MR Measured Oxygen Metabolic Index in Ischemic Stroke

来自正电子发射断层扫描（PET）研究的几条证据表明， 脑氧代谢率（CMRO 2）的测量提供了脑组织 在脑缺血期间的存活率。尽管PET是目前可用于测量CMRO 2的技术， 对现场回旋加速器的需求限制了其仅在少数医疗中心的可用性。因此，替代 能够提供与PET CMRO 2类似的生理信息的方法可能具有 具有深远的临床意义。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性，我们称之为MR脑氧 代谢指数（MR_COMI）。虽然物理上不同于PET CMRO 2，但基于 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 PET CMRO 2的信息。然而，为了确定MR_COMI是否可以描绘组织 缺血期间的存活率，MR_COMI预测的组织梗死和最终组织梗死之间的直接比较 在高度临床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。 损伤，随后使用该MR_COMI阈值来评估 MR_COMI定义的病变对脑缺血的反应（目的1），其次，经验性地确定 MR_COMI阈值的预测值，利用已知改变梗死体积的实验条件 (Aim 2）。此外，由于这种新开发的MR方法需要了解局部大脑的 红细胞压积（Hct）在脑缺血期间可能发生变化，提出了一个平行目标（目标3）， 使用小动物单光子发射确定脑缺血如何诱导cHct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-99 m标记的红血 细胞和Tc-99 m标记的血清人白蛋白将用于获得SPECT图像以用于估计 的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损伤，并可提供用于 急性脑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.