The Role of Aortic-Carotid Hemodynamics and Aberrant Flow in HIV Cerebral Injury

主动脉-颈动脉血流动力学和异常血流在 HIV 脑损伤中的作用

• 批准号: 10266136
• 负责人: ANN B RAGIN
• 金额: $ 24万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10266136
• 关键词: 4D MRI; AIDS dementia; Age; Aging; Aorta; Basal Ganglia; Blood Vessels; Blood flow; Brain; Brain Injuries; Brain Stem; Cardiac; Cardiac Output; Cardiovascular Diseases; Carotid Arteries; Cerebral small vessel disease; Cerebrovascular Circulation; Cerebrum; Cessation of life; Chest; Cognitive; Complication; Corpus Callosum; Coupling; Data; Dementia; Devices; Enrollment; Evaluation; Follow-Up Studies; Funding; HIV; HIV-1; HIV-associated neurocognitive disorder; Heart; Image; Imaging technology; Impaired cognition; Incidence; Individual; Individual Differences; Infection; Injury; Investigation; Magnetic Resonance Imaging; Measures; Memory; Microvascular Dysfunction; Participant; Pathologic Processes; Pathology; Perfusion; Persons; Phenotype; Physiologic pulse; Physiological; Play; Race; Risk; Risk Factors; Role; Severities; Stroke; Stroke Volume; Structure; Subcortical Infarctions; Thalamic structure; Thinness; Time; Vascular Cognitive Impairment; Vascular blood supply; Viral; Virus Replication; White Matter Hyperintensity; antiretroviral therapy; archive data; archived data; cerebral artery; cerebral hemodynamics; cerebrovascular; cognitive function; cohort; comorbidity; executive function; follow-up; functional decline; heart function; hemodynamics; in vivo imaging; indexing; insight; interest; neuropathology; neurovascular; neurovascular unit; novel therapeutic intervention; pressure; processing speed; sex; treatment response

Project Summary While viral suppression can be achieved with combination antiretroviral therapy (cART), persons living with HIV (PLWH) remain at considerable risk of brain involvement and cognitive impairment. Despite evidence of vascular pathology in PLWH, these mechanisms are not well understood. This investigation will use new 4D Flow MRI capabilities to evaluate specific vascular mechanisms that may play a role in brain alterations and cognitive decline in suppressed PLWH (Aim 1). Neurovascular 4D flow MRI will be used to quantify total blood flow to the brain (TCBF) and to derive flow rates, peak velocities and the Pulsatility Index for the cerebral arteries (Aim 1). We will use Cardiac 4D Flow MRI to quantify ascending aortic flow, cardiac output/index and derive the aortic-carotid pulse wave velocity (PWV) ratio. This approach, which has not yet been used to evaluate virally suppressed PLWH, may provide new insights into vascular mechanisms. We are particularly interested in whether there are differences in the aortic-carotid PWV ratio and cerebral Pulsatility Index compared to age- matched seronegative controls (Aim 1). We will enroll participants for our hemodynamic analysis from a unique cohort with imaging and cognitive data available for early infection with well-documented cART initiation dates (PLWH and age-matched seronegative controls). By leveraging the archived data, this R21 funding can also accomplish a 10 year follow-up study to determine brain changes and cognitive decline over the first decade of infection in cART suppressed PLWH (Aim 2). We can determine whether the hypothesized vascular mechanisms are associated with the severity of cerebral small vessel disease (SVD), cortical thinning, localized volume loss and decline in specific cognitive functions in cART suppressed PLWH (Aim 3). If confirmed, these vascular mechanisms may inform new therapeutic strategies and these hemodynamic parameters may provide new measures of vascular risk and response to treatment in suppressed PLWH.

项目概要 虽然可以通过联合抗逆转录病毒疗法（cART）来实现病毒抑制， 艾滋病毒感染者（PLWH）仍然面临相当大的大脑受累和认知障碍的风险 损害。尽管有感染者血管病理学证据，但这些机制并不完善 明白了。这项调查将使用新的 4D Flow MRI 功能来评估特定的 可能在大脑改变和认知能力下降中发挥作用的血管机制 抑制 PLWH（目标 1）。神经血管 4D 血流 MRI 将用于量化总血量 流向大脑 (TCBF) 并得出流速、峰值速度和脉动指数 脑动脉（目标 1）。我们将使用心脏 4D Flow MRI 来量化升主动脉 流量、心输出量/指数并得出主动脉-颈动脉脉搏波速度 (PWV) 比。这 尚未用于评估病毒抑制的 PLWH 的方法可能会提供 对血管机制的新见解。我们特别感兴趣的是是否有 与年龄相比，主动脉-颈动脉 PWV 比值和脑搏动指数存在差异 匹配的血清阴性对照（目标 1）。我们将招募参与者进行血流动力学研究 来自独特队列的分析，具有可用于早期感染的成像和认知数据 有详细记录的 cART 启动日期（PLWH 和年龄匹配的血清阴性对照）。经过 利用存档数据，这项 R21 资金还可以完成一项为期 10 年的后续研究 确定 cART 感染前十年的大脑变化和认知能力下降 抑制 PLWH（目标 2）。我们可以确定假设的血管是否 机制与脑小血管疾病（SVD）的严重程度、皮质 cART 中的变薄、局部体积损失和特定认知功能下降 抑制 PLWH（目标 3）。如果得到证实，这些血管机制可能会提供新的信息 治疗策略和这些血流动力学参数可能提供新的衡量标准 受抑制的 PLWH 的血管风险和治疗反应。