MRI-based Quantitative Brain Perfusion Mapping for Sickle Cell Disease

描述（由申请人提供）：SCD是一种以血红蛋白S （HbS）合成异常为特征的遗传性血液疾病，镰状细胞性贫血（SCA）是最常见的亚型。中风是儿童和成人SCD患者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的大血管和小血管均有异常。目前，主要的临床筛查试验是使用经颅多普勒（TCD）对无神经症状的SCD儿童进行筛查。TCD检测阳性预测值较低，不能有效筛查成人SCD患者的脑卒中风险。脑血流量（CBF）是衡量大脑微血管灌注的指标，已被认为是儿童和成人SCD早期脑血管损伤的潜在更敏感和特异性指标。基于动脉自旋标记（ASL） MRI技术的脑血流测量是有前途的，因为它不需要造影剂，而且没有辐射。然而，现有的ASL技术通常在单个标记后延迟获得二维多层灌注加权MRI，并且在计算CBF时，假设了许多与血液特性相关的参数，如动脉到达时间（AAT）、血液的纵向松弛时间（T1）和标记效率。该研究的总体目标是开发和验证一种多延迟3D ASL方案，结合每个受试者的血液T1测量和标记效率，为SCD患者提供准确可靠的灌注指标（CBF和AAT）。测量的CBF和AAT有望同时检测SCD的小血管和大血管疾病。本研究的具体目的是首先建立一个全面、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（Aim 1），然后进行验证

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).