TY  - JOUR
AB  - The total diffuse reflectance RT and the effective attenuation coefficient µeff of an optically diffuse medium map uniquely onto its absorption and reduced scattering coefficients. Using this premise, we developed a methodology where RT and the slope of the logarithmic spatially resolved reflectance, a quantity related to µeff, are the inputs of a look-up table to correct the dependence of fluorescent signals on the media's optical properties. This methodology does not require an estimation of the medium's optical property, avoiding elaborate simulations and their errors to offer accurate and fast corrections. The experimental demonstration of our method yielded a mean relative error in fluorophore concentrations of less than 4% over a wide range of optical property variations. We discuss how the method developed can be employed to improve image fidelity and fluorochrome quantification in fluorescence molecular imaging clinical applications.
AU  - Arias, A.
AU  - Anastasopoulou, M.
AU  - Gorpas, D.
AU  - Ntziachristos, V.
C1  - 68719
C2  - 54928
CY  - 2010 Massachusetts Ave Nw, Washington, Dc 20036 Usa
SP  - 5499-5511
TI  - Using reflectometry to minimize the dependence of fluorescence intensity on optical absorption and scattering.
JO  - Biomed. Opt. Express
VL  - 14
IS  - 10
PB  - Optica Publishing Group
PY  - 2023
SN  - 2156-7085
ER  - 

TY  - JOUR
AB  - Cerebrovascular imaging of rodents is one of the trending applications 
      of optoacoustics aimed at studying brain activity and pathology. Imaging
       of deep brain structures is often hindered by sub-optimal arrangement 
      of the light delivery and acoustic detection systems. In our work we 
      revisit the physics behind opto-acoustic signal generation for 
      theoretical evaluation of optimal laser wavelengths to perform 
      cerebrovascular optoacoustic angiography of rodents beyond the 
      penetration barriers imposed by light diffusion in highly scattering and
       absorbing brain tissues. A comprehensive model based on diffusion 
      approximation was developed to simulate optoacoustic signal generation 
      using optical and acoustic parameters closely mimicking a typical murine
       brain. The model revealed three characteristic wavelength ranges in the
       visible and near-infrared spectra optimally suited for imaging cerebral
       vasculature of different size and depth. The theoretical conclusions 
      are confirmed by numerical simulations while in vivo imaging experiments
       further validated the ability to accurately resolve brain vasculature 
      at depths ranging between 0.7 and 7 mm.
AU  - Subochev, P.*
AU  - Smolina, E.*
AU  - Sergeeva, E.*
AU  - Kirillin, M.*
AU  - Orlova, A.*
AU  - Kurakina, D.*
AU  - Emyanov, D.*
AU  - Razansky, D.
C1  - 58509
C2  - 48119
SP  - 1477-1488
TI  - Toward whole-brain in vivo optoacoustic angiography of rodents: Modeling and experimental observations
JO  - Biomed. Opt. Express
VL  - 11
IS  - 3
PY  - 2020
SN  - 2156-7085
ER  - 

TY  - JOUR
AB  - Intravenously administered liposomes and other nano-sized particles are known to passively accumulate in solid tumors via the enhanced permeability and retention (EPR) effect, which is extensively explored toward the improvement of diagnosis and drug delivery in oncology. Agent extravasation into tumors is often hampered by the mononuclear phagocytic and renal systems, which sequester and/or eliminate most of the nanoparticles from the body. Dynamic imaging of the tumor microcirculation and bolus perfusion can thus facilitate optimization of the nanoparticle delivery. When it comes to non-invasive visualization of rapid biological dynamics in whole tumors, the currently available preclinical imaging modalities are commonly limited by shallow penetration, lack of suitable contrast or otherwise insufficient spatial or temporal resolution. Herein, we demonstrate the unique capabilities of a combined epi-fluorescence and optoacoustic tomography (FLOT) system for characterizing contrast agent dynamics in orthotopic breast tumors in mice. A liposomal indocyanine green (Lipo-ICG) preparation was administered intravenously with the time-lapse data continuously acquired during and after the injection procedure. In addition to the highly sensitive detection of the fluorescence agent by the epi-fluorescence modality, the volumetric multi-spectral optoacoustic tomography readings further enabled resolving deep-seated vascular structures with high spatial resolution and hence provided accurate readings of the dynamic bio-distribution of nanoparticles in the entire tumor in 3D. The synergetic combination of the two modalities can become a powerful tool in cancer research and potentially aid the diagnosis, staging and treatment guidance of certain types of cancer in the clinical setting.
AU  - Chen, Z.
AU  - Dean-Ben, X.L.
AU  - Liu, N.
AU  - Gujrati, V.
AU  - Gottschalk, S.
AU  - Ntziachristos, V.
AU  - Razansky, D.
C1  - 57132
C2  - 47565
CY  - 2010 Massachusetts Ave Nw, Washington, Dc 20036 Usa
SP  - 5093-5102
TI  - Concurrent fluorescence and volumetric optoacoustic tomography of nanoagent perfusion and bio-distribution in solid tumors.
JO  - Biomed. Opt. Express
VL  - 10
IS  - 10
PB  - Optical Soc Amer
PY  - 2019
SN  - 2156-7085
ER  - 

TY  - JOUR
AB  - A new type of bimodal contrast agent was made that is based on the self-quenching of indocyanine green (ICG) encapsulated in a biocompatible and biodegradable polymer shell. The increasing of a local ICG concentration that is necessary for the obtaining of self-quenching effect was achieved by freezing-induced loading and layer-by-layer assembly. As a result, an efficient photoacoustic(optoacoustic)/fluorescent contrast agent based on composite indocyanine green/polymer particles was successfully prepared and was characterized by fluorescence and photoacoustic(optoacoustic) tomography in vitro. This type of contrast agent holds good promise for clinical application owing to its high efficiency and biosafety.
AU  - Mokrousov, M.D.*
AU  - Novoselova, M.*
AU  - Nolan, J.*
AU  - Harrington, W.*
AU  - Rudakovskaya, P.*
AU  - Bratashov, D.N.*
AU  - Galanzha, E.*
AU  - Fuenzalida Werner, J.P.
AU  - Yakimov, B.P.*
AU  - Nazarikov, G.*
AU  - Drachev, V.P.*
AU  - Shirshin, E.A.*
AU  - Ntziachristos, V.
AU  - Stiel, A.-C.
AU  - Zharov, V.P.*
AU  - Gorin, D.A.*
C1  - 56926
C2  - 47336
CY  - 2010 Massachusetts Ave Nw, Washington, Dc 20036 Usa
SP  - 4775-4788
TI  - Amplification of photoacoustic effect in bimodal polymer particles by self-quenching of indocyanine green.
JO  - Biomed. Opt. Express
VL  - 10
IS  - 9
PB  - Optical Soc Amer
PY  - 2019
SN  - 2156-7085
ER  - 

TY  - JOUR
AB  - Fluorescent contrast agents are widely employed in biomedical research. While many studies have reported deep tissue imaging of fluorescent moieties using either fluorescence-based or absorption-based (optoacoustic) imaging systems, no systematic comparison has been performed regarding the actual performance of these imaging modalities in detecting deep-seated fluorescent agents. Herein, an integrated imager combining epifluorescence and volumetric optoacoustic imaging capabilities has been employed in order to evaluate image degradation with depth for several commonly-used near-infrared dyes in both modes. We performed controlled experiments in tissue-mimicking phantoms containing deeply embedded targets filled with different concentrations of Alexa Fluor 700, Alexa Fluor 750, indocyanine green (ICG) and IRDye 800CW. The results are further corroborated by multi-modal imaging of ICG through mouse tissues in vivo. It is shown that optoacoustics consistently provides better sensitivity in differentiating fluorescent targets located at depths beyond 2 mm in turbid tissues, as quantified by evaluating image contrast, signal to noise ratio and spatial resolution performance.
AU  - Chen, Z.
AU  - Dean-Ben, X.L.
AU  - Gottschalk, S.
AU  - Razansky, D.
C1  - 53493
C2  - 44596
SP  - 2229-2239
TI  - Performance of optoacoustic and fluorescence imaging in detecting deepseated fluorescent agents.
JO  - Biomed. Opt. Express
VL  - 9
IS  - 5
PY  - 2018
SN  - 2156-7085
ER  - 

TY  - JOUR
AB  - The guest editors introduce a feature issue containing papers based on research presented at the OSA Biophotonics Congress (the former BIOMED) held in Hollywood, FL, 2-6 April, 2018.
AU  - Razansky, D.
AU  - Smith, S.L.*
AU  - Giacomelli, M.*
AU  - Hendon, C.P.*
AU  - Sroka, R.*
C1  - 54963
C2  - 45997
CY  - 2010 Massachusetts Ave Nw, Washington, Dc 20036 Usa
SP  - 6398-6399
TI  - Introduction to the Biophotonics Congress 2018 feature issue.
JO  - Biomed. Opt. Express
VL  - 9
IS  - 12
PB  - Optical Soc Amer
PY  - 2018
SN  - 2156-7085
ER  - 

TY  - JOUR
AB  - Label-free multispectral optoacoustic tomography (MSOT) has recently shown superior performance in visualizing the morphology of human vasculature, especially of smaller vessels, compared to ultrasonography. Herein, we extend these observations towards MSOT interrogation of macrovascular endothelial function. We employed a real-time handheld MSOT scanner to assess flow-mediated dilatation (FMD), a technique used to characterize endothelial function. A data processing scheme was developed to quantify the dimensions and diameter changes of arteries in humans and determine wall distensibility parameters. By enabling high-resolution delineation of the blood-vessel wall in a cross-sectional fashion, the findings suggest MSOT as a capable alternative to ultrasonography for clinical FMD measurements.
AU  - Karlas, A.
AU  - Reber, J.
AU  - Diot, G.*
AU  - Bozhko, D.
AU  - Anastasopoulou, M.
AU  - Ibrahim, T.*
AU  - Schwaiger, M.*
AU  - Hyafil, F.*
AU  - Ntziachristos, V.
C1  - 51549
C2  - 43214
CY  - Washington
SP  - 3395-3403
TI  - Flow-mediated dilatation test using optoacoustic imaging: A proof-of-concept.
JO  - Biomed. Opt. Express
VL  - 8
IS  - 7
PB  - Optical Soc Amer
PY  - 2017
SN  - 2156-7085
ER  - 

TY  - JOUR
AB  - There is a need for contrast agents for non-invasive diagnostic imaging of tumors. Herein, Multispectral Optoacoustic Tomography (MSOT) was employed to evaluate phthalocyanines commonly used in photodynamic therapy as photoacoustic contrast agents. We studied the photoacoustic activity of three water-soluble phthalocyanine photosensitizers: phthalocyanine tetrasulfonic acid (PcS4), Zn(II) phthalocyanine tetrasulfonic acid (ZnPcS4) and Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) in phantom and in tumor-bearing mice to investigate the biodistribution and fate of the phthalocyanines in the biological tissues. PcS4 was observed to grant good contrast between the different reticuloendothelial organs and accumulate in the tumor within an hour of post-administration. ZnPcS4 and AlPcS4 offered little contrast in photoacoustic signals between the organs. PcS4 is a promising photoacoustic contrast agent and can be exploited as a photodiagnostic agent.
AU  - Attia, A.B.E.*
AU  - Balasundaram, G.*
AU  - Driessen, W.H.P.
AU  - Ntziachristos, V.
AU  - Olivo, M.*
C1  - 43798
C2  - 36663
CY  - Washington
SP  - 591-598
TI  - Phthalocyanine photosensitizers as contrast agents for in vivo photoacoustic tumor imaging.
JO  - Biomed. Opt. Express
VL  - 6
IS  - 2
PB  - Optical Soc Amer
PY  - 2015
SN  - 2156-7085
ER  - 

TY  - JOUR
AB  - Optical mesoscopy extends the capabilities of biological visualization beyond the limited penetration depth achieved by microscopy. However, imaging of opaque organisms or tissues larger than a few hundred micrometers requires invasive tissue sectioning or chemical treatment of the specimen for clearing photon scattering, an invasive process that is regardless limited with depth. We developed previously unreported broadband optoacoustic mesoscopy as a tomographic modality to enable imaging of optical contrast through several millimeters of tissue, without the need for chemical treatment of tissues. We show that the unique combination of three-dimensional projections over a broad 500 kHz-40 MHz frequency range combined with multi-wavelength illumination is necessary to render broadband multispectral optoacoustic mesoscopy (2B-MSOM) superior to previous optical or optoacoustic mesoscopy implementations.
AU  - Chekkoury, A.
AU  - Gateau, J.
AU  - Driessen, W.H.P.
AU  - Symvoulidis, P.
AU  - Bézière, N.
AU  - Feuchtinger, A.
AU  - Walch, A.K.
AU  - Ntziachristos, V.
C1  - 46899
C2  - 39021
SP  - 3134-3148
TI  - Optical mesoscopy without the scatter: Broadband multispectral optoacoustic mesoscopy.
JO  - Biomed. Opt. Express
VL  - 6
IS  - 9
PY  - 2015
SN  - 2156-7085
ER  - 

TY  - JOUR
AB  - Oxidative-based diseases including diabetes, chronic renal failure, cardiovascular diseases and neurological disorders are accompanied by accumulation of advanced glycation endproducts (AGE). Therefore, AGE-associated changes in tissue optical properties could yield a viable pathological indicator for disease diagnostics and monitoring. We investigated whether skin glycation could be detected based on absorption changes associated with AGE accumulation using spectral optoacoustic measurements and interrogated the optimal spectral band for skin glycation determination. Glycated and non-glycated skin was optoacoustically measured at multiple wavelengths in the visible region. The detected signals were spectrally processed and compared to measurements of skin autofluorescence and to second harmonic generation multiphoton microscopy images. Optoacoustic measurements are shown to be capable of detecting skin glycolysis based on AGE detection. A linear dependence was observed between optoacoustic intensity and the progression of skin glycation. The findings where corroborated by autofluorescence observations. Detection sensitivity is enhanced by observing normalised tissue spectra. This result points to a ratiometric method for skin glycation detection, specifically at 540 nm and 620 nm. We demonstrate that optoacoustic spectroscopy could be employed to detect AGE accumulation, and possibly can be employed as a non-invasive quick method for monitoring tissue glycation.
AU  - Ghazaryan, A.*
AU  - Omar, M.*
AU  - Tserevelakis, G.J.*
AU  - Ntziachristos, V.
C1  - 46901
C2  - 39020
SP  - 3149-3156
TI  - Optoacoustic detection of tissue glycation.
JO  - Biomed. Opt. Express
VL  - 6
IS  - 9
PY  - 2015
SN  - 2156-7085
ER  - 

TY  - JOUR
AB  - White-light surveillance colonoscopy is the standard of care for the detection and removal of premalignant lesions to prevent colorectal cancer, and the main screening recommendation following treatment for recurrence detection. However, it lacks sufficient diagnostic yield, exhibits unacceptable adenoma miss-rates and is not capable of revealing functional and morphological information of the detected lesions. Fluorescence molecular guidance in the near-infrared (NIR) is expected to have outstanding relevance regarding early lesion detection and heterogeneity characterization within and among lesions in these interventional procedures. Thereby, superficial and sub-surface tissue biomarkers can be optimally visualized due to a minimization of tissue attenuation and autofluorescence by comparison with the visible, which simultaneously enhance tissue penetration and assure minimal background. At present, this potential is challenged by the difficulty associated with the clinical propagation of disease-specific contrast agents and the absence of a commercially available endoscope that is capable of acquiring wide-field, NIR fluorescence at video-rates. We propose two alternative flexible endoscopic fluorescence imaging methods, each based on a CE certified commercial, clinical grade endoscope, and the employment of an approved monoclonal antibody labeled with a clinically applicable NIR fluorophore. Pre-clinical validation of these two strategies that aim at bridging NIR fluorescence molecular guidance to clinical translation is demonstrated in this study.
AU  - Garcia-Allende, P.
AU  - Glatz, J.
AU  - Koch, M.
AU  - Tjalma, J.J.*
AU  - Hartmans, E.*
AU  - Terwisscha van Scheltinga, A.G.*
AU  - Symvoulidis, P.
AU  - van Dam, G.M.*
AU  - Nagengast, W.B.*
AU  - Ntziachristos, V.
C1  - 29239
C2  - 32200
SP  - 78-92
TI  - Towards clinically translatable NIR fluorescence molecular guidance for colonoscopy.
JO  - Biomed. Opt. Express
VL  - 5
IS  - 1
PB  - Optical Soc. Amer.
PY  - 2014
SN  - 2156-7085
ER  - 

TY  - JOUR
AB  - Breast tumors are blindly identified using Principal (PCA) and Independent Component Analysis (ICA) of localized reflectance measurements. No assumption of a particular theoretical model for the reflectance needs to be made, while the resulting features are proven to have discriminative power of breast pathologies. Normal, benign and malignant breast tissue types in lumpectomy specimens were imaged ex vivo and a surgeon-guided calibration of the system is proposed to overcome the limitations of the blind analysis. A simple, fast and linear classifier has been proposed where no training information is required for the diagnosis. A set of 29 breast tissue specimens have been diagnosed with a sensitivity of 96% and specificity of 95% when discriminating benign from malignant pathologies. The proposed hybrid combination PCA-ICA enhanced diagnostic discrimination, providing tumor probability maps, and intermediate PCA parameters reflected tissue optical properties.
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  - 24969
C2  - 31742
SP  - 1104-1118
TI  - Direct identification of breast cancer pathologies using blind separation of label-free localized reflectance measurements.
JO  - Biomed. Opt. Express
VL  - 4
IS  - 7
PB  - Optical Soc. Amer.
PY  - 2013
SN  - 2156-7085
ER  - 

TY  - JOUR
AB  - The hybrid nature of optoacoustic imaging might impose limitations on concurrent placement of optical and ultrasonic detection components, especially in high resolution microscopic applications that require dense arrangements and miniaturization of components. This hinders optimal deployment of the optical excitation and ultrasonic detection paths, leading to reduction of imaging speed and spatial resolution performance. We suggest a compact coaxial design for optoacoustic microscopy that allows optimizing both the light illumination and ultrasonic detection parameters of the imaging system. System performance is showcased in phantoms and in vivo imaging of microvasculature, achieving real time operation in two dimensions and penetration of 6 mm into optically dense human tissues.
AU  - Ma, R.
AU  - Söntges, S.
AU  - Shoham, S.
AU  - Ntziachristos, V.
AU  - Razansky, D.
C1  - 8235
C2  - 30033
SP  - 1724-1731
TI  - Fast scanning coaxial optoacoustic microscopy.
JO  - Biomed. Opt. Express
VL  - 3
IS  - 7
PB  - Optical Soc. Amer.
PY  - 2012
SN  - 2156-7085
ER  - 

TY  - JOUR
AB  - We have developed a spectral inversion method for three-dimensional tomography of far-red and near-infrared fluorescent proteins in animals. The method was developed in particular to address the steep light absorption transition of hemoglobin from the visible to the far-red occurring around 600 nm. Using an orthotopic mouse model of brain tumors expressing the red-shifted fluorescent protein mCherry, we demonstrate significant improvements in imaging accuracy over single-wavelength whole body reconstructions. Furthermore, we show an improvement in sensitivity of at least an order of magnitude over green fluorescent protein (GFP) for whole body imaging. We discuss how additional sensitivity gains are expected with the use of further red-shifted fluorescent proteins and we explain the differences and potential advantages of this approach over two-dimensional planar imaging methods.
AU  - Deliolanis, N.C.
AU  - Wurdinger, T.*
AU  - Pike, L.*
AU  - Tannous, B.A.*
AU  - Breakefield, X.O.*
AU  - Weissleder, R.*
AU  - Ntziachristos, V.
C1  - 4733
C2  - 28532
SP  - 887-900
TI  - In vivo tomographic imaging of red-shifted fluorescent proteins.
JO  - Biomed. Opt. Express
VL  - 2
IS  - 4
PB  - Optical Society of America
PY  - 2011
SN  - 2156-7085
ER  - 

TY  - JOUR
AB  - Hybrid FMT/XCT systems enable us to improve optical tomography image quality by using image priors in the reconstruction algorithm. We propose segmentation techniques to extract those priors and demonstrate their utilization in FMT image reconstruction.
AU  - Freyer, M.
AU  - Ale, A.B.F.
AU  - Schulz, R.B.
AU  - Ntziachristos, V.
AU  - Englmeier, K.-H.
C1  - 930
C2  - 27207
CY  - Washington, DC
TI  - Exploiting the potential of hybrid FMT/XCT imaging by means of segmentation.
JO  - Biomed. Opt. Express
PB  - Optical Soc.
PY  - 2010
SN  - 2156-7085
ER  -