Gas-free cerebrovascular reactivity (CVR) MRI in vascular cognitive impairment

项目摘要/摘要 血管认知障碍(VCI)是继阿尔茨海默病之后导致痴呆的第二大原因 (Ad)。然而，虽然AD生物标记物相对发达，但大脑中VCI病理的生物标记物 是更有限的。脑血管反应性(CVR)，脑血管扩张能力的指标 对刺激来说，是一个很有希望的大脑血管功能的标志。我们的主要假设是CVR是 一个看似合理的VCI诊断生物标记物，目前还没有其他生物标记物可用。 尽管有一些承诺，但CVR在临床实践中并不常见，主要是由于后勤方面的原因 在成像过程中应用血管“挑战”的困难。在当前的临床环境中，CVR测量 在成像过程中需要血管挑战，包括注射药理学试剂(例如 乙酰唑胺)或吸入二氧化碳气体。然而，这些策略对于两个患者来说都不是理想的 负担和费用，因为程序复杂，需要特殊设备，以及可能 诱导血管挑战的生理动作的副作用。因此，无级变速器的研制 不需要明确的血管挑战的技术将扩大CVR在 VCI与血管性痴呆的诊断。 该项目的中心目标是开发一种无气体的CVR MRI技术，该技术可以提供类似的 对吸入二氧化碳的CVR的敏感性仍然保持了对受试者的高舒适性。这项新技术是 主要基于静息状态扫描并利用受试者呼吸模式的自发波动， 而且还对它们的呼吸节律进行了间歇性的调制，以增强其潮气末的波动 二氧化碳(ETCO2)。该项目分为三个合乎逻辑的步骤。首先，我们将开发无气体CVR技术 在健康受试者中，分别进行BOLD和CBF MRI采集(目标1)。第二，由于之前在 基于气体的CVR表明，无论是在受试者内部还是在受试者之间，CVR都存在相当大的差异 设置，我们将确定正常变化的生理机制(S)的正常变化，然后 对它们进行核算/控制，以减少差异(目标2)。最后，我们将应用无气CVR 有血管危险因素和无血管危险因素的轻度认知障碍患者的技术检查 无气体CVR作为一种潜在的生物标志物在诊断血管性认知功能障碍中的应用 痴呆症(目标3)。 影响：一旦这些特定的目标实现，CVR的临床实用方法将被 这将对理解血管疾病的神经生物学和 用于诊断和治疗的生物标记物(与其他生物标记物联合)的发展 监测血管性认知障碍和痴呆。

Project Summary/Abstract Vascular cognitive impairment (VCI) is the second leading cause of dementia after Alzheimer’s disease (AD). However, while AD biomarkers are relatively well developed, biomarkers for VCI pathology in the brain are more limited. Cerebrovascular reactivity (CVR), an index of cerebral vessel’s capacity to dilate in response to stimulation, is a promising marker of the brain’s vascular function. Our overarching hypothesis is that CVR is a plausible biomarker for the diagnosis of VCI, for which no other biomarkers are currently available. Despite some promises, CVR is not commonly measured in clinical practice, primarily due to logistical difficulties in applying a vascular “challenge” during imaging. In current clinical settings, CVR measurement requires a vascular challenge during imaging, involving either the injection of pharmacological agent (e.g. acetazolamide) or inhalation of CO2 gas. However, these strategies are not ideal in terms of both patient burden and costs, due to the complexity of the procedure, requirement of special equipment, and possible side-effect of physiological maneuver to induce vascular challenge. Therefore, development of a CVR technique that does not need an explicit vascular challenge will broaden the clinical utility of CVR in the diagnosis of VCI and vascular dementia. The central goal of this project is to develop a gas-free CVR MRI technique that can provide comparable sensitivity to CO2-inhalation CVR yet maintains a high comfort level to the subjects. This new technique is largely based on resting-state scan and exploits spontaneous fluctuations in the subject’s breathing pattern, but also introduces intermittent modulations of their breathing rhythm to enhance fluctuations in their end-tidal CO2 (EtCO2). This project is divided into three logical steps. First, we will develop the gas-free CVR technique in healthy subjects, separately for BOLD and CBF MRI acquisitions (in Aim 1). Second, since previous work on gas-based CVR has suggested that there exist fairly large variations in CVR in both within and across subjects settings, we will identify physiological mechanism(s) of normal variations in gas-free CVR and then account/control for them in order to reduce variations (in Aim 2). Finally, we will apply the gas-free CVR technique in patients with mild cognitive impairment with and without vascular risk factors, in order to examine the utility of gas-free CVR as a potential biomarker in the diagnosis of vascular cognitive impairment and dementia (in Aim 3). Impact: Once these specific aims are accomplished, clinically practical methods of CVR will have been developed that will have important applications for understanding the neurobiology of vascular disease and for the development of biomarkers (in conjunction with other biomarkers) for the diagnosis and treatment monitoring of vascular cognitive impairment and dementia.