Administrative supplement of gas-free cerebrovascular reactivity (CVR) MRI in vascular cognitive impairment

无气脑血管反应性 (CVR) MRI 在血管性认知障碍中的管理补充

• 批准号: 10844887
• 负责人: LINDA CHANG
• 金额: $ 38.62万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-16 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10844887
• 关键词: Acetazolamide; Administrative Supplement; Affect; Age Years; Anti-Retroviral Agents; Award; Biological Markers; Blood Pressure; Blood Vessels; Brain; Breathing; Caffeine; Carbon Dioxide; Categories; Cerebrovascular Disorders; Cerebrum; Clinical; Clinical Research; Cognitive; Cognitive deficits; Complex; Core-Binding Factor; Data; Development; Diagnosis; Elderly; Equipment; Etiology; Face; Functional Magnetic Resonance Imaging; Funding; Future; Gases; General Population; Goals; HIV; HIV Seropositivity; HIV-associated neurocognitive disorder; Heart Rate; High Prevalence; Image; Incidence; Individual; Inhalation; Injections; Life; Life Expectancy; Link; Magnetic Resonance Imaging; Maps; Measurement; Measures; Methods; Nature; Neurocognitive Deficit; Noise; Outcome; Parents; Participant; Patients; Pattern; Persons; Pharmaceutical Preparations; Phase; Physiological; Pilot Projects; Prevalence; Protocols documentation; Resolution; Rest; Risk; Sampling; Severities; Special Equipment; Standardization; Stroke; Techniques; Variant; Vascular Cognitive Impairment; Venous; Viral; White Matter Hyperintensity; Work; cerebrovascular; clinical application; clinical practice; cloud based; cognitive function; computerized data processing; cost; early detection biomarkers; functional MRI scan; immune reconstitution; indexing; mild cognitive impairment; novel; parent grant; parent project; pharmacologic; recruit; research study; response; side effect; tool

Project Summary/Abstract This is a supplemental request to perform additional work on parent grant R01NS115771, in response to NOT-AG-23-008. Effective antiretroviral medications for viral suppression have led to near-normal life expectancies in persons with HIV (PWH). However, since PWHs are living longer, more than half (52.7% in 2020) are 50 years of age or older in the U.S. Despite viral suppression and immune reconstitution, PWHs face increased rates of stroke and neurocognitive impairment compared with the general population. The prevalence of HIV-associated neurocognitive disorders (HAND) was estimated to be 30-50% of all HIV-positive individuals, with higher prevalence in the older PWH. Cerebrovascular dysfunction has been linked to the increased incidence of cerebrovascular diseases in PWH, which may be a key contributor to HAND. However, direct evidence of cerebrovascular dysfunction as a contributory etiology for HAND is still lacking. The parent award (R01NS115771) focuses on the development of a novel MRI technique for the mapping of cerebrovascular reactivity (CVR) and its utility as an early biomarker of vascular cognitive impairment (VCI). CVR, an index of cerebral vessel’s capacity to dilate in response to stimulation, is a measure of the brain’s vascular function. Previous studies demonstrated reduced CVR in VCI. Despite these well-documented findings, CVR is not commonly measured in clinical practice, primarily due to logistical difficulties in applying a vascular “challenge” during imaging. The current CVR measurements typically require a vascular challenge during imaging, involving either the injection of a pharmacological agent (e.g., acetazolamide) or the inhalation of CO2 gas. However, these techniques are complex and costly, requiring special equipment, and possible side-effects of physiological maneuver to induce the vascular challenge. Therefore, development of a CVR technique that does not need an explicit vascular challenge will broaden the clinical utility of CVR, making it a feasible tool to study cerebrovascular dysfunction in PWH, and possibly become a biomarker for HAND. In this supplement, we propose a supplement project, using the novel technique proposed in the parent protocol to measure CVR and cognitive function in PWHs. We aim to: 1) compare the CVR in three groups of participants (50-85 years of age): 20 PWHs with HAND, 20 PWHs without HAND, and 10 HIV-seronegative (SN) controls (the parent project also studies healthy controls 60-85 years); 2) determine whether CVR can predict HAND status, cognitive scores, and WMH on FLAIR MRI. We hypothesize that 1) across the three participant groups, PWH with HAND will show the lowest CVR, with lower than normal CVR in PWH without HAND, compared to SN controls; 2) the CVR measures will predict the severity of cognitive deficits and cerebrovascular outcomes. This pilot study will provide preliminary data and analyses needed for a larger more comprehensive study through a future R01 application.

项目概要/摘要 这是对家长补助金 R01NS115771 进行额外工作的补充请求，以回应 不是-AG-23-008。有效抑制病毒的抗逆转录病毒药物使人们的生活接近正常 HIV 感染者 (PWH) 的预期。然而，由于感染者的寿命越来越长，超过一半（52.7%） 2020）在美国年满 50 岁。尽管进行了病毒抑制和免疫重建，但感染者仍面临着 与一般人群相比，中风和神经认知障碍的发生率增加。这 HIV 相关神经认知障碍 (HAND) 的患病率估计占所有 HIV 阳性患者的 30-50% 个体，在老年 PWH 中患病率更高。脑血管功能障碍与 PWH 中脑血管疾病的发病率增加，这可能是 HAND 的一个关键因素。然而， 目前仍缺乏脑血管功能障碍作为 HAND 病因的直接证据。 家长奖 (R01NS115771) 专注于开发一种用于映射的新型 MRI 技术 脑血管反应性（CVR）及其作为血管性认知障碍（VCI）早期生物标志物的实用性。 CVR 是脑血管响应刺激而扩张的能力的指数，是大脑功能的衡量标准 血管功能。先前的研究表明 VCI 的 CVR 降低。尽管有这些有据可查的 研究结果表明，CVR 在临床实践中并不常见，主要是由于应用 CVR 的后勤困难 成像过程中的血管“挑战”。当前的 CVR 测量通常需要血管挑战 在成像过程中，涉及注射药物（例如乙酰唑胺）或吸入 二氧化碳气体。然而，这些技术复杂且成本高，需要特殊设备，并且可能 引起血管挑战的生理操作的副作用。因此，开发CVR 不需要明确血管挑战的技术将扩大 CVR 的临床用途，使其成为 研究 PWH 脑血管功能障碍的可行工具，并可能成为 HAND 的生物标志物。 在本补充中，我们提出了一个补充项目，使用父级中提出的新技术 测量 PWH 的 CVR 和认知功能的协议。我们的目标是：1）比较三组的 CVR 参与者（50-85 岁）：20 名患有 HAND 的 PWH，20 名未患有 HAND 的 PWH，以及 10 名 HIV 血清阴性的患者 (SN) 对照（父项目还研究 60-85 岁的健康对照）； 2）判断CVR是否可以 在 FLAIR MRI 上预测 HAND 状态、认知评分和 WMH。我们假设 1）跨越三个 参与者组中，使用 HAND 的 PWH 将显示最低的 CVR，而未使用 HAND 的 PWH 的 CVR 低于正常值 HAND，与 SN 控件相比； 2) CVR 测量将预测认知缺陷的严重程度 脑血管结局。这项试点研究将为更大规模的研究提供所需的初步数据和分析。 通过未来的 R01 应用进行综合研究。