BOLD MRI: Application to Intrarenal Oxygenation

高血压，也称为高血压，在美国每四个成年人中就有一个受到影响，是一个主要风险 中风、心脏病和肾脏疾病的致病因素。它有时被称为“沉默的杀手”，因为它通常没有 症状。预防和治疗高血压的进展因缺乏彻底的 了解其潜在的病理生理学。血管生物学在过去十年中取得的重大进展 允许更好地理解许多潜在的机制，这随后导致了 治疗高血压的新药物疗法。现在许多人认为肾脏在病理生理学中起着重要作用。 高血压的症状。具体地说，人们认为肾髓质血流量对高血压有直接影响。它是 关于肾脏的变化是高血压的原因或后果，仍然是一个有争议的话题。在任何一种中 在这种情况下，提供一种非侵入性方法来探测肾脏内区域水平的血流将允许 验证了许多将在人体上进行测试的假设。 基于以往血氧水平依赖(BOLD)磁共振成像(MRI)的经验 对于肾脏，我们假设该技术对髓内血流的变化很敏感。 更具体地说，我们认为该技术与适当的内皮依赖性血管活性物质相结合 将允许以非侵入性方式进行肾微血管反应性研究。血管反应性 研究寻找血管壁对血管活性物质或生理范式的反应，这些物质或生理范例会引发 内源性血管活性反应。人们认为，这些微血管水平的功能变化发生得很多。 早于高血压的发展，如果足够早地发现，可能会被新的治疗方法逆转 接近了。在这个提案中，我们将进行实验，以几种形式验证我们的假设 在先前建立的动物模型中发现高血压，然后将其扩展到人类肾脏。动物模型 将允许直接比较大胆的MRI测量和侵入性激光探头评估。我们的人类 研究旨在检验这样一种假设，即有高血压风险的受试者将表现出肾脏减少。 微血管反应性。成功的结果将使人们更好地了解人类的病理生理学 高血压。 Performmanceite(S)(组织、市、州) 伊利诺伊州埃文斯顿西北医疗中心 KEYPERSONNEL参见说明。使用需要提供以下格式所需信息的二次使用页面。 从首席调查员开始。按字母顺序列出所有其他关键人员，姓氏在前。 命名项目上的组织角色 Pottomarthi V.Prasad博士，埃文斯顿西北医疗保健首席研究员 李鲁平，博士，埃文斯顿西北医疗保健高级研究员 皮帕·斯托里博士，埃文斯顿西北医疗保健合作者 TBA埃文斯顿西北医疗研究助理 肖恩·塔顿，医学博士埃文斯顿西北医疗保健合作者 琳达·皮尔查拉，R.N.Evanston西北医疗保健研究协调员 劳拉·福格森·埃文斯顿西北医疗兽医 丹尼尔·巴特勒，医学博士范伯格医学院顾问 西北大学 小艾伦·考利，威斯康星医学院顾问，博士 邹爱平，医学博士，威斯康星医学院顾问 David Basile，博士，威斯康星医学院顾问 富兰克林·H·爱泼斯坦，医学博士贝丝·以色列女执事医疗中心顾问 披露许可声明。适用于SBIR/STRONNY。请参阅说明。[]是[]否 O小灵通398(05/01版)第_2页表单第2页o N首席研究项目主任(最后、第一、中间)：Prasad，Pottomarthi Fara，博士 披露许可声明。仅适用于SBIPJSTTR。请参阅说明。[]是[]否 必须在每张打印页和每张续页的顶部提供首席调查员/项目主任的姓名。 研究补助金 目录 页码 主页........................................................................................................................1 描述，

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. PERFORMANCESITE(S) (organization,city,state) Evanston Northwestern Healthcare, Evanston, IL KEYPERSONNEL.Seeinstructions. Usecontinuationpagesas neededto providethe requiredinformationinthe formatshownbelow. Startwith PrincipalInvestigator.List all otherkey personnelin alphabeticalorder,last namefirst. Name Organization Role onProject Pottumarthi V. Prasad, Ph.D. Evanston Northwestern Healthcare Principal Investigator Luping Li, Ph.D. Evanston Northwestern Healthcare Sr. Research Associate Pippa Storey, Ph.D. Evanston Northwestern Healthcare Collaborator TBA Evanston Northwestern Healthcare Research Assistant Sean Tutton, M.D. Evanston Northwestern Healthcare Collaborator Linda Pierchala, R.N. Evanston Northwestern Healthcare Research Coordinator Laura Fogelson Evanston Northwestern Healthcare Veterinary Technician Daniel Batlle, M.D. Feinberg School of Medicine at Consultant Northwestern University Allen Cowley Jr, Ph.D. Medical College of Wisconsin Consultant Ai-ping Zou, M.D., Ph.D. Medical College of Wisconsin Consultant David Basile, Ph.D. Medical College of Wisconsin Consultant Franklin H. Epstein, M.D. Beth Israel Deaconess Medical Center Consultant Disclosure Permission Statement. Applicableto SBIR/STTROnly. Seeinstructions. [] Yes [] No o PHS 398(Rev.05/01) Page_2 Form Page2 o n Principal InvestigatodProgram Director (Last, first, middle): Prasad, Pottumarthi Fara, Ph.D. Disclosure Permission Statement. Applicable to SBIPJSTTR Only. See instructions. [] Yes [] No The name of the principal investigator/program director must be provided at the top of each printed page and each continuation page. RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page .................................................................................................................................................. 1 Description,