Functional Imaging in Hypoxic-Ischemic Retinal Disease

缺氧缺血性视网膜疾病的功能成像

• 批准号: 10456440
• 负责人: Amir H Kashani
• 金额: $ 10.35万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10456440
• 关键词: Functional; Imaging; Hypoxic; Ischemic; Retinal

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.

项目概要 缺血和缺氧在常见致盲疾病的病理生理学中发挥着关键作用 不幸的是，例如糖尿病视网膜病变（DR）和视网膜静脉阻塞（RVO）。 毛细血管灌注受损（通常称为缺血或“无灌注”）与 由于成像方法有限，缺氧在临床环境中很大程度上是未知的。 毛细血管灌注受损在临床上几乎完全由荧光素证明 血管造影 (FA) 但组织学研究表明 FA 低估了毛细血管密度 高达 30-40%，因此对“无灌注”的诊断不足。 研究表明缺氧是 DR 和 RVO 后遗症的根源。 糖尿病患者呼吸氧气后，敏感性缺陷和视网膜增厚得到逆转。 然而，由于侵入性视网膜损伤，几乎没有直接证据表明人类视网膜缺氧。 由于没有直接的临床测量方法，因此需要测量视网膜内氧水平的方法。 适用于轻度至中度缺氧以及对毛细血管灌注受损的有限评估 （缺血），目前 DR 和 RVO 的治疗假定存在直接且静态的关系 然而，大量的临床证据表明缺血和缺氧。 这些观察结果证实了缺血之间的直接相关性， 缺氧和视网膜血管疾病的后遗症尚不完全清楚。 微血管缺氧和缺血之间的关系不是静态的也不一定 直接；我认为这是当前治疗的局限性和治疗失败的原因。 我的基本建议和临床研究与实时眼内 pO2 测量相关 使用光学相干等非侵入性成像方法建立缺血动物模型 断层扫描血管造影 (OCTA) 用于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（HCTIS）用于评估组织缺氧。 然后将方法转化为临床，它们已被证明是安全有效的 我进行的试点研究中的成像方式是这些方法的结合。 利用金标准眼内 pO2 测量来验证和校准非 最后，我提出可以在人类受试者中安全有效地使用的侵入性方法。 使用 OCTA 和 HCTIS 关联人体缺血和缺氧的程度和持续时间 因 DR 和 RVO 导致视力丧失的受试者。

项目成果

Surgically Induced Focal Retinal Detachment Does Not Cause Detectable SD-OCT Retinal Changes in Normal Human Retina.

• DOI: 10.1167/iovs.17-22737
• 发表时间: 2017-10-01
• 期刊: Investigative ophthalmology & visual science
• 影响因子: 4.4
• 作者: Kogachi K;Wolfe JD;Kashani AH
• 通讯作者: Kashani AH

Quantitative microvascular analysis of retinal venous occlusions by spectral domain optical coherence tomography angiography.

• DOI: 10.1371/journal.pone.0176404
• 发表时间: 2017
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Koulisis N;Kim AY;Chu Z;Shahidzadeh A;Burkemper B;Olmos de Koo LC;Moshfeghi AA;Ameri H;Puliafito CA;Isozaki VL;Wang RK;Kashani AH
• 通讯作者: Kashani AH