Real-time whole-brain imaging of hemodynamics and oxygenation at micro-vessel resolution with ultrafast wide-field photoacoustic microscopy


<jats:title>Abstract</jats:title><jats:p>High-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 (sO<jats:sub>2</jats:sub>) 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 mm<jats:sup>3</jats:sup> 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.</jats:p>






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Publication Info

Zhu, Xiaoyi, Qiang Huang, Anthony DiSpirito, Tri Vu, Qiangzhou Rong, Xiaorui Peng, Huaxin Sheng, Xiling Shen, et al. (2022). Real-time whole-brain imaging of hemodynamics and oxygenation at micro-vessel resolution with ultrafast wide-field photoacoustic microscopy. Light: Science & Applications, 11(1). 10.1038/s41377-022-00836-2 Retrieved from

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Huaxin Sheng

Associate Professor in Anesthesiology

We have successfully developed various rodent models of brain and spinal cord injuries in our lab, such as focal cerebral ischemia, global cerebral ischemia, head trauma, subarachnoid hemorrhage, intracerebral hemorrhage, spinal cord ischemia and compression injury. We also established cardiac arrest and hemorrhagic shock models for studying multiple organ dysfunction.  Our current studies focus on two projects. One is to examine the efficacy of catalytic antioxidant in treating cerebral ischemia and the other is to examine the efficacy of post-conditioning on outcome of subarachnoid hemorrhage induced cognitive dysfunction.


Xiling Shen

Adjunct Professor in the Department of Pathology

Dr. Shen’s research interests lie at precision medicine and systems biology. His lab integrates engineering, computational and biological techniques to study cancer, stem cells, microbiota and the nervous system in the gut. This multidisciplinary work has been instrumental in initiating several translational clinical trials in precision therapy. He is the director of the Woo Center for Big Data and Precision Health (DAP) and a core member of the Center for Genomics and Computational Biology (GCB).


Junjie Yao

Associate Professor of Biomedical Engineering

Our mission at PI-Lab is to develop state-of-the-art photoacoustic tomography (PAT) technologies and translate PAT advances into diagnostic and therapeutic applications, especially in functional brain imaging and early cancer theranostics. PAT is the most sensitive modality for imaging rich optical absorption contrast over a wide range of spatial scales at high speed, and is one of the fastest growing biomedical imaging technologies. Using numerous endogenous and exogenous contrasts, PAT can provide high-resolution images at scales covering organelles, cells, tissues, organs, small-animal organisms, up to humans, and can reveal tissue’s anatomical, functional, metabolic, and even histologic properties, with molecular and neuronal specificity.

At PI-Lab, we develop PAT technologies with novel and advanced imaging performance, in terms of spatial resolutions, imaging speed, penetration depth, detection sensitivity, and functionality. We are interested with all aspects of PAT technology innovations, including efficient light illumination, high-sensitivity ultrasonic detection, super-resolution PAT, high-speed imaging acquisition, novel PA genetic contrast, and precise image reconstruction. On top of the technological advancements, we are devoted to serve the broad life science and medical communities with matching PAT systems for various research and clinical needs. With its unique contrast mechanism, high scalability, and inherent functional and molecular imaging capabilities, PAT is well suited for a variety of pre-clinical applications, especially for studying tumor angiogenesis, cancer hypoxia, and brain disorders; it is also a promising tool for clinical applications in procedures such as cancer screening, melanoma staging, and endoscopic examination.

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