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.
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.
|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|
|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:|
|Jiang, Xiaoyun; Johnson, Elaine; Cepurna, William et al. (2018) The effect of age on the response of retinal capillary filling to changes in intraocular pressure measured by optical coherence tomography angiography. Microvasc Res 115:12-19|
|Choi, Woo J; Pepple, Kathryn L; Wang, Ruikang K (2018) Automated three-dimensional cell counting method for grading uveitis of rodent eye in vivo with optical coherence tomography. J Biophotonics 11:e201800140|
|Richter, Grace M; Chang, Ryuna; Situ, Betty et al. (2018) Diagnostic Performance of Macular Versus Peripapillary Vessel Parameters by Optical Coherence Tomography Angiography for Glaucoma. Transl Vis Sci Technol 7:21|
|Wang, Fupeng; Zhang, Qinqin; Deegan, Anthony J et al. (2018) Comparing imaging capabilities of spectral domain and swept source optical coherence tomography angiography in healthy subjects and central serous retinopathy. Eye Vis (Lond) 5:19|
|Zhang, Qinqin; Zheng, Fang; Motulsky, Elie H et al. (2018) A Novel Strategy for Quantifying Choriocapillaris Flow Voids Using Swept-Source OCT Angiography. Invest Ophthalmol Vis Sci 59:203-211|
|Richter, Grace M; Sylvester, Beau; Chu, Zhongdi et al. (2018) Peripapillary microvasculature in the retinal nerve fiber layer in glaucoma by optical coherence tomography angiography: focal structural and functional correlations and diagnostic performance. Clin Ophthalmol 12:2285-2296|
|Chu, Zhongdi; Zhou, Hao; Cheng, Yuxuan et al. (2018) Improving visualization and quantitative assessment of choriocapillaris with swept source OCTA through registration and averaging applicable to clinical systems. Sci Rep 8:16826|
Showing the most recent 10 out of 72 publications