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: 8635179
• 负责人: Amani A Fawzi
• 金额: $ 57.66万
• 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/8635179
• 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; public health relevance; 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（由申请人提供）：糖尿病性视网膜病变（DR）是工作年龄成年人不可逆失明的主要原因，这是一种典型的缺血驱动的视网膜疾病，其特征是糖尿病患者的视网膜微血管损害。博士通过一系列可识别的阶段进行，这些阶段始于视网膜微循环的结构和功能危险，甚至在早期临床迹象发生之前。 DR的最早临床迹象是毛细管周细胞和内皮细胞损害导致的微型神经瘤和点内出血。这种毛细管损伤导致视网膜血管通透性增加，毛细血管的局部损失导致缺血，并且在DR的最后阶段，视网膜血管异常的生长（病理性视网膜新血管形成）被称为增殖性糖尿病性视网膜疾病（PDR）。 我们的长期目标是对人类视网膜血管提供临床综合功能和解剖学评估。在拟议的项目中，我们首先通过基于功能性光声眼镜检查（PAOM），光学相干断层扫描（OCT）/光学多普勒断层扫描（ODT）开发多模式技术来满足技术的需求。多模式成像技术将通过成像动物模型验证和优化。然后，我们将检验以下假设：基于PAOM和OCT/ODT的多模式成像技术可以为DR的早期诊断提供全面的功能信息，以便在氧气诱导的视网膜病变（OIR）大鼠模型中发生临床迹象之前。为了进一步检验假设，我们将在OIR大鼠模型上提出的成像系统发现的血液动力学阈值（最早的血液动力学变化表示DR）进行干预以显示早期干预益处 - 在血液动力学阈值的时间点之后，无法阻止PDR。目标1。开发一个PAOM以测量视网膜血管中的SO2。 PAOM通过直接感测氧和脱氧 - 血红蛋白的不同光学吸收来对视网膜血管中SO2进行准确的定量。将开发与超声传感器集成的无能隐形眼镜，用于成像眼睛。 AIM 2。开发双光光谱域OCT以形象视网膜血流动力学。 OCT系统具有两个在视网膜上受控距离的探测梁。因此，消除了多普勒角在血流测量中的影响，并且可以实时测量绝对血流速度。 AIM 3。整合POAM和OCT，以提供视网膜血管的SO2和血流的多模式功能成像。通过成像幻象以及正常大鼠和兔子的眼睛来验证和优化集成系统。 AIM 4。通过研究在OIR大鼠模型中缺血性视网膜病变过程中视网膜血管功能的变化来检验假设。