Magnetic Resonance Imaging and Laboratory Assessment of Stroke Recovery

摘要 在美国，中风是导致长期严重残疾的主要原因。约40%的 患者有中等程度的功能障碍，15%-30%的患者有严重残疾。在某种程度上 缺血性中风后会出现自然恢复，但这通常是不完整的。五花八门 神经恢复性疗法，旨在通过恢复和重组存活的大脑来减少残疾 正在对元素进行测试，但尚未批准任何元素，其最佳处方仍然存在 未知。目前，大脑发生变化的过程是自发的，或治疗诱发的， 恢复情况仍不确定，也没有可用的恢复生物标志。的底物 临床上对康复的了解还很不完全。它可能包括几个不同的子流程，其中 血管和轴突的重塑以及大脑内在的修复能力是相当突出的。定义 这些过程通过使用非侵入性核磁共振、实验室和遗传学方法和测量，如果得到证实 有效和可靠，将具有巨大的潜力，为临床医生提供合理指导的工具 未来中风康复的医疗治疗。拟议研究的主要目的有三个方面：1) 确定特定的多参数磁共振测量，即脑血容量和血脑比 转移常数值与磁化率加权成像的定性评估相结合，如 以及分数各向异性、表观峰度系数、T1和T2值 Q-ball成像的定性评估，能够表征正在进行的血管和轴突 分别在缺血性中风康复患者的大脑中进行重塑，这些措施 其动态时间演变与缺血性卒中的功能恢复程度相关 在卒中发病90天后，2)确定血管内皮生长因子或基质来源的水平 因子1和循环内皮祖细胞的数量以及这些水平/数量和 它们的动态时间演变与90岁时缺血性中风的功能恢复程度相关 以及，3)探讨卒中后是否存在血管重构。 存在特定的基因类型，主要是脑源性神经营养因子Val66Met多态和 载脂蛋白E亚型，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构减弱和减慢。将对60名患者进行研究。我们 预计拟议的研究将产生新的数据，提供关于以下方面的新的重要信息 伴随着自发性中风康复的脑形态变化，并将导致 为合理的、影像引导的未来神经恢复性治疗方案开发最佳模型。

Abstract 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.