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类的肾单位和肾小球容积。每个肾单位包含一个肾小球，其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。目前还没有无创技术来计算体内功能性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。我们建议，对比增强MRI，使用MRI可检测的纳米粒子靶向肾小球基底膜，可用于准确计数肾小球总数和测量肾小球体积在整个完整的肾脏。该提案的重点是在小鼠中建立这种技术。我们还建议评估该技术在小鼠肾单位捐赠系统缺陷的存在下的准确性。一旦完成，拟议的工作将打开实时的可能性，在动物和人类的肾脏和全身性疾病的研究中的体内肾小球计数和体积。

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.