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)
Project #
Application #
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Charette, Marc F
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Washington
Biomedical Engineering
Schools of Engineering
United States
Zip Code
Zhi, Zhongwei; Chao, Jennifer R; Wietecha, Tomasz et al. (2014) Noninvasive imaging of retinal morphology and microvasculature in obese mice using optical coherence tomography and optical microangiography. Invest Ophthalmol Vis Sci 55:1024-30
Wang, Hequn; Baran, Utku; Li, Yuandong et al. (2014) Does optical microangiography provide accurate imaging of capillary vessels?: validation using multiphoton microscopy. J Biomed Opt 19:106011
Yousefi, Siavash; Wang, Ruikang K (2014) Simultaneous estimation of bidirectional particle flow and relative flux using MUSIC-OCT: phantom studies. Phys Med Biol 59:6693-708
Nguyen, Thu-Mai; Song, Shaozhen; Arnal, Bastien et al. (2014) Shear wave pulse compression for dynamic elastography using phase-sensitive optical coherence tomography. J Biomed Opt 19:16013
Wang, Hequn; Shi, Lei; Qin, Jia et al. (2014) Multimodal optical imaging can reveal changes in microcirculation and tissue oxygenation during skin wound healing. Lasers Surg Med 46:470-8
Choi, Woo June; Wang, Hequn; Wang, Ruikang K (2014) Optical coherence tomography microangiography for monitoring the response of vascular perfusion to external pressure on human skin tissue. J Biomed Opt 19:056003
Nguyen, Thu-Mai; Song, Shaozhen; Arnal, Bastien et al. (2014) Visualizing ultrasonically induced shear wave propagation using phase-sensitive optical coherence tomography for dynamic elastography. Opt Lett 39:838-41
Yousefi, Siavash; Qin, Jia; Dziennis, Suzan et al. (2014) Assessment of microcirculation dynamics during cutaneous wound healing phases in vivo using optical microangiography. J Biomed Opt 19:76015
Qin, Jia; Shi, Lei; Wang, Hequn et al. (2014) Functional evaluation of hemodynamic response during neural activation using optical microangiography integrated with dual-wavelength laser speckle imaging. J Biomed Opt 19:026013
Reif, Roberto; Baran, Utku; Wang, Ruikang K (2014) Motion artifact and background noise suppression on optical microangiography frames using a naïve Bayes mask. Appl Opt 53:4164-71

Showing the most recent 10 out of 60 publications