MR DIFFUSION AND SPECTROSCOPIC IMAGING FOR ACUTE STROKE

缺血性卒中的早期治疗药物， 发病，现在可用，并在临床试验中进行评估。然而，在这方面， 没有确定的诊断技术用于识别和 在这个早期阶段定位进展中的缺血性中风。 最近，弥散加权磁共振。(MR)成像已经被用于 在缺血性脑损伤后1小时内观察脑实质变化， 血管闭塞这种新的MR模式对扩散敏感， 质子在水中，并提供了表观扩散常数的图像 （ADC）。在缺血区域，弥散加权图像的强度 (DWI)增加，ADC图像减小。MR还可以产生 无脂质污染的脑乳酸盐图像，尽管 空间细节，通过使用双量子技术与开槽管 谐振器该建议的一般假设是， 半暗带，即在缺血早期阶段可挽救区域 中风，可以通过这些新的MR成像方法来识别。我们 最初的目的是探索的生化和细胞机制， 局灶性缺血中的强DWI信号，使用皮质灌注， 冷冻损伤模型，以将脑缺血性水肿分离成其单独的 细胞毒性和血管源性水肿成分。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DWI在检测和定位缺血性卒中中的实用性， 比较区域DWI随时间的变化与脑血流分布 （CBF）.特异性目标2A将研究以下指标的灵敏度和特异性： DWI用于检测局灶性脑缺血，使用栓塞模型 局灶性脑缺血与梗死体积的固有变异性， 与不同磁梯度和梗死体积的关系。具体目标 2B将比较MR ADC图像和值与CBF， 同一动物的放射自显影。我们的目标是调查 用于定位缺血区域的ADC的空间和时间保真度。 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，提供了一种笔划模型，其给出了一致的体积和 将使用位置，以便可以进行时间上的比较。我们的第三 目的是比较局部ADC和CBF与乳酸，在缺血核心和 缺血核心周围的半暗带，在缺血的演变过程中， 缺血至梗死。乳酸盐在生物能量学中具有核心作用， 缺血我们假设，乳酸不会遵循时间进程， 半暗带中的ADC以及ADC和乳酸的比较将提供 增强了半暗带定位的特异性。问题 在缺血性卒中中至关重要的是这些目标的基础： 有没有可能在缺血性脑血管病发作前 进展为梗死？这些新技术具有潜力， 通过提供对人类中风和中风治疗的早期评估， 描述病理生理异质性，尽管临床相似 缺血早期的症状。

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.