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BOLD MRI: Application to Intrarenal Oxygenation

BOLD MRI：在肾内氧合中的应用

基本信息

批准号：
7169889
负责人：
POTTUMARTHI V PRASAD
金额：
$ 42万
依托单位：
NORTHSHORE UNIVERSITY HEALTHSYSTEM
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-02-01 至 2008-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7169889
关键词：
Acute Kidney Failure Adenosine Adult Affect African American Age Aminophylline Angiotensin II Animal Experiments Animal Model Animal Technicians Animals Arginine Atrial Natriuretic Factor Authorization documentation Biological Availability Biology Blood Pressure Blood Vessels Blood flow Cities Condition Control Animal Cyclosporine Cyclosporins Data Development Diabetes Mellitus Diabetic Angiopathies Diet Disclosure Disease Diuresis Doctor of Medicine Doctor of Philosophy Early Diagnosis Elderly Endothelium Essential Hypertension Exhibits Face Feasibility Studies Free Radical Scavengers Functional disorder Furosemide Genetic Models Glomerular Filtration Rate Health Services Research Healthcare Hemoglobin High Blood Pressure High Prevalence Human Hypertension Hypokalemia Hypoxia Ibuprofen Imaging Techniques Inbred Dahl Rats Inbred WKY Rats Individual Injury Instruction Invasive Investigational Drugs Iontophoresis Israel Journals Kidney Kidney Diseases Kinins Lasers Lead Magnetic Resonance Imaging Measurement Measures Medical Medical center Medicine Methods Modeling Monitor Muscle strain Myocardial Infarction Names New England Nitric Oxide Numbers Organ Outcome Oxygen Oxygen Consumption Pathway interactions Peripheral Personal Satisfaction Pharmaceutical Preparations Physiological Pimonidazole Play Plethysmography Population Postdoctoral Fellow Potassium Potassium Deficiency Prevention strategy Principal Investigator Printing Production Prostaglandins Publishing Rattus Recording of previous events Regional Blood Flow Registered nurse Relative (related person)Renal Artery Stenosis Renal Blood Flow Renal function Research Design Research Project Grants Risk Risk Factors Role Secondary Hypertension Skin Stroke Symptoms Techniques Technology Testing Therapeutic Thinking Ultrasonography United States United States Food and Drug Administration Universities Variant Vasodilation Vasodilator Agents Water Wisconsin base blood flow measurement blood oxygen level dependent brachial artery college diabetic experience falls healthy aging hemodynamics human study human subject hypertension treatment improved inhibitor/antagonist kidney medulla medical schools normotensive novel novel therapeutics omega-N-Methylarginine paracrine pressure prevent programs renal hypoxia renal ischemia research study response sex tempol theories tissue oxygenation vasoactive agent vasoconstriction

项目摘要

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,

高血压，也被称为高血压，影响四分之一的美国成年人，是一个主要的风险中风心脏病和肾病的危险因素它有时被称为“沉默的杀手”，因为它往往没有症状预防和治疗高血压的进展一直受到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使人们能够更好地了解许多潜在的机制，从而导致了治疗高血压的新药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具体地说，认为肾髓质血流对高血压有直接影响。是关于肾脏的改变是高血压的原因还是结果，仍然是一个争论的话题。在任一在这种情况下，在肾脏内的区域水平上探测血流的非侵入性方法的可用性将允许验证了许多在人类身上进行测试的假设。基于既往血氧水平依赖性（BOLD）磁共振成像（MRI）的经验由于该技术应用于肾脏，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，该技术与适当的内皮依赖性血管活性药物相结合，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的反应或引起血管收缩的生理范例。内源性血管活性反应据信，这些微血管水平的功能变化发生得多，早于高血压的发展，如果发现得足够早，可以用新的治疗方法逆转接近。在这个提议中，我们将进行实验，以几种形式验证我们的假设，高血压在以前建立的动物模型，然后将其扩展到人类肾脏。动物模型将允许将BOLD MRI测量结果与侵入性激光探针评估进行直接比较。我们人类设计研究以检验这样的假设，即处于发展高血压风险的受试者将表现出肾功能降低，微血管反应性成功的结果将提供更好地了解人类的病理生理学高血压地点（组织、城市、州）埃文斯顿西北医疗保健，埃文斯顿，IL KEYPERSONNEL.Seeinstructions.需要使用第二个续页来提供所需的信息，格式如下所示。从主要研究者开始。按职业顺序列出所有其他关键人员，姓在前。名称组织项目角色 Pottumarthi V. Prasad博士Evanston Northwestern Healthcare首席研究员李露萍博士Evanston Northwestern Healthcare高级研究助理 Pippa Storey博士埃文斯顿西北医疗合作者 TBA埃文斯顿西北医疗保健研究助理 Sean Tutton，医学博士埃文斯顿西北医疗合作者琳达·皮尔查拉埃文斯顿西北医疗保健研究协调员 Laura Fogelson Evanston西北医疗保健兽医技术员丹尼尔巴特列，医学博士范伯格医学院顾问西北大学小艾伦考利博士威斯康星州医学院顾问邹爱平，医学博士，博士威斯康星州医学院顾问大卫巴西勒博士威斯康星州医学院顾问富兰克林H. Epstein，医学博士贝斯以色列女执事医疗中心顾问披露许可声明。仅适用于SBIR/STTR。请参阅说明。[]是[]否 o PHS 398（Rev.05/01）第2页表格第2页o n主要研究项目负责人（最后一位，第一位，中间）：Prasad，Pottumarthi Fara，Ph.D. 披露许可声明。仅适用于SBIPJSTTR。参见说明。[]是[]否主要研究者/项目负责人的姓名必须在打印页和续页的顶部提供。研究资助目录页码首页...... 1 产品描述：