volunteers and 2 excised plaques, were scanned with handheld MSOT. Spectral unmixing allowed visualization of lipid and hemoglobin content within three ROIs: whole arterial cross-section, plaque and arterial lumen. Calculation of the fat-blood-ratio (FBR) value within the ROIs enabled the differentiation between patients and healthy volunteers (P = 0.001) and between plaque and lumen in patients (P = 0.04). Our results introduce MSOT as a tool for molecular imaging of human carotid atherosclerosis and open new possibilities for research and clinical assessment of carotid plaques.
AU  - Karlas, A.
AU  - Kallmayer, M.*
AU  - Bariotakis, M.
AU  - Fasoula, N.-A.
AU  - Liapis, E.
AU  - Hyafil, F.*
AU  - Pelisek, J.*
AU  - Wildgruber, M.*
AU  - Eckstein, H.H.*
AU  - Ntziachristos, V.
C1  - 62713
C2  - 50981
CY  - Hackerbrucke 6, 80335 Munich, Germany
TI  - Multispectral optoacoustic tomography of lipid and hemoglobin contrast in human carotid atherosclerosis.
JO  - Photoacoustics
VL  - 23
PB  - Elsevier Gmbh
PY  - 2021
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Contrast enhancement in optoacoustic (photoacoustic) imaging can be achieved with agents that exhibit high absorption cross-sections, high photostability, low quantum yield, low toxicity, and preferential bio-distribution and clearance profiles. Based on advantageous photophysical properties of croconaine dyes, we explored croconaine-based nanoparticles (CR780RGD-NPs) as highly efficient contrast agents for targeted optoacoustic imaging of challenging preclinical tumor targets. Initial characterization of the CR780 dye was followed by modifications using polyethylene glycol and the cancer-targeting c(RGDyC) peptide, resulting in self-assembled ultrasmall particles with long circulation time and active tumor targeting. Preferential bio-distribution was demonstrated in orthotopic mouse brain tumor models by multispectral optoacoustic tomography (MSOT) imaging and histological analysis. Our findings showcase particle accumulation in brain tumors with sustainable strong optoacoustic signals and minimal toxic side effects. This work points to CR780RGD-NPs as a promising optoacoustic contrast agent for potential use in the diagnosis and image-guided resection of brain tumors.
AU  - Liu, N.
AU  - Gujrati, V.
AU  - Malekzadeh-Najafabadi, J.*
AU  - Werner, J.P,F.
AU  - Klemm, U.
AU  - Tang, L.*
AU  - Chen, Z.*
AU  - Prakash, J.
AU  - Huang, Y.
AU  - Stiel, A.-C.
AU  - Mettenleiter, G.
AU  - Aichler, M.
AU  - Blutke, A.
AU  - Walch, A.K.
AU  - Kleigrewe, K.*
AU  - Razansky, D.*
AU  - Sattler, M.
AU  - Ntziachristos, V.
C1  - 61868
C2  - 50488
CY  - Hackerbrucke 6, 80335 Munich, Germany
TI  - Croconaine-based nanoparticles enable efficient optoacoustic imaging of murine brain tumors.
JO  - Photoacoustics
VL  - 22
PB  - Elsevier Gmbh
PY  - 2021
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Multispectral Optoacoustic Tomography (MSOT) resolves oxy- (HbO2) and deoxy-hemoglobin (Hb) to perform vascular imaging. MSOT suffers from gradual signal attenuation with depth due to light-tissue interactions: an effect that hinders the precise manual segmentation of vessels. Furthermore, vascular assessment requires functional tests, which last several minutes and result in recording thousands of images. Here, we introduce a deep learning approach with a sparse-UNET (S-UNET) for automatic vascular segmentation in MSOT images to avoid the rigorous and time-consuming manual segmentation. We evaluated the S-UNET on a test-set of 33 images, achieving a median DICE score of 0.88. Apart from high segmentation performance, our method based its decision on two wavelengths with physical meaning for the task-at-hand: 850 nm (peak absorption of oxy-hemoglobin) and 810 nm (isosbestic point of oxy-and deoxy-hemoglobin). Thus, our approach achieves precise data-driven vascular segmentation for automated vascular assessment and may boost MSOT further towards its clinical translation.
AU  - Chlis, N.-K.
AU  - Karlas, A.
AU  - Fasoula, N.-A.
AU  - Kallmayer, M.*
AU  - Eckstein, H.H.*
AU  - Theis, F.J.
AU  - Ntziachristos, V.
AU  - Marr, C.
C1  - 60477
C2  - 49473
CY  - Hackerbrucke 6, 80335 Munich, Germany
TI  - A sparse deep learning approach for automatic segmentation of human vasculature in multispectral optoacoustic tomography.
JO  - Photoacoustics
VL  - 20
PB  - Elsevier Gmbh
PY  - 2020
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Bone microvasculature plays a paramount role in bone marrow maintenance, development, and hematopoiesis. Studies of calvarian vascular patterns within living mammalian skull with the available intravital microscopy techniques are limited to small scale observations. We developed an optical-resolution optoacoustic microscopy method combined with ultrasound biomicroscopy in order to reveal and discern the intricate networks of calvarian and cerebral vasculature over large fields of view covering majority of the murine calvaria. The vasculature segmentation method is based on an angle-corrected homogeneous model of the rodent skull, generated using simultaneously acquired three-dimensional pulse-echo ultrasound images. The hybrid microscopy design along with the appropriate skull segmentation method enable high throughput studies of a living bone while facilitating correct anatomical interpretation of the vasculature images acquired with optical resolution optoacoustic microscopy.
AU  - Estrada, H.*
AU  - Rebling, J.*
AU  - Hofmann, U.*
AU  - Razansky, D.
C1  - 58690
C2  - 48282
CY  - Hackerbrucke 6, 80335 Munich, Germany
TI  - Discerning calvarian microvascular networks by combined optoacoustic ultrasound microscopy.
JO  - Photoacoustics
VL  - 19
PB  - Elsevier Gmbh
PY  - 2020
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - The Hessian-based Frangi vesselness filter is commonly used to enhance vasculature in optoacoustic (photoacoustic) images, but its accuracy and limitations have never been rigorously assessed. Here we validate the ability of the filter to enhance vessel-like structures in phantoms, and we introduce an experimental approach that uses measurements before and after the administration of gold nanorods (AuNRs) to examine filter performance in vivo. We evaluate the influence of contrast, filter scales, angular tomographic coverage, out-of-plane signals and light fluence on image quality, and gain insight into the performance of the filter. We observe the generation of artifactual structures that can be misinterpreted as vessels and provide recommendations to ensure appropriate use of Frangi and other vesselness filters and avoid misinterpretation of post-processed optoacoustic images.
AU  - Longo, A.
AU  - Morscher, S.*
AU  - Malekzadeh Najafabadi, J.
AU  - Jüstel, D.
AU  - Zakian Dominguez, C.M.
AU  - Ntziachristos, V.
C1  - 59716
C2  - 48980
CY  - Hackerbrucke 6, 80335 Munich, Germany
TI  - Assessment of hessian-based Frangi vesselness filter in optoacoustic imaging.
JO  - Photoacoustics
VL  - 20
PB  - Elsevier Gmbh
PY  - 2020
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - The fidelity and quality of reconstructed images in optoacoustic mesoscopy (OPAM) can be significantly improved by considering the spatial impulse response (SIR) of the employed focused transducer into reconstruction. However, the traditional method fully taking the SIR into account can hardly meet the data-intensive requirements of high resolution OPAM because of excessive memory and time consumption. Herein, a modified back-projection method using a space-variant filter for full-frequency correction of the SIR is presented, and applied to the OPAM system with a sphere-focused transducer. The proposed method can readily manage the large datasets of the OPAM and effectively reduce the extra time consumption. The performance of the proposed method is showcased by simulations and experiments of phantoms and biological tissue. The results demonstrate that the modified back-projection method exhibits better image fidelity, resolution and contrast compared to the common and weighted back-projection methods that are not or not fully accounting for the SIR.
AU  - Lu, T.*
AU  - Wang, Y.*
AU  - Li, J.*
AU  - Prakash, J.*
AU  - Gao, F.*
AU  - Ntziachristos, V.
C1  - 59264
C2  - 48742
CY  - Hackerbrucke 6, 80335 Munich, Germany
TI  - Full-frequency correction of spatial impulse response in back-projection scheme using space-variant filtering for optoacoustic mesoscopy.
JO  - Photoacoustics
VL  - 19
PB  - Elsevier Gmbh
PY  - 2020
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - To date, the vast majority of intra-vital neuroimaging systems applied in clinic and diagnostics is stationary with a rigid scanning element, requires specialized facilities and costly infrastructure. Here, we describe a simple yet radical approach for optoacoustic (photoacoustic) brain imaging in vivo using a light-weight handheld probe. It enables multispectral video-rate visualization of hemoglobin gradient changes in the cortex of adult rats induced by whisker and forelimb sensory inputs, as well as by optogenetic stimulation of intra-cortical connections. With superb penetration and molecular specificity, described here in method holds major promises for future applications in research, routine ambulatory neuroimaging, and diagnostics.
AU  - Ovsepian, S.V.
AU  - Jiang, Y.*
AU  - Sardella, T.C.P.*
AU  - Malekzadeh Najafabadi, J.
AU  - Burton, N.C.*
AU  - Yu, X.*
AU  - Ntziachristos, V.
C1  - 58533
C2  - 48211
CY  - Hackerbrucke 6, 80335 Munich, Germany
TI  - Visualizing cortical response to optogenetic stimulation and sensory inputs using multispectral handheld optoacoustic imaging.
JO  - Photoacoustics
VL  - 17
PB  - Elsevier Gmbh
PY  - 2020
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Using the same ultrasound detector, hybrid optoacoustic-ultrasound (OPUS) imaging provides concurrent scans of tissue slices or volumes and visualizes complementary sound- and light-based contrast at similar resolutions. In addition to the benefit of hybrid contrast, spatial co-registration enables images from one modality to be employed as prior information for improving an aspect of the performance of the other modality. We consider herein a handheld OPUS system and utilize structural information from ultrasound images to guide regional Laplacian regularization-based reconstruction of optoacoustic images. Using phantoms and data from OPUS scans of human radial and carotid arteries, we show that ultrasound-driven optoacoustic inversion reduces limited-view artefacts and improves image contrast. In phantoms, prior-integrated reconstruction leads to a 50 % higher contrast-to-noise ratio (CNR) of the image than standard reconstruction, and a 17 % higher structural similarity (SSIM) index. In clinical data, prior-integrated reconstruction detects deep-seated radial arteries with higher CNR than the standard method at three different depths. In this way, the prior-integrated method offers unique insights into atherosclerotic carotid plaques in humans (with p < 0.01 between patients and healthy volunteers), potentially paving the way for new abilities in vascular imaging and more generally in optoacoustic imaging.
AU  - Yang, H.
AU  - Jüstel, D.
AU  - Prakash, J.*
AU  - Karlas, A.
AU  - Helfen, A.*
AU  - Masthoff, M.*
AU  - Wildgruber, M.*
AU  - Ntziachristos, V.
C1  - 58832
C2  - 48342
CY  - Hackerbrucke 6, 80335 Munich, Germany
TI  - Soft ultrasound priors in optoacoustic reconstruction: Improving clinical vascular imaging.
JO  - Photoacoustics
VL  - 19
PB  - Elsevier Gmbh
PY  - 2020
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Photoacoustic imaging (or optoacoustic imaging) is an upcoming biomedical imaging modality availing the benefits of optical resolution and acoustic depth of penetration. With its capacity to offer structural, functional, molecular and kinetic information making use of either endogenous contrast agents like hemoglobin, lipid, melanin and water or a variety of exogenous contrast agents or both, PAI has demonstrated promising potential in a wide range of preclinical and clinical applications. This review provides an overview of the rapidly expanding clinical applications of photoacoustic imaging including breast imaging, dermatologic imaging, vascular imaging, carotid artery imaging, musculoskeletal imaging, gastrointestinal imaging and adipose tissue imaging and the future directives utilizing different configurations of photoacoustic imaging. Particular emphasis is placed on investigations performed on human or human specimens.
AU  - Attia, A.B.E.*
AU  - Balasundaram, G.*
AU  - Moothanchery, M.*
AU  - Dinish, U.S.*
AU  - Bi, R.*
AU  - Ntziachristos, V.
AU  - Olivo, M.*
C1  - 57623
C2  - 47880
CY  - Hackerbrucke 6, 80335 Munich, Germany
TI  - A review of clinical photoacoustic imaging: Current and future trends.
JO  - Photoacoustics
VL  - 16
PB  - Elsevier Gmbh
PY  - 2019
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Imaging has become an indispensable tool in the research and clinical management of cardiovascular disease (CVD). An array of imaging technologies is considered for CVD diagnostics and therapeutic assessment, ranging from ultrasonography, X-ray computed tomography and magnetic resonance imaging to nuclear and optical imaging methods. Each method has different operational characteristics and assesses different aspects of CVD pathophysiology; nevertheless, more information is desirable for achieving a comprehensive view of the disease. Optoacoustic (photoacoustic) imaging is an emerging modality promising to offer novel information on CVD parameters by allowing high-resolution imaging of optical contrast several centimeters deep inside tissue. Implemented with illumination at several wavelengths, multi-spectral optoacoustic tomography (MSOT) in particular, is sensitive to oxygenated and deoxygenated hemoglobin, water and lipids allowing imaging of the vasculature, tissue oxygen saturation and metabolic or inflammatory parameters. Progress with fast-tuning lasers, parallel detection and advanced image reconstruction and data-processing algorithms have recently transformed optoacoustics from a laboratory tool to a promising modality for small animal and clinical imaging. We review progress with optoacoustic CVD imaging, highlight the research and diagnostic potential and current applications and discuss the advantages, limitations and possibilities for integration into clinical routine.
AU  - Karlas, A.
AU  - Fasoula, N.-A.
AU  - Paul-Yuan, K.
AU  - Reber, J.
AU  - Kallmayer, M.*
AU  - Bozhko, D.
AU  - Seeger, M.
AU  - Eckstein, H.H.*
AU  - Wildgruber, M.*
AU  - Ntziachristos, V.
C1  - 55924
C2  - 46655
CY  - Hackerbrucke 6, 80335 Munich, Germany
SP  - 19-30
TI  - Cardiovascular optoacoustics: From mice to men - A review.
JO  - Photoacoustics
VL  - 14
PB  - Elsevier Gmbh
PY  - 2019
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Nailfold capillaroscopy, based on bright-field microscopy, is widely used to diagnose systemic sclerosis (SSc). However it cannot reveal information about venules and arterioles lying deep under the nailfold, nor can it provide detailed data about surface microvasculature when the skin around the nail is thick. These limitations reflect the fact that capillaroscopy is based on microscopy methods whose penetration depth is restricted to about 200 μm. We investigated whether ultra-wideband raster-scan optoacoustic mesoscopy (UWB-RSOM) can resolve small capillaries of the nailfold in healthy volunteers and compared the optoacoustic data to conventional capillaroscopy examinations. We quantified UWB-RSOM-resolved capillary density and capillary diameter as features that relate to SSc biomarkers, and we obtained the first three-dimensional, images of the deeper arterioles and venules. These results establish the potential of UWB-RSOM for analyzing SSc-relevant markers.
AU  - Aguirre Bueno, J.
AU  - Hindelang, B.*
AU  - Berezhnoi, A.
AU  - Darsow, U.*
AU  - Lauffer, F.*
AU  - Eyerich, K.*
AU  - Biedermann, T.*
AU  - Ntziachristos, V.
C1  - 53273
C2  - 44704
SP  - 31-37
TI  - Assessing nailfold microvascular structure with ultra-wideband raster-scan optoacoustic mesoscopy.
JO  - Photoacoustics
VL  - 10
PY  - 2018
SN  - 2213-5979
ER  - 

TY  - JOUR
AU  - Dean-Ben, X.L.
AU  - Razansky, D.
C1  - 53724
C2  - 44965
SP  - 1-5
TI  - Optoacoustic signal excitation with a tone-burst of short pulses.
JO  - Photoacoustics
VL  - 11
PY  - 2018
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - The Grüneisen parameter is an essential factor in biomedical photoacoustic (PA) diagnostics. In most PA imaging applications, the variation of the Grüneisen parameter with tissue type is insignificant. This is not the case for PA imaging and characterization of lipids, as they have a very distinct Grüneisen parameter compared with other tissue types. One example of PA applications involving lipids is the imaging and characterization of atherosclerotic plaques. Intravascular photoacoustic (IVPA) imaging is a promising diagnostic tool that can evaluate both plaque severity and composition. The literature for IVPA has mainly focused on using the difference in absorption coefficients between plaque components and healthy arterial tissues. However, the Grüneisen parameters for lipids and their behavior with temperature have not been well established in the literature. In this study we employ frequency-domain photoacoustic measurements to estimate the Grüneisen parameter by virtue of the ability of this modality to independently measure the absorption coefficient and the Grüneisen parameter through the use of the phase channel. The values of the Grüneisen parameters of some lipids are calculated as functions of temperature in the range 25-45 °C.
AU  - Liang, S.*
AU  - Lashkari, B.*
AU  - Choi, S.S.S.*
AU  - Ntziachristos, V.
AU  - Mandelis, A.
C1  - 54125
C2  - 45267
SP  - 56-64
TI  - The application of frequency-domain photoacoustics to temperature-dependent measurements of the Grüneisen parameter in lipids.
JO  - Photoacoustics
VL  - 11
PY  - 2018
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Changes in hemodynamic parameters are directly linked to biological function and physiological activity. Characterization of hemodynamics is commonly performed by Doppler ultrasound, which provides accurate measurements of blood flow velocity. Multi-spectral optoacoustic tomography is rapidly undergoing clinical translation fostered by its unique and complementary capacity for label-free mapping of the blood volume and the distribution of oxy- and deoxy-hemoglobin in blood. Here we report on a hybrid optoacoustic and ultrasound imaging approach that enables multi-modal imaging of blood flow and oxygen state using a multi-segment detector array. We further demonstrate rendering of multi-modal pulse-echo ultrasound, multi-spectral optoacoustic tomography, and color Doppler images from carotid artery of a healthy subject.
AU  - Mercep, E.
AU  - Dean-Ben, X.L.
AU  - Razansky, D.
C1  - 53546
C2  - 44619
SP  - 48-53
TI  - Imaging of blood flow and oxygen state with a multi-segment optoacoustic ultrasound array.
JO  - Photoacoustics
VL  - 10
PY  - 2018
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Pulsed laser diodes may offer a smaller, less expensive alternative to conventional optoacoustic laser sources; however they do not provide pulse rates faster than a few tens of kHz and emit at wavelengths only within the near-infrared region. We investigated whether continuous wave (CW) laser diodes, which are available in visible and near-infrared regions, can be good optoacoustic light sources when overdriven with a peak current >40-fold higher than the CW absolute maximum. We found that overdriven CW diodes provided ∼10 ns pulses of ∼200 nJ/pulse and repetition rates higher than 600 kHz without being damaged, outperforming many pulsed laser diodes. Using this system, we obtained images of phantoms and mouse ear and human arm in vivo, confirming their use in optoacoustic imaging and sensing.
AU  - Stylogiannis, A.
AU  - Prade, L.
AU  - Bühler, A.
AU  - Aguirre, J.
AU  - Sergiadis, G.
AU  - Ntziachristos, V.
C1  - 52859
C2  - 44210
SP  - 31-38
TI  - Continuous wave laser diodes enable fast optoacoustic imaging.
JO  - Photoacoustics
VL  - 9
PY  - 2018
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Currently, imaging technologies that enable dermsurgeons to visualize non-melanoma skin cancers (NMSC) in vivo preoperatively are lacking, resulting in excessive or incomplete removal. Multispectral optoacoustic tomography (MSOT) is a volumetric imaging tool to differentiate tissue chromophores and exogenous contrast agents, based on differences in their spectral signatures and used for high-resolution imaging of functional and molecular contrast at centimeter scale depth. We performed MSOT imaging with two- and three-dimensional handheld scanners on 21 Asian patients with NMSC. The tumors and their oxygenation parameters could be distinguished from normal skin endogenously. The lesion dimensions and depths were extracted from the spectral melanin component with three-dimensional spatial resolution up to 80 μm. The intraclass correlation coefficient correlating tumor dimension measurements between MSOT and ex vivo histology of excised tumors, showed good correlation. Real-time 3D imaging was found to provide information on lesion morphology and its underlying neovasculature, indicators of the tumor's aggressiveness.
AU  - Attia, A.B.E.*
AU  - Chuah, S.Y.*
AU  - Razansky, D.
AU  - Ho, C.J.H.*
AU  - Malempati, P.*
AU  - Dinish, U.S.*
AU  - Bi, R.*
AU  - Fu, C.Y.*
AU  - Ford, S.J.*
AU  - Lee, J.S.*
AU  - Tan, M.W.P.*
AU  - Olivo, M.*
AU  - Thng, S.T.G.*
C1  - 51417
C2  - 42998
SP  - 20-26
TI  - Noninvasive real-time characterization of non-melanoma skin cancers with handheld optoacoustic probes.
JO  - Photoacoustics
VL  - 7
PY  - 2017
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - The distribution of intramyocardially injected rabbit MSCs, labeled with the near-infrared dye 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbo-cyanine-iodide (DiR) using hybrid Fluorescence Molecular Tomography-X-ray Computed Tomography (FMT-XCT) and Multispectral Optoacoustic Tomography (MSOT) imaging technologies, was investigated. Viability and induction of apoptosis of DiR labeled MSCs were assessed by XTT- and Caspase-3/-7-testing in vitro. 2 × 106, 2 × 105 and 2 × 104 MSCs labeled with 5 and 10 μg DiR/ml were injected into fresh frozen rabbit hearts. FMT-XCT, MSOT and fluorescence cryosection imaging were performed. Concentrations up to 10 μg DiR/ml did not cause apoptosis in vitro (p > 0.05). FMT and MSOT imaging of labeled MSCs led to a strong signal. The imaging modalities highlighted a difference in cell distribution and concentration correlated to the number of injected cells. Ex-vivo cryosectioning confirmed the molecular fluorescence signal. FMT and MSOT are sensitive imaging techniques offering high-anatomic resolution in terms of detection and distribution of intramyocardially injected stem cells in a rabbit model.
AU  - Berninger, M.T.*
AU  - Mohajerani, P.
AU  - Wildgruber, M.*
AU  - Bézière, N.
AU  - Kimm, M.A.*
AU  - Ma, X.
AU  - Haller, B.*
AU  - Fleming, M.J.*
AU  - Vogt, S.*
AU  - Anton, M.*
AU  - Imhoff, A.B.*
AU  - Ntziachristos, V.
AU  - Meier, R.*
AU  - Henning, T.D.*
C1  - 51170
C2  - 42927
SP  - 37-47
TI  - Detection of intramyocardially injected DiR-labeled mesenchymal stem cells by optical and optoacoustic tomography.
JO  - Photoacoustics
VL  - 6
PY  - 2017
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Optoacoustic imaging is a rapidly expanding field for the diagnosis, characterization, and treatment evaluation of cancer. However, the availability of tumor specific exogenous contrast agents is still limited. Here, we report on a small targeted contrast agent for optoacoustic imaging using a black hole quencher® (BHQ) dye. The sonophore BHQ-1 exhibited strong, concentration-dependent, optoacoustic signals in phantoms, demonstrating its ideal suitability for optoacoustic imaging. After labeling BHQ-1 with cyclic RGD-peptide, BHQ-1-cRGD specifically bound to αvβ3-integrin expressing glioblastoma cell spheroids in vitro. The excellent optoacoustic properties of BHQ-1-cRGD could furthermore be proven in vivo. Together with this emerging imaging modality, our sonophore labeled small peptide probe offers new possibilities for non-invasive detection of molecular structures with high resolution in vivo and furthers the specificity of optoacoustic imaging. Ultimately, the discovery of tailor-made sonophores might offer new avenues for various molecular optoacoustic imaging applications, similar to what we see with fluorescence imaging.
AU  - Haedicke, K.*
AU  - Brand, C.*
AU  - Omar, M.
AU  - Ntziachristos, V.
AU  - Reiner, T.*
AU  - Grimm, J.*
C1  - 50895
C2  - 42552
SP  - 1-8
TI  - Sonophore labeled RGD: A targeted contrast agent for optoacoustic imaging.
JO  - Photoacoustics
VL  - 6
PY  - 2017
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Similar to pulse-echo ultrasound, optoacoustic imaging encodes the location of optical absorbers by the time-of-flight of ultrasound waves. Yet, signal generation mechanisms are fundamentally different for the two modalities, leading to significant distinction between the optimum image formation strategies. While interference of back-scattered ultrasound waves with random phases causes speckle noise in ultrasound images, speckle formation is hindered by the strong correlation between the optoacoustic responses corresponding to individual sources. However, visibility of structures is severely hampered when attempting to acquire optoacoustic images under limited-view tomographic geometries. In this tutorial article, we systematically describe the basic principles of optoacoustic signal generation and image formation for objects ranging from individual sub-resolution absorbers to a continuous absorption distribution. The results are of relevance for the proper interpretation of optoacoustic images acquired under limited-view scenarios and may also serve as a basis for optimal design of tomographic acquisition geometries and image formation strategies.
AU  - Dean-Ben, X.L.
AU  - Razansky, D.
C1  - 50052
C2  - 41994
SP  - 133-140
TI  - On the link between the speckle free nature of optoacoustics and visibility of structures in limited-view tomography.
JO  - Photoacoustics
VL  - 4
IS  - 4
PY  - 2016
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - We interrogated the application and imaging features obtained by non-invasive and handheld optoacoustic imaging of the thyroid in-vivo. Optoacoustics can offer complementary contrast to ultrasound, by resolving optical absorption-based and offering speckle-free imaging. In particular we inquired whether vascular structures could be better resolved using optoacoustics. For this reason we developed a compact handheld version of real-time multispectral optoacoustic tomography (MSOT) using a detector adapted to the dimensions and overall geometry of the human neck. For delivering high-fidelity performance, a curved ultrasound array was employed. The feasibility of handheld thyroid MSOT was assessed on healthy human volunteers at single wavelength. The results were contrasted to ultrasound and Doppler ultrasound images obtained from the same volunteers. Imaging findings demonstrate the overall MSOT utility to accurately retrieve optical features consistent with the thyroid anatomy and the morphology of surrounding structures.
AU  - Dima, A.
AU  - Ntziachristos, V.
C1  - 49801
C2  - 40942
SP  - 65-69
TI  - In-vivo handheld optoacoustic tomography of the human thyroid.
JO  - Photoacoustics
VL  - 4
IS  - 2
PY  - 2016
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - A handheld approach to optoacoustic imaging is essential for the clinical translation. The first 2- and 3-dimensional handheld multispectral optoacoustic tomography (MSOT) probes featuring real-time unmixing have recently been developed. Imaging performance of both probes was determined in vitro and in a brain melanoma metastasis mouse model in vivo. T1-weighted MR images were acquired for anatomical reference. The limit of detection of melanoma cells in vitro was significantly lower using the 2D than the 3D probe. The signal decrease was more profound in relation to depth with the 3D versus the 2D probe. Both approaches were capable of imaging the melanoma tumors qualitatively at all time points. Quantitatively, the 2D approach enabled closer anatomical resemblance of the tumor compared to the 3D probe, particularly at depths beyond 3 mm. The 3D probe was shown to be superior for rapid 3D imaging and, thus, holds promise for more superficial target structures.
AU  - Neuschmelting, V.*
AU  - Burton, N.C.*
AU  - Lockau, H.*
AU  - Urich, A.*
AU  - Harmsen, S.*
AU  - Ntziachristos, V.
AU  - Kircher, M.F.*
C1  - 47673
C2  - 39457
SP  - 1-10
TI  - Performance of a Multispectral Optoacoustic Tomography (MSOT) system equipped with 2D vs. 3D handheld probes for potential clinical translation.
JO  - Photoacoustics
VL  - 4
IS  - 1
PY  - 2016
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Carotid artery atherosclerosis is a main cause of stroke. Understanding atherosclerosis biology is critical in the development of targeted prevention and treatment strategies. Consequently, there is demand for advanced tools investigating atheroma pathology. We consider hybrid optoacoustic and multiphoton microscopy for the integrated and complementary interrogation of plaque tissue constituents and their mutual interactions. Herein, we visualize human carotid plaque using a hybrid multimodal imaging system that combines optical resolution optoacoustic (photoacoustic) microscopy, second and third harmonic generation microscopy, and two-photon excitation fluorescence microscopy. Our data suggest more comprehensive insights in the pathophysiology of atheroma formation and destabilization, by enabling congruent visualization of structural and biological features critical for the atherosclerotic process and its acute complications, such as red blood cells and collagen.
AU  - Seeger, M.
AU  - Karlas, A.
AU  - Soliman, D.
AU  - Pelisek, J.*
AU  - Ntziachristos, V.
C1  - 49299
C2  - 41806
SP  - 102-111
TI  - Multimodal optoacoustic and multiphoton microscopy of human carotid atheroma.
JO  - Photoacoustics
VL  - 4
IS  - 3
PY  - 2016
SN  - 2213-5979
ER  - 

TY  - JOUR
AU  - Zhang, H.F.*
AU  - Razansky, D.
C1  - 49797
C2  - 40941
SP  - 81-82
TI  - Special issue introduction: Photoacoustic microscopy.
JO  - Photoacoustics
VL  - 4
IS  - 3
PY  - 2016
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Efficient segmentation of optoacoustic images has importance in enhancing the diagnostic and quantification capacity of this modality. It may also aid in improving the tomographic reconstruction accuracy by accounting for heterogeneous optical and acoustic tissue properties. In particular, when imaging through complex biological tissues, the real acoustic properties often deviate considerably from the idealized assumptions of homogenous conditions, which may lead to significant image artifacts if not properly accounted for. Although several methods have been proposed aiming at estimating and accounting for the complex acoustic properties in the image domain, accurate delineation of structures is often hindered by low contrast of the images and other artifacts produced due to incomplete tomographic coverage and heuristic assignment of the tissue properties during the reconstruction process. In this letter, we propose instead a signal domain analysis approach that retrieves acoustic properties of the object to be reconstructed from characteristic features of the detected optoacoustic signals prior to image reconstruction. Performance of the proposed method is first tested in simulation and experiment using two-dimensional tissue-mimicking phantoms. Significant improvements in the segmentation abilities and overall reconstructed image quality are further showcased in experimental cross-sectional data acquired from a human finger.
AU  - Lutzweiler, C.
AU  - Meier, R.*
AU  - Razansky, D.
C1  - 47529
C2  - 40645
SP  - 151-158
TI  - Optoacoustic image segmentation based on signal domain analysis.
JO  - Photoacoustics
VL  - 3
IS  - 4
PY  - 2015
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - In tomographic optoacoustic imaging, multiple parameters related to both light and ultrasound propagation characteristics of the medium need to be adequately selected in order to accurately recover maps of local optical absorbance. Speed of sound in the imaged object and surrounding medium is a key parameter conventionally assumed to be uniform. Mismatch between the actual and predicted speed of sound values may lead to image distortions but can be mitigated by manual or automatic optimization based on metrics of image sharpness. Although some simple approaches based on metrics of image sharpness may readily mitigate distortions in the presence of highly contrasting and sharp image features, they may not provide an adequate performance for smooth signal variations as commonly present in realistic whole-body optoacoustic images from small animals. Thus, three new hybrid methods are suggested in this work, which are shown to outperform well-established autofocusing algorithms in mouse experiments in vivo.
AU  - Mandal, S.
AU  - Nasonova, E.*
AU  - Dean-Ben, X.L.
AU  - Razansky, D.
C1  - 32588
C2  - 35181
SP  - 128-136
TI  - Optimal self-calibration of tomographic reconstruction parameters in whole-body small animal optoacoustic imaging.
JO  - Photoacoustics
VL  - 2
IS  - 3
PY  - 2014
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - We introduce optoacoustic tomographic imaging using intensity modulated light sources and collecting amplitude and phase information in the frequency domain. Imaging is performed at multiple modulation frequencies. The forward modeling uses the Green's function solution to the pressure wave equation in frequency domain and the resulting inverse problem is solved using regularized least squares minimization. We study the effect of the number of frequencies and of the bandwidth employed on the image quality achieved. The possibility of employing an all-frequency domain optoacoustic imaging for experimental measurements is studied as a function of noise. We conclude that frequency domain optoacoustic tomography may evolve to a practical experimental method using light intensity modulated sources, with advantages over time-domain optoacoustics.
AU  - Mohajerani, P.
AU  - Kellnberger, S.
AU  - Ntziachristos, V.
C1  - 31961
C2  - 34910
SP  - 111-118
TI  - Frequency domain optoacoustic tomography using amplitude and phase.
JO  - Photoacoustics
VL  - 2
IS  - 3
PY  - 2014
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Optoacoustic imaging provides a unique combination of high optical contrast and excellent spatial resolution, making it ideal for simultaneous imaging of tissue anatomy as well as functional and molecular contrast in deep optically opaque tissues. We report on development of a portable clinical system for three-dimensional optoacoustic visualization of deep human tissues at video rate. Studies in human volunteers have demonstrated powerful performance in delivering high resolution volumetric multispectral optoacoustic tomography (vMSOT) images of tissue morphology and function, such as blood oxygenation parameters, in real time. Whilst most imaging modalities currently in clinical use are not able to deliver volumetric data with comparable time resolution, the presented imaging approach holds promise to attain new diagnostic and treatment monitoring value for multiple indications, such as cardiovascular and peripheral vascular disease, disorders related to the lymphatic system, breast lesions, arthritis and inflammation.
AU  - Dean-Ben, X.L.
AU  - Razansky, D.
C1  - 28568
C2  - 33458
SP  - 68-73
TI  - Functional optoacoustic human angiography with handheld video rate three dimensional scanner.
JO  - Photoacoustics
VL  - 1
IS  - 3-4
PB  - Elsevier
PY  - 2013
SN  - 2213-5979
ER  - 

TY  - JOUR
AU  - Ntziachristos, V.
C1  - 32604
C2  - 35169
SP  - 1-2
TI  - Editorial.
JO  - Photoacoustics
VL  - 1
PY  - 2013
SN  - 2213-5979
ER  - 

TY  - JOUR
AB  - Objectives To investigate the feasibility of a high resolution optical imaging strategy for myocardial infarction. Background Near-infrared approaches to imaging cardiovascular disease enable visualization of disease-associated biological processes in vivo. However, even at the scale of small animals, the strong scattering of light prevents high resolution imaging after the first 1–2 mm of tissue, leading to degraded signal localization. Methods Multispectral optoacoustic tomography (MSOT) was used to non-invasively image myocardial infarction (MI) in a murine model of coronary artery ligation at resolutions not possible with current deep-tissue optical imaging methods. Post-MI imaging was based on resolving the spectral absorption signature of a dendritic polyglycerol sulfate-based (dPGS) near-infrared imaging agent targeted to P- and L-selectin. Results In vivo imaging succeeded in detection of the agent in the injured myocardium after intravenous injection. The high anatomic resolution (<200 μm) achieved by the described method allowed signals originating in the infarcted heart to be distinguished from uptake in adjacent regions. Histological analysis found dPGS signal in infarcted areas, originating from leukocytes and endothelial cells. Conclusions MSOT imaging of myocardial infarction provides non-invasive visualization of optical contrast with a high spatial resolution that is not degraded by the scattering of light.
AU  - Taruttis, A.
AU  - Wildgruber, M.*
AU  - Kosanke, K.*
AU  - Bézière, N.
AU  - Licha, K.*
AU  - Haag, R.*
AU  - Aichler, M.
AU  - Walch, A.K.
AU  - Rummeny, E.*
AU  - Ntziachristos, V.
C1  - 24400
C2  - 31541
SP  - 3-8
TI  - Multispectral optoacoustic tomography of myocardial infarction.
JO  - Photoacoustics
VL  - 1
IS  - 1
PB  - Elsevier
PY  - 2013
SN  - 2213-5979
ER  -