Browsing by Author "Yao, Junjie"
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Item Open Access A practical guide to photoacoustic tomography in the life sciences.(Nat Methods, 2016-07-28) Wang, Lihong V; Yao, JunjieThe life sciences can benefit greatly from imaging technologies that connect microscopic discoveries with macroscopic observations. One technology uniquely positioned to provide such benefits is photoacoustic tomography (PAT), a sensitive modality for imaging optical absorption contrast over a range of spatial scales at high speed. In PAT, endogenous contrast reveals a tissue's anatomical, functional, metabolic, and histologic properties, and exogenous contrast provides molecular and cellular specificity. The spatial scale of PAT covers organelles, cells, tissues, organs, and small animals. Consequently, PAT is complementary to other imaging modalities in contrast mechanism, penetration, spatial resolution, and temporal resolution. We review the fundamentals of PAT and provide practical guidelines for matching PAT systems with research needs. We also summarize the most promising biomedical applications of PAT, discuss related challenges, and envision PAT's potential to lead to further breakthroughs.Item Open Access Author Correction: Deep-tissue SWIR imaging using rationally designed small red-shifted near-infrared fluorescent protein.(Nature methods, 2023-02) Oliinyk, Olena S; Ma, Chenshuo; Pletnev, Sergei; Baloban, Mikhail; Taboada, Carlos; Sheng, Huaxin; Yao, Junjie; Verkhusha, Vladislav VIn the version of this article originally published, the surname of Carlos Taboada was misspelled (Toboada) and has now been corrected in the HTML and PDF versions of the article.Item Open Access Deep image prior for undersampling high-speed photoacoustic microscopy.(Photoacoustics, 2021-06) Vu, Tri; DiSpirito, Anthony; Li, Daiwei; Wang, Zixuan; Zhu, Xiaoyi; Chen, Maomao; Jiang, Laiming; Zhang, Dong; Luo, Jianwen; Zhang, Yu Shrike; Zhou, Qifa; Horstmeyer, Roarke; Yao, JunjiePhotoacoustic microscopy (PAM) is an emerging imaging method combining light and sound. However, limited by the laser's repetition rate, state-of-the-art high-speed PAM technology often sacrifices spatial sampling density (i.e., undersampling) for increased imaging speed over a large field-of-view. Deep learning (DL) methods have recently been used to improve sparsely sampled PAM images; however, these methods often require time-consuming pre-training and large training dataset with ground truth. Here, we propose the use of deep image prior (DIP) to improve the image quality of undersampled PAM images. Unlike other DL approaches, DIP requires neither pre-training nor fully-sampled ground truth, enabling its flexible and fast implementation on various imaging targets. Our results have demonstrated substantial improvement in PAM images with as few as 1.4 % of the fully sampled pixels on high-speed PAM. Our approach outperforms interpolation, is competitive with pre-trained supervised DL method, and is readily translated to other high-speed, undersampling imaging modalities.Item Open Access Deep Photoacoustic Imaging and Acoustic Cavitation Mapping in Shockwave Lithotripsy(2022) Li, MucongKidney stone disease is a major health problem worldwide. Shockwave lithotripsy (SWL), which uses high-energy shockwave pulses to break up kidney stones, is extensively used in clinic. However, SWL can produce cavitation in vivo, and the rapid expansion and violent collapse of cavitation bubbles in small blood vessels may result in renal vascular injury. Current imaging modalities used in SWL (e.g., C-arm fluoroscopy and B-mode ultrasound) are not sensitive to vascular injuries. To better understand the mechanism of tissue injury and improve treatment safety and efficiency, it is highly desirable to concurrently detect cavitation and vascular injury during SWL. Photoacoustic imaging that is sensitive to hemoglobin can be used to monitor hemorrhage during shockwave treatment. An internal illumination strategy combined with a graded scattering fiber diffuser was applied to achieve uniform light distribution and extend the imaging depth to ~10 cm. Moreover, a sliding-window passive cavitation mapping approach was developed and validated to provide accurate temporal and spatial information about cavitation bubble collapses. Finally, we have seamlessly integrated shockwave treatment, photoacoustic imaging, and cavitation detection into a single system. Our experiment results based on phantoms and in vivo animal studies have collectively demonstrated that the integrated system is capable of capturing shockwave-induced cavitation and deeply located vascular injury during the stone treatment.
Item Open Access Deep-tissue SWIR imaging using rationally designed small red-shifted near-infrared fluorescent protein.(Nature methods, 2023-01) Oliinyk, Olena S; Ma, Chenshuo; Pletnev, Sergei; Baloban, Mikhail; Taboada, Carlos; Sheng, Huaxin; Yao, Junjie; Verkhusha, Vladislav VApplying rational design, we developed 17 kDa cyanobacteriochrome-based near-infrared (NIR-I) fluorescent protein, miRFP718nano. miRFP718nano efficiently binds endogenous biliverdin chromophore and brightly fluoresces in mammalian cells and tissues. miRFP718nano has maximal emission at 718 nm and an emission tail in the short-wave infrared (SWIR) region, allowing deep-penetrating off-peak fluorescence imaging in vivo. The miRFP718nano structure reveals the molecular basis of its red shift. We demonstrate superiority of miRFP718nano-enabled SWIR imaging over NIR-I imaging of microbes in the mouse digestive tract, mammalian cells injected into the mouse mammary gland and NF-kB activity in a mouse model of liver inflammation.Item Open Access Dissimilar cavitation dynamics and damage patterns produced by parallel fiber alignment to the stone surface in holmium:yttrium aluminum garnet laser lithotripsy.(Physics of fluids (Woodbury, N.Y. : 1994), 2023-03) Xiang, Gaoming; Li, Daiwei; Chen, Junqin; Mishra, Arpit; Sankin, Georgy; Zhao, Xuning; Tang, Yuqi; Wang, Kevin; Yao, Junjie; Zhong, PeiRecent studies indicate that cavitation may play a vital role in laser lithotripsy. However, the underlying bubble dynamics and associated damage mechanisms are largely unknown. In this study, we use ultra-high-speed shadowgraph imaging, hydrophone measurements, three-dimensional passive cavitation mapping (3D-PCM), and phantom test to investigate the transient dynamics of vapor bubbles induced by a holmium:yttrium aluminum garnet laser and their correlation with solid damage. We vary the standoff distance (SD) between the fiber tip and solid boundary under parallel fiber alignment and observe several distinctive features in bubble dynamics. First, long pulsed laser irradiation and solid boundary interaction create an elongated "pear-shaped" bubble that collapses asymmetrically and forms multiple jets in sequence. Second, unlike nanosecond laser-induced cavitation bubbles, jet impact on solid boundary generates negligible pressure transients and causes no direct damage. A non-circular toroidal bubble forms, particularly following the primary and secondary bubble collapses at SD = 1.0 and 3.0 mm, respectively. We observe three intensified bubble collapses with strong shock wave emissions: the intensified bubble collapse by shock wave, the ensuing reflected shock wave from the solid boundary, and self-intensified collapse of an inverted "triangle-shaped" or "horseshoe-shaped" bubble. Third, high-speed shadowgraph imaging and 3D-PCM confirm that the shock origins from the distinctive bubble collapse form either two discrete spots or a "smiling-face" shape. The spatial collapse pattern is consistent with the similar BegoStone surface damage, suggesting that the shockwave emissions during the intensified asymmetric collapse of the pear-shaped bubble are decisive for the solid damage.Item Open Access High-speed label-free functional photoacoustic microscopy of mouse brain in action.(Nat Methods, 2015-05) Yao, Junjie; Wang, Lidai; Yang, Joon-Mo; Maslov, Konstantin I; Wong, Terence TW; Li, Lei; Huang, Chih-Hsien; Zou, Jun; Wang, Lihong VWe 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.Item Open Access High-speed widefield photoacoustic microscopy of small-animal hemodynamics.(Biomedical optics express, 2018-10) Lan, Bangxin; Liu, Wei; Wang, Ya-Chao; Shi, Junhui; Li, Yang; Xu, Song; Sheng, Huaxin; Zhou, Qifa; Zou, Jun; Hoffmann, Ulrike; Yang, Wei; Yao, JunjieOptical-resolution photoacoustic microscopy (OR-PAM) has become a popular tool in small-animal hemodynamic studies. However, previous OR-PAM techniques variously lacked a high imaging speed and/or a large field of view, impeding the study of highly dynamic physiologic and pathophysiologic processes over a large region of interest. Here we report a high-speed OR-PAM system with an ultra-wide field of view, enabled by an innovative water-immersible hexagon-mirror scanner. By driving the hexagon-mirror scanner with a high-precision DC motor, the new OR-PAM has achieved a cross-sectional frame rate of 900 Hz over a 12-mm scanning range, which is 3900 times faster than our previous motor-scanner-based system and 10 times faster than the MEMS-scanner-based system. Using this hexagon-scanner-based OR-PAM system, we have imaged epinephrine-induced vasoconstriction in the whole mouse ear and vascular reperfusion after ischemic stroke in the mouse cortex in vivo, with a high spatial resolution and high volumetric imaging speed. We expect that the hexagon-scanner-based OR-PAM system will become a powerful tool for small animal imaging where the hemodynamic responses over a large field of view are of interest.Item Open Access Longitudinal intravital imaging of mouse placenta.(Science advances, 2024-03) Zhu, Xiaoyi; Huang, Qiang; Jiang, Laiming; Nguyen, Van-Tu; Vu, Tri; Devlin, Garth; Shaima, Jabbar; Wang, Xiaobei; Chen, Yong; Ma, Lijun; Xiang, Kun; Wang, Ergang; Rong, Qiangzhou; Zhou, Qifa; Kang, Yubin; Asokan, Aravind; Feng, Liping; Hsu, Shiao-Wen D; Shen, Xiling; Yao, JunjieStudying placental functions is crucial for understanding pregnancy complications. However, imaging placenta is challenging due to its depth, volume, and motion distortions. In this study, we have developed an implantable placenta window in mice that enables high-resolution photoacoustic and fluorescence imaging of placental development throughout the pregnancy. The placenta window exhibits excellent transparency for light and sound. By combining the placenta window with ultrafast functional photoacoustic microscopy, we were able to investigate the placental development during the entire mouse pregnancy, providing unprecedented spatiotemporal details. Consequently, we examined the acute responses of the placenta to alcohol consumption and cardiac arrest, as well as chronic abnormalities in an inflammation model. We have also observed viral gene delivery at the single-cell level and chemical diffusion through the placenta by using fluorescence imaging. Our results demonstrate that intravital imaging through the placenta window can be a powerful tool for studying placenta functions and understanding the placental origins of adverse pregnancy outcomes.Item Open Access Multi-spectral Deep Tissue Quantitative Photoacoustic Imaging(2023) Tang, YuqiPhotoacoustic tomography (PAT) detects the acoustic signals generated by optical absorption from chromophores. Using oxy- and deoxy-hemoglobin, multi-spectral PAT can image vasculature structure, and provide functional information. Most of the current PAT imaging studies face four challenges: heterogeneous fluence distribution in the field of view, shallow penetration depth with external illumination, the limited view problem, and the lack of blood flow sensitivity. These challenges degrade the PAT image quality and limit the functional information accuracy. To improve image fidelity, four approaches were proposed to address the challenges. A 3D Monte Carlo simulation was performed on a mouse brain model for optical fluence estimation at different imaging wavelengths, and the 3D optical fluence map was used for fluence heterogeneity correction. Moreover, an internal illumination strategy combined with a treatment catheter was applied to achieve a deep tissue PAT imaging, allowing PAT imaging guided sonothrombolysis with clot characterization. Additionally, we develop a clinical-translatable method to preserve the functional information from the hemoglobin while improving the structure visibility from vessels at arbitrary orientation. Finally, we integrated ultrasound localization microscopy with PAT to allow non-invasive and comprehensive functional imaging at low frequency. Our experiment results based on phantoms and in vivo animal studies have collectively demonstrated that the PAT image fidelity can be greatly improved.
Item Open Access Multiscale photoacoustic tomography using reversibly switchable bacterial phytochrome as a near-infrared photochromic probe.(Nat Methods, 2016-01) Yao, Junjie; Kaberniuk, Andrii A; Li, Lei; Shcherbakova, Daria M; Zhang, Ruiying; Wang, Lidai; Li, Guo; Verkhusha, Vladislav V; Wang, Lihong VPhotoacoustic tomography (PAT) of genetically encoded probes allows for imaging of targeted biological processes deep in tissues with high spatial resolution; however, high background signals from blood can limit the achievable detection sensitivity. Here we describe a reversibly switchable nonfluorescent bacterial phytochrome for use in multiscale photoacoustic imaging, BphP1, with the most red-shifted absorption among genetically encoded probes. BphP1 binds a heme-derived biliverdin chromophore and is reversibly photoconvertible between red and near-infrared light-absorption states. We combined single-wavelength PAT with efficient BphP1 photoswitching, which enabled differential imaging with substantially decreased background signals, enhanced detection sensitivity, increased penetration depth and improved spatial resolution. We monitored tumor growth and metastasis with ∼ 100-μm resolution at depths approaching 10 mm using photoacoustic computed tomography, and we imaged individual cancer cells with a suboptical-diffraction resolution of ∼ 140 nm using photoacoustic microscopy. This technology is promising for biomedical studies at several scales.Item Embargo On the Development of Full-view Photoacoustic Computed Tomography System for Biomedical Applications(2024) Vu, Tri QuangNoninvasive deep-tissue functional and molecular imaging for small animal has long been the interest of photoacoustic (PA) computed tomography (PACT). However, due to limitation in transducer’s geometry, existing functional PACT methods have severe limited-view artifact leading to image degradation. Worsened by limited bandwidth and insensitivity in low-frequency ranges, these systems potentially have decreased molecular and quantitative sensitivity. In this thesis, we introduce the development of full-view PACT system with ring-array transducer that overcomes these challenges. Its full detection angle along the imaging plane eliminates limited-view artifact for wide-field high-resolution PACT. Exploring the lower band of the frequency spectrum, from the wide bandwidth of the full-view PACT, we illustrate the importance of low-frequency signals to improve functional and quantitative imaging. Biomedical applications such as life-science imaging and therapeutic integration show that the full-view PACT system is a potential solution for in vivo functional imaging at multiscale and multispectral levels.
Item Open Access Photoacoustic imaging of in vivo hemodynamic responses to sodium nitroprusside.(Journal of biophotonics, 2021-03-26) Zhang, Dong; Li, Ran; Chen, Maomao; Vu, Tri; Sheng, Huaxin; Yang, Wei; Hoffmann, Ulrike; Luo, Jianwen; Yao, JunjieThe in vivo hemodynamic impact of sodium nitroprusside (SNP), a widely used antihypertensive agent, has not been well studied. Here, we applied functional optical-resolution photoacoustic microscopy (OR-PAM) to study the hemodynamic responses to SNP in mice in vivo. As expected, after the application of SNP, the systemic blood pressure (BP) was reduced by 53%. The OR-PAM results show that SNP induced an arterial vasodilation of 24% and 23% in the brain and skin, respectively. A weaker venous vasodilation of 9% and 5% was also observed in the brain and skin, respectively. The results show two different types of blood oxygenation response. In mice with decreased blood oxygenation, the arterial and venous oxygenation was respectively reduced by 6% and 13% in the brain, as well as by 7% and 18% in the skin. In mice with increased blood oxygenation, arterial and venous oxygenation was raised by 4% and 22% in the brain, as well as by 1% and 9% in the skin. We observed venous change clearly lagged the arterial change in the skin, but not in the brain. Our results collectively show a correlation among SNP induced changes in systemic BP, vessel size and blood oxygenation.Item Open Access Photoacoustic tomography: principles and advances.(Electromagn Waves (Camb)) Xia, Jun; Yao, Junjie; Wang, Lihong VPhotoacoustic tomography (PAT) is an emerging imaging modality that shows great potential for preclinical research and clinical practice. As a hybrid technique, PAT is based on the acoustic detection of optical absorption from either endogenous chromophores, such as oxy-hemoglobin and deoxy-hemoglobin, or exogenous contrast agents, such as organic dyes and nanoparticles. Because ultrasound scatters much less than light in tissue, PAT generates high-resolution images in both the optical ballistic and diffusive regimes. Over the past decade, the photoacoustic technique has been evolving rapidly, leading to a variety of exciting discoveries and applications. This review covers the basic principles of PAT and its different implementations. Strengths of PAT are highlighted, along with the most recent imaging results.Item Open Access Real-time whole-brain imaging of hemodynamics and oxygenation at micro-vessel resolution with ultrafast wide-field photoacoustic microscopy(Light: Science & Applications, 2022-12) Zhu, Xiaoyi; Huang, Qiang; DiSpirito, Anthony; Vu, Tri; Rong, Qiangzhou; Peng, Xiaorui; Sheng, Huaxin; Shen, Xiling; Zhou, Qifa; Jiang, Laiming; Hoffmann, Ulrike; Yao, JunjieAbstractHigh-speed high-resolution imaging of the whole-brain hemodynamics is critically important to facilitating neurovascular research. High imaging speed and image quality are crucial to visualizing real-time hemodynamics in complex brain vascular networks, and tracking fast pathophysiological activities at the microvessel level, which will enable advances in current queries in neurovascular and brain metabolism research, including stroke, dementia, and acute brain injury. Further, real-time imaging of oxygen saturation of hemoglobin (sO2) can capture fast-paced oxygen delivery dynamics, which is needed to solve pertinent questions in these fields and beyond. Here, we present a novel ultrafast functional photoacoustic microscopy (UFF-PAM) to image the whole-brain hemodynamics and oxygenation. UFF-PAM takes advantage of several key engineering innovations, including stimulated Raman scattering (SRS) based dual-wavelength laser excitation, water-immersible 12-facet-polygon scanner, high-sensitivity ultrasound transducer, and deep-learning-based image upsampling. A volumetric imaging rate of 2 Hz has been achieved over a field of view (FOV) of 11 × 7.5 × 1.5 mm3 with a high spatial resolution of ~10 μm. Using the UFF-PAM system, we have demonstrated proof-of-concept studies on the mouse brains in response to systemic hypoxia, sodium nitroprusside, and stroke. We observed the mouse brain’s fast morphological and functional changes over the entire cortex, including vasoconstriction, vasodilation, and deoxygenation. More interestingly, for the first time, with the whole-brain FOV and micro-vessel resolution, we captured the vasoconstriction and hypoxia simultaneously in the spreading depolarization (SD) wave. We expect the new imaging technology will provide a great potential for fundamental brain research under various pathological and physiological conditions.Item Open Access Three-dimensional super-resolution passive cavitation mapping in laser lithotripsy(IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control, 2024-01-01) Li, Daiwei; Wang, Nanchao; Li, Mucong; Mishra, Arpit; Tang, Yuqi; Vu, Tri; Xiang, Gaoming; Chen, Junqin; Lipkin, Michael; Zhong, Pei; Yao, JunjieKidney stone disease is a major public health issue. By breaking stones with repeated laser irradiation, laser lithotripsy (LL) has become the main treatment for kidney stone disease. Laser-induced cavitation is closely associated with the stone damage in LL. Monitoring the cavitation activities during LL is thus crucial to optimizing the stone damage and maximizing LL efficiency. In this study, we have developed three-dimensional super-resolution passive cavitation mapping (3D-SRPCM), in which the cavitation bubble positions can be localized with an accuracy of 40 μm, which is 1/10th of the acoustic diffraction limit. Moreover, the 3D-SRPCM reconstruction speed has been improved by 300 times by adopting a GPU-based sparse-matrix beamforming approach. Using 3D-SRPCM, we studied LL-induced cavitation activities on BegoStones, both in free space of water and confined space of a kidney phantom. The dose-dependence analysis provided by 3D-SRPCM revealed that accumulated impact pressure on the stone surface has the highest correlation with the stone damage. By providing high-resolution cavitation mapping during LL treatment, we expect that 3D-SRPCM may become a powerful tool to improve the clinical LL efficiency and patient outcome.