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

光学相干断层扫描（OCT）通过使用扫描的激光束并测量反向散射光的振幅和时间延迟来生成微米分辨率的组织的体积3D图像。OCT在眼科学中产生了强大的影响，成为诊断、监测疾病进展和治疗反应以及研究糖尿病视网膜病变、年龄相关性黄斑变性和青光眼等疾病发病机制的标准成像模式。OCT血管造影术（OCTA）的最新发展极大地促进了基础和临床研究。OCTA通过重复成像相同的视网膜位置并检测来自移动血细胞的运动对比度来执行视网膜微血管的深度分辨（3-D）成像。与基于注射造影剂的传统方法相比，OCTA具有非侵入性的优势，因此可以在每次患者就诊时进行成像，从而实现纵向研究。然而，OCTA也有一些局限性。由于需要重复成像来检测血流，因此采集时间很长，并且数据可能会因眼睛运动和成像伪影而失真，从而难以进行定量纵向分析。OCTA算法可以检测血流的存在，但在解决可能是疾病早期标志物的细微变化方面能力有限。由心动周期或视网膜功能反应引起的血流时间变化难以研究。 我们建议开发一个新的框架OCTA，使运动校正的毛细血管水平，区分血流速度，并允许在多个时间尺度上的分析（4-D OCTA）。超越微血管可视化和评估流量及其时间变化的能力将能够评估微血管灌注的细微损伤以及心动周期和对功能刺激的反应。结合血管结构成像，这些进展有望在早期阶段提供新的疾病标志物，能够更准确地测量疾病进展和药物研究中对治疗的反应，并有助于阐明视网膜疾病的发病机制。

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.