Non-invasive techniques for quantifying blood flow, vascular remodeling and blood oxygen saturation (SaO2) down to capillary-level resolution are of paramount importance for the improved understanding, diagnosis and treatment of neurovascular and neurometabolic disorders such as stroke. Currently there are no imaging techniques that can non-invasively and simultaneously measure these parameters without the use of exogenous contrast agents in the microcirculation in vivo. We have pioneered a non-invasive 3D optical imaging technology, optical microangiography (OMAG), that meets this challenge. In the parent R01 project, we have successfully demonstrated that OMAG generates real-time 3D images of both tissue structure and blood flow at capillary level resolution with an imaging depth up to 2 mm without the need for exogenous contrast agents (see publication list in the progress report). In addition, we also demonstrated a number of novel methods to successfully extract the blood flow signals from huge 'noise'background of optical scattering, an obstacle married with almost all high-resolution optical imaging techniques. As a direct result of our research, it is now practical to image functional 3D microvascular networks in pre-clinical (small animal models) and clinical settings (human retina). Since our first publication that reported OMAG, the field has grown exponentially, and there are several companies planning to market the OMAG product. Now that we have successfully developed OMAG for imaging functional microcirculations, we will direct our research efforts towards the development of the next generation OMAG imaging modality. This next generation technology will allow depth-resolved cerebral blood flow (CBF), microvascular morphology and SaO2 at the capillary level to be simultaneously monitored within a scanned tissue volume. To achieve this goal, we will first develop a multifunctional OMAG (mfOMAG) system capable of measuring rapid and long term responses of cerebral blood flow and oxygenation. We will then combine this system with a novel spectral laser-speckle imaging which we will use as a guide to immediately hone into injured regions for a thorough evaluation with mfOMAG. Finally, we will determine the utility of mfOMAG for serial monitoring of cerebral blood flow changes and vascular remodeling following experimental stroke in mice.

Public Health Relevance

We propose to develop a novel, non-invasive optical imaging technology that can simultaneously provide quantitative assessment of cerebral blood flow and blood oxygenation in the brain of small animal models with the skull left intact. This novel imaging technique will become an important tool to investigate the cerebral vascular responses to an ischemic injury, and may help diagnosis, monitoring, and therapeutic interventions for other diseases with vascular involvement.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Biomedical Imaging Technology Study Section (BMIT)
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Charette, Marc F
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University of Washington
Biomedical Engineering
Schools of Engineering
United States
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Le, Nhan; Song, Shaozhen; Zhang, Qinqin et al. (2017) Robust principal component analysis in optical micro-angiography. Quant Imaging Med Surg 7:654-667
Li, David S; Yoon, Soon Joon; Pelivanov, Ivan et al. (2017) Polypyrrole-Coated Perfluorocarbon Nanoemulsions as a Sono-Photoacoustic Contrast Agent. Nano Lett 17:6184-6194
Park, Kwan S; Choi, Woo June; Song, Shaozhen et al. (2017) Multifunctional in vivo imaging for monitoring wound healing using swept-source polarization-sensitive optical coherence tomography. Lasers Surg Med :
Xu, Jingjiang; Song, Shaozhen; Li, Yuandong et al. (2017) Complex-based OCT angiography algorithm recovers microvascular information better than amplitude- or phase-based algorithms in phase-stable systems. Phys Med Biol 63:015023
Song, Shaozhen; Xu, Jingjiang; Wang, Ruikang K (2017) Flexible wide-field optical micro-angiography based on Fourier-domain multiplexed dual-beam swept source optical coherence tomography. J Biophotonics :
Men, S J; Chen, C-L; Wei, W et al. (2017) Repeatability of vessel density measurement in human skin by OCT-based microangiography. Skin Res Technol 23:607-612
Kirby, Mitchell A; Pelivanov, Ivan; Song, Shaozhen et al. (2017) Optical coherence elastography in ophthalmology. J Biomed Opt 22:1-28
Jia, Jia; Davis, Catherine M; Zhang, Wenri et al. (2016) Sex- and isoform-specific mechanism of neuroprotection by transgenic expression of P450 epoxygenase in vascular endothelium. Exp Neurol 279:75-85
Choi, Woo June; Li, Yuandong; Qin, Wan et al. (2016) Cerebral capillary velocimetry based on temporal OCT speckle contrast. Biomed Opt Express 7:4859-4873
Qin, Wan; Roberts, Meredith A; Qi, Xiaoli et al. (2016) Depth-resolved 3D visualization of coronary microvasculature with optical microangiography. Phys Med Biol 61:7536-7550

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