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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL093140-06A1
Application #
8636271
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Charette, Marc F
Project Start
2008-08-01
Project End
2018-03-31
Budget Start
2014-06-01
Budget End
2015-03-31
Support Year
6
Fiscal Year
2014
Total Cost
$691,551
Indirect Cost
$203,026
Name
University of Washington
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Song, Shaozhen; Xu, Jingjiang; Wang, Ruikang K (2018) Flexible wide-field optical micro-angiography based on Fourier-domain multiplexed dual-beam swept source optical coherence tomography. J Biophotonics 11:
Baran, U; Swanson, E; Sanders, J E et al. (2018) OCT-based microangiography for reactive hyperaemia assessment within residual limb skin of people with lower limb loss. Skin Res Technol 24:152-155
Li, Yuandong; Wei, Wei; Wang, Ruikang K (2018) Capillary flow homogenization during functional activation revealed by optical coherence tomography angiography based capillary velocimetry. Sci Rep 8:4107
Park, Kwan S; Choi, Woo June; Song, Shaozhen et al. (2018) Multifunctional in vivo imaging for monitoring wound healing using swept-source polarization-sensitive optical coherence tomography. Lasers Surg Med 50:213-221
Li, David S; Lee, Yi-Ting; Xi, Yuyin et al. (2018) A small-angle scattering environment for in situ ultrasound studies. Soft Matter 14:5283-5293
Deegan, Anthony J; Wang, Wendy; Men, Shaojie et al. (2018) Optical coherence tomography angiography monitors human cutaneous wound healing over time. Quant Imaging Med Surg 8:135-150
Li, Yuandong; Choi, Woo June; Wei, Wei et al. (2018) Aging-associated changes in cerebral vasculature and blood flow as determined by quantitative optical coherence tomography angiography. Neurobiol Aging 70:148-159
Deegan, Anthony J; Talebi-Liasi, Faezeh; Song, Shaozhen et al. (2018) Optical coherence tomography angiography of normal skin and inflammatory dermatologic conditions. Lasers Surg Med 50:183-193
Wei, Wei; Choi, Woo June; Wang, Ruikang K (2018) Microvascular imaging and monitoring of human oral cavity lesions in vivo by swept-source OCT-based angiography. Lasers Med Sci 33:123-134
Song, Shaozhen; Xu, Jingjiang; Men, Shaojie et al. (2017) Robust numerical phase stabilization for long-range swept-source optical coherence tomography. J Biophotonics 10:1398-1410

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