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.

项目摘要缺血和缺氧在普通盲疾病的病理生理中起关键作用例如糖尿病性视网膜病（DR）和视网膜静脉阻塞（RVO）。不幸的是，毛细血管灌注受损（通常称为缺血或“非灌注”）之间的相关性，由于成像方法有限，在临床环境中缺氧在很大程度上是未知的。受损的毛细血管灌注几乎在诊所中仅由荧光素证明血管造影（FA），但组织学研究表明，FA低估了毛细血管密度为因此，多达30-40％的诊断“非灌注”。间接临床证据和动物研究表明，缺氧是DR和RVO后遗症的基础。例如，对比敏感性定义并仍在糖尿病受试者呼吸氧气中逆转。但是，由于侵入性，几乎没有直接证据表明人类残留缺氧测量视网膜内氧水平所需的方法。由于没有直接的临床测量对于轻度中度缺氧，仅对受损毛细血管灌注的评估有限（缺血），DR和RVO的当前治疗方法假定直接和静态关系在这两个之间。但是，丰富的临床证据表明缺血和缺氧不直接相关。这些观察结果证实，缺血，残留血管疾病的缺氧和后遗症尚不完全了解。我假设微血管低氧和缺血之间的关系不是静态的也不是必需的直接的;我建议这是当前治疗和治疗失败的局限性。我提出了基础研究和临床研究，以将实时的人眼内PO2测量相关联缺血的动物模型，具有非侵入性成像方法，例如光学连贯性层析成像血管造影（八八片），以评估视网膜毛细血管灌注和高光谱计算机断层扫描成像光谱（HCTI）评估组织缺氧。这些然后将方法转化为诊所，在那里它们已经被证明是安全有效的我已经进行的试点研究中的成像方式。这些方法的结合利用金标准的眼内PO2测量来验证和校准非 - 可以在人类受试者中安全有效地使用的侵入性方法。最后，我建议使用八八和HCTI与人缺血和缺氧的程度和持续时间相关联 DR和RVO视力丧失的受试者。