MRI Techniques to Measure Whole-Kidney Nephron

描述（由申请人提供）：这项工作的广泛、长期目标是在体内测量人体肾单位和肾小球的体积禀赋。每个肾元包含一个肾小球，它的功能是血液大分子的高压过滤器。肾单位和肾小球的缺陷与肾脏疾病如糖尿病、肥胖和高血压有关。目前还没有一种无创技术来计算体内功能正常的肾小球和肾单位的总数。这种技术将使人类肾脏和全身性疾病的研究成为可能，并将开辟肾脏疾病易感性动物研究的新领域。我们提出，利用MRI可检测的纳米颗粒靶向肾小球基底膜的对比增强MRI，可以准确地计算肾小球的总数，并测量整个完整肾脏的肾小球体积。本提案的重点是在小鼠身上建立这种技术。我们进一步建议评估该技术在小鼠肾元供体存在系统性缺陷时的准确性。一旦完成，拟议的工作将为动物和人类肾脏和全系统疾病研究中实时、体内肾小球计数和体积的研究开辟可能性。

DESCRIPTION (provided by applicant): The broad, long-term goal of this work is to measure kidney nephron and glomerular volume endowment in humans, in vivo. Each nephron contains a glomerulus, which functions as a high-pressure filter of blood macromolecules. Deficits in nephrons and glomeruli have been correlated with renal diseases such as diabetes, obesity, and hypertension. There is currently no noninvasive technique to count the total number of functioning renal glomeruli and nephrons in vivo. Such a technique would enable studies of kidney and systemic disease in humans, and would open a new area of animal studies of the susceptibility to renal disease. We propose that contrast-enhanced MRI, using MRI-detectable nanoparticles targeted to the glomerular basement membrane, can be used to accurately count the total number of glomeruli and measure glomerular volume in the whole, intact kidney. This proposal is focused on establishing this technique in mice. We further propose to assess the accuracy of the technique in the presence of systemic deficits in nephron endowment in mice. Once completed, the proposed work will open the possibility of real-time, in vivo glomerular counts and volume in studies of renal and systemic diseases in animals and humans. PUBLIC HEALTH RELEVANCE: The purpose of this project is to develop a molecular MRI technique to count the number of kidney glomeruli and volume ex vivo and in vivo. This work will lay the foundation for the use of MRI-detectable nanoparticle probes to study single nephron structure and function in animal models and humans.