Magnetic Resonance Imaging of Glucose Analogs in Stroke

项目摘要/摘要 这个项目的目标是进一步开发一种新的mr分子成像技术来描绘葡萄糖摄取。 并将这项技术应用于中风成像。葡萄糖摄取对细胞功能至关重要，而葡萄糖摄取 评估其在疾病中的变化在包括神经退行性变在内的许多医学领域都有很大的前景， 创伤性脑损伤，肿瘤，特别是中风。在急性缺血性中风中，主要的 治疗的目标是挽救半影区，即有梗死风险的组织，但可以及时挽救 干预。可靠地识别半暗带是至关重要的，因为它可能会扩大治疗范围 窗口，这是获得急性卒中干预的主要限制因素，并有助于选择新的 血管内治疗和神经保护治疗的发展。但是，准确和及时 半影区的成像仍然是临床上的一大障碍。我们最近开发了一种化学交换敏感的自旋- 锁定(CESL)磁共振技术通过葡萄糖之间的快速化学交换间接检测葡萄糖 羟基和水质子。与血糖的直接测量相比，这种间接检测 通过水可以显著提高灵敏度，使在体绘制葡萄糖摄取图谱成为可能。 我们的初步结果表明，在中风动物中，注射葡萄糖类似物的CESL MRI可以迅速 (在几分钟内)确定缺血区附近葡萄糖摄取的明显增加 核心。这一区域的高反应性与最终的组织结局密切相关。而对自然资源的管理 D-葡萄糖导致高血糖并恶化缺血组织结局，木糖是FDA批准的一种葡萄糖 类似物，可能有助于减轻有害的代谢影响，并潜在地改善组织结局。在目标1中， 我们将进一步开发木糖-CESL，以提高其对葡萄糖摄取成像的信号灵敏度。在目标2中，我们 将研究缺血时木糖-CESL信号的信号来源、灵敏度和时空特征 老鼠的大脑。在目标3中，我们将评估木糖-CESL在半影区成像中的效果。成功完成 该项目将为急性缺血性中风提供一种强大的磁共振分子成像工具，它将立即 影响临床前研究，并具有巨大的临床翻译潜力。

PROJECT SUMMARY/ABSTRACT The goal of this project is to further develop a novel MR molecular imaging technique for mapping glucose uptake and to apply this technique for stroke imaging. Glucose uptake is critical for cellular function, and the ability to assess its alteration in diseases holds great promise in many fields of medicine including neurodegeneration, traumatic brain injury, tumors, and specifically for this application, stroke. In acute ischemic stroke, a major therapeutic goal is to rescue the penumbra, i.e., tissue at risk of infarction but can be rescued with timely intervention. Robust identification of penumbra is crucial because it would potentially expand the therapeutic window, a major limiting factor in access to acute stroke intervention, and help with patient selection for novel endovascular therapies and the development of neuroprotective treatments. However, accurate and prompt imaging of penumbra is still a clinical barrier. We have recently developed a chemical-exchange sensitive spin- lock (CESL) MRI technique to indirectly detect glucose via the rapid chemical exchange between glucose hydroxyl groups and water protons. In contrast to direct measurements of glucose, such indirect detection through water offers substantial sensitivity enhancement, making in vivo mapping of glucose uptake feasible. Our preliminary results show that in stroke animals, CESL MRI with injection of a glucose analog can quickly (within several minutes) identify an apparent elevation of glucose uptake in a region adjacent to the ischemic core. This region of elevated response correlates well with final tissue outcome. While administration of natural D-glucose leads to hyperglycemia and worsens the ischemic tissue outcome, xylose, an FDA-approved glucose analog, may help alleviate the harmful metabolic effects and potentially improve the tissue outcome. In Aim 1, we will further develop xylose-CESL to increase its signal sensitivity for glucose uptake imaging. In Aim 2, we will study the signal source, sensitivity, and spatiotemporal characteristics of the xylose-CESL signal in ischemic rat brain. In Aim 3, we will evaluate the efficacy of xylose-CESL for penumbra imaging. Successful completion of this project will provide a powerful MR molecular imaging tool for acute ischemic stroke, which would immediately impact preclinical studies and have a great potential for clinical translation.