The Experts below are selected from a list of 4389 Experts worldwide ranked by ideXlab platform
Lihong V Wang - One of the best experts on this subject based on the ideXlab platform.
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High-throughput, label-free, single-cell Photoacoustic Microscopy of intratumoral metabolic heterogeneity
Nature Biomedical Engineering, 2019Co-Authors: Toru Imai, Ruiying Zhang, Song Xu, Lihong V WangAbstract:Single-cell Photoacoustic Microscopy can perform high-throughput measurements of intratumoral metabolic heterogeneity in specimens from patients with breast cancer. Intratumoral heterogeneity, which is manifested in almost all of the hallmarks of cancer, including the significantly altered metabolic profiles of cancer cells, represents a challenge to effective cancer therapy. High-throughput measurements of the metabolism of individual cancer cells would allow direct visualization and quantification of intratumoral metabolic heterogeneity, yet the throughputs of current measurement techniques are limited to about 120 cells per hour. Here, we show that single-cell Photoacoustic Microscopy can reach throughputs of approximately 12,000 cells per hour by trapping single cells with blood in an oxygen-diffusion-limited high-density microwell array and by using Photoacoustic imaging to measure the haemoglobin oxygen change (that is, the oxygen consumption rate) in the microwells. We demonstrate the capability of this label-free technique by performing high-throughput single-cell oxygen-consumption-rate measurements of cultured cells and by imaging intratumoral metabolic heterogeneity in specimens from patients with breast cancer. High-throughput single-cell Photoacoustic Microscopy of oxygen consumption rates should enable the faster characterization of intratumoral metabolic heterogeneity.
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high throughput ultraviolet Photoacoustic Microscopy with multifocal excitation
Journal of Biomedical Optics, 2018Co-Authors: Junhui Shi, Terence T. W. Wong, Toru Imai, Liren Zhu, Lihong V WangAbstract:Ultraviolet Photoacoustic Microscopy (UV-PAM) is a promising intraoperative tool for surgical margin assessment (SMA), one that can provide label-free histology-like images with high resolution. In this study, using a microlens array and a one-dimensional (1-D) array ultrasonic transducer, we developed a high-throughput multifocal UV-PAM (MF-UV-PAM). Our new system achieved a 1.6 ± 0.2 μm lateral resolution and produced images 40 times faster than the previously developed point-by-point scanning UV-PAM. MF-UV-PAM provided a readily comprehensible Photoacoustic image of a mouse brain slice with specific absorption contrast in ∼16 min, highlighting cell nuclei. Individual cell nuclei could be clearly resolved, showing its practical potential for intraoperative SMA.
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label free cell nuclear imaging by gruneisen relaxation Photoacoustic Microscopy
Optics Letters, 2018Co-Authors: Xiaowei Liu, Junhui Shi, Terence T. W. Wong, Qing Yang, Lihong V WangAbstract:Photoacoustic Microscopy (PAM) with ultraviolet (UV) laser illumination has recently been demonstrated as a promising tool that provides fast, label-free, and multilayered histologic imaging of human breast tissue. Thus far, the axial resolution has been determined ultrasonically. To enable optically defined axial resolution, we exploit the Gruneisen relaxation (GR) effect. By imaging mouse brain slices, we show that GRUV-PAM reveals detailed information about three-dimensional cell nuclear distributions and internal structures, which are important diagnostic features for cancers. Due to the nonlinear effect, GRUV-PAM also provides better contrast in images of cell nuclei.
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motionless volumetric Photoacoustic Microscopy with spatially invariant resolution
Nature Communications, 2017Co-Authors: Jiamiao Yang, Lei Gong, Pengfei Hai, Yuecheng Shen, Yuta Suzuki, Lihong V WangAbstract:Photoacoustic Microscopy (PAM) is uniquely positioned for biomedical applications because of its ability to visualize optical absorption contrast in vivo in three dimensions. Here we propose motionless volumetric spatially invariant resolution Photoacoustic Microscopy (SIR-PAM). To realize motionless volumetric imaging, SIR-PAM combines two-dimensional Fourier-spectrum optical excitation with single-element depth-resolved Photoacoustic detection. To achieve spatially invariant lateral resolution, propagation-invariant sinusoidal fringes are generated by a digital micromirror device. Further, SIR-PAM achieves 1.5 times finer lateral resolution than conventional PAM. The superior performance was demonstrated in imaging both inanimate objects and animals in vivo with a resolution-invariant axial range of 1.8 mm, 33 times the depth of field of the conventional PAM counterpart. Our work opens new perspectives for PAM in biomedical sciences.
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handheld optical resolution Photoacoustic Microscopy
Journal of Biomedical Optics, 2016Co-Authors: Li Lin, Lidai Wang, Junhui Shi, Junjie Yao, Pengfei Zhang, Jun Zou, Lihong V WangAbstract:Optical-resolution Photoacoustic Microscopy (OR-PAM) offers label-free in vivo imaging with high spatial resolution by acoustically detecting optical absorption contrasts via the Photoacoustic effect. We developed a compact handheld OR-PAM probe for fast Photoacoustic imaging. Different from benchtop microscopes, the handheld probe provides flexibility in imaging various anatomical sites. Resembling a cup in size, the probe uses a two-axis water-immersible microelectromechanical system mirror to scan both the illuminating optical beam and resultant acoustic beam. The system performance was tested in vivo by imaging the capillary bed in a mouse ear and both the capillary bed and a mole on a human volunteer.
Konstantin Maslov - One of the best experts on this subject based on the ideXlab platform.
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high speed label free functional Photoacoustic Microscopy of mouse brain in action
Nature Methods, 2015Co-Authors: Junjie Yao, Konstantin Maslov, Terence T. W. Wong, Lidai Wang, Jun Zou, Joonmo Yang, Chihhsien Huang, Lihong V WangAbstract:We present fast functional Photoacoustic Microscopy (PAM) for three-dimensional high-resolution, high-speed imaging of the mouse brain, complementary to other imaging modalities. We implemented a single-wavelength pulse-width-based method with a one-dimensional imaging rate of 100 kHz to image blood oxygenation with capillary-level resolution. We applied PAM to image the vascular morphology, blood oxygenation, blood flow and oxygen metabolism in both resting and stimulated states in the mouse brain.
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near infrared optical resolution Photoacoustic Microscopy
Optics Letters, 2014Co-Authors: Pengfei Hai, Konstantin Maslov, Junjie Yao, Yong Zhou, Lihong V WangAbstract:Compared with visible light (380–700 nm), near-infrared light (700–1400 nm) undergoes weaker optical attenuation in biological tissue; thus, it can penetrate deeper. Herein, we demonstrate near-infrared optical-resolution Photoacoustic Microscopy (NIR-OR-PAM) with 1046 nm illumination. A penetration depth of 3.2 mm was achieved in chicken breast tissue ex vivo using optical fluence within the American National Standards Institute (ANSI) limit (100 mJ/cm^2). Beyond ∼0.6 mm deep in chicken breast tissue, NIR-OR-PAM has shown finer resolution than the visible counterpart with 570 nm illumination. The deep imaging capability of NIR-OR-PAM was validated in both a mouse ear and a mouse brain. NIR-OR-PAM of possible lipid contrast was explored as well.
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handheld Photoacoustic Microscopy to detect melanoma depth in vivo
Optics Letters, 2014Co-Authors: Yong Zhou, Konstantin Maslov, Wenxin Xing, Lynn A Cornelius, Lihong V WangAbstract:We developed handheld Photoacoustic Microscopy (PAM) to detect melanoma and determine tumor depth in nude mice in vivo. Compared to our previous PAM system for melanoma imaging, a new light delivery mechanism is introduced to improve light penetration. We show that melanomas with 4.1 and 3.7 mm thicknesses can be successfully detected in phantom and in in vivo experiments, respectively. With its deep melanoma imaging ability and handheld design, this system can be tested for clinical melanoma diagnosis, prognosis, and surgical planning for patients at the bedside.
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fully motorized optical resolution Photoacoustic Microscopy
IEEE Transactions on Biomedical Engineering, 2014Co-Authors: Chenghung Yeh, Kirk K. Shung, Konstantin Maslov, Lidai Wang, Ruimin Chen, Qifa Zhou, Brian T Soetikno, Lihong V WangAbstract:Fully motorized optical-resolution Photoacoustic Microscopy integrates five complementary scanning modes and simultaneously provides a high imaging speed (2 kHz B-scan rate) and a large field of view (10×8 mm2) for fast quantitative imaging.
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fully motorized optical resolution Photoacoustic Microscopy
Optics Letters, 2014Co-Authors: Chenghung Yeh, Kirk K. Shung, Konstantin Maslov, Lidai Wang, Ruimin Chen, Qifa Zhou, Brian T Soetikno, Lihong V WangAbstract:We have developed fully motorized optical-resolution Photoacoustic Microscopy (OR-PAM), which integrates five complementary scanning modes and simultaneously provides a high imaging speed and a wide field of view (FOV) with 2.6 μm lateral resolution. With one-dimensional (1D) motion-mode mechanical scanning, we measured the blood flow through a cross section of a blood vessel in vivo. With two-dimensional (2D) optical scanning at a laser repetition rate of 40 kHz, we achieved a 2 kHz B-scan rate over a range of 50 μm with 20 A-lines and 50 Hz volumetric-scan rate over a FOV of 50 μm×50 μm with 400 A-lines, which enabled real-time tracking of cellular dynamics in vivo. With synchronized 1D optical and 2D mechanical hybrid scanning, we imaged a 10 mm×8 mm FOV within three minutes, which is 20 times faster than the conventional mechanical scan in our second-generation OR-PAM. With three-dimensional mechanical contour scanning, we maintained the optimal signal-to-noise ratio and spatial resolution of OR-PAM while imaging objects with uneven surfaces, which is essential for quantitative studies.
Hao Zhang - One of the best experts on this subject based on the ideXlab platform.
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isometric multimodal Photoacoustic Microscopy based on optically transparent micro ring ultrasonic detection
Optica, 2015Co-Authors: Biqin Dong, Zhen Zhang, Kevin Zhang, Siyu Chen, Cheng Sun, Hao ZhangAbstract:Photoacoustic Microscopy (PAM) is an attractive imaging tool complementary to established optical microscopic modalities by providing additional molecular specificities through imaging optical absorption contrast. While the development of optical resolution Photoacoustic Microscopy (ORPAM) offers high lateral resolution, the acoustically-determined axial resolution is limited due to the constraint in ultrasonic detection bandwidth. ORPAM with isometric spatial resolution along both axial and lateral direction is yet to be developed. Although recently developed sophisticated optical illumination and reconstruction methods offer improved axial resolution in ORPAM, the image acquisition procedures are rather complicated, limiting their capabilities for high-speed imaging and being easily integrated with established optical microscopic modalities. Here we report an isometric ORPAM based on an optically transparent micro-ring resonator ultrasonic detector and a commercial inverted microscope platform. Owing to the superior spatial resolution and the ease of integrating our ORPAM with established microscopic modalities, single cell imaging with extrinsic fluorescence staining, intrinsic autofluorescence, and optical absorption can be achieved simultaneously. This technique holds promise to greatly improve the accessibility of PAM to the broader biomedical researchers.
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in vivo corneal neovascularization imaging by optical resolution Photoacoustic Microscopy
Photoacoustics, 2014Co-Authors: Wenzhong Liu, Kathry M Schultz, Kevi Zhang, Amy Sasma, Fengli Gao, Tsutomu Kume, Hao ZhangAbstract:Corneal neovascularization leads to blurred vision, thus in vivo visualization is essential for pathological studies in animal models. Photoacoustic (PA) imaging can delineate microvasculature and hemodynamics noninvasively, which is suitable for investigating corneal neovascularization. In this study, we demonstrate in vivo imaging of corneal neovascularization in the mouse eye by optical-resolution Photoacoustic Microscopy (OR-PAM), where corneal neovascularization is induced by deliberate alkali burn injuries in C57BL6/J inbred mice corneas on the left eye. We used OR-PAM to image five mice with corneal alkali burn injuries; the uninjured eyes (right eye) in these mice are then used as the controls. Corneal images acquired by OR-PAM with and without alkali burn injury are compared, clear signs of corneal neovascularization are present in the OR-PAM images of injured eyes; the OR-PAM results are also confirmed by postmortem fluorescence-labeled confocal Microscopy.
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laser scanning Photoacoustic Microscopy with ultrasonic phased array transducer
Biomedical Optics Express, 2012Co-Authors: Fan Zheng, Chi Tat Chiu, Bill L Zhou, Kirk K. Shung, Xiangyang Zhang, Hao Zhang, Shuliang JiaoAbstract:In this paper, we report our latest progress on proving the concept that ultrasonic phased array can improve the detection sensitivity and field of view (FOV) in laser-scanning Photoacoustic Microscopy (LS-PAM). A LS-PAM system with a one-dimensional (1D) ultrasonic phased array was built for the experiments. The 1D phased array transducer consists of 64 active elements with an overall active dimension of 3.2 mm × 2 mm. The system was tested on imaging phantom and mouse ear in vivo. Experiments showed a 15 dB increase of the signal-to-noise ratio (SNR) when beamforming was employed compared to the images acquired with each single element. The experimental results demonstrated that ultrasonic phased array can be a better candidate for LS-PAM in high sensitivity applications like ophthalmic imaging.
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optical coherence Photoacoustic Microscopy accomplishing optical coherence tomography and Photoacoustic Microscopy with a single light source
Journal of Biomedical Optics, 2012Co-Authors: Xiangyang Zhang, Hao Zhang, Shuliang JiaoAbstract:We developed optical coherence Photoacoustic Microscopy (OC-PAM) to demonstrate that the functions of optical coherence tomography (OCT) and Photoacoustic Microscopy (PAM) can be achieved simultaneously by using a single illuminating light source. We used a pulsed broadband laser centered at 580 nm and detected the absorbed photons through Photoacoustic detection and the back-scattered photons with an interferometer. In OC-PAM, each laser pulse generates both one OCT A-line and one PAM A-line simultaneously; as a result, the two imaging modalities are intrinsically co-registered in the lateral directions. In vivo images of the mouse ear were acquired to demonstrate the capabilities of OC-PAM.
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collecting back reflected photons in Photoacoustic Microscopy
Optics Express, 2010Co-Authors: Hao Zhang, Shuliang Jiao, Jing Wang, Qing Wei, Tan Liu, Carmen A PuliafitoAbstract:Since the Photoacoustic effect relies only on the absorbed optical energy, the back-reflected photons from samples in optical-resolution Photoacoustic Microscopy are usually discarded. By employing a 2 × 2 single-mode fiber optical coupler in a laser-scanning optical-resolution Photoacoustic microscope for delivering the illuminating laser light and collecting the back reflected photons, a fiber-optic confocal microscope is integrated with the Photoacoustic microscope. Thus, simultaneous multimodal imaging can be achieved with a single light source and images from the two modalities are intrinsically registered. Such capabilities are demonstrated in imaging both phantoms and small animals in vivo.
Shuliang Jiao - One of the best experts on this subject based on the ideXlab platform.
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optical coherence Photoacoustic Microscopy for in vivo multimodal retinal imaging
Optics Letters, 2015Co-Authors: Yiwen Li, Hao F. Zhang, Carmen A Puliafito, Shuliang JiaoAbstract:We developed an optical coherence Photoacoustic Microscopy (OC-PAM) system, which can accomplish optical coherence tomography (OCT) and Photoacoustic Microscopy (PAM) simultaneously by using a single pulsed broadband light source. With a center wavelength of 800 nm and a bandwidth of 30 nm, the system is suitable for imaging the retina. Generated from the same group of photons, the OCT and PAM images are intrinsically registered in the lateral directions. To test the capabilities of the system on multimodal ophthalmic imaging, we imaged the retina of pigmented rats. The OCT images showed the retinal structures with quality similar to conventional OCT, while the PAM images revealed the distribution of absorbers in the retina. Since the absorption of hemoglobin is relatively weak at around 800 nm, the NIR PAM signals are generated mainly from melanin in the posterior segment of the eye, thus providing melanin-specific imaging of the retina.
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laser scanning Photoacoustic Microscopy with ultrasonic phased array transducer
Biomedical Optics Express, 2012Co-Authors: Fan Zheng, Chi Tat Chiu, Bill L Zhou, Kirk K. Shung, Xiangyang Zhang, Hao Zhang, Shuliang JiaoAbstract:In this paper, we report our latest progress on proving the concept that ultrasonic phased array can improve the detection sensitivity and field of view (FOV) in laser-scanning Photoacoustic Microscopy (LS-PAM). A LS-PAM system with a one-dimensional (1D) ultrasonic phased array was built for the experiments. The 1D phased array transducer consists of 64 active elements with an overall active dimension of 3.2 mm × 2 mm. The system was tested on imaging phantom and mouse ear in vivo. Experiments showed a 15 dB increase of the signal-to-noise ratio (SNR) when beamforming was employed compared to the images acquired with each single element. The experimental results demonstrated that ultrasonic phased array can be a better candidate for LS-PAM in high sensitivity applications like ophthalmic imaging.
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optical coherence Photoacoustic Microscopy accomplishing optical coherence tomography and Photoacoustic Microscopy with a single light source
Journal of Biomedical Optics, 2012Co-Authors: Xiangyang Zhang, Hao Zhang, Shuliang JiaoAbstract:We developed optical coherence Photoacoustic Microscopy (OC-PAM) to demonstrate that the functions of optical coherence tomography (OCT) and Photoacoustic Microscopy (PAM) can be achieved simultaneously by using a single illuminating light source. We used a pulsed broadband laser centered at 580 nm and detected the absorbed photons through Photoacoustic detection and the back-scattered photons with an interferometer. In OC-PAM, each laser pulse generates both one OCT A-line and one PAM A-line simultaneously; as a result, the two imaging modalities are intrinsically co-registered in the lateral directions. In vivo images of the mouse ear were acquired to demonstrate the capabilities of OC-PAM.
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collecting back reflected photons in Photoacoustic Microscopy
Optics Express, 2010Co-Authors: Hao Zhang, Shuliang Jiao, Jing Wang, Qing Wei, Tan Liu, Carmen A PuliafitoAbstract:Since the Photoacoustic effect relies only on the absorbed optical energy, the back-reflected photons from samples in optical-resolution Photoacoustic Microscopy are usually discarded. By employing a 2 × 2 single-mode fiber optical coupler in a laser-scanning optical-resolution Photoacoustic microscope for delivering the illuminating laser light and collecting the back reflected photons, a fiber-optic confocal microscope is integrated with the Photoacoustic microscope. Thus, simultaneous multimodal imaging can be achieved with a single light source and images from the two modalities are intrinsically registered. Such capabilities are demonstrated in imaging both phantoms and small animals in vivo.
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simultaneous multimodal imaging with integrated Photoacoustic Microscopy and optical coherence tomography
Optics Letters, 2009Co-Authors: Shuliang Jiao, Hao Zhang, Zhixing Xie, Carmen A PuliafitoAbstract:We have developed a multimodal imaging technique by integrating Photoacoustic Microscopy and spectral-domain optical coherence tomography to provide simultaneous volumetric microscopic imaging of both optical absorption and scattering contrasts in biological tissues. In the integrated system, the two imaging modalities share the same optical scanning and delivery mechanisms after their probing and illumination light beams are combined. By further synchronizing the image acquisitions, the images from the two modalities are intrinsically registered. The capabilities of this novel technique were demonstrated by imaging both the microanatomy and microvasculature in mouse ears in vivo.
Liang Song - One of the best experts on this subject based on the ideXlab platform.
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delay multiply and sum based synthetic aperture focusing in Photoacoustic Microscopy
Journal of Biomedical Optics, 2016Co-Authors: Jongin Park, Liang Song, Jing Meng, Seungwan Jeon, Jin S Lee, Chulhong KimAbstract:We propose an improved version of a synthetic aperture focusing technique (SAFT) based on a delay-multiply-and-sum algorithm for acoustic-resolution Photoacoustic Microscopy (AR-PAM). In this method, the Photoacoustic (PA) signals from multiple scan-lines are combinatorially coupled, multiplied, and then summed. This process can be considered a correlation operation of the PA signals in each scan-line, so the spatial coherent information between the PA signals can be efficiently extracted. By applying this method in conventional AR-PAM, lateral resolution and signal-to-noise ratio in out-of-focus regions are much improved compared with those estimated from the previously developed SAFT, respectively, thereby achieving the extension of the imaging focal region. Our phantom and in vivo imaging experiments prove the validity of our proposed method.
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reflection mode in vivo Photoacoustic Microscopy with subwavelength lateral resolution
Biomedical Optics Express, 2014Co-Authors: Wei Song, Riqiang Lin, Wei Zheng, Ruimin Liu, Hongtao Huang, Xiaojing Gong, Shousheng Yang, Rui Zhang, Liang SongAbstract:We developed a reflection-mode subwavelength-resolution Photoacoustic Microscopy system capable of imaging optical absorption contrast in vivo. The simultaneous high-resolution and reflection-mode imaging capacity of the system was enabled by delicately configuring a miniature high-frequency ultrasonic transducer tightly under a water-immersion objective with numerical aperture of 1.0. At 532-nm laser illumination, the lateral resolution of the system was measured to be ~320 nm. With this system, subcellular structures of red blood cells and B16 melanoma cells were resolved ex vivo; microvessels, including individual capillaries, in a mouse ear were clearly imaged label-freely in vivo, using the intrinsic optical absorption from hemoglobin. The current study suggests that, the optical-absorption contrast, subwavelength resolution, and reflection-mode ability of the developed Photoacoustic Microscopy may empower a wide range of biomedical studies for visualizing cellular and/or subcellular structures.
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blind deconvolution optical resolution Photoacoustic Microscopy in vivo
Optics Express, 2013Co-Authors: Jianhua Chen, Riqiang Lin, Huina Wang, Jing Meng, Hairong Zheng, Liang SongAbstract:Optical-resolution Photoacoustic Microscopy (OR-PAM) is becoming a vital tool for studying the microcirculation system in vivo. By increasing the numerical aperture of optical focusing, the lateral resolution of OR-PAM can be improved; however, the depth of focus and thus the imaging range will be sacrificed correspondingly. In this work, we report our development of blind-deconvolution optical-resolution Photoacoustic Microscopy (BD-PAM) that can provide a lateral resolution ~2-fold finer than that of conventional OR-PAM (3.04 vs. 5.78μm), without physically increasing the system's numerical aperture. The improvement achieved with BD-PAM is demonstrated by imaging graphene nanoparticles and the microvasculature of mice ears in vivo. Our results suggest that BD-PAM may become a valuable tool for many biomedical applications that require both fine spatial resolution and extended depth of focus.
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multifocal optical resolution Photoacoustic Microscopy in vivo
Optics Letters, 2011Co-Authors: Liang Song, Konstantin Maslov, Lihong V WangAbstract:Although ultrasound arrays have been exploited in Photoacoustic imaging to improve imaging speed, ultrasound-array-based optical-resolution Photoacoustic Microscopy (OR-PAM) has never been achieved previously to our knowledge. Here we present our development of multifocal OR-PAM using a microlens array for optical illumination and an ultrasound array for Photoacoustic detection. Our system is capable of imaging hemoglobin concentration and oxygenation in individual microvessels in vivo at high speed. Compared with a single focus, multiple foci reduce the scanning load and increase the imaging speed significantly. The current multifocal system can acquire 1000×500×200 voxels at ∼10 μm lateral resolution within 4 min.
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Fast 3-D dark-field reflection-mode Photoacoustic Microscopy in vivo with a 30-MHz ultrasound linear array
Journal of Biomedical Optics, 2008Co-Authors: Liang Song, Rachel Bitton, Kirk K. Shung, Konstantin Maslov, Lihong V WangAbstract:We present an in vivo dark-field reflection-mode Photoacoustic Microscopy system that performs cross-sectional (B-scan) imaging at 50Hz with real-time beamforming and 3-D imaging consisting of 166 B-scan frames at 1Hz with postbeamforming. To our knowledge, this speed is currently the fastest in Photoacoustic imaging. A custom-designed light delivery system is integrated with a 30-MHz ultrasound linear array to realize dark-field reflection-mode imaging. Linear mechanical scanning of the array produces 3-D images. The system has axial, lateral, and elevational resolutions of 25, 70, and 200μm, respectively, and can image 3mm deep in scattering biological tissues. Volumetric images of subcutaneous vasculature in rats are demonstrated in vivo. Fast 3-D Photoacoustic Microscopy is anticipated to facilitate applications of Photoacoustic imaging in biomedical studies that involve dynamics and clinical procedures that demand immediate diagnosis.