Temporally resolved 3-D retinal blood flow quantification using advanced motion correction and signal reconstruction in optical coherence tomography angiography

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Optical coherence tomography (OCT) generates micron resolution, volumetric 3-D images of tissue by using a scanned laser beam and measuring the amplitude and time delay of back-scattered light. OCT has had a powerful impact in ophthalmology, becoming a standard imaging modality for diagnosis, monitoring disease progression and treatment response, as well as for investigating pathogenesis in diseases such as diabetic retinopathy, age-related macular degeneration, and glaucoma. The recent development of OCT angiography (OCTA) has dramatically accelerated fundamental and clinical research. OCTA performs depth-resolved (3-D) imaging of retinal microvasculature by repeatedly imaging the same retinal position and detecting motion contrast from moving blood cells. Compared to traditional approaches based on injected contrast agents, OCTA has the advantage that it is non-invasive, so imaging can be performed on every patient visit, enabling longitudinal studies. However, OCTA also has several limitations. Since repeated imaging is required to detect blood flow, acquisition times are long and data can be distorted by eye motion and imaging artifacts, making quantitative longitudinal analysis difficult. OCTA algorithms can detect the presence of blood flow, but have limited ability to resolve subtle alterations in flow, which may be early markers of disease. Temporal variations in flow caused by the cardiac cycle or retinal functional response are difficult to investigate. We propose to develop a new framework for OCTA which enables motion correction on the capillary level, differentiates blood flow speeds, and allows analysis on multiple time scales (4-D OCTA). The ability to go beyond visualization of microvasculature and assess flow and its temporal variations will enable assessment of subtle impairments of microvascular perfusion as well as cardiac cycle and response to functional stimulation. Combined with vascular structural imaging, these advances promise to provide new markers of disease at earlier stages, enable more accurate measurement of disease progression and response to therapy in pharmaceutical studies, and help elucidate pathogenesis in retinal disease.