MR PERFUSION IMAGING FOR BRAIN FUNCTIONAL STUDIES

本次申请临床研究者发展奖的目的是 （加拿大国际开发署）将开发和验证准确、高分辨率和高分辨率的 用于脑成像的灵敏度磁共振（MR）方法 灌注和脑功能。 这些方法将广泛适用于 适用于人类群体，以帮助检测和了解神经系统 紊乱 一些神经系统疾病有一个病因，原发性 组织血流的改变（例如，中风、短暂性脑缺血发作、血管炎）， 其它的具有次要的、相关的流动改变（例如，肿瘤， 癫痫发作）。 重要的是不仅要检测和了解这些 灌注障碍，但也寻找灌注变化，在许多 其他神经系统疾病使用敏感的成像方法。 作为 大脑活动和组织血流之间存在耦合， 许多神经系统疾病可能与微妙的 由脑功能改变引起的灌注异常。 灌注成像还可以提供监测治疗的手段， 神经系统疾病的大脑活动。 CIDA的另一个目标是 期间是在脑灌注生物学的复杂领域进行培训， 大脑激活生理学通过马库斯·赖希勒博士的赞助 和他的正电子发射断层扫描神经科学小组 的 培训还将包括对医学生和研究生的指导。 磁共振造影剂的磁化率对信号的影响 强度最近已被用于定性评估大脑 灌注。 然而，这种信号损失（deltaR*）方法具有潜在的 依赖于血管几何形状的缺点（例如，毛细管直径， 间距和取向）和组织水扩散。 作为 或者，磁化率对信号相移的影响（deltaphi） 最近被用于定性评估脑灌注。 初步的理论预测这种deltaphi方法对 毛细血管几何形状、造影剂的区室化和扩散。 加拿大国际开发署请求中提出的工作是为了更好地说明这一点， 德尔菲效应 一个完整的理论的物理过程造成这一点 现象将进行，实验旨在验证 的理论假设。 物理、化学和生物 将测试几种MR造影剂的性能，以确定 药剂用作灌注示踪剂。deltaphi和deltaR+ 方法将与团注造影剂一起使用， 脑血容量，结果将通过许多方法验证， 包括正电子发射断层扫描。 这两种方法将是 在中风和血脑屏障（BBB）的动物模型中研究 分解以评估扩散和造影剂变化的影响 精确度的划分。 红细胞（RBC）造影剂将 进一步开发和测试，以实现高灵敏度功能 使用deltaR+和deltaphi灌注成像的脑成像 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.