MRI-based Quantitative Brain Perfusion Mapping for Sickle Cell Disease

描述(申请人提供)：SCD是一种遗传性血液疾病，以血红蛋白S(HbS)合成异常为特征，最常见的亚型为镰状细胞性贫血(SCA)。中风是SCD儿童和成人最常见的死亡和长期残疾原因。对局灶性神经功能障碍患者的研究显示，SCD的大血管和小血管都有异常。目前，临床上主要的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试验阳性预测值低，不能有效筛查成年SCD患者的卒中风险。脑血流量(CBF)是衡量脑微血管灌注量的指标，已被公认为是儿童和成人SCD早期脑血管损害的更敏感和更特异的指标。基于动脉自旋标记(ASL)MRI技术的CBF测量具有不需要造影剂和无辐射的优点，具有广阔的应用前景。然而，现有的ASL技术通常在单个标记后延迟获得2D多层灌注加权MRI，并且在计算CBF时，对与血液特性有关的许多参数进行假设，如动脉到达时间(AAT)、血液纵向松弛时间(T1)和标记效率。这项研究的总体目标是开发和验证多延迟3D ASL方案，结合每个受试者的血液T1和标记效率的测量，为SCD患者提供准确可靠的血流灌注指标(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。这项研究的具体目的是首先开发一种全面和快速的基于ASL的灌流方案，并在健康志愿者中证明其可靠性和重复性(目标1)，然后验证 用相位对比磁共振血管成像(PC-MRA)和动态磁化率对比(DSC)MRI对一组无卒中病史的SCA患者进行CBF和AAT的检测(AIM 2)，最后监测有卒中病史的SCD患者的CBF和AAT，以探讨CBF和AAT与复发性脑损伤的关系(AIM 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).