MRI-based Quantitative Brain Perfusion Mapping for Sickle Cell Disease

描述（由申请人提供）：SCD是一种遗传性血液疾病，其特征为血红蛋白S（HbS）合成异常，镰状细胞性贫血（SCA）是最常见的亚型。中风是SCD儿童和成人死亡和长期残疾的最常见原因。对局灶性神经功能缺损患者的研究显示，SCD患者的大血管和小血管均异常。目前，主要的临床筛选测试是使用经颅多普勒（TCD）的神经系统无症状的儿童与SCD。TCD检测阳性预测值较低，对筛查成人SCD患者卒中风险无效。脑血流量（CBF）是脑微血管灌注的一种测量方法，已被认为是SCD儿童和成人早期脑血管损伤的潜在更敏感和更特异的指标。基于动脉自旋标记（ASL）MRI技术的CBF测量是有前途的，因为它不需要造影剂，并且没有辐射。然而，现有的ASL技术通常在单个标记后延迟处获取2D多层灌注加权MRI，并且对于CBF计算，对与血液特性相关的许多参数进行假设，例如动脉到达时间（AAT）、血液的纵向弛豫时间（T1）和标记效率。提出的研究的总体目标是开发和验证多延迟3D ASL方案，结合血液T1和标记效率的每个受试者测量，为SCD患者提供准确可靠的灌注指标（CBF和AAT）。预计测量的CBF和AAT可以同时检测SCD的小血管和大血管疾病。本研究的具体目的是首先开发一种全面和快速的基于ASL的灌注方案，并在健康志愿者中证明其可靠性和可重复性（目标1），然后验证 对一组无脑卒中史的SCA患者进行相位对比MR血管造影（PC-MRA）和动态磁敏感对比（DSC）MRI测量CBF和AAT（目的2），最后对有脑卒中史的SCD患者进行CBF和AAT监测，探讨CBF和AAT与脑损伤复发的关系（目的3）。

DESCRIPTION (provided by applicant): SCD is a genetic blood disorder characterized by abnormal hemoglobin S (HbS) synthesis with sickle cell anemia (SCA) as the most common subtype. Stroke is the most frequent cause of death and long-term disability in both children and adults with SCD. Studies of patients with focal neurologic deficits have revealed abnormalities of both large and small vessels in SCD. Currently, the main clinical screening test is the use of transcranial Doppler (TCD) for neurologically asymptomatic children with SCD. The TCD test has a low positive predictive value and is not effective to screen stroke risk in adult SCD patients. Cerebral blood flow (CBF), a measure of the microvascular perfusion of the brain, has been recognized as a potentially more sensitive and specific indicator of early cerebrovascular impairment in both children and adults with SCD. CBF measurement based on the arterial spin labeling (ASL) MRI technique is promising as it does not require a contrast agent and is free of radiation. However, the existing ASL techniques often acquire 2D multi-slice perfusion-weighted MRI at a single post-labeling delay and, for CBF calculation, make assumptions on a number of parameters that are related to blood properties, such as arterial arrival time (AAT), longitudinal relaxation time (T1) of blood and labeling efficiency. The overall goal of the research proposed is to develop and validate a multi-delay 3D ASL protocol combined with per-subject measurements of blood T1 and labeling efficiency, which provides accurate and reliable perfusion metrics (CBF and AAT) for SCD patients. The measured CBF and AAT are expected to allow detection of both small and large vessel disease simultaneously for SCD. The specific aims of this study is first to develop a comprehensive and fast ASL-based perfusion protocol and demonstrate its reliability and reproducibility in healthy volunteers (Aim 1), then to validate the measured CBF and AAT with phase-contrast MR Angiography (PC-MRA) and dynamic susceptibility contrast (DSC) MRI in a group of SCA patients without a history of stroke (Aim 2), and finally to monitor CBF and AAT in patients with SCD and a history of stroke to explore the association between CBF and AAT and recurrent brain injury (Aim 3).