Magnetic Resonance Imaging and Laboratory Assessment of Stroke Recovery

描述(申请人提供)：在美国，中风是导致长期严重残疾的主要原因。大约40%的患者有中度功能障碍，15%-30%的患者有严重残疾。缺血性中风后会出现某种程度的自发恢复，但这往往是不完整的。旨在通过恢复和重组幸存的大脑元素来减少残疾的各种神经恢复疗法正在进行测试，但尚未获得批准，其最佳处方仍不清楚。目前，在自发或治疗诱导的恢复过程中，大脑的变化仍然不确定，也没有可用的恢复生物标志物。临床痊愈的基础还很不清楚。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固有的修复能力相当突出。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，为临床医生提供工具，合理指导未来中风康复的医疗治疗。这项研究的主要目的有三个方面：1)明确特定的多参数MRI指标，即脑血容量和血脑转移常数值与磁化率加权成像的定性评估相结合，以及分数各向异性、表观峰度系数、T1和T2值与Q-ball成像的定性评估相结合，是否能够分别表征脑内正在进行的血管和轴突重构，以及这些测量及其动态时间演变是否与卒中后90天缺血性中风的功能恢复程度相关。2)明确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/数量及其动态的时间演变是否与卒中后90天的功能恢复程度和血管重塑的MRI标志物相关；3)探讨特定的基因类型(主要是脑源性神经营养因子Val66Met多态和载脂蛋白E亚型)的存在是否影响缺血性卒中的自发恢复程度，从而导致卒中后血管和轴突重塑的减弱和减慢。将对60名患者进行研究。我们期望这项拟议的研究将产生新的数据，提供有关伴随着自发性中风恢复的脑形态变化的新的和重要的信息，并将导致开发一个合理的、图像引导的未来神经恢复治疗方案的最佳模型。 公共卫生相关性：在这项研究中，我们将使用系列、新的非侵入性磁共振成像技术、实验室和临床评估来研究中风患者症状出现后的前三个月。我们的目标是确定与中风后临床康复相关的脑结构和实验室结果的演变变化。我们期望这项研究产生的新数据将为旨在促进卒中后恢复的治疗方案的优化设计奠定基础。

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.