Non-invasive Real-time Label-free 3D Imaging of Retinal Microcirculations PROJECT SUMMARY Non-invasive and label-free imaging techniques for assessing retinal blood perfusion in humans - down to capillary-level resolution, are of paramount importance for improved understanding, diagnosis, treatment and management of diseases that have a vascular component in their pathogenesis, e.g., age related macular degeneration (AMD), diabetic retinopathy (DR), and open angle glaucoma (OAG). Invasive imaging techniques, e.g., fluorescein angiography (FA) and indo-cyanine green angiography (ICGA), are currently used to visualize ocular perfusion and detect abnormal vessels. Both techniques have traditionally been utilized to make diagnoses and treatment decisions, but they can only provide two-dimensional (2D) images and require intravascular injections that risk complications, including anaphylaxis. No clinical imaging techniques currently exist that can offer detailed visualization and quantification of retinal microcirculation at capillary level resolution and at defined tissue depths. It would be highly advantageous to be capable of three-dimensional (3D) visualization of vascular perfusion with capillary-level resolution, both to revea the detailed functional architecture of the perfused microvascular network and to permit quantification of the perfusion status of the retina through volumetric rheology. This information would be fundamental to better understanding of vascular retinal and choroidal diseases, resulting in more informed and targeted treatment decisions. In this project, we propose to develop a clinically applicable 3D functional retinal optical microangiography (rOMAG) system. We envision that this novel, non-invasive, and label-free optical imaging method will quantify the morphology of blood vessels and permit assessment of their spatial relations in three dimensions. Concurrently, total retinal blood flow (RBF) and vascular volumes of the retina and choroid can be quantitatively assessed. To achieve this goal, we will first design and construct a novel, ultrafast rOMAG system based on spectral domain optical coherence tomography. The focus will be on solving challenges associated with creating a retinal imaging system that is capable of, simultaneously: 1) having increased light penetration into the choroid, 2) providing an imaging range of >6mm with acceptable system sensitivity roll-off characteristics so that it is able to image the whole posterior segment from anterior retina to posterior choroid in one scan, and 3) achieving an unprecedented imaging speed of 300kHz to enable acquiring 3D images within an acceptable time frame (~1 sec), an important requirement for patient examination comfort and minimization of motion artifact. We will then utilize a bench top setup to validate rOMAG's accuracy for visualizing the retinal and choroidal microvasculature, using an animal model and traditional histopathology approaches. After the technology has been tested and validated in animals, we will perform in vivo rOMAG pilot imaging studies in 140 subjects to demonstrate clinical feasibility and usefulness of this new non-invasive label-free 3D microangiography of vascular structure and function. This study will serve as the foundation for interpretation of rOMAG data in future.

Public Health Relevance

The project aims to develop and validate a new, non-invasive, label-free in vivo imaging tool that will image human retinal and choroidal microcirculations at true capillary level detail. The imaging modality is also coupled with an ability to provide volumetric microstructural information. This advance will dramatically alter 1) research currently based on fluorescein angiography and indo-cyanine green angiography, and other imaging techniques (eg laser Doppler velocimetry), 2) investigation of animal model retinal as well as human pathology in vivo, and 3) patient diagnosis, monitoring, early preventive decisions, and informed therapeutic guidance.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
1R01EY024158-01
Application #
8639862
Study Section
(NOIT)
Program Officer
Greenwell, Thomas
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Washington
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
City
Seattle
State
WA
Country
United States
Zip Code
98195
Zhang, Qinqin; Lee, Cecilia S; Chao, Jennifer et al. (2016) Wide-field optical coherence tomography based microangiography for retinal imaging. Sci Rep 6:22017
Kam, Jason; Zhang, Qinqin; Lin, Jason et al. (2016) Optical coherence tomography based microangiography findings in hydroxychloroquine toxicity. Quant Imaging Med Surg 6:178-83
Chu, Zhongdi; Lin, Jason; Gao, Chen et al. (2016) Quantitative assessment of the retinal microvasculature using optical coherence tomography angiography. J Biomed Opt 21:66008
Chen, Chieh-Li; Bojikian, Karine D; Xin, Chen et al. (2016) Repeatability and reproducibility of optic nerve head perfusion measurements using optical coherence tomography angiography. J Biomed Opt 21:65002
Chen, Chieh-Li; Zhang, Anqi; Bojikian, Karine D et al. (2016) Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Glaucoma Using Optical Coherence Tomography-Based Microangiography. Invest Ophthalmol Vis Sci 57:OCT475-85
Roisman, Luiz; Zhang, Qinqin; Wang, Ruikang K et al. (2016) Optical Coherence Tomography Angiography of Asymptomatic Neovascularization in Intermediate Age-Related Macular Degeneration. Ophthalmology 123:1309-19
Choi, Woo June; Qin, Wan; Chen, Chieh-Li et al. (2016) Characterizing relationship between optical microangiography signals and capillary flow using microfluidic channels. Biomed Opt Express 7:2709-28
Xin, Chen; Johnstone, Murray; Wang, Ningli et al. (2016) OCT Study of Mechanical Properties Associated with Trabecular Meshwork and Collector Channel Motion in Human Eyes. PLoS One 11:e0162048
Lee, Aaron Y; Zhang, Qinqin; Baughman, Douglas M et al. (2016) Evaluation of bilateral central retinal artery occlusions with optical coherence tomography-based microangiography: a case report. J Med Case Rep 10:307
Kim, Alice Y; Rodger, Damien C; Shahidzadeh, Anoush et al. (2016) Quantifying Retinal Microvascular Changes in Uveitis Using Spectral-Domain Optical Coherence Tomography Angiography. Am J Ophthalmol 171:101-112

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