BOLD MRI--APPLICATION TO INTRA-RENAL OXYGENATION

急性肾衰竭（ARF）是一种综合征，可广泛定义为： 肾功能迅速恶化，导致 含氮废物如尿素和肌酸酐。这是一个重大的临床 是一种常见的医院获得性综合征，死亡率高 率（约50%）。缺血性急性脑梗死的病理生理学 肾衰竭是临床ARF最常见的形式，是复杂的， 却又被人理解。 基于先前对动物模型的研究， 已知急性肾衰竭涉及骨髓损伤，甚至 在正常情况下必须在缺氧环境中发挥作用。 因此，了解影响延髓缺氧的机制 在ARF的病理生理学研究中具有重要意义。 到目前为止，肾内氧分压的测量仅 将氧敏微电极植入肾脏 动物的薄壁组织，一个微妙和繁琐的程序，不切实际的 用于人类研究。 BOLD（血氧水平依赖性）MRI具有 显示出作为一种非侵入性方法的潜力， 氧气供需平衡的变化。 我们有 先前证明了BOLD MRI与 人体肾脏的体内测量和早期动物数据， 侵入性微电极。这些研究为第一个 表明人肾实质性缺氧程度的时间 髓质 在本提案中，我们将通过比较 在氧合动物模型中获得的BOLD MRI数据 先前用侵入性微电极获得的测量值 法 然后，我们将把这项技术应用于动物模型， 人类受试者获得有关肾脏生理学的新信息/ 病理生理学，特别是与ARF相关的病理生理学。 一种非侵入性方法评估区域性 体内肾脏中的氧合应有助于表征治疗性 和保护机制，从而导致改善的治疗和 急性肾衰竭的预防措施。

Acute renal failure (ARF) is a syndrome that can be broadly defined as rapid deterioration of renal function resulting in the accumulation of nitrogenous wastes such as urea and creatinine. It is a major clinical problem and is a common hospital acquired syndrome with high mortality rates (approximately 50 percent). The pathophysiology of ischemic acute renal failure, the most common form of clinical ARF, is complex and not yet well understood. Based on previous studies on animal models, it is known that acute renal failure involves damage to the medulla which even under normal circumstances must function in an hypoxic environment. Hence an understanding of mechanisms that influence medullary hypoxia is important in the study of pathophysiology of ARF. To date, measurements of intrarenal oxygen tension have been made only with oxygen-sensitive microelectrodes implanted into the renal parenchyma of animals, a delicate and tedious procedure and impractical for human studies. BOLD (Blood Oxygenation Level Dependent) MRI has shown potential as a noninvasive method to assess on a regional basis the changes in the balance of oxygen supply and demand. We have previously demonstrated a strong correspondence between BOLD MRI measurements in vivo in human kidneys and earlier animal data using invasive microelectrodes. These studies provided evidence for the first time indicating a substantial degree of hypoxia in the human renal medulla. In this proposal, we will further evaluate this technique by comparing the BOLD MRI data obtained in an animal model with oxygenation measurements previously obtained with an invasive microelectrode technique. We will then apply the technique to both animal models and human subjects to derive new information about renal physiology/ pathophysiology especially related to ARF. The availability of a noninvasive method to evaluate regional oxygenation in kidneys in vivo should help to characterize therapeutic and protective mechanisms and thus lead to improved therapeutic and preventive measures for acute renal failure.