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Find video protocols related to scientific articles indexed in Pubmed.
Universal Hand-held Three-dimensional Optoacoustic Imaging Probe for Deep Tissue Human Angiography and Functional Preclinical Studies in Real Time.
J Vis Exp
PUBLISHED: 11-20-2014
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The exclusive combination of high optical contrast and excellent spatial resolution makes optoacoustics (photoacoustics) ideal for simultaneously attaining anatomical, functional and molecular contrast in deep optically opaque tissues. While enormous potential has been recently demonstrated in the application of optoacoustics for small animal research, vast efforts have also been undertaken in translating this imaging technology into clinical practice. We present here a newly developed optoacoustic tomography approach capable of delivering high resolution and spectrally enriched volumetric images of tissue morphology and function in real time. A detailed description of the experimental protocol for operating with the imaging system in both hand-held and stationary modes is provided and showcased for different potential scenarios involving functional and molecular studies in murine models and humans. The possibility for real time visualization in three dimensions along with the versatile handheld design of the imaging probe make the newly developed approach unique among the pantheon of imaging modalities used in today's preclinical research and clinical practice.
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Spatiospectral denoising framework for multispectral optoacoustic imaging based on sparse signal representation.
Med Phys
PUBLISHED: 11-06-2014
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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.
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Three-dimensional optoacoustic monitoring of lesion formation in real time during radiofrequency catheter ablation.
J. Cardiovasc. Electrophysiol.
PUBLISHED: 08-22-2014
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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.
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Real-time optoacoustic tomography of indocyanine green perfusion and oxygenation parameters in human finger vasculature.
Opt Lett
PUBLISHED: 08-15-2014
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We interrogated whether optoacoustic tomography could be employed to study blood functional parameters and biodistribution of injected fluorescent agents in humans. Using a multichannel scanner at a frame rate of 10 images per second, we obtained cross-sectional images of the human finger in real time, before and after the administration of indocyanine green. We demonstrated that multispectral optoacoustic tomography can sense fast flow kinetics and resolve spatiotemporal characteristics of a common fluorochrome in human vasculature at clinically relevant concentrations. We further register ICG images with oxygen saturation maps and anatomical views of the proximal interphalangeal joint of a healthy volunteer.
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Estimation of optoacoustic contrast agent concentration with self-calibration blind logarithmic unmixing.
Phys Med Biol
PUBLISHED: 08-06-2014
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Chromophore quantification in optoacoustic tomography is challenging due to signal contributions from strongly absorbing background tissue chromophores and the depth-dependent light attenuation. Herein we present a procedure capable of correcting for wavelength-dependent light fluence variations using a logarithmic representation of the images taken at different wavelengths assisted with a blind unmixing approach. It is shown that the serial expansion of the logarithm of an optoacoustic image contains a term representing the ratio between absorption of the probe of interest and other background components. Under assumptions of tissue-like background absorption variations, this term can be readily isolated with an unmixing algorithm, attaining quantitative maps of photo-absorbing agent distribution.
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Effects of small variations of speed of sound in optoacoustic tomographic imaging.
Med Phys
PUBLISHED: 07-04-2014
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Speed of sound difference in the imaged object and surrounding coupling medium may reduce the resolution and overall quality of optoacoustic tomographic reconstructions obtained by assuming a uniform acoustic medium. In this work, the authors investigate the effects of acoustic heterogeneities and discuss potential benefits of accounting for those during the reconstruction procedure.
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Improved optoacoustic microscopy through three-dimensional spatial impulse response synthetic aperture focusing technique.
Opt Lett
PUBLISHED: 07-01-2014
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Synthetic aperture focusing technique (SAFT) is effective in restoring lateral resolution of ultrasonic images for scans with focusing-related distortions. Although successfully applied in pulse-echo ultrasonics, the physical nature of an optoacoustic modality requires a modified algorithm to return accurate results. The SIR-SAFT method reported here uses the spatial impulse response (SIR) of the transducer to weight the contributions to the SAFT and is tailored to provide significant resolution and signal gains for out-of-focus sources in scanning optoacoustic microscopy systems. Furthermore, the SIR-SAFT is implemented in full three dimensions, applicable to signals both far of and at the focus of the ultrasonic detector. The method has been further shown to outperform conventional SAFT algorithms for both simulated and experimental optoacoustic data.
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Wideband optical detector of ultrasound for medical imaging applications.
J Vis Exp
PUBLISHED: 06-05-2014
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Optical sensors of ultrasound are a promising alternative to piezoelectric techniques, as has been recently demonstrated in the field of optoacoustic imaging. In medical applications, one of the major limitations of optical sensing technology is its susceptibility to environmental conditions, e.g. changes in pressure and temperature, which may saturate the detection. Additionally, the clinical environment often imposes stringent limits on the size and robustness of the sensor. In this work, the combination of pulse interferometry and fiber-based optical sensing is demonstrated for ultrasound detection. Pulse interferometry enables robust performance of the readout system in the presence of rapid variations in the environmental conditions, whereas the use of all-fiber technology leads to a mechanically flexible sensing element compatible with highly demanding medical applications such as intravascular imaging. In order to achieve a short sensor length, a pi-phase-shifted fiber Bragg grating is used, which acts as a resonator trapping light over an effective length of 350 µm. To enable high bandwidth, the sensor is used for sideway detection of ultrasound, which is highly beneficial in circumferential imaging geometries such as intravascular imaging. An optoacoustic imaging setup is used to determine the response of the sensor for acoustic point sources at different positions.
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Deep-tissue reporter-gene imaging with fluorescence and optoacoustic tomography: a performance overview.
Mol Imaging Biol
PUBLISHED: 03-11-2014
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A primary enabling feature of near-infrared fluorescent proteins (FPs) and fluorescent probes is the ability to visualize deeper in tissues than in the visible. The purpose of this work is to find which is the optimal visualization method that can exploit the advantages of this novel class of FPs in full-scale pre-clinical molecular imaging studies.
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Functional optoacoustic imaging of moving objects using microsecond-delay acquisition of multispectral three-dimensional tomographic data.
Sci Rep
PUBLISHED: 02-19-2014
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The breakthrough capacity of optoacoustics for three-dimensional visualization of dynamic events in real time has been recently showcased. Yet, efficient spectral unmixing for functional imaging of entire volumetric regions is significantly challenged by motion artifacts in concurrent acquisitions at multiple wavelengths. Here, we introduce a method for simultaneous acquisition of multispectral volumetric datasets by introducing a microsecond-level delay between excitation laser pulses at different wavelengths. Robust performance is demonstrated by real-time volumetric visualization of functional blood parametrers in human vasculature with a handheld matrix array optoacoustic probe. This approach can avert image artifacts imposed by velocities greater than 2?m/s, thus, does not only facilitate imaging influenced by respiratory, cardiac or other intrinsic fast movements in living tissues, but can achieve artifact-free imaging in the presence of more significant motion, e.g. abrupt displacements during handheld-mode operation in a clinical environment.
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Expediting model-based optoacoustic reconstructions with tomographic symmetries.
Med Phys
PUBLISHED: 01-07-2014
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Image quantification in optoacoustic tomography implies the use of accurate forward models of excitation, propagation, and detection of optoacoustic signals while inversions with high spatial resolution usually involve very large matrices, leading to unreasonably long computation times. The development of fast and memory efficient model-based approaches represents then an important challenge to advance on the quantitative and dynamic imaging capabilities of tomographic optoacoustic imaging.
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Functional real-time optoacoustic imaging of middle cerebral artery occlusion in mice.
PLoS ONE
PUBLISHED: 01-01-2014
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Longitudinal functional imaging studies of stroke are key in identifying the disease progression and possible therapeutic interventions. Here we investigate the applicability of real-time functional optoacoustic imaging for monitoring of stroke progression in the whole brain of living animals.
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Real-time monitoring of incision profile during laser surgery using shock wave detection.
J Biophotonics
PUBLISHED: 09-23-2013
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Lack of sensory feedback during laser surgery prevents surgeons from discerning the exact location of the incision, which increases duration and complexity of the treatment. In this study we demonstrate a new method for monitoring of laser ablation procedures. Real-time tracking of the exact three dimensional (3D) lesion profile is accomplished by detection of shock waves emanating from the ablation spot and subsequent reconstruction of the incision location using time-of-flight data obtained from multiple acoustic detectors. Here, incisions of up to 9 mm in depth, created by pulsed laser ablation of fresh bovine tissue samples, were successfully monitored in real time. It was further observed that, by utilizing as little as 12 detection elements, the incision profile can be characterized with accuracy below 0.5 mm in all three dimensions and in good agreement with histological examinations. The proposed method holds therefore promise for delivering high precision real-time feedback during laser surgeries. (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).
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Optical and opto-acoustic imaging.
Recent Results Cancer Res.
PUBLISHED: 09-17-2013
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 Since the inception of the microscope, optical imaging is serving the biological discovery for more than four centuries. With the recent emergence of methods appropriate for in vivo staining, such as bioluminescence, fluorescent molecular probes, and proteins, as well as nanoparticle-based targeted agents, significant attention has been shifted toward in vivo interrogations of different dynamic biological processes at the molecular level. This progress has been largely supported by the development of advanced optical tomographic imaging technologies suitable for obtaining volumetric visualization of biomarker distributions in small animals at a whole-body or whole-organ scale, an imaging frontier that is not accessible by the existing tissue-sectioning microscopic techniques due to intensive light scattering beyond the depth of a few hundred microns. Biomedical optoacoustics has also emerged in the recent decade as a powerful tool for high-resolution visualization of optical contrast, overcoming a variety of longstanding limitations imposed by light scattering in deep tissues. By detecting tiny sound vibrations, resulting from selective absorption of light at multiple wavelengths, multispectral optoacoustic tomography methods can now "hear color" in three dimensions, i.e., deliver volumetric spectrally enriched (color) images from deep living tissues at high spatial resolution and in real time. These new-found imaging abilities directly relate to preclinical screening applications in animal models and are foreseen to significantly impact clinical decision making as well.
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Volumetric optoacoustic imaging with multi-bandwidth deconvolution.
IEEE Trans Med Imaging
PUBLISHED: 09-16-2013
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Optoacoustic (photoacoustic) imaging based on cylindrically focused one-dimensional transducer arrays comes with powerful characteristics in visualizing optical contrast. Parallel reading of multiple detectors arranged around a tissue crosssection enables capturing data for generating images of this plane within micro-seconds. Dedicated small animals scanners and handheld systems using one-dimensional cylindrically focused ultrasound transducer arrays have demonstrated real-time crosssectional imaging and high in-plane resolution. Yet, the resolution achieved along the axis perpendicular to the focal plane, i.e. the elevation resolution, is determined by the focusing capacities of the detector and is typically lower than the in-plane resolution. Herein, we investigated whether deconvolution of the sensitivity field of the transducer could lead to tangible image improvements. We showcase the findings on experimental measurements from phantoms and animals and discuss the features and the limitations of the approach in improving resolution along the elevation dimension.
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Optoacoustic monitoring of cutting efficiency and thermal damage during laser ablation.
Lasers Med Sci
PUBLISHED: 08-27-2013
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Successful laser surgery is characterized by a precise cut and effective hemostasis with minimal collateral thermal damage to the adjacent tissues. Consequently, the surgeon needs to control several parameters, such as power, pulse repetition rate, and velocity of movements. In this study we propose utilizing optoacoustics for providing the necessary real-time feedback of cutting efficiency and collateral thermal damage. Laser ablation was performed on a bovine meat slab using a Q-switched Nd-YAG laser (532 nm, 4 kHz, 18 W). Due to the short pulse duration of 7.6 ns, the same laser has also been used for generation of optoacoustic signals. Both the shockwaves, generated due to tissue removal, as well as the normal optoacoustic responses from the surrounding tissue were detected using a single broadband piezoelectric transducer. It has been observed that the rapid reduction in the shockwave amplitude occurs as more material is being removed, indicating decrease in cutting efficiency, whereas gradual decrease in the optoacoustic signal likely corresponds to coagulation around the ablation crater. Further heating of the surrounding tissue leads to carbonization accompanied by a significant shift in the optoacoustic spectra. Our results hold promise for real-time monitoring of cutting efficiency and collateral thermal damage during laser surgery. In practice, this could eventually facilitate development of automatic cut-off mechanisms that will guarantee an optimal tradeoff between cutting and heating while avoiding severe thermal damage to the surrounding tissues.
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Weighted model-based optoacoustic reconstruction in acoustic scattering media.
Phys Med Biol
PUBLISHED: 07-29-2013
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Model-based optoacoustic inversion methods are capable of eliminating image artefacts associated with the widely adopted back-projection reconstruction algorithms. Yet, significant image artefacts might also occur due to reflections and scattering of optoacoustically-induced waves from strongly acoustically-mismatched areas in tissues. Herein, we modify the model-based reconstruction methodology to incorporate statistically-based weighting in order to minimize these artefacts. The method is compared with another weighting procedure termed half-image reconstruction, yielding generally better results. The statistically-based weighting is subsequently verified experimentally, attaining quality improvement of the optoacoustic image reconstructions in the presence of acoustic mismatches in tissue phantoms and small animals ex-vivo.
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Modeling the shape of cylindrically focused transducers in three-dimensional optoacoustic tomography.
J Biomed Opt
PUBLISHED: 07-19-2013
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Cross sectional tomographic systems based on cylindrically focused transducers are widely used in optoacoustic (photoacoustic) imaging due to important advantages they provide such as high-cross sectional resolution, real-time imaging capacity, and high-throughput performance. Tomographic images in such systems are commonly obtained by means of two-dimensional (2-D) reconstruction procedures assuming point-like detectors, and volumetric (whole-body) imaging is performed by superimposing the cross sectional images for different positions along the scanning direction. Such reconstruction strategy generally leads to in-plane and out-of-plane artifacts as well as significant quantification errors. Herein, we introduce two equivalent full three-dimensional (3-D) models capable of accounting for the shape of cylindrically focused transducers. The performance of these models in 3-D reconstructions considering several scanning positions is analyzed in this work. Improvements of the results rendered with the introduced reconstruction procedure as compared with the 2-D-based approach are described and discussed for simulations and experiments with phantoms and biological tissues.
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Volumetric real-time tracking of peripheral human vasculature with GPU-accelerated three-dimensional optoacoustic tomography.
IEEE Trans Med Imaging
PUBLISHED: 07-03-2013
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Optoacoustic tomography provides a unique possibility for ultra-high-speed 3-D imaging by acquiring complete volumetric datasets from interrogation of tissue by a single nanosecond-duration laser pulse. Yet, similarly to ultrasound, optoacoustics is a time-resolved imaging method, thus, fast 3-D imaging implies real-time acquisition and processing of high speed data from hundreds of detectors simultaneously, which presents significant technological challenges. Herein we present a highly efficient graphical processing unit (GPU) framework for real-time reconstruction and visualization of 3-D tomographic optoacoustic data. By utilizing a newly developed 3-D optoacoustic scanner, which simultaneously acquires signals with a handheld 256-element spherical ultrasonic array system, we further demonstrate tracking of deep tissue human vasculature rendered at a rate of 10 volumetric frames per second. The flexibility provided by the handheld hardware design, combined with the real-time operation, makes the developed platform highly usable for both clinical imaging practice and small animal research applications.
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Optoacoustic imaging and tomography: reconstruction approaches and outstanding challenges in image performance and quantification.
Sensors (Basel)
PUBLISHED: 03-21-2013
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This paper comprehensively reviews the emerging topic of optoacoustic imaging from the image reconstruction and quantification perspective. Optoacoustic imaging combines highly attractive features, including rich contrast and high versatility in sensing diverse biological targets, excellent spatial resolution not compromised by light scattering, and relatively low cost of implementation. Yet, living objects present a complex target for optoacoustic imaging due to the presence of a highly heterogeneous tissue background in the form of strong spatial variations of scattering and absorption. Extracting quantified information on the actual distribution of tissue chromophores and other biomarkers constitutes therefore a challenging problem. Image quantification is further compromised by some frequently-used approximated inversion formulae. In this review, the currently available optoacoustic image reconstruction and quantification approaches are assessed, including back-projection and model-based inversion algorithms, sparse signal representation, wavelet-based approaches, methods for reduction of acoustic artifacts as well as multi-spectral methods for visualization of tissue bio-markers. Applicability of the different methodologies is further analyzed in the context of real-life performance in small animal and clinical in-vivo imaging scenarios.
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Multispectral optoacoustic tomography by means of normalized spectral ratio.
Opt Lett
PUBLISHED: 11-04-2011
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Quantification of biomarkers using multispectral optoacoustic tomography can be challenging due to photon fluence variations with depth and spatially heterogeneous tissue optical properties. Herein we introduce a spectral ratio approach that accounts for photon fluence variations. The performance and imaging improvement achieved with the proposed method is showcased both numerically and experimentally in phantoms and mice.
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The effects of acoustic attenuation in optoacoustic signals.
Phys Med Biol
PUBLISHED: 08-26-2011
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In this paper, it is demonstrated that the effects of acoustic attenuation may play a significant role in establishing the quality of tomographic optoacoustic reconstructions. Accordingly, spatially dependent reduction of signal amplitude leads to quantification errors in the reconstructed distribution of the optical absorption coefficient while signal broadening causes loss of image resolution. Here we propose a correction algorithm for accounting for attenuation effects, which is applicable in both the time and frequency domains. It is further investigated which part of the optoacoustic signal spectrum is practically affected by those effects in realistic imaging scenarios. The validity and benefits of the suggested modelling and correction approaches are experimentally validated in phantom measurements.
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Model-based optoacoustic inversion with arbitrary-shape detectors.
Med Phys
PUBLISHED: 08-24-2011
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Optoacoustic imaging enables mapping the optical absorption of biological tissue using optical excitation and acoustic detection. Although most image-reconstruction algorithms are based on the assumption of a detector with an isotropic sensitivity, the geometry of the detector often leads to a response with spatially dependent magnitude and bandwidth. This effect may lead to attenuation or distortion in the recorded signal and, consequently, in the reconstructed image.
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Volumetric real-time multispectral optoacoustic tomography of biomarkers.
Nat Protoc
PUBLISHED: 07-07-2011
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Multispectral optoacoustic tomography (MSOT) has recently been developed to enable visualization of optical contrast and tissue biomarkers, with resolution and speed representative of ultrasound. In the implementation described here, MSOT enables operation in real-time mode by capturing single cross-sectional images in <1 ms from living small animals (e.g., mice) and other tissues of similar dimensions. At the core of the method is illumination of the object using multiple wavelengths in order to resolve spectrally distinct biomarkers over background tissue chromophores. The system allows horizontal placement of a mouse in the imaging chamber and three-dimensional scanning of the entire body without the need to immerse the mouse in water. Here we provide a detailed description of the MSOT scanner components, system calibration, selection of image reconstruction algorithms and animal handling. Overall, the entire protocol can be completed within 15-30 min for acquisition of a whole-body multispectral data set from a living mouse.
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High-sensitivity compact ultrasonic detector based on a pi-phase-shifted fiber Bragg grating.
Opt Lett
PUBLISHED: 05-20-2011
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A highly sensitive compact hydrophone, based on a pi-phase-shifted fiber Bragg grating, has been developed for the measurement of wideband ultrasonic fields. The grating exhibits a sharp resonance, whose centroid wavelength is pressure sensitive. The resonance is monitored by a continuous-wave (CW) laser to measure ultrasound-induced pressure variations within the grating. In contrast to standard fiber sensors, the high finesse of the resonance--which is the reason for the sensors high sensitivity--is not associated with a long propagation length. Light localization around the phase shift reduces the effective size of the sensor below that of the grating and is scaled inversely with the resonance spectral width. In our system, an effective sensor length of 270 ?m, pressure sensitivity of 440 Pa, and effective bandwidth of 10 MHz were achieved. This performance makes our design attractive for medical imaging applications, such as optoacoustic tomography, in which compact, sensitive, and wideband acoustic detectors are required.
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Near-field thermoacoustic tomography of small animals.
Phys Med Biol
PUBLISHED: 05-16-2011
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Near-field radiofrequency thermoacoustic (NRT) tomography is a new imaging method that was developed to mitigate limitations of conventional thermoacoustic imaging approaches, related to hard compromises between signal strength and spatial resolution. By utilizing ultrahigh-energy electromagnetic impulses at ?20 ns duration along with improved energy absorption coupling in the near-field, this method can deliver high-resolution images without compromising signal to noise ratio. NRT is a promising modality, offering cost-effectiveness and ease of implementation and it can be conveniently scaled to image small animals and humans. However, several of the performance metrics of the method are not yet documented. In this paper, we characterize the expected imaging performance via numerical simulations based on a finite-integration time-domain (FITD) technique and experiments using tissue mimicking phantoms and different biological samples. Furthermore, we show for the first time whole-body tomographic imaging results from mice, revealing clear anatomical details along with highly dissipative inclusions introduced for control. The best spatial resolution achieved for those experiments was 150 µm.
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Model-based optoacoustic inversions with incomplete projection data.
Med Phys
PUBLISHED: 04-28-2011
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Optoacoustic imaging is an emerging noninvasive imaging modality that can resolve optical contrast through several millimeters to centimeters of tissue with diffraction-limited resolution of ultrasound. Yet, quantified reconstruction of tissue absorption maps requires optoacoustic signals to be collected from as many locations around the object as possible. In many tomographic imaging scenarios, however, only limited-view or partial projection data are available, which has been shown to generate image artifacts and overall loss of quantification accuracy.
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Blind source unmixing in multi-spectral optoacoustic tomography.
Opt Express
PUBLISHED: 03-04-2011
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Multispectral optoacoustic (photoacoustic) tomography (MSOT) is a hybrid modality that can image through several millimeters to centimeters of diffuse tissues, attaining resolutions typical of ultrasound imaging. The method can further identify tissue biomarkers by decomposing the spectral contributions of different photo-absorbing molecules of interest. In this work we investigate the performance of blind source unmixing methods and spectral fitting approaches in decomposing the contributions of fluorescent dyes from the tissue background, based on MSOT measurements in mice. We find blind unmixing as a promising method for accurate MSOT decomposition, suitable also for spectral unmixing in fluorescence imaging. We further demonstrate its capacity with temporal unmixing on real-time MSOT data obtained in-vivo for enhancing the visualization of absorber agent flow in the mouse vascular system.
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Optoacoustic methods for frequency calibration of ultrasonic sensors.
IEEE Trans Ultrason Ferroelectr Freq Control
PUBLISHED: 02-24-2011
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The frequency response of ultrasonic detectors is commonly calibrated by finding their sensitivity to incident plane waves at discrete frequencies. For certain applications, such as the emerging field of optoacoustic tomography, it is the response to point sources emitting broadband spectra that needs to be found instead. Although these two distinct sensitivity characteristics are interchangeable in the case of a flat detector and a point source at infinity, it is not the case for detectors with size considerably larger than the acoustic wavelength of interest or those having a focused aperture. Such geometries, which are common in optoacoustics, require direct calibration of the acoustic detector using a point source placed in the relevant position. In this paper, we report on novel cross-validating optoacoustic methods for measuring the frequency response of wideband acoustic sensors. The approach developed does not require pre-calibrated hydrophones and therefore can be readily adopted in any existing optoacoustic measurement configuration. The methods are successfully confirmed experimentally by measuring the frequency response of a common piezoelectric detector having a cylindrically focused shape.
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Optoacoustic tomography with varying illumination and non-uniform detection patterns.
J Opt Soc Am A Opt Image Sci Vis
PUBLISHED: 11-04-2010
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Quantification of tissue morphology and biomarker distribution by means of optoacoustic tomography is an important and longstanding challenge, mainly caused by the complex heterogeneous structure of biological tissues as well as the lack of accurate and robust reconstruction algorithms. The recently introduced model-based inversion approaches were shown to mitigate some of reconstruction artifacts associated with the commonly used back-projection schemes, while providing an excellent platform for obtaining quantified maps of optical energy deposition in experimental configurations of various complexity. In this work, we introduce a weighted model-based approach, capable of overcoming reconstruction challenges caused by per-projection variations of objects illumination and other partial illumination effects. The universal weighting procedure is equally shown to reduce reconstruction artifacts associated with other experimental imperfections, such as non-uniform transducer sensitivity fields. Significant improvements in image fidelity and quantification are showcased both numerically and experimentally on tissue phantoms and mice.
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Near-field radiofrequency thermoacoustic tomography with impulse excitation.
Med Phys
PUBLISHED: 10-23-2010
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Imaging performance of radiofrequency and microwave-based thermoacoustic tomography systems is mainly determined by the ability to deposit a substantial amount of electromagnetic energy within ultrashort time duration. Pulses of nanosecond-range duration that can carry hundreds of millijoules energy are ideal for obtaining good signal-to-noise and spatial resolution in many biological imaging applications. However, existing implementations are based on modulated-carrier-frequency amplification solutions, which are generally costly and cannot achieve ultrahigh-peak-power requirements essential for optimal thermoacoustic signal generation.
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Real-time imaging of cardiovascular dynamics and circulating gold nanorods with multispectral optoacoustic tomography.
Opt Express
PUBLISHED: 10-14-2010
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Macroscopic visualization of functional and molecular features of cardiovascular disease is emerging as an important tool in basic research and clinical translation of new diagnostic and therapeutic strategies. We showcase the application of Multispectral Optoacoustic Tomography (MSOT) techniques to noninvasively image different aspects of the mouse cardiovascular system macroscopically in real-time and in vivo, an unprecedented ability compared to optical or optoacoustic (photoacoustic) imaging approaches documented so far. In particular, we demonstrate imaging of the carotid arteries, the aorta and the cardiac wall. We further demonstrate the ability to dynamically visualize circulating gold nanorods that can be used to enhance contrast and be extended to molecular imaging applications. We discuss the potential of this imaging ability in cardiovascular disease (CVD) research and clinical applications.
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Statistical approach for optoacoustic image reconstruction in the presence of strong acoustic heterogeneities.
IEEE Trans Med Imaging
PUBLISHED: 09-27-2010
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A method is presented to reduce artefacts produced in optoacoustic tomography images due to internal reflection or scattering of the acoustic waves. It is based on weighting the tomographic contribution of each detector with the probability that a signal affected by acoustic mismatches is measured at that position. The correction method does not require a priori knowledge of the acoustic or optical properties of the imaged sample. Performance tests were made with agar phantoms that included air gaps for mimicking strong acoustic reflections as well as with an acoustically heterogeneous adult Zebrafish. The results obtained with the method proposed show a clear reduction of the artefacts with respect to the original images reconstructed with filtered back-projection algorithm. This performance is directly related to in vivo small animal imaging applications involving imaging in the presence of bones, lungs, and other highly mismatched organs.
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Video rate optoacoustic tomography of mouse kidney perfusion.
Opt Lett
PUBLISHED: 07-17-2010
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Optoacoustic tomography can visualize optical contrast in tissues while capitalizing on the advantages of ultrasound, such as high spatial resolution and fast imaging capabilities. We report a novel multispectral optoacoustic tomography system for deep tissue small animal imaging. The previously undocumented capacity of whole-body optoacoustic tomography at a video rate has been demonstrated by visualizing mouse kidney perfusion using Indocyanine Green in vivo.
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Near-infrared fluorescence catheter system for two-dimensional intravascular imaging in vivo.
Opt Express
PUBLISHED: 07-01-2010
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Detection of high-risk coronary arterial plaques prior to rupture remains an unmet clinical challenge, in part due to the stringent resolution and sensitivity requirements for in vivo human coronary arterial imaging. To address this need, we have developed a near-infrared (NIR) fluorescence imaging catheter system for intra-vascular molecular imaging of atherosclerosis in coronary artery-sized vessels, capable of resolving two-dimensional fluorescence activity in hollow organs, such as blood vessels. Based on a rotational fiber design, the catheter system illuminates and detects perpendicular to the rotational axis, while an automated pullback mechanism enables visualization along blood vessels with a scan speed of up to 1.5 mm/sec. We demonstrate the previously undocumented capacity to produce intravascular NIR fluorescence images of hollow organs in vivo and showcase the performance metrics of the system developed using blood vessel mimicking phantoms. This imaging approach is geared toward in vivo molecular imaging of atherosclerotic biomarkers and is engineered to allow seamless integration into the cardiac catheterization laboratory.
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Anatomical and microstructural imaging of angiogenesis.
Eur. J. Nucl. Med. Mol. Imaging
PUBLISHED: 05-13-2010
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This article reviews and discusses different options for visualizing the microarchitecture of vessels ex vivo and in vivo with respect to reliability, practicability and availability.
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Imaging of molecular probe activity with Born-normalized fluorescence optical projection tomography.
Opt Lett
PUBLISHED: 04-06-2010
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Optical projection tomography is a new ex vivo imaging technique that allows imaging of whole organs in three dimensions at high spatial resolutions. In this Letter we demonstrate its capability to tomographically visualize molecular activity in whole organs of mice. In particular, eosinophil activity in asthmatic lungs is resolved using a Born-normalized fluorescence optical projection tomography and employing a near-IR molecular probe. The possibility to achieve molecularly sensitive imaging contrast in optical projection tomography by means of targeted and activatable imaging reporter agents adds a new range of capabilities for investigating molecular signatures of pathophysiological processes and a wide variety of diseases and their development.
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Fast semi-analytical model-based acoustic inversion for quantitative optoacoustic tomography.
IEEE Trans Med Imaging
PUBLISHED: 03-18-2010
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We present a fast model-based inversion algorithm for quantitative 2-D and 3-D optoacoustic tomography. The algorithm is based on an accurate and efficient forward model, which eliminates the need for regularization in the inversion process while providing modeling flexibility essential for quantitative image formation. The resulting image-reconstruction method eliminates stability problems encountered in previously published model-based techniques and, thus, enables performing image reconstruction in real time. Our model-based framework offers a generalization of the forward solution to more comprehensive optoacoustic propagation models, such as including detector frequency response, without changing the inversion procedure. The reconstruction speed and other algorithmic performances are demonstrated using numerical simulation studies and experimentally on tissue-mimicking optically heterogeneous phantoms and small animals. In the experimental examples, the model-based reconstructions manifested correctly the effect of light attenuation through the objects and did not suffer from the artifacts which usually afflict the commonly used filtered backprojection algorithms, such as negative absorption values.
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Multifunctional Nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: perspectives on tracking and neuroimaging.
Part Fibre Toxicol
PUBLISHED: 03-03-2010
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Nanotechnology has brought a variety of new possibilities into biological discovery and clinical practice. In particular, nano-scaled carriers have revolutionalized drug delivery, allowing for therapeutic agents to be selectively targeted on an organ, tissue and cell specific level, also minimizing exposure of healthy tissue to drugs. In this review we discuss and analyze three issues, which are considered to be at the core of nano-scaled drug delivery systems, namely functionalization of nanocarriers, delivery to target organs and in vivo imaging. The latest developments on highly specific conjugation strategies that are used to attach biomolecules to the surface of nanoparticles (NP) are first reviewed. Besides drug carrying capabilities, the functionalization of nanocarriers also facilitate their transport to primary target organs. We highlight the leading advantage of nanocarriers, i.e. their ability to cross the blood-brain barrier (BBB), a tightly packed layer of endothelial cells surrounding the brain that prevents high-molecular weight molecules from entering the brain. The BBB has several transport molecules such as growth factors, insulin and transferrin that can potentially increase the efficiency and kinetics of brain-targeting nanocarriers. Potential treatments for common neurological disorders, such as stroke, tumours and Alzheimers, are therefore a much sought-after application of nanomedicine. Likewise any other drug delivery system, a number of parameters need to be registered once functionalized NPs are administered, for instance their efficiency in organ-selective targeting, bioaccumulation and excretion. Finally, direct in vivo imaging of nanomaterials is an exciting recent field that can provide real-time tracking of those nanocarriers. We review a range of systems suitable for in vivo imaging and monitoring of drug delivery, with an emphasis on most recently introduced molecular imaging modalities based on optical and hybrid contrast, such as fluorescent protein tomography and multispectral optoacoustic tomography. Overall, great potential is foreseen for nanocarriers in medical diagnostics, therapeutics and molecular targeting. A proposed roadmap for ongoing and future research directions is therefore discussed in detail with emphasis on the development of novel approaches for functionalization, targeting and imaging of nano-based drug delivery systems, a cutting-edge technology poised to change the ways medicine is administered.
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Multispectral optoacoustic tomography (MSOT) scanner for whole-body small animal imaging.
Opt Express
PUBLISHED: 12-10-2009
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A major difficulty arising from whole-body optoacoustic imaging is the long acquisition times associated with recording signals from multiple spatial projections. The acquired signals are also generally weak and the signal-to-noise-ratio is low, problems often solved by signal averaging, which complicates acquisition and increases acquisition times to an extent that makes many in vivo applications challenging or even impossible. Herein we present a fast acquisition multispectral optoacoustic tomography (MSOT) scanner for whole-body visualization of molecular markers in small animals. Multi-wavelength illumination offers the possibility to resolve exogenously administered fluorescent probes, biomarkers, and other intrinsic and exogenous chromophores. The system performance is determined in phantom experiments involving molecular probes and validated by imaging of small animals of various scales.
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Transillumination fluorescence imaging in mice using biocompatible upconverting nanoparticles.
Opt Lett
PUBLISHED: 09-03-2009
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We report on a systematic study of upconverting fluorescence signal generation within turbid phantoms and real tissues. An accurate three-point Greens function, describing the forward model of photon propagation, is established and experimentally validated. We further demonstrate, for the first time to our knowledge, autofluorescence-free transillumination imaging of mice that have received biocompatible upconverting nanoparticles. The method holds great promise for artifact-free whole-body visualization of optical molecular probes.
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Mesoscopic fluorescence tomography for in-vivo imaging of developing Drosophila.
J Vis Exp
PUBLISHED: 08-22-2009
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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.
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Quantitative optoacoustic signal extraction using sparse signal representation.
IEEE Trans Med Imaging
PUBLISHED: 07-21-2009
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We report on a new quantification methodology of optoacoustic tomographic reconstructions under heterogeneous illumination conditions representative of realistic whole-body imaging scenarios. Our method relies on the differences in the spatial characteristics of the absorption coefficient and the optical energy density within the medium. By using sparse-representation based decomposition, we exploit these different characteristics to extract both the absorption coefficient and the photon density within the imaged object from the optoacoustic image. In contrast to previous methods, this algorithm is not based on the solution of theoretical light transport equations and it does not require explicit knowledge of the illumination geometry or the optical properties of the object and other unknown or loosely defined experimental parameters, leading to highly robust performance. The method was successfully examined with numerically and experimentally generated data and was found to be ideally suited for practical implementations in tomographic schemes of varying complexity, including multiprojection illumination systems and multispectral optoacoustic tomography (MSOT) studies of tissue biomarkers.
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Born normalization for fluorescence optical projection tomography for whole heart imaging.
J Vis Exp
PUBLISHED: 07-07-2009
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Optical projection tomography is a three-dimensional imaging technique that has been recently introduced as an imaging tool primarily in developmental biology and gene expression studies. The technique renders biological sample optically transparent by first dehydrating them and then placing in a mixture of benzyl alcohol and benzyl benzoate in a 2:1 ratio (BABB or Murray s Clear solution). The technique renders biological samples optically transparent by first dehydrating them in graded ethanol solutions then placing them in a mixture of benzyl alcohol and benzyl benzoate in a 2:1 ratio (BABB or Murray s Clear solution) to clear. After the clearing process the scattering contribution in the sample can be greatly reduced and made almost negligible while the absorption contribution cannot be eliminated completely. When trying to reconstruct the fluorescence distribution within the sample under investigation, this contribution affects the reconstructions and leads, inevitably, to image artifacts and quantification errors.. While absorption could be reduced further with a permanence of weeks or months in the clearing media, this will lead to progressive loss of fluorescence and to an unrealistically long sample processing time. This is true when reconstructing both exogenous contrast agents (molecular contrast agents) as well as endogenous contrast (e.g. reconstructions of genetically expressed fluorescent proteins).
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Surface modification and size dependence in particle translocation during early embryonic development.
Inhal Toxicol
PUBLISHED: 06-30-2009
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Since the mid-1990 s, the number of studies linking air pollutants to preterm and low birth weight, as well as to cardiac birth defects, has grown steadily each year. The critical period in the development of mouse embryos begins with the commencement of gastrulation at day 7.5 of gestation. Our aim is to examine the role of particles size and surface modification in particle translocation during this early embryonic development. Fluorescent polystyrene particles (PS) were employed because they offer an efficient and safe tracking method. Pregnant female mice were sacrificed at 7.5 days of gestation. After cutting open the deciduas, the parietal endoderm was carefully separated and removed. Different sizes of amine- and carboxyl-modified PS beads were injected via the extraembryonic tissue. The embryos were incubated for 12 h, and were investigated under fluorescent microscopy, confocal microscopy, and mesoscopic fluorescence tomography. The results show that 20-nm carboxylic PS distribute in the embryonic and extraembryonic germ layers of ectoderm, mesoderm, and endoderm. Moreover, when the particles are bigger than 100 nm, PS accumulate in extraembryonic tissue, but nevertheless 200-nm amine-modified particles can pass into the embryos. Interestingly, a growth inhibition was observed in the embryos containing nanoparticles. Finally, the stronger translocation effect is associated with amine-modified PS beads (200 nm) instead of the smaller (20 nm, 100 nm) carboxyl ones.
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Sensitivity of molecular target detection by multispectral optoacoustic tomography (MSOT).
Med Phys
PUBLISHED: 04-22-2009
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Optoacoustic imaging is emerging as a noninvasive imaging modality that can resolve optical contrast through several millimeters to centimeters of tissue with the resolution achieved by ultrasound imaging. More recently, applied at multiple illumination wavelengths, multispectral optoacoustic tomography (MSOT) offered the ability to effectively visualize tissue biomarkers by resolving their distinct spectral signatures. While the imaging potential of the method has been demonstrated, little is known on the sensitivity performance in resolving chromophoric and fluorescent substances, such as optical functional and molecular reporters. Herein the authors investigate the detection capacity and physical limits of tomographic optoacoustic imaging by simulating signals originating from absorbing spheres in tissue-mimicking media. To achieve this, a modified optoacoustic equation is employed to incorporate wavelength-dependent propagation and attenuation of diffuse light and ultrasound. The theoretical predictions are further validated in phantom experiments involving Cy5.5, a common near-infrared fluorescent molecular agent.
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Imaging of mesoscopic-scale organisms using selective-plane optoacoustic tomography.
Phys Med Biol
PUBLISHED: 04-15-2009
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Mesoscopic-scale living organisms (i.e. 1 mm to 1 cm sized) remain largely inaccessible by current optical imaging methods due to intensive light scattering in tissues. Therefore, imaging of many important model organisms, such as insects, fishes, worms and similarly sized biological specimens, is currently limited to embryonic or other transparent stages of development. This makes it difficult to relate embryonic cellular and molecular mechanisms to consequences in organ function and animal behavior in more advanced stages and adults. Herein, we have developed a selective-plane illumination optoacoustic tomography technique for in vivo imaging of optically diffusive organisms and tissues. The method is capable of whole-body imaging at depths from the sub-millimeter up to centimeter range with a scalable spatial resolution in the order of magnitude of a few tenths of microns. In contrast to pure optical methods, the spatial resolution here is not determined nor limited by light diffusion; therefore, such performance cannot be achieved by any other optical imaging technology developed so far. The utility of the method is demonstrated on several whole-body models and small-animal extremities.
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Normalized Born ratio for fluorescence optical projection tomography.
Opt Lett
PUBLISHED: 02-03-2009
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We present a normalized Born approach for fluorescence optical projection tomography that takes into account tissue absorption properties. This approach can be particularly useful to study fluorochrome distribution within tissue. We use the algorithm to three-dimensionally reconstruct and characterize a fluorescein isothiocyanate containing absorptive phantom and an infarcted mouse heart previously injected with a fluorescent molecular probe.
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Artefact reduction in optoacoustic tomographic imaging by estimating the distribution of acoustic scatterers.
J Biomed Opt
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The quality of optoacoustic tomographic reconstructions can be severely affected by acoustic reflections or scattering arising at interfaces of highly mismatched organs, such as bones, lungs, or other air-containing cavities. We present a procedure to reduce the associated artefacts based on estimation of the acoustic scatterers distribution within the imaged object. Signals generated by a strong optical absorber are processed and used in a weighted back-projection algorithm. Experimental results in a tissue-mimicking phantom clearly demonstrate improved performance as compared to the case in which no information on the distribution of acoustic scatterers is available.
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Non-invasive whole-body imaging of adult zebrafish with optoacoustic tomography.
Phys Med Biol
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Zebrafish has emerged as an excellent vertebrate model organism for studies of evolution, development and disease. Due to its external development and optical transparency in embryonic stages, zebrafish offers a major advantage over other vertebrate model organisms by being amenable for microscopic studies of biological processes within their natural environment directly in the living organism. However, commonly used zebrafish strains lose their transparency within their first two weeks of development and thus are no longer accessible for optical imaging approaches at juvenile or adult stages. In this study we successfully apply optoacoustic imaging for non-invasive three-dimensional imaging of adult zebrafish. Since optoacoustics does not necessarily require labeling, but can instead rely on the intrinsic tissue contrast, this imaging method has the potential to become a versatile tool for developmental studies from juvenile to adult stages in the intact zebrafish.
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Wideband optical sensing using pulse interferometry.
Opt Express
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Advances in fabrication of high-finesse optical resonators hold promise for the development of miniaturized, ultra-sensitive, wide-band optical sensors, based on resonance-shift detection. Many potential applications are foreseen for such sensors, among them highly sensitive detection in ultrasound and optoacoustic imaging. Traditionally, sensor interrogation is performed by tuning a narrow linewidth laser to the resonance wavelength. Despite the ubiquity of this method, its use has been mostly limited to lab conditions due to its vulnerability to environmental factors and the difficulty of multiplexing - a key factor in imaging applications. In this paper, we develop a new optical-resonator interrogation scheme based on wideband pulse interferometry, potentially capable of achieving high stability against environmental conditions without compromising sensitivity. Additionally, the method can enable multiplexing several sensors. The unique properties of the pulse-interferometry interrogation approach are studied theoretically and experimentally. Methods for noise reduction in the proposed scheme are presented and experimentally demonstrated, while the overall performance is validated for broadband optical detection of ultrasonic fields. The achieved sensitivity is equivalent to the theoretical limit of a 6 MHz narrow-line width laser, which is 40 times higher than what can be usually achieved by incoherent interferometry for the same optical resonator.
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Accurate model-based reconstruction algorithm for three-dimensional optoacoustic tomography.
IEEE Trans Med Imaging
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In many practical optoacoustic imaging implementations, dimensionality of the tomographic problem is commonly reduced into two dimensions or 1-D scanning geometries in order to simplify technical implementation, improve imaging speed or increase signal-to-noise ratio. However, this usually comes at a cost of significantly reduced quality of the tomographic data, out-of-plane image artifacts, and overall loss of image contrast and spatial resolution. Quantitative optoacoustic image reconstruction implies therefore collection of point 3-D (volumetric) data from as many locations around the object as possible. Here, we propose and validate an accurate model-based inversion algorithm for 3-D optoacoustic image reconstruction. Superior performance versus commonly-used backprojection inversion algorithms is showcased by numerical simulations and phantom experiments.
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Model-based optoacoustic imaging using focused detector scanning.
Opt Lett
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Optoacoustic (photoacoustic) mesoscopic and microscopic imaging is often implemented by linearly scanning a spherically focused ultrasound transducer. In this case, the resolution and sensitivity along the scan direction are limited by diffraction and therefore degrade rapidly for imaging depths away from the focal point. Partial restoration of the lost resolution can be achieved by using data-processing techniques, such as the virtual detector delay-and-sum method. However, these techniques are based on an approximate description of the detector properties, which limits the improvement in image quality they achieve. Herein we propose a reconstruction method based on an exact model of the optoacoustic generation and propagation that incorporates the spatial response of the sensor. The proposed method shows superior imaging performance over previously considered techniques.
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Multispectral opto-acoustic tomography (MSOT) of the brain and glioblastoma characterization.
Neuroimage
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Brain research depends strongly on imaging for assessing function and disease in vivo. We examine herein multispectral opto-acoustic tomography (MSOT), a novel technology for high-resolution molecular imaging deep inside tissues. MSOT illuminates tissue with light pulses at multiple wavelengths and detects the acoustic waves generated by the thermoelastic expansion of the environment surrounding absorbing molecules. Using spectral unmixing analysis of the data collected, MSOT can then differentiate the spectral signatures of oxygenated and deoxygenated hemoglobin and of photo-absorbing agents and quantify their concentration. By being able to detect absorbing molecules up to centimeters deep in the tissue it represents an ideal modality for small animal brain imaging, simultaneously providing anatomical, hemodynamic, functional, and molecular information. In this work we examine the capacity of MSOT in cross-sectional brain imaging of mice. We find unprecedented optical imaging performance in cross-sectional visualization of anatomical and physiological parameters of the mouse brain. For example, the potential of MSOT to characterize ischemic brain areas was demonstrated through the use of a carbon dioxide challenge. In addition, indocyanine green (ICG) was injected intravenously, and the kinetics of uptake and clearance in the vasculature of the brain was visualized in real-time. We further found that multiparameter, multispectral imaging of the growth of U87 tumor cells injected into the brain could be visualized through the intact mouse head, for example through visualization of deoxygenated hemoglobin in the growing tumor. We also demonstrate how MSOT offers several compelling features for brain research and allows time-dependent detection and quantification of brain parameters that are not available using other imaging methods without invasive procedures.
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Spatial characterization of the response of a silica optical fiber to wideband ultrasound.
Opt Lett
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Optical fibers have long been recognized as a promising technology for remote sensing of ultrasound. Nonetheless, very little is known about the characteristics of their spatial response, which is significantly affected by the strong acoustic mismatches between the fiber and surrounding medium. In this Letter, a new method is demonstrated for wideband spatial acoustic characterization of optical fibers. The method is based on the excitation of a point-like acoustic source via the opto-acoustic effect, while a miniature fiber sensor is implemented by a ?-phase-shifted fiber Bragg grating. Despite the relative complexity of acoustic wave propagation in the fiber, its spatial sensitivity in the high frequency band (6-30 MHz) exhibited an orderly pattern, which can be described by a simple model. This property reveals new possibilities for high-performance imaging using fiber-based ultrasound sensors, where knowledge of the sensors spatial sensitivity map is generally required.
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Near-field thermoacoustic imaging with transmission line pulsers.
Med Phys
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Near-field radiofrequency thermoacoustic (NRT) tomography has been recently introduced for imaging electromagnetic (EM) properties of tissues using ultrawideband, high-energy impulses, which induce thermoacoustic responses. Operation in the near-field allows for more effective energy coupling into tissue, compared to using radiating sources, which in turn enables the use of shorter excitation pulses and leads to higher image resolution. This work aimed at investigating transmission lines as a method to generate excitation pulses to improve the NRT resolution over previous implementations without compromising the energy coupled into tissue.
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Fast scanning coaxial optoacoustic microscopy.
Biomed Opt Express
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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.
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Optical imaging of cancer heterogeneity with multispectral optoacoustic tomography.
Radiology
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To investigate whether multispectral optoacoustic tomography (MSOT) can reveal the heterogeneous distributions of exogenous agents of interest and vascular characteristics through tumors of several millimeters in diameter in vivo.
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Mapping molecular agents distributions in whole mice hearts using born-normalized optical projection tomography.
PLoS ONE
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To date there is a lack of tools to map the spatio-temporal dynamics of diverse cells in experimental heart models. Conventional histology is labor intensive with limited coverage, whereas many imaging techniques do not have sufficiently high enough spatial resolution to map cell distributions. We have designed and built a high resolution, dual channel Born-normalized near-infrared fluorescence optical projection tomography system to quantitatively and spatially resolve molecular agents distribution within whole murine heart. We validated the use of the system in a mouse model of monocytes/macrophages recruitment during myocardial infarction. While acquired, data were processed and reconstructed in real time. Tomographic analysis and visualization of the key inflammatory components were obtained via a mathematical formalism based on left ventricular modeling. We observed extensive monocyte recruitment within and around the infarcted areas and discovered that monocytes were also extensively recruited into non-ischemic myocardium, beyond that of injured tissue, such as the septum.
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High resolution tumor targeting in living mice by means of multispectral optoacoustic tomography.
EJNMMI Res
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Tumor targeting is of high clinical and biological relevance, and major efforts have been made to develop molecular imaging technologies for visualization of the disease markers in tissue. Of particular interest is apoptosis which has a profound role within tumor development and has significant effect on cancer malignancy.
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Motion clustering for deblurring multispectral optoacoustic tomography images of the mouse heart.
J Biomed Opt
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Cardiac imaging in small animals is a valuable tool in basic biological research and drug discovery for cardiovascular disease. Multispectral optoacoustic tomography (MSOT) represents an emerging imaging modality capable of visualizing specific tissue chromophores at high resolution and deep in tissues in vivo by separating their spectral signatures. Whereas single-wavelength images can be acquired by multielement ultrasound detection in real-time imaging, using multiple wavelengths at separate times can lead to image blurring due to motion during acquisition. Therefore, MSOT imaging of the heart results in degraded resolution because of the heartbeat. In this work, we applied a clustering algorithm, k-means, to automatically separate a sequence of single-pulse images at multiple excitation wavelengths into clusters corresponding to different stages of the cardiac cycle. We then performed spectral unmixing on each cluster to obtain images of tissue intrinsic chromophores at different cardiac stages, showing reduced sensitivity to motion compared to signal averaging without clustering. We found that myocardium images of improved resolution and contrast can be achieved using MSOT motion clustering correction. The correction method presented could be generally applied to other MSOT imaging applications prone to motion artifacts, for example, by respiration and heartbeat.
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Efficient framework for model-based tomographic image reconstruction using wavelet packets.
IEEE Trans Med Imaging
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The use of model-based algorithms in tomographic imaging offers many advantages over analytical inversion methods. However, the relatively high computational complexity of model-based approaches often restricts their efficient implementation. In practice, many modern imaging modalities, such as computed-tomography, positron-emission tomography, or optoacoustic tomography, normally use a very large number of pixels/voxels for image reconstruction. Consequently, the size of the forward-model matrix hinders the use of many inversion algorithms. In this paper, we present a new framework for model-based tomographic reconstructions, which is based on a wavelet-packet representation of the imaged object and the acquired projection data. The frequency localization property of the wavelet-packet base leads to an approximately separable model matrix, for which reconstruction at each spatial frequency band is independent and requires only a fraction of the projection data. Thus, the large model matrix is effectively separated into a set of smaller matrices, facilitating the use of inversion schemes whose complexity is highly nonlinear with respect to matrix size. The performance of the new methodology is demonstrated for the case of 2-D optoacoustic tomography for both numerically generated and experimental data.
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Acceleration of optoacoustic model-based reconstruction using angular image discretization.
IEEE Trans Med Imaging
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Optoacoustic tomography has recently demonstrated powerful performance in small animal imaging and initial clinical trials in terms of the high spatial resolution, versatile contrast, and dynamic imaging capabilities it can provide. Yet, the current optoacoustic image reconstruction methods are usually based on inaccurate forward modelling approaches or otherwise demand a high computational cost, which imposes certain practical limitations and hinders image quantification. Herein, we introduce a new method for accelerating optoacoustic reconstructions, based on angular image discretization of the forward model solution. The method is particularly suitable for accurate image reconstruction with arbitrary meshes and space-dependent resolution, while it can also readily account for small speed of sound variations without compromising the calculation speed. It is further anticipated that the new approach will greatly facilitate development of high performance 3-D optoacoustic reconstruction methods.
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Fast multispectral optoacoustic tomography (MSOT) for dynamic imaging of pharmacokinetics and biodistribution in multiple organs.
PLoS ONE
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The characterization of pharmacokinetic and biodistribution profiles is an essential step in the development process of new candidate drugs or imaging agents. Simultaneously, the assessment of organ function related to the uptake and clearance of drugs is of great importance. To this end, we demonstrate an imaging platform capable of high-rate characterization of the dynamics of fluorescent agents in multiple organs using multispectral optoacoustic tomography (MSOT). A spatial resolution of approximately 150 µm through mouse cross-sections allowed us to image blood vessels, the kidneys, the liver and the gall bladder. In particular, MSOT was employed to characterize the removal of indocyanine green from the systemic circulation and its time-resolved uptake in the liver and gallbladder. Furthermore, it was possible to track the uptake of a carboxylate dye in separate regions of the kidneys. The results demonstrate the acquisition of agent concentration metrics at rates of 10 samples per second at a single wavelength and 17 s per multispectral sample with 10 signal averages at each of 5 wavelengths. Overall, such imaging performance introduces previously undocumented capabilities of fast, high resolution in vivo imaging of the fate of optical agents for drug discovery and basic biological research.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.