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Photothermal therapy and ablation are commonplace medical procedures employed for treatment of tumors, vascular and brain abnormalities as well as other disorders that require selective destruction of tissues. Yet, accurate mapping of the dynamic temperature field distribution in the treated region represents an unmet clinical need, strongly affecting the clinical outcome of these interventions. We introduce a fast three-dimensional temperature mapping method based on real-time optoacoustic sensing of the treated region coupled with a thermal-diffusion-based model of heat distribution in tissues. Deviations of the optoacoustic temperature readings provided at 40 ms intervals remained below 10% in tissue-mimicking phantom experiments for temperature elevations above 3 °C, as validated by simultaneous thermocouple measurements. Performance of the new method to dynamically estimate the volumetric temperature distribution was further showcased in post-mortem mouse imaging experiments. The newly discovered capacity to non-invasively measure the temperature map in an entire treated volume with both high spatial and temporal resolutions holds potential for improving safety and efficacy of light-based therapeutic interventions.

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. 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 kinetics and motion in whole organs to high-resolution imaging of longitudinal dynamics at the whole body level. &nbsp

Optimal optoacoustic tomographic sampling is often hindered by the frequency-dependent directivity of ultrasound sensors, which can only be accounted for with an accurate three-dimensional (3D) model. Herein, we introduce a 3D modelbased reconstruction method applicable to optoacoustic imaging systems employing detection elements with arbitrary size and shape. The computational complexity and memory requirements are mitigated by introducing an efficient graphics processing unit (GPU)-based implementation of the iterative inversion. On-the-fly calculation of the entries of the model-matrix via a small look-up table avoids otherwise unfeasible storage of matrices typically occupying more than 300GB of memory. Superior imaging performance of the suggested method with respect to standard optoacoustic image reconstruction methods is first validated quantitatively using tissue-mimicking phantoms. Significant improvements in the spatial resolution, contrast to noise ratio and overall 3D image quality are also reported in real tissues by imaging the finger of a healthy volunteer with a hand-held volumetric optoacoustic imaging system.

The complementary contrast features of the optoacoustic (OA) and pulse-echo ultrasound (US) modalities make the combined usage of these imaging technologies highly advantageous. Due to the fundamentally different physical contrast mechanisms development of a detector array optimally suited for both modalities is one of the challenges to efficient implementation of a single OA-US imaging device. We demonstrate imaging performance of the first hybrid detector array whose novel design, incorporating array segments of linear and concave geometry, optimally supports image acquisition in both reflection-mode ultrasonography and optoacoustic tomography modes.

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.

Non-invasive observation of spatiotemporal activity of large neural populations distributed over entire brains is a longstanding goal of neuroscience. We developed a volumetric multispectral optoacoustic tomography platform for imaging neural activation deep in scattering brains. It can record 100 volumetric frames per second across scalable fields of view ranging between 50 and 1000 mm3 with respective spatial resolution of 35–200 μm. Experiments performed in immobilized and freely swimming larvae and in adult zebrafish brains expressing the genetically encoded calcium indicator GCaMP5G demonstrate, for the first time, the fundamental ability to directly track neural dynamics using optoacoustics while overcoming the longstanding penetration barrier of optical imaging in scattering brains. The newly developed platform thus offers unprecedented capabilities for functional whole-brain observations of fast calcium dynamics; in combination with optoacoustics' well-established capacity for resolving vascular hemodynamics, it could open new vistas in the study of neural activity and neurovascular coupling in health and disease. Scientists from Germany and Israel have developed an optoacoustic tomography method that can directly image fast neural activity in whole scattering brains. The team led by Daniel Razansky at the Helmholtz Center and Technical University in Munich and Shy Shoham from the Technion - Israel Institute of Technology discovered that genetically encoded calcium indicators have an optoacoustic signature and devised a rapid functional optoacoustic neuro-tomography system that can simultaneously record neural activity across volumes of 50 to 1000 cubic mm at 10 msec temporal resolution. The breakthrough technique was used to image the indicator GCaMP5G across adult zebrafish brains, thus overcoming the longstanding problem of light scattering that hindered penetration depth of fluorescence microscopy. The team says the technique could be readily customized to work with additional probes operating at longer wavelengths.

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.

One of the major challenges in dynamic multispectral optoacoustic imaging is its relatively low signal-to-noise ratio which often requires repetitive signal acquisition and averaging, thus limiting imaging rate. The development of denoising methods which prevent the need for signal averaging in time presents an important goal for advancing the dynamic capabilities of the technology. Methods: In this paper, a denoising method is developed for multispectral optoacoustic imaging which exploits the implicit sparsity of multispectral optoacoustic signals both in space and in spectrum. Noise suppression is achieved by applying thresholding on a combined wavelet-Karhunen–Loève representation in which multispectral optoacoustic signals appear particularly sparse. The method is based on inherent characteristics of multispectral optoacoustic signals of tissues, offering promise for general application in different incarnations of multispectral optoacoustic systems. Results: The performance of the proposed method is demonstrated on mouse images acquired in vivo for two common additive noise sources: time-varying parasitic signals and white noise. In both cases, the proposed method shows considerable improvement in image quality in comparison to previously published denoising strategies that do not consider multispectral information. Conclusions: The suggested denoising methodology can achieve noise suppression with minimal signal loss and considerably outperforms previously proposed denoising strategies, holding promise for advancing the dynamic capabilities of multispectral optoacoustic imaging while retaining image quality. &nbsp

INTRODUCTION: Due to lack of reliable imaging contrast from catheter radiofrequency ablation (RFA) lesions, the vast majority of current procedures rely on indirect indicators of ablation activity, resulting in a significant number of arrhythmia reoccurrences after RFA procedures and the need for repeat surgeries. The objective of this work is to develop an accurate method for on-the-fly assessment of the durability and size of lesions formed during RFA procedures. METHOD AND RESULTS: Radiofrequency catheter ablation on freshly-excised porcine ventricular myocardial tissue was optoacoustically monitored by means of pulsed-laser illumination in the near-infrared spectrum. Lesion formation during ablation was captured at a rate of 10 Hz with a 256-detector optoacoustic imaging probe. Post-ablated samples were imaged using multispectral excitation in the wavelength range 740 nm to 860 nm to determine the lesion contrast spectrum. Tomographic reconstruction was performed to generate three-dimensional images of the lesions, which were compared to photographs depicting the final ablated tissue samples. Video-rate three-dimensional tomographic reconstructions depict formation of the lesion with high contrast and spatial resolution. The size and geometry of the lesion was shown to be in excellent agreement with the histological examinations. The wavelength dependence of the lesion contrast shows a contrast peak near 780 nm. CONCLUSION: Deep-tissue three-dimensional monitoring of RFA lesion generation in real time was demonstrated for the first time in this work. The results suggest the potential of optoacoustic monitoring for providing critical feedback on lesion position and size during radiofrequency catheter ablation, improving safety and efficacy of these treatments.

Tissue modification under laser radiation is emerging as one of the advanced applications of lasers in medicine, with treatments ranging from reshaping and regeneration of cartilage to normalization of the intraocular pressure. Laser-induced structural alterations can be studied using conventional microscopic techniques applied to thin specimen. Yet, development of non-invasive imaging methods for deep tissue monitoring of structural alterations under laser radiation is of great importance, especially for attaining efficient feedback during the procedures. We developed a fast scanning biomicroscopy system that can simultaneously deliver both optoacoustic and pulse-echo ultrasound contrast from intact tissues and show that both modalities allow manifesting the laser-induced changes in cartilage and sclera. Furthermore, images of the sclera samples reveal a crater developing around the center of the laser-irradiated spot as well as a certain degree of thickening within the treated zone, presumably due to pore formation. Finally, we were able to observe selective impregnation of magnetite nanoparticles into the cartilage, thus demonstrating a possible contrast enhancement approach for studying specific treatment effects. Overall, the new imaging approach holds promise for development of noninvasive feedback control systems that could guarantee efficacy and safety of laser-based medical procedures.

Objective: Repetitive non-invasive cerebral imaging in mice is still challenging due to small body / brain size and limited overall availability of advanced technical equipment. In particular, addressing disease models with ischemic pathophysiological episodes, measuring tissue oxygenation is of[for full text, please go to the a.m. URL], 63. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie (JNS)

Visualizing developing organ formation as well as progession and treatment of disease often heavily relies on the ability to optically interrogate molecular and functional changes in intact living organisms. Most existing optical imaging methods are inadequate for imaging at dimensions that lie between the penetration limits of modern optical microscopy (0.5-1mm) and the diffusion-imposed limits of optical macroscopy (>1cm) [1]. Thus, many important model organisms, e.g. insects, animal embryos or small animal extremities, remain inaccessible for in-vivo optical imaging. Although there is increasing interest towards the development of nanometer-resolution optical imaging methods, there have not been many successful efforts in improving the imaging penetration depth. The ability to perform in-vivo imaging beyond microscopy limits is in fact met with the difficulties associated with photon scattering present in tissues. Recent efforts to image entire embryos for example [2,3] require special chemical treatment of the specimen, to clear them from scattering, a procedure that makes them suitable only for post-mortem imaging. These methods however evidence the need for imaging larger specimens than the ones usually allowed by two-photon or confocal microscopy, especially in developmental biology and in drug discovery. We have developed a new optical imaging technique named Mesoscopic Fluorescence Tomography [4], which appropriate for non-invasive in-vivo imaging at dimensions of 1mm-5mm. The method exchanges resolution for penetration depth, but offers unprecedented tomographic imaging performance and it has been developed to add time as a new dimension in developmental biology observations (and possibly other areas of biological research) by imparting the ability to image the evolution of fluorescence-tagged responses over time. As such it can accelerate studies of morphological or functional dependencies on gene mutations or external stimuli, and can importantly, capture the complete picture of development or tissue function by allowing longitudinal time-lapse visualization of the same, developing organism. The technique utilizes a modified laboratory microscope and multi-projection illumination to collect data at 360-degree projections. It applies the Fermi simplification to Fokker-Plank solution of the photon transport equation, combined with geometrical optics principles in order to build a realistic inversion scheme suitable for mesoscopic range. This allows in-vivo whole-body visualization of non-transparent three-dimensional structures in samples up to several millimeters in size. We have demonstrated the in-vivo performance of the technique by imaging three-dimensional structures of developing Drosophila tissues in-vivo and by following the morphogenesis of the wings in the opaque Drosophila pupae in real time over six consecutive hours. © JoVE 2006-2011 All Rights Reserved. Cited By :8

We report a technique for fluorescence tomography that operates beyond the penetration limits of tissue-sectioning fluorescence microscopy. The method uses multi-projection illumination and photon transport description in opaque tissues. We demonstrate whole-body three-dimensional visualization of the morphogenesis of GFP-expressing salivary glands and wing imaginal discs in living Drosophila melanogaster pupae in vivo and over time. 5 45 47 Cited By :79