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

项目摘要 虽然病毒抑制可以通过联合抗逆转录病毒治疗(CART)实现， 艾滋病毒携带者(PLWH)仍有相当大的脑部受累和认知风险 减损。尽管有证据表明PLWH存在血管病理，但这些机制并不清楚。 明白了。此调查将使用新的4D Flow MRI功能来评估特定的 血管机制可能在脑改变和认知功能减退中发挥作用 已抑制PLWH(目标1)。将使用神经血管4D Flow MRI来量化总血液 脑血流(TCBF)，并推导出血流速度、峰值速度和脉搏指数 脑动脉(目标1)。我们将使用心脏4D Flow MRI对升主动脉进行量化 血流、心输出量/指数，并得出主动脉-颈动脉脉搏波速度(PWV)比率。这 尚未用于评估病毒抑制的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，是否有 主动脉-颈动脉PWV比率和脑搏动指数与年龄的差异 匹配的血清阴性对照(目标1)。我们将招募参与者参加我们的血液动力学课程 来自一个独特队列的分析，包括早期感染的影像和认知数据 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 利用归档数据，这笔R21资金还可以完成10年的跟踪研究，以 确定在CART感染的第一个十年中大脑的变化和认知能力的下降 已抑制PLWH(目标2)。我们可以确定假想的血管 机制与大脑小血管疾病(SVD)的严重程度有关，皮质 CART中的变薄、局限性体积丧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告诉新的 治疗策略和这些血流动力学参数可能提供新的措施 抑制的PLWH患者的血管风险和治疗反应。

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.