Functional Optical Coherence Tomography-derived Biomarkers for Diabetic Retinopathy

功能性光学相干断层扫描衍生的糖尿病视网膜病变生物标志物

• 批准号: 8832474
• 负责人: Yali Jia
• 金额: $ 103.67万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8832474
• 关键词: Adverse effects; Affect; Age; Algorithms; Anaphylaxis; Anatomy; Angiography; Applications Grants; Area; Arteriosclerosis; Biological Markers; Blindness; Blood Circulation; Blood Vessels; Blood capillaries; Blood flow; Clinical; Clinical Research; Clinical Trials; Clinical assessments; Computer software; Control Groups; Cyst; Detection; Diabetes Mellitus; Diabetic Retinopathy; Diagnosis; Disease; Dropout; Dyes; Early Diagnosis; Enrollment; Evaluation; Extravasation; Fluorescein; Fluorescein Angiography; Fundus photography; Generations; Glaucoma; Goals; Gold; Image; Injection of therapeutic agent; Intravenous; Life; Liquid substance; Manuals; Maps; Measurement; Measures; Methods; Microcirculation; Monitor; Motion; Nausea; Optical Coherence Tomography; Participant; Patients; Pattern; Perfusion; Reading; Research; Research Project Grants; Resistance; Retina; Retinal; Retinal Diseases; Retinal Edemas; Retinal Neovascularization; Role; Sampling; Scanning; Sensitivity and Specificity; Severities; Speed; Staging; Structure; System; Techniques; Technology; Testing; United States; Visit; Visual Acuity; capillary; clinical practice; diabetic; diabetic patient; follow-up; image processing; imaging modality; improved; indexing; instrument; intravenous injection; macular edema; neovascularization; non-diabetic; novel; optic nerve disorder; prototype; public health relevance; screening; tool

 DESCRIPTION (provided by applicant): Diabetic retinopathy (DR), associated with long-term diabetes mellitus, is a leading cause of blindness in the US. Structural optical coherence tomography (OCT) has become the standard method for evaluating diabetic macular edema; however, fluorescein angiography (FA), which requires an invasive intravenous dye injection, is still needed to assess capillary dropout and confirm neovascularization. Recently, we have used a high- speed OCT system to make non-invasive functional measurements such as angiography, total retinal blood flow, and retinal arterial pulsatility. The goal of the proposed project is to improve these functional OCT-derived biomarkers and determine their roles in the early detection and management of DR. 1. Develop quantitative OCT angiography of capillary dropout and retinal neovascularization (RNV). Three dimensional (3D) OCT angiography has been made practical (6x6 mm scan in 3 seconds) by a novel split-spectrum amplitude-decorrelation algorithm. The algorithm will be improved and OCT angiograms will be calibrated by physical flow phantoms. Automated software will be developed to quantify the following angiographic biomarkers: non-perfusion area, RNV area and flow index, and parafoveal and perifoveal flow indexes. 2. Improve Doppler OCT measurement of total retinal blood flow (TRBF) and retinal arterial pulsatility. A 3-second 3D Doppler OCT scan will be used to measure TRBF using an en face summation algorithm. A 4-second cylindrical Doppler OCT scan will be used to measure retinal arterial pulsatility. Automated measurement algorithms will be developed for these novel biomarkers. 3. Improve structural OCT measurement of macular edema. By registering several volumetric scans, we have demonstrated detailed mapping and quantification of retinal thickening and fluid spaces (cysts). Fully automated quantification of these structural biomarkers will be developed. 4. Evaluate functional and structural OCT-derived biomarkers in clinical studies. The specificity and sensitivity of OCT angiography for detection of capillary dropout and RNV will be determined in 50 severe non-proliferative (NPDR) and proliferative (PDR) subjects (Group A) and 30 age-matched non-diabetic controls (Group C). The utility of OCT-derived biomarkers for early detecting retinal abnormalities will be evaluated in 80 subjects with or without mild to moderate NPDR (Group B). The capability of biomarkers for assessing the disease change will be evaluated with Groups A and B over a 12-month interval. The proposed functional OCT-derived biomarkers will be more sensitive to early vascular change compared to standard fundus photography and are likely to provide more reliable endpoints for diabetic clinical trials. Unlike FA, functional OCT is non-invasive and coul be used in routine clinical screening and monitoring of DR.

 描述（由申请人提供）：糖尿病视网膜病变（DR）与长期糖尿病相关，是美国失明的主要原因。结构光学相干断层扫描（OCT）已成为评价糖尿病黄斑水肿的标准方法;然而，仍需要荧光素血管造影（FA）（需要侵入性静脉内染料注射）来评估毛细血管脱落并确认新生血管形成。最近，我们已经使用高速OCT系统来进行非侵入性功能测量，例如血管造影、总视网膜血流量和视网膜动脉搏动。该项目的目标是改善这些功能性OCT衍生的生物标志物，并确定它们在DR早期检测和管理中的作用。发展毛细血管脱落和视网膜新生血管（RNV）的定量OCT血管造影。 三维（3D）OCT血管造影术已通过一种新型分谱振幅去相关算法实现（3秒内扫描6x6 mm）。将改进算法，并将使用物理流量模型校准OCT血管造影片。将开发自动化软件，以量化以下血管造影生物标志物：非灌注面积、RNV面积和血流指数以及脑旁和中央凹周围血流指数。2.改进多普勒OCT测量视网膜总血流量（TRBF）和视网膜动脉搏动。 将使用3秒3D多普勒OCT扫描，通过正面求和算法测量TRBF。将使用4秒圆柱形多普勒OCT扫描测量视网膜动脉搏动。将为这些新的生物标志物开发自动测量算法。3.改善黄斑水肿的结构OCT测量。通过配准几个体积扫描，我们已经证明了视网膜增厚和液体空间（囊肿）的详细映射和量化。将开发这些结构生物标志物的全自动定量。4.在临床研究中评价OCT衍生的功能和结构生物标志物。将在50例重度非增殖性（NPDR）和增殖性（PDR）受试者（A组）和30例年龄匹配的非糖尿病对照（C组）中确定OCT血管造影术检测毛细血管脱落和RNV的特异性和灵敏度。将在80名患有或不患有轻度至中度NPDR的受试者（B组）中评价OCT衍生的生物标志物用于早期检测视网膜异常的效用。将在12个月的时间间隔内评价A组和B组生物标志物评估疾病变化的能力。与标准眼底照相相比，拟议的OCT衍生功能性生物标志物对早期血管变化更敏感，可能为糖尿病临床试验提供更可靠的终点。与FA不同，功能性OCT是非侵入性的，可用于DR的常规临床筛查和监测。

项目成果

Three-dimensional structural and angiographic evaluation of foveal ischemia in diabetic retinopathy: method and validation.

• DOI: 10.1364/boe.10.003522
• 发表时间: 2019-06
• 期刊: Biomedical optics express
• 影响因子: 3.4
• 作者: Bingjie Wang;Acner Camino;Shaohua Pi;Yukun Guo;Jie Wang;David Huang;T. Hwang;Yali Jia