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.

项目摘要/摘要 这是对父母授予R01NS115771进行其他工作的补充请求，以回应 非AG-23-008。有效用于病毒抑制的抗逆转录病毒药物已导致近期寿命 艾滋病毒（PWH）的人的期望。但是，由于PWH的寿命更长，超过一半（52.7％ 2020年）在美国，尽管病毒抑制和免疫机构，PWHS面对了50岁以上的年龄 与普通人群相比，中风和神经认知障碍的速度增加。这 据估计，与HIV相关的神经认知障碍（手）的患病率为所有HIV阳性的30-50％ 个体，较旧的PWH患病率较高。脑血管功能障碍已与 PWH中脑血管疾病的发生增加，这可能是手的关键因素。然而， 仍然缺乏脑血管功能障碍作为手部的病因的直接证据。 父级奖（R01NS115771）着重于开发用于映射的新型MRI技术 脑血管反应性（CVR）及其作为血管认知障碍的早期生物标志物（VCI）的实用性。 CVR是大脑响应刺激的扩张能力的指数，是大脑的量度 血管功能。先前的研究表明，VCI中的CVR降低。尽管有这些有据可查的文献 调查结果，CVR通常在临床实践中通常无法测量，这是由于后勤困难在应用A 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）或感染 二氧化碳气体。但是，这些技术是复杂且昂贵的，需要特殊设备，并且可能 物理操作的副作用引起血管挑战。因此，开发CVR 不需要显式血管挑战的技术将扩大CVR的临床实用性，使其成为 在PWH中研究脑血管功能障碍的可行工具，并可能成为手的生物标志物。 在此补充中，我们使用父母提出的新技术提出了一个补充项目 测量PWH中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个PWHS，无手的20个PWH和10个艾滋病毒感染者 （SN）控制（父项目还研究健康对照60 - 85年）； 2）确定CVR是否可以 在FLAIR MRI上预测手状态，认知得分和WMH。我们假设这是1）在这三个 参与者组，手动的PWH将显示最低的CVR，而PWH中的CVR低于正常CVR 手，与SN对照相比； 2）CVR措施将预测认知缺陷的严重性和 脑血管结局。这项试点研究将提供更多较大的数据和分析的初步数据和分析 通过未来的R01应用程序进行全面研究。