Resting state MRI to map autoregulation of the kidney

项目概要/摘要 肾脏维持肾小球滤过，尽管恒定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维持细胞的结构和功能完整性至关重要。 肾脏的功能，以及自身调节的失败强烈地牵涉到与肾脏病理学相关的进展。 患有糖尿病和高血压肾病有几种已确定的局部免疫调节机制， 血压和流量，包括肌源性反应和肾小管肾小球反馈（TGF）。这些 机制与灌注压中低频振荡的不同频带相关，但 目前还没有工具来研究这些机制的空间定位或开发它们的潜力。 临床应用。在这里，我们开发了静息态磁共振成像（MRI）的工具来测量和映射 与这两种机制相关的血管直径振荡。这是基于我们最近的 在MRI中观察到可重复的静息状态波动，其频带与肌源性 TGF机制。我们将首先在健康大鼠肾脏中研究这种工具，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成像 使用光学显微镜进行测量，并确定检测到的自动调节是否被消除或 随着呋塞米的服用而减少。最后，我们将研究使用静息状态MRI来测量 在自发性高血压大鼠模型中，肾病发展过程中自身调节的降低。 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， 开发预测标记物以研究遗传模型，指导新疗法，为同种异体移植提供信息， 并监测肾脏健康。

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.