BOLD MRI: Application to Intrarenal Oxygenation

BOLD MRI：在肾内氧合中的应用

• 批准号: 6706262
• 负责人: POTTUMARTHI V PRASAD
• 金额: $ 40.56万
• 依托单位: NORTHSHORE UNIVERSITY HEALTHSYSTEM
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-01 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6706262
• 关键词: BOLD; MRI; Application; Intrarenal; Oxygenation

DESCRIPTION (provided by applicant): Hypertension, also known as high blood pressure, affects one in four adults in the United States, and is a major risk factor for stroke, heart attack and kidney disease. It is sometimes called the "silent killer" because it often has no symptoms. Progress towards preventing and curing hypertension has been impeded by a lack of thorough understanding of its underlying pathophysiology. Significant progress made over the last decade in vascular biology has allowed for better understanding of many of the underlying mechanisms, which then has led to development of novel drug treatments for hypertension. Many now believe that kidney plays an important role in the pathophysiology of hypertension. Specifically, it is thought that renal medullary blood flow has a direct influence on hypertension. It is still a topic of debate as to the alterations in the kidney being the cause or the consequence of hypertension. In either case, availability of a non-invasive method to probe blood flow at a regional level within the kidney would allow for verifying many of the hypotheses to be tested in humans. Based on previous experience with blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) technique to the kidney, we hypothesize that the technique would be sensitive to changes in medullary blood flow. More specifically, we believe that the technique in combination with suitable endothelium-dependent vasoactive agents would allow for renal microvascular reactivity studies to be performed in a non-invasive way. Vascular reactivity studies look for responses in the vessel walls to vasoactive substances or physiological paradigms that elicit an endogenous vasoactive response. It is believed that these functional changes at the microvascular level take place much earlier than the development of hypertension and if detected early enough, may be reversed with novel therapeutic approaches. In this proposal, we will perform experiments that will validate our hypothesis in several forms of hypertension in previously well established animal models and then extend them to human kidneys. Animal models will allow for direct comparison of BOLD MRI measurements against invasive laser probe assessments. Our human studies are designed to test the hypothesis that subjects at risk for developing hypertension will exhibit reduced renal microvascular reactivity. Successful outcome will provide better understanding of pathophysiology of human hypertension.

描述（由申请人提供）： 高血压，也称为高血压，会影响美国四分之一的成年人，是中风，心脏病发作和肾脏疾病的主要危险因素。有时被称为“沉默杀手”，因为它通常没有症状。缺乏对其潜在的病理生理学的彻底了解，阻碍了预防和治愈高血压的进展。在过去的十年中，血管生物学取得的重大进展使得更好地了解许多基本机制，这随后导致了新型药物治疗高血压的发展。现在，许多人认为肾脏在高血压的病理生理学中起着重要作用。具体而言，人们认为肾脏髓质血流对高血压有直接影响。关于肾脏的改变是高血压的原因或后果，这仍然是一个辩论。在任何一种情况下，都有一种非侵入性方法可在肾脏内探测血液流量的血流，都可以验证在人类中测试的许多假设。基于先前具有血液氧合水平的经验（BOLD）磁共振成像（MRI）技术，我们假设该技术对髓质血流的变化敏感。更具体地说，我们认为该技术与合适的内皮依赖性血管活性剂结合使用，可以以非侵入性的方式进行肾脏微血管反应性研究。血管反应性研究寻找血管壁对引起内源性血管活性反应的血管活性物质或生理范式的反应。人们认为，微血管水平的这些功能变化比高血压的发展要早得多，如果足够早，则可能会使用新颖的治疗方法逆转。在此提案中，我们将进行实验，以在先前建立的动物模型中以几种形式的高血压验证我们的假设，然后将其扩展到人类肾脏。动物模型将可以直接比较大胆的MRI测量值与侵入性激光探针评估。我们的人类研究旨在检验以下假设：患有高血压风险的受试者将表现出肾脏微血管反应的降低。成功的结果将更好地理解人类高血压的病理生理学。