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%的患者留下中度功能障碍和15-30%的严重残疾。缺血性中风后会出现一定程度的自发恢复，但通常是不完全的。各种旨在通过恢复和重组幸存的大脑元素来减少残疾的神经恢复疗法正在进行测试，但尚未获得批准，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未确定，也没有可用的恢复生物标志物。临床康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是相当突出的。通过使用非侵入性MRI、实验室和遗传学方法和测量来定义这些过程，如果被证明是有效和可靠的，将具有巨大的潜力，为临床医生提供合理指导未来中风恢复医学治疗的工具。拟议研究的主要目标有三个方面：1）定义特定的多参数MRI测量，即脑血容量和血脑转移常数值，结合磁共振加权成像的定性评估，以及分数各向异性、表观峰度系数和T1和T2值，结合q球成像的定性评估，能够分别表征从缺血性中风恢复的患者的脑中正在进行的血管和轴突重塑，并且这些测量及其动态时间演变与中风发作后90天缺血性中风的功能恢复程度相关，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/数字及其动态时间演变与卒中发作后90天缺血性卒中的功能恢复程度相关，血管重塑的MRI标志物，以及，3）探索特定基因型（主要是脑源性神经营养因子Val 66 Met多态性和ApoE亚型）的存在是否影响缺血性卒中的自发恢复程度，并导致卒中后血管和轴突重塑减弱和减慢。将对60名患者进行研究。我们希望这项研究将产生新的数据，提供新的和重要的信息，伴随自发性中风恢复的脑形态学变化，并将导致合理的，图像引导的未来神经修复治疗方案的最佳模型的发展。 公共卫生相关性：在这项研究中，我们将研究中风患者的前三个月后，他们的症状发作，使用系列，新的非侵入性磁共振成像技术，实验室和临床评估。我们的目的是确定脑结构的演变变化和与中风后临床恢复相关的实验室发现。我们期望这项研究产生的新数据将成为旨在促进中风后恢复的治疗方案的最佳设计的基础。

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.