Magnetic Resonance Imaging and Laboratory Assessment of Stroke Recovery

描述（由申请人提供）：中风是美国严重长期残疾的主要原因。大约40%的患者有中度功能障碍，15-30%的患者有严重残疾。缺血性中风后会有一定程度的自发恢复，但这通常是不完全的。各种旨在通过恢复和重组残存的大脑元素来减少残疾的神经修复疗法正在测试中，但尚未有一种获得批准，其最佳处方仍然未知。目前，在自发或治疗诱导的恢复过程中发生的大脑变化仍不确定，也没有可用的恢复生物学标志物。临床恢复的基础是非常不完全了解。它可能包括几个不同的子过程，其中血管和轴突重塑以及大脑的内在修复能力相当突出。通过非侵入性MRI、实验室和遗传方法和测量来定义这些过程，如果被证明是有效和可靠的，将有巨大的潜力为临床医生提供工具，合理指导未来中风康复的医学治疗。拟议研究的主要目的有三个方面：1)定义特定的多参数MRI测量，即结合敏感性加权成像定性评估的脑血容量和血脑转移常数，以及结合q球成像定性评估的分数各向异性、表观峰度系数和T1、T2值，是否能够分别表征正在进行的血管重构和轴突重构；在缺血性脑卒中患者恢复后的大脑中，这些测量及其动态时间演变与中风发作后90天缺血性脑卒中功能恢复程度相关，2)确定血管内皮生长因子或基质衍生因子1的水平和循环内皮祖细胞的数量，以及这些水平/数量及其动态时间演变是否与卒中后90天缺血性卒中功能恢复程度和血管重构的MRI标记物相关；3)探讨特异性基因型是否存在；主要是脑源性神经营养因子Val66Met多态性和ApoE亚型，影响缺血性脑卒中的自发恢复程度，导致脑卒中后血管和轴突重构减弱和减慢。将对60名患者进行研究。我们期望这项研究将产生新的数据，为自发性中风恢复过程中大脑形态学变化提供新的重要信息，并将为合理的、图像引导的未来神经修复治疗方案提供最佳模型。

DESCRIPTION (provided by applicant): Stroke is the leading cause of serious long-term disability in the United States. Approximately 40% of patients are left with moderate functional impairments and 15-30% with severe disability. Some degree of spontaneous recovery occurs after an ischemic stroke, but very often this is incomplete. Various neurorestorative therapies, aiming at reducing disability by restoring and reorganizing the surviving brain elements are being tested but none has yet been approved and their optimal prescription remains unknown. At present, the brain changes occurring in the process of spontaneous, or treatment-induced, recovery remain undetermined and there are no available biological markers of recovery. The substrate of clinical recovery is very incompletely understood. It likely includes several different sub-processes, of which vascular and axonal remodeling and the brain's intrinsic ability to repair, are rather prominent. Defining these processes by using non-invasive MRI, laboratory and genetic methods and measurements, if proven valid and reliable, will have the tremendous potential to provide clinicians with tools to rationally guide future medical treatments for stroke recovery. The mains aims of the proposed study are three fold: 1) to define whether specific multiparametric MRI measures, namely cerebral blood volume and blood-to-brain transfer constant values in conjunction with qualitative assessment with susceptibility-weighted imaging, as well as fractional anisotropy, apparent kurtosis coefficient and T1 and T2 values in conjunction with qualitative assessment with q-ball imaging, are capable of characterizing ongoing vascular and axonal remodeling, respectively, in the brain of patients recovering from ischemic stroke, and that these measures and their dynamic temporal evolution correlate with the degree of functional recovery from ischemic stroke at 90 days after stroke onset, 2) to define the levels of vascular endothelial growth factor or stromal derived factor 1 and the numbers or circulating endothelial progenitor cells and whether these levels/numbers and their dynamic temporal evolution correlate with the degree of functional recovery from ischemic stroke at 90 days after stroke onset and with the MRI markers of vascular remodeling, and, 3) to explore whether the presence of specific genotypes, mainly the brain-derived neurotrophic factor Val66Met polymorphism and ApoE subtypes, influence the degree of spontaneous recovery from ischemic stroke and result in attenuated and slower post-stroke vascular and axonal remodeling. Sixty patients will be studied. We expect that the proposed study will produce novel data that will provide new and important information on the morphological brain changes that accompany spontaneous stroke recovery, and will result in the development of an optimal model for rational, image-guided future neurorestorative treatment protocols. PUBLIC HEALTH RELEVANCE: In this study we will study stroke patients for the first three months after their symptom onset using serial, novel non-invasive magnetic resonance imaging techniques, laboratory and clinical assessments. Our aim is to define the evolving changes in brain structure and laboratory findings that correlate with clinical recovery after stroke. We expect that the novel data produced by this study will form the basis for the optimal design of treatment protocols aiming at enhancing post-stroke recovery.