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Functional Imaging in Hypoxic-Ischemic Retinal Disease

缺氧缺血性视网膜疾病的功能成像

基本信息

批准号：
9321457
负责人：
Amir H Kashani
金额：
$ 22.16万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-01 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9321457
关键词：
Angiography Animal Model Animals Award Blindness Blood Vessels Blood capillaries Brain Hypoxia-Ischemia Breathing Clinic Clinical Clinical Research Contrast Sensitivity Correlation Studies Data Diabetic Retinopathy Diagnosis Disease Failure Fluorescein Angiography Functional Imaging Functional disorder Gold Human Hypoxia Image Impairment Injury Investigation Ischemia Knowledge Lasers Light Coagulation Manuscripts Measurement Measures Mentors Methodology Methods Optical Coherence Tomography Oxygen Oxygen saturation measurement Partial Pressure Perfusion Pilot Projects Play Research Retinal Retinal Diseases Retinal Vein Occlusion Role Severities Steroids Testing Therapeutic Time TimeLine Tissues Training Activity Translating Vascular Diseases Vision Visual bevacizumab blood flow measurement capillary central retinal vein occlusion density diabetic experience experimental study histological studies human subject imaging modality improved macular edema meetings neovascularization non-invasive imaging novel prophylactic retinal ischemia skills spectroscopic imaging symposium

项目摘要

Project Summary Ischemia and hypoxia play critical roles in the pathophysiology of common blinding diseases such as diabetic retinopathy (DR) and retinal vein occlusions (RVO). Unfortunately, the correlation between impaired capillary perfusion, often called ischemia or “nonperfusion,” and hypoxia is largely unknown in a clinical setting because of limited imaging methodologies. Impaired capillary perfusion is almost exclusively demonstrated in clinic by fluorescein angiography (FA) but histological studies show that FA underestimates capillary density as much as 30-40% thereby under-diagnosing “nonperfusion.” Indirect clinical evidence and animal studies suggest that hypoxia underlies sequelae of DR and RVO. For example, contrast sensitivity deficits and retinal thickening are reversed in diabetic subjects breathing oxygen. However, there is little direct evidence of retinal hypoxia in humans because of the invasive methods needed to measure intraretinal oxygen levels. Since there is no direct clinical measure for mild-moderate hypoxia and only limited assessments of impaired capillary perfusion (ischemia), current treatments for DR and RVO presume a direct and static relationship between these two. However, abundant clinical evidence suggests that ischemia and hypoxia are not directly correlated. These observations confirm that the correlation between ischemia, hypoxia and sequelae of retinal vascular diseases are incompletely understood. I hypothesize that the relationship between microvascular hypoxia and ischemia is not static nor necessarily direct; and I suggest that this underlies limitations in current treatments and therapeutic failures. I propose basic and clinical studies that correlate real time intraocular pO2 measurements in animal models of ischemia with non-invasive imaging methods such as optical coherence tomography angiography (OCTA) to assess retinal capillary perfusion and hyperspectral computed tomographic imaging spectroscopy (HCTIS) to assess tissue hypoxia. These methods are then translated to the clinic where they are already shown to be safe and effective imaging modalities in pilot studies I have performed. The combination of these approaches leverages the gold standard intraocular pO2 measurements to validate and calibrate non- invasive methods that can be used safely and effectively in human subjects. Lastly, I propose to use OCTA and HCTIS to correlate the extent and duration of ischemia and hypoxia in human subjects with vision loss from DR and RVO.

项目总结