BOLD MRI: Application to Intra-renal Oxygenation

BOLD MRI：在肾内氧合中的应用

• 批准号: 7746476
• 负责人: POTTUMARTHI V PRASAD
• 金额: $ 36.23万
• 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 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7746476
• 关键词: Accounting; Acute; Acute Kidney Failure; Animal Model; Animal Testing; Animals; Antioxidants; Belief; Cessation of life; Clinic; Consensus; Contrast Media; Creatinine; Cyclooxygenase Inhibitors; Dependence; Development; Diabetes Mellitus; Diagnostic Imaging; Diagnostic Procedure; Dinoprostone; Disease model; Excretory function; Funding; Furosemide; Grant; Hospitals; Hour; Human; Hydration status; Hypoxia; Hypoxia Inducible Factor; Imaging Techniques; Incidence; Indomethacin; Injury; Intervention; Iodine; Isosorbide Dinitrate; Kidney; Kidney Diseases; Kidney Failure; Lead; Learning; Limb structure; Measurement; Measures; Mimosine; Modeling; Monitor; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase; Operative Surgical Procedures; Osmolalities; Outcome; Outcome Measure; Oxygen; Oxygen Consumption; Pathogenesis; Pathway interactions; Phase; Physiological; Physiology; Prevention; Prevention strategy; Procollagen-Proline Dioxygenase; Prostaglandin-Endoperoxide Synthase; Radio; Rattus; Renal Blood Flow; Reporting; Risk; Rodent; Rodent Model; Serum; Sodium; Stimulus; Stress; Superoxides; Syndrome; System; Techniques; Technology; Testing; Thick; Time; Tissues; Tubular formation; Up-Regulation; Viscosity; Water; Work; autocrine; base; blood oxygen level dependent; chemical property; diabetic rat; efficacy testing; hemodynamics; improved; in vivo; inhibitor/antagonist; novel; paracrine; physical property; preconditioning; public health relevance; renal hypoxia; response; tempol; theories

DESCRIPTION (provided by applicant): Radiocontrast nephropathy (RCN) is a third common cause of hospital acquired renal failure, accounting for 11% of incidence. With the continuing rise in the number of diagnostic imaging procedures and because it is a hospital acquired syndrome, the need for prevention is most compelling. However, the mechanisms behind the development of RCN remain not fully understood. Many interventions proposed based on animal testing have failed in human trials. The possible reasons for this disconnect may be due to: (1) animal models not adequately representing the human physiology, (2) outcome measures used in animal models differ from those used in the clinic, (3) invalid hypothesis etc.. Over the last two decades significant progress has been made in terms of understanding the oxygenation status within the kidney and it is now well appreciated that regions within the kidney survive under hypoxic conditions. In order for the kidney to survive in the hypoxic milieu, powerful control mechanisms have evolved that maintain oxygen sufficiency even under the threat of external stimuli such as during administration of contrast media. It is believed that compromise in the ability of the kidney to activate these control mechanisms during a "stress" may be the cause for the development of renal failure following stimuli such as contrast media. Based on these hypotheses, novel animal models have been proposed and validated. These are simpler compared to previous models that necessitate surgical manipulations, and more importantly better represent the functional aspect of the human condition. Additionally, the techniques available for monitoring intra-renal oxygenation have continuously improved. Blood oxygenation level dependent (BOLD) MRI technique has been shown to be sensitive and efficacious in evaluating renal oxygenation both in rat and human kidneys. In addition, better understanding of the oxygenation status has given rise to new targets for intervention. Based on this background, this proposal extends our present findings in healthy and hypertensive kidneys with BOLD MRI to better understand the acute hemodynamic responses following contrast administration in functional models of RCN and in RCN prone diabetic rats. We will additionally acquire markers that are used in the clinic. We will also test the efficacy of novel interventions targeted at relieving hypoxia. We will further use sodium MRI to monitor acute changes following contrast media and correlate them with BOLD MRI measurements. Successful outcome should have a significant impact on the development of preventive strategies for RCN. PUBLIC HEALTH RELEVANCE Radiocontrast induced renal failure is a common hospital acquired syndrome and because the consequences could be severe including death, preventive strategies are highly sought after. With the continuous increase in the number diagnostic procedures, the relevance and significance of this problem is growing. Our proposed study will allow for better understanding of the mechanisms behind the development of this syndrome and develop novel preventive strategies.

描述（由申请人提供）：放射性对称性肾病（RCN）是医院获得的肾衰竭的第三个常见原因，占发病率的11％。随着诊断成像程序数量的持续增加，并且由于它是医院获得的综合症，因此预防的需求最具吸引力。但是，RCN发展背后的机制尚未完全理解。基于动物测试的许多干预措施在人类试验中都失败了。这种断开连接的可能原因可能是由于：（1）动物模型不能充分代表人类生理学，（2）动物模型中使用的结果指标与诊所中使用的动物模型不同，（3）在过去的二十年中。在过去的二十年中，在理解肾脏中的氧合状态以良好的态度在过去的二十年中取得了重大进展。为了使肾脏在低氧环境中生存，即使在外部刺激的威胁下，例如对比造影介质的给药，也会发展出强大的控制机制，即使在外部刺激的威胁下也能保持氧气充足。据认为，在肾脏在“压力”期间激活这些控制机制的能力的妥协可能是导致刺激后肾衰竭（例如对比介质）发展的原因。基于这些假设，已经提出并验证了新型动物模型。与以前需要手术操作的模型相比，这些更简单，更重要的是更好地代表人类状况的功能方面。此外，可用于监测肾脏内氧合的技术不断改进。血液氧合水平依赖性（BOLD）MRI技术已被证明在评估大鼠和人肾脏的肾脏氧合方面是敏感和有效的。此外，更好地了解氧合状态已引起新的干预目标。基于此背景，该提案扩展了我们目前在具有BOLD MRI的健康和高血压肾脏中的发现，以更好地了解RCN功能模型和易RCN易于糖尿病大鼠的急性血液动力学反应。我们还将获得诊所中使用的标记。我们还将测试针对缓解缺氧的新型干预措施的疗效。我们将进一步使用钠MRI来监测对比介质后的急性变化，并将其与大胆的MRI测量相关联。成功的结果应该对RCN的预防策略的发展产生重大影响。公共卫生相关性放射性对称性引起的肾衰竭是一种常见的医院综合症，因为后果可能是严重的，包括死亡，预防策略是高度追捧的。随着数量诊断程序的持续增加，该问题的相关性和意义正在增长。我们提出的研究将使人们可以更好地了解该综合征发展背后的机制并制定新颖的预防策略。