Resting state MRI to map autoregulation of the kidney

静息态 MRI 绘制肾脏的自动调节图

• 批准号: 10539432
• 负责人: Kevin M Bennett
• 金额: $ 26.3万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-20 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10539432
• 关键词: 3-Dimensional; Address; Allografting; Anatomy; Animal Model; Animals; Biological Markers; Blood Pressure; Blood Vessels; Blood flow; Brain; Caliber; Clinical; Coupling; Development; Diabetes Mellitus; Diabetic Nephropathy; Disease; Disease Progression; Dysbarism; Feedback; Frequencies; Functional disorder; Furosemide; Genetic Engineering; Genetic Models; Glomerular Capillary; Glomerular Filtration Rate; Goals; Health; Homeostasis; Human; Hypertension; Image; Imaging Device; Impairment; Inbred SHR Rats; Individual; Kidney; Kidney Diseases; Kidney Failure; Knowledge; Life; Life Cycle Stages; Location; Longevity; Magnetic Resonance Imaging; Maps; Measurement; Measures; Methods; Microscopy; Modeling; Monitor; Nephrons; Optics; Outcome; Pathology; Patients; Pattern; Perfusion; Pharmacology; Physiological Processes; Rattus; Regulation; Renal Blood Flow; Renal Hypertension; Renal function; Reproducibility; Rest; Scanning; Signal Transduction; Source; Systemic blood pressure; Testing; Time; Transplantation; Work; aging population; base; cohort; design; experimental study; glomerular filtration; in vivo; kidney allograft; lens; non-invasive imaging; novel therapeutics; predictive marker; pressure; respiratory; response; spectrograph; therapy development; tool; treatment response

Project Summary/Abstract The kidney maintains glomerular filtration, despite constant and potentially damaging natural fluctuations in systemic blood pressure. This autoregulation is critical to maintaining the structural and functional integrity of the kidney, and failure of autoregulation is strongly implicated in progression of kidney pathologies associated with diabetic and hypertensive nephropathy. There are several identified mechanisms of autoregulation of local blood pressure and flow, including a myogenic response and tubuloglomerular feedback (TGF). These mechanisms are associated with distinct bands of low frequencies of oscillation in perfusion pressure, but there are currently no tools to investigate the spatial localization of these mechanisms or develop them for potential clinical use. Here we develop the tool of resting- state magnetic resonance imaging (MRI) to measure and map oscillations in vascular diameters associated with these two mechanisms. This is based on our recent observations of reproducible resting- state fluctuations in MRI with frequency bands consistent with myogenic and TGF mechanisms. We will first investigate this tool in the healthy rat kidney and measure patterns in the spectra within and between kidneys during the life course of the animal. We will validate the MRI measurements using optical microscopy, and determine whether the detected autoregulation is eliminated or reduced with administration of furosemide. Finally, we will investigate the use of resting- state MRI to measure a decrease in autoregulation during development of nephropathy in the spontaneously hypertensive rat model. If successful, this work will provide a noninvasive tool to more completely understand mechanisms and develop predictive markers to investigate genetic models, guide new therapies, inform allograft transplantation, and monitor kidney health.

项目摘要/摘要 肾脏维持肾小球滤过，尽管持续的和潜在的破坏性的自然波动 全身血压。这种自动调节对于保持结构和功能的完整性至关重要 肾脏和自身调节的失败与肾脏病理的进展密切相关。 患有糖尿病和高血压肾病。有几种已确定的局部自动调节机制 血压和流量，包括肌源性反应和肾小管小球反馈(TGF)。这些 机制与灌流压力的低频振荡的明显频带有关，但 目前还没有工具来研究这些机制的空间局部化或开发它们的潜力 临床应用。在这里，我们开发了静息状态磁共振成像(MRI)工具来测量和绘制地图 与这两种机制相关的血管直径的波动。这是基于我们最近 与肌源性频段一致的MRI可重复静息状态波动的观察 和转化生长因子的作用机制。我们将首先在健康的大鼠肾脏中研究这一工具，并测量 在动物的生命过程中，肾脏内和肾脏之间的光谱。我们会验证核磁共振 使用光学显微镜进行测量，并确定检测到的自动调节是消除还是 服用速尿后减少。最后，我们将研究使用静息状态MRI来测量 自发性高血压大鼠模型肾病发生过程中自身调节功能的降低。 如果成功，这项工作将提供一个非侵入性的工具，以更全面地了解机制和 开发预测标记物来研究遗传模型，指导新的治疗方法，为同种异体移植提供信息， 并监测肾脏健康状况。