MR Measured Oxygen Metabolic Index in Ischemic Stroke

正电子发射断层扫描(PET)研究得出的几条证据表明 脑氧利用代谢率(CMRO2)的测量为脑组织提供了一个指标 脑缺血时的生存能力。虽然PET是目前可以用来测量CMRO2的技术，但 对现场回旋加速器的需求使其仅限于少数几个医疗中心。因此，替代方案 能够提供与PET CMRO2相似的生理信息的方法 具有深刻的临床意义。为此，我们最近开发了一种磁共振成像方法 能够测量脑氧代谢活动，我们称之为MR脑氧 代谢指数(MR_COMI)。尽管物理上与PET CMRO2不同，但初步结果基于 MR_COMI是令人鼓舞的，这表明这种方法可能确实揭示了类似的生理 信息与PET CMRO2的信息相同。然而，为了确定MR_COMI是否可以描绘组织 缺血期间的生存能力：MR_COMI预测组织梗塞和最终组织的直接比较 在与临床高度相关的实验条件下的结果是至关重要的。 因此，本申请的总体重点是首先确定不可逆的MR_COMI阈值 并随后使用这个MR_COMI阈值来评估动态时间和空间演变 MR_COMI定义了对脑缺血的反应(目标1)，第二，经验性地确定了 利用已知的改变梗塞体积的实验条件预测MR_COMI阈值的价值 (目标2)。此外，由于这种新开发的磁共振方法需要区域大脑的知识 脑缺血时可能改变的红细胞压积(Hct)，提出了一个平行的目标(目标3)以 用小动物单光子发射法确定脑缺血如何引起cHct的改变 计算机断层扫描(SAI SPECT)。具体地说，连续注射两种示踪剂：TC-99M标记的红血 细胞和99m标记的人血清白蛋白将被用于获得用于评估的SPECT图像 CHct.拟议研究的成功将证明新开发的MR方法是 能够描绘脑缺血下存活组织的不可逆转损伤，并可能提供一种工具 急性卒中患者的个体化治疗。

Several lines of evidence derived from positron emission tomography (PET) studies suggest that measures of cerebral metabolic rate of oxygen utilization (CMRO2) provide an indication of brain tissue viability during cerebral ischemia. Although PET is a currently available technology to measure CMRO2, the need for an onsite cyclotron has limited its availability to only a few medical centers. Therefore, alternative approaches capable of providing similar physiological information as that of PET CMRO2 could have profound clinical implications. Towards this end, we have recently developed an MR imaging approach capable of measuring cerebral oxygen metabolic activity, which we have termed MR cerebral oxygen metabolic index (MR_COMI). Although physically different from PET CMRO2, preliminary results based on MR_COMI are encouraging, suggesting that this approach may indeed reveal similar physiological information as that of PET CMRO2. However, in order to determine if MR_COMI can delineate tissue viability during ischemia, a direct comparison between MR_COMI predicted tissue infarction and final tissue outcome under experimental conditions that are highly clinically relevant is of paramount importance. Therefore, the overall focus of this application is to first determine an MR_COMI threshold for irreversible injury and subsequently use this MR_COMI threshold to assess dynamic temporal and spatial evolution of MR_COMI defined lesions in response to cerebral ischemia (Aim 1) and second, empirically determine the predictive value of MR_COMI threshold, exploiting experimental conditions known to alter infarct volume (Aim 2). In addition, since this newly developed MR approach requires knowledge of regional cerebral hematocrit (Hct) which may change during cerebral ischemia, a parallel aim is proposed (Aim 3) to determine how cerebral ischemia induces alterations of cHct using small animal single photon emission computed tomography (SAI SPECT). Specifically, serial injections of two tracers: Tc-99m labeled red blood cells and Tc-99m labeled serum human albumin will be used to obtained SPECT images for the estimates of cHct. The success of the proposed studies will demonstrate that the newly developed MR approach is capable of delineate irreversibly injured from viable tissues under cerebral ischemia and may offer a tool for individualized treatment of acute stroke patients.