Multimodal Retinal Functional Imaging for Diabetic Retinopathy

糖尿病视网膜病变的多模态视网膜功能成像

• 批准号: 8665940
• 负责人: Amani A Fawzi
• 金额: $ 54.71万
• 依托单位: FLORIDA INTERNATIONAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-12 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8665940
• 关键词: Address; Adult; Age; Anatomy; Animal Model; Blindness; Blood; Blood Flow Velocity; Blood Vessels; Blood capillaries; Blood flow; Clinical; Clinical Research; Contact Lenses; Development; Diabetes Mellitus; Diabetic Retinopathy; Diagnosis; Disease; Doppler Effect; Early Diagnosis; Early Intervention; Endothelial Cells; Eye; Functional Imaging; Functional disorder; Goals; Growth; Hemoglobin; Hemorrhage; Homeostasis; Human; Hypoxia; Image; Imaging Device; Imaging Phantoms; Imaging technology; Intervention; Ischemia; Measures; Medical; Microaneurysm; Microcirculation; Modeling; Multimodal Imaging; Ophthalmoscopy; Optical Coherence Tomography; Optics; Oryctolagus cuniculus; Oxygen; Pathway interactions; Patients; Pericytes; Rattus; Research; Research Personnel; Retina; Retinal; Retinal Diseases; Retinal Neovascularization; Staging; Stress; System; Technology; Testing; Thromboxane Receptor; Time; Ultrasonic Transducer; Variant; Vascular Permeabilities; Work; absorption; base; blood flow measurement; capillary; diabetic patient; drug discovery; early onset; hemodynamics; improved; novel; prevent; proliferative diabetic retinopathy; retina blood vessel structure; retinal damage; tomography; tool; vasoconstriction

DESCRIPTION (provided by applicant): Diabetic retinopathy (DR) is a leading cause of irreversible blindness among working-age adults, which is a typical type of ischemia driven retinal disease characterized by microvascular damage to the retina in patients with diabetes. DR progresses through a sequence of recognizable stages, which begin with structural and functional derangement of the retinal microcirculation even before the early clinical signs occur. The earliest clinical signs of DR are microaneurysms and dot intraretinal hemorrhages resulting from damage to the capillary pericytes and endothelial cells. This capillary damage leads to an increase in retinal vascular permeability, localized loss of capillaries with resulting ischemia, and, in the final stage of DR, the growth of abnormal retinal blood vessels (pathological retinal neovascularization) known as proliferative diabetic retinopathy (PDR). Our long term goal is to provide clinical comprehensive functional and anatomical assessment of retinal vessels in humans. In the proposed project, we first address the need for technology by developing multimodal technologies based on functional photoacoustic ophthalmoscopy (PAOM), optical coherence tomography (OCT)/optical Doppler tomography (ODT). The multimodal imaging technology will be validated and optimized through imaging animal models. Then we will test the hypothesis that the multimodal imaging technology based on PAOM and OCT/ODT can provide comprehensive functional information for the early diagnosis of DR before clinical signs occur in the oxygen induced retinopathy (OIR) rat model. To further test the hypothesis we will apply intervention at the hemodynamic threshold (the earliest hemodynamic changes signifying DR) found by the proposed imaging system on the OIR rat model to show the early intervention benefits - after the time point of hemodynamic threshold interventions cannot prevent PDR. Aim 1. Develop a PAOM to measure sO2 in retinal vessels. PAOM provides accurate quantification of sO2 in retinal vessels by directly sensing the different optical absorption of oxy- and deoxy-hemoglobins. A powerless contact lens integrated with an ultrasonic transducer will be developed for imaging the eye. Aim 2. Develop a dual beam spectral domain OCT to image retinal hemodynamics. The OCT system features two probing beams separated by a controlled distance on retina. Thus, effects of the Doppler angle in blood flow measurement are eliminated and the absolute blood flow velocity can be measured in real-time. Aim 3. Integrate POAM and OCT to provide multimodal functional imaging of both sO2 and blood flow of retinal blood vessels. Validate and optimize the integrated system by imaging phantoms and the eyes of normal rats and rabbits. Aim 4. Test the hypothesis using the developed technology by studying the variation of retinal vascular functions during ischemic retinopathy development in the OIR rat model.

描述（申请人提供）：糖尿病视网膜病变（DR）是导致工作年龄成年人不可逆性失明的主要原因，是一种典型的缺血性视网膜疾病，其特征是糖尿病患者视网膜微血管损伤。 DR 会经历一系列可识别的阶段，这些阶段甚至在早期临床症状出现之前就开始于视网膜微循环的结构和功能紊乱。 DR 最早的临床症状是毛细血管周细胞和内皮细胞损伤导致的微动脉瘤和点状视网膜出血。这种毛细血管损伤会导致视网膜血管通透性增加、局部毛细血管损失并导致缺血，并且在 DR 的最后阶段，异常视网膜血管生长（病理性视网膜新生血管），称为增殖性糖尿病视网膜病变 (PDR)。 我们的长期目标是提供人类视网膜血管的临床综合功能和解剖学评估。在拟议的项目中，我们首先通过开发基于功能光声检眼镜（PAOM）、光学相干断层扫描（OCT）/光学多普勒断层扫描（ODT）的多模态技术来满足技术需求。多模态成像技术将通过成像动物模型进行验证和优化。然后我们将验证基于PAOM和OCT/ODT的多模态成像技术可以在氧诱导性视网膜病变（OIR）大鼠模型出现临床症状之前为DR早期诊断提供全面的功能信息的假设。为了进一步检验这一假设，我们将在 OIR 大鼠模型上所提出的成像系统发现的血流动力学阈值（表示 DR 的最早血流动力学变化）处进行干预，以显示早期干预的益处 - 在血流动力学阈值时间点之后干预不能预防 PDR 。目标 1. 开发 PAOM 来测量视网膜血管中的 sO2。 PAOM 通过直接感测氧合血红蛋白和脱氧血红蛋白的不同光学吸收来准确定量视网膜血管中的 sO2。将开发一种与超声波换能器集成的无动力隐形眼镜，用于对眼睛进行成像。目标 2. 开发双光束谱域 OCT 来成像视网膜血流动力学。 OCT 系统具有两个探测光束，它们在视网膜上以受控距离分开。这样就消除了血流测量中多普勒角的影响，可以实时测量绝对血流速度。目标 3. 集成 POAM 和 OCT，提供 sO2 和视网膜血管血流的多模态功能成像。通过对正常大鼠和兔子的模型和眼睛进行成像来验证和优化集成系统。目标 4. 通过研究 OIR 大鼠模型缺血性视网膜病变发展过程中视网膜血管功能的变化，使用开发的技术检验假设。