Development of techniques to map cerebrovascular reactivity with resting-state MRI

项目摘要/摘要 脑血管疾病的诊断和治疗监测，如中风、动脉狭窄、血管 痴呆症和小血管疾病需要准确评估脑血管参数。的确有 大量证据表明，脑血管反应性(CVR)是反映血管储备能力的指标 血管的扩张或收缩，是早期发现缺血最敏感的标志物之一。 在目前的临床环境中，CVR测量需要在成像过程中遇到血管挑战，涉及 注射药剂(如乙酰唑胺)、吸入二氧化碳气体或屏气。 然而，这些策略在患者负担和成本方面都不理想，因为 特殊设备的程序、要求和生理动作可能产生的副作用 血管挑战。因此，开发一种不需要显性血管的CVR技术 挑战将对脑血管疾病产生重大影响。 静息状态的BOLD MRI信号表现出随时间的自发波动。而这个信号的一部分 已经被用来绘制大脑网络的功能连接图，并已经彻底改变了fMRI领域， 由于呼吸的自发变化，信号波动的另一个分量来自血管 导致动脉二氧化碳随时间变化的速率和深度。这种二氧化碳的变化导致了波动 在BOLD信号中，其幅度与CVR有关。我们的初步研究强烈表明 利用这种二氧化碳波动绘制CVR图的可行性，以及它描绘血管缺陷的能力 有颅内动脉狭窄的患者。 因此，本研究的中心目标是扩大这些初步发现，并发展和 基于静息状态(即无气体)下采集的MRI数据验证CVR标测技术 挑战。首先，我们将开发采集和分析方法来分离二氧化碳波动分量 来自静息状态的粗体信号用于CVR标测(目标1的研究1)。潜在的方法来增加 将评估该技术的敏感性(目标1的研究2)。第二，我们将同时进行核磁共振， 脑电(EEG)和呼气末二氧化碳记录，以验证我们的方法测量的信号 包含最小的神经贡献，但主要是二氧化碳波动，并验证所提出的CVR 采用黄金标准的二氧化碳吸入法测绘技术(目标2)。最后，我们将进行初步的 这项技术在颅内动脉狭窄患者中的临床演示(见目标3)。 影响：对临床实践的影响是脑血管疾病患者，包括 无法适应血管挑战的患者，可以在标准MRI期间接受CVR成像 会议。这将大大提高CVR在临床诊断和预后中的应用。

Project Summary/Abstract Diagnosis and treatment monitoring of brain vascular diseases, such as stroke, arterial stenosis, vascular dementia, and small vessel diseases, requires accurate assessment of cerebrovascular parameters. There is substantial evidence that cerebrovascular reactivity (CVR), an index of vascular reserve reflecting the ability of the blood vessels to dilate or constrict, is one of the most sensitive markers for early detection of ischemia. In current clinical settings, CVR measurement requires a vascular challenge during imaging, involving either the injection of pharmacological agent (e.g. acetazolamide), inhalation of CO2 gas, or breath-hold. 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 have a significant impact in cerebrovascular diseases. Resting-state BOLD MRI signal manifests spontaneous fluctuations with time. While portions of this signal have been exploited to map functional connectivity of brain networks and have revolutionized the fMRI field, another component of the signal fluctuation is of a vascular origin, due to spontaneous variations in breathing rate and depth that result in time-dependent changes in arterial CO2. This CO2 variation results in a fluctuation in BOLD signal, the amplitude of which is related to CVR. Our preliminary studies have strongly suggested the feasibility of mapping CVR using this CO2 fluctuation, as well as its ability to delineate vascular deficits in patients with intracranial arterial stenosis. Therefore, the central goal of the present study is to expand these preliminary findings and to develop and validate a CVR mapping technique based on MRI data acquired under resting-state, i.e. without gas challenges. First, we will develop acquisition and analysis methods to isolate the CO2 fluctuation component from resting-state BOLD signal for CVR mapping (Study 1 of Aim 1). Potential approaches to augment the sensitivity of the technique will be evaluated (Study 2 of Aim 1). Second, we will conduct simultaneous MRI, electroencephalogram (EEG), and end-tidal CO2 recordings to verify that the signal measured with our method contains minimal neural contribution but predominantly CO2 fluctuation, and validate the proposed CVR mapping technique with the gold-standard CO2-inhalation method (in Aim 2). Finally, we will conduct initial clinical demonstration of this technique in patients with intracranial arterial stenosis (in Aim 3). Impact: The impact on clinical practice is that patients with cerebrovascular diseases, including ones whose are unable to comply with vascular challenges, can receive CVR imaging during a standard MRI session. This will greatly enhance the utility of CVR in clinical diagnosis and prognosis.