MR DIFFUSION AND SPECTROSCOPIC IMAGING FOR ACUTE STROKE

早期治疗缺血性中风的药物，在1至2小时内 起效，现已上市，并正在进行临床试验评估。然而， 目前还没有既定的诊断技术来识别和 在这一早期时间段内定位进行性缺血性中风。 最近，扩散加权磁共振(MR)成像已经被使用 1小时内观察脑缺血后实质改变 血管闭塞。这一新的磁共振成像方式对弥散的 水中的质子，并提供了表观扩散常数的图像 (ADC)。在缺血区，弥散加权图像的强度 (DWI)增加，ADC图像减少。MR还可以产生一个 无脂质污染的脑乳酸盐图像，尽管较少 空间细节，通过使用带有缝隙管的双量子技术 谐振器。这一提议的一般假设是，脑缺血 半影区，在缺血早期可挽救的区域 中风，可以通过这些新的磁共振成像方法来识别。我们的 最初的目的是探索细胞的生化和细胞机制 局灶性脑缺血的高弥散加权成像信号，使用皮质灌流和 冷冻损毁模型将脑缺血水肿分离为 细胞毒性和血管源性水肿组分。我们假设ADC是 对细胞毒性比对血管源性水肿更敏感。我们的第二个目标是 评价磁共振弥散加权成像在检测和定位缺血性卒中中的作用 比较局部DWI随时间变化与脑血流分布的关系 (CBF)。特定目标2A将调查其敏感性和特异性 使用栓子模型检测局灶性脑缺血的弥散加权成像 脑梗塞体积的固有变异性的局灶性脑缺血 与不同的磁梯度和脑梗塞体积的关系。特定目标 2B会将MR ADC图像和值与以下确定的CBF进行比较 同一只动物的放射自显影。我们的目标是调查 ADC定位缺血区的时空保真度。我们 假设CBF和ADC通常在空间或时间上相关， 但出现的例外情况将预示着可挽救的缺血组织。 为此目的，提供一致体积和 将使用位置，以便可以随着时间的推移进行比较。我们的第三个 AIM将比较局部ADC和CBF与乳酸在缺血核心和 缺血核心周围的半影区，以及在脑缺血的演变过程中 从缺血到梗死。乳酸在人体内的生物能量学中起着核心作用。 缺血症。我们假设乳酸不会遵循 半影区的ADC和比较ADC和乳酸将提供 半影区定位的特异性增加。问题是 在缺血性中风中，最重要的是这些目标中的每一个： 是否有可能在抢救之前识别出可挽救的缺血组织 进展为脑梗塞吗？这些新技术有可能在 对中风和人类中风治疗的早期评估通过提供 尽管临床相似，但病理生理异质性的描述 在非常早的几个小时的缺血症状。

Agents for the early treatment of ischemic stroke, within 1 to 2 hours of onset, are now available and being evaluated in clinical trials. However, there is no established diagnostic technique for identifying and localizing evolving ischemic stroke within this early time period. Recently, diffusion-weighted magnetic resonance.(MR) imaging has been used to visualize parenchymal changes in ischemic brain within one hour from vascular occlusion. This new MR modality is sensitive to the diffusion of protons in water and provides an image of the apparent diffusion constant (ADC). In ischemic regions, the intensity of the diffusion-weighted image (DWI) is increased and the ADC image is decreased. MR can also produce a brain lactate image with no lipid contamination, although with less spatial detail, by using the double quantum technique with a slotted tube resonator. The general hypothesis of this proposal is that the ischemic penumbra, that region which is salvageable in the early stages of ischemic stroke, can be identified by these new MR imaging methodologies. Our initial aim is to explore the biochemical and cellular mechanisms of the intense DWI signal in focal ischemia, using cortical superfusion and freeze lesion models to separate cerebral ischemic edema into its separate cytotoxic and vasogenic edema components. We hypothesize that the ADC is more sensitive to cytotoxic than to vasogenic edema. Our second aim will evaluate DWI for its utility in detecting and locating ischemic stroke and compare regional DWI over time to the distribution of cerebral blood flow (CBF). Specific Aim 2A will investigate the sensitivity and specificity of DWI for the detection of focal cerebral ischemia, using an embolic model of focal cerebral ischemia with inherent variability of infarct volume, in relation to different magnetic gradients and infarct volumes. Specific Aim 2B will compare MR ADC images and values to CBF determined by autoradiography in the same animal. Our goal will be to investigate the spatial and temporal fidelity of ADC for locating the ischemic region. We hypothesize that CBF and ADC will generally correlate in space or time, but the exceptions that occur will predict salvageable ischemic tissue. For this purpose, a stroke model which gives consistent volume and location will be used so that comparisons over time can be made. Our third aim will compare regional ADC and CBF to lactate, in the ischemic core and the penumbra around the core of ischemia, and during the evolution of ischemia to infarction. Lactate has a central role in the bioenergetics of ischemia. We hypothesize that lactate will not follow the time course of ADC in the penumbra and that comparing ADC and lactate will provide increased specificity for the localization of the penumbra. The question of paramount importance in ischemic stroke underlies each of these aims: Is it possible to identify salvageable ischemic tissue before it progresses to infarction? These new techniques have potential for the early evaluation of stroke and stroke therapy in humans by providing delineation of pathophysiological heterogeneity despite similar clinical symptoms in the very early hours of ischemia.