MR Measured Oxygen Metabolic Index in Ischemic Stroke

描述(由申请人提供)：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)的测量提供了脑缺血期间脑组织活性的指标。虽然PET是目前可用于测量CMRO2的技术，但由于需要现场回旋加速器，其可用性仅限于少数几个医疗中心。因此，能够提供与PET CMRO2相似的生理信息的替代方法可能具有深远的临床意义。为此，我们最近开发了一种能够测量脑氧代谢活动的磁共振成像方法，我们称之为MR脑氧代谢指数(MR_COMI)。虽然物理上与PET CMRO2不同，但基于MR_COMI的初步结果令人鼓舞，表明该方法可能确实揭示了与PET CMRO2相似的生理信息。然而，为了确定MR_COMI是否能够描绘缺血期间的组织活性，在具有高度临床相关性的实验条件下，将MR_COMI预测的组织梗死与最终的组织结果进行直接比较是至关重要的。因此，本申请的总体重点是首先确定不可逆损伤的MR_COMI阈值，然后使用该MR_COMI阈值来评估MR_COMI定义的损伤响应于脑缺血的动态时间和空间演变(目标1)，其次，利用已知改变脑梗塞体积的实验条件，经验性地确定MR_COMI阈值的预测价值(目标2)。此外，由于这种新开发的磁共振方法需要了解脑缺血时可能改变的局部脑红细胞压积(Hct)，因此提出了一个平行的目标(目标3)，即利用小动物单光子发射计算机断层扫描(SAI SPECT)来确定脑缺血如何引起cHct的改变。具体地说，连续注射两种示踪剂：TC-99m标记的红细胞和TC-99m标记的血清白蛋白将被用来获得用于估计cHct的SPECT图像。这些研究的成功将证明，新开发的MR方法能够区分脑缺血时存活组织的不可逆损伤，并可能为急性卒中患者的个体化治疗提供一种工具。

DESCRIPTION (provided by applicant): 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.