MR PERFUSION IMAGING FOR BRAIN FUNCTIONAL STUDIES

申请临床研究人员发展奖的目标 (CIDA)是开发和验证准确、高分辨率和高分辨率的 用于脑成像的灵敏磁共振(MR)方法 脑血流灌注和脑功能。方法论将得到广泛的应用 适用于人类群体，帮助检测和了解神经学 精神错乱。一些神经系统疾病具有病因、原发病、 组织血流量改变(如中风、短暂性脑缺血发作、血管炎)，而 其他人具有继发性相关的血流改变(例如，肿瘤， 癫痫)。重要的是不仅要检测和理解这些 血流灌注紊乱，还要寻找很多血流灌注的变化 使用敏感成像方法的其他神经疾病。AS 大脑活动和组织血液流动之间存在耦合，这是 许多神经系统疾病可能与微妙的 由脑功能改变引起的血流灌注异常。 灌注成像也可能提供一种监测治疗和治疗的手段 神经性疾病中的大脑活动。加拿大国际开发署的另一个目标 期间是在脑灌注生物学的复杂领域进行培训和 由Marcus Raichle博士赞助的脑激活生理学 和他的正电子发射断层扫描(PET)神经科学小组。这个 培训还将包括对医学和研究生的指导。 磁共振对比剂对信号的磁化率影响 最近，强度被用来定性地评估大脑 灌流。然而，这种信号损失(增量*)方法具有潜在的 依赖于血管几何形状的缺点(例如，毛细血管直径， 间隔和取向)和组织水扩散。作为一种 或者，磁化率对信号相移的影响(增量) 最近被用来定性评估脑血流灌注。 初步理论预测该增量法对 毛细血管几何、造影剂的分隔和扩散。 本CIDA请求中提议的工作是更好地描述这一点 三角洲效应。关于导致这种现象的物理过程的完整理论 将进行现象，并进行实验设计以验证 理论上的假设。物理、化学和生物 将测试几种磁共振造影剂的性能，以确定哪种 试剂起到了灌流示踪剂的作用。Delta和Deltar+都是 方法将与团注造影剂一起使用，以产生 脑血容量，结果将通过许多方法进行验证， 包括正电子发射断层扫描。这两种方法将是 卒中与血脑屏障动物模型的研究 分解以评估扩散和造影剂变化的影响 精确度上的划分。红细胞(RBC)造影剂将 进一步开发和测试，以实现高敏感度功能 Deltar+和Delaphi脑血流灌注成像 方法论。

The goals of this request for a Clinical Investigator Development Award (CIDA) are to develop and validate accurate, high-resolution and high- sensitivity magnetic resonance (MR) methodologies for imaging cerebral perfusion and brain function. The methodologies are to be widely applicable to human populations to help detect and understand neurological disorders. Some neurological disorders have a causative, primary alteration in tissue blood flow (e.g., stroke, TIA, vasculitis), while others have a secondary, associated flow alteration (e.g., tumors, seizures). It is important not only to detect and understand these perfusion disorders, but also to search for perfusion changes in many other neurological disorders using sensitive imaging methodology. As there is a coupling between brain activity and tissue blood flow, it is possible that many neurological disorders might be associated with subtle perfusion abnormalities that are caused by alterations in brain function. Perfusion imaging might also provide a means of monitoring therapy and brain activity in neurological disorders. A further goal of this CIDA period is to train in the complex fields of cerebral perfusion biology and brain activation physiology through the sponsorship of Dr. Marcus Raichle and his positron emission tomography (PET) neuroscience group. The training will also involve instruction of medical and graduate students. The magnetic susceptibility effect of MR contrast media on signal intensity has been used recently to qualitatively assess cerebral perfusion. However, this signal loss (deltaR*) method has the potential disadvantage of a dependence on vessel geometry (e.g., capillary diameter, spacings, and orientations) and tissue water diffusion. As an alternative, the susceptibility effect on signal phase shift (deltaphi) has more recently been used to qualitatively assess cerebral perfusion. Preliminary theory predicts this deltaphi method to be insensitive to capillary geometry, compartmentation of contrast agent, and diffusion. The work proposed in this CIDA request is to better characterize this deltaphi effect. A complete theory of the physical processes causing this phenomenon will be undertaken, with experimentation designed to validate the theoretical assumptions. The physical, chemical and biological properties of several MR contrast agents will be tested to determine which agents behave as perfusion tracers. Both the deltaphi and the deltaR+ methods will be used with bolus contrast agents to produce images of cerebral blood volume, and results will be validated by many approaches, including positron emission tomography. The two methods will be investigated in animal models of stroke and blood brain barrier (BBB) breakdown to assess the effects of changes in diffusion and contrast agent compartmentation on accuracy. A red blood cell (RBC) contrast agent will be further developed and tested to enable high-sensitivity functional brain imaging using the deltaR+ and deltaphi perfusion imaging methodology.