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.

项目摘要 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功能障碍的风险。 损伤尽管有证据表明PLWH中存在血管病理学，但这些机制并不完全清楚。 明白本研究将使用新的4D Flow MRI功能来评价特定的 血管机制可能在大脑改变和认知能力下降中发挥作用， 抑制PLWH（目标1）。神经血管4D血流MRI将用于量化总血液 脑血流（TCBF），并推导出流速、峰值速度和脉动指数， 脑动脉（Aim 1）。我们将使用心脏4D Flow MRI量化升主动脉 血流、心输出量/指数，并得出动脉-颈动脉脉搏波速度（PWV）比。这 一种尚未用于评价病毒抑制的PLWH的方法，可能提供 对血管机制的新见解。我们特别感兴趣的是， 与年龄相比，动脉-颈动脉PWV比和脑脉动指数的差异- 匹配的血清阴性对照（Aim 1）。我们将招募参与者进行血流动力学检查， 来自具有可用于早期感染的成像和认知数据的独特队列的分析 记录良好的cART开始日期（PLWH和年龄匹配的血清阴性对照）。通过 利用存档的数据，这项R21基金还可以完成一项为期10年的随访研究， 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 机制与脑小血管病（SVD）、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以提供新的措施， 抑制性PLWH的血管风险和治疗反应。