Noninvasive MRI techniques to detect pathology in murine models of renal disease

项目摘要/摘要 这个由生物医学工程师和医生组成的多学科合作的广泛、长期目标是- 科学家们正在开发早期的、非侵入性的方法来识别有慢性肾脏疾病风险的个体 疾病(CKD)。目前检测肾脏疾病的方法只有在超过一半的滤过时才有用 肾脏的单位，即肾单位，是没有功能的。肾单位的数量是在出生时确定的，随着年龄的增加而下降。 人类的寿命，与慢性肾脏疾病和心血管疾病的发展直接相关。 不幸的是，没有技术来计算活着的个体中功能正常的肾单位的总数。 此外，没有办法整合肾脏的主要部分，例如肾小球改变为 那些位于血管系统或小管间质的细胞。一种用于评估肾脏微结构的诊断生物标志物，如 随着肾小球的数量和体积的增加，患者可以显著受益：早期治疗干预，新颖 用于在药物开发和肾移植分配的临床试验中评估肾脏安全性的终点。 这项工作有三个具体的目标：1)我们将通过MRI来评估肾小球在 用两种小鼠模型发展慢性肾脏病：先天性肾单位数量减少和 慢性肾脏病肾小球硬化模型。我们将比较肾小球微结构的变化与血管 和管状室以及肾脏疾病的传统生物标志物。2)我们将确定时间进程 小鼠急性肾损伤模型肾小管间质病理变化的MRI研究 慢性肾脏疾病。3)我们将确定血管紧张素转换酶抑制对小鼠肾脏微结构的影响 高血压病小鼠模型。在这个项目结束的时候，我们将拥有第一个全面的， 基于MRI的肾脏综合评估，强大的数据提示，这些基于MRI的翻译 未来研究的生物标志物，以预测肾脏疾病的进展。

Project Summary/Abstract The broad, long-term goal of this multi-disciplinary collaborative of biomedical engineers and physician- scientists is to develop early, non-invasive methods to identify individuals at risk of developing chronic kidney disease (CKD). Current methods to detect kidney disease are only useful when more than half of the filtering units of the kidney, nephrons, are nonfunctional. Nephron number is determined at birth, declines over the lifespan of a human and is directly related to the development of chronic kidney and cardiovascular disease. Unfortunately, there are no techniques to count the total number of functioning nephrons in living individuals. Additionally, there is no way to integrate the major compartments of the kidney, such as glomerular changes to those in the vasculature or tubulointerstitial space. A diagnostic biomarker to assess renal microstructure, such as number and volume of glomeruli, could significantly benefit patients: earlier therapeutic intervention, novel endpoints for assessing renal safety in clinical trials for drug development, and for renal allografts allocation. This work has three Specific Aims: 1) We will assess the changes in the glomeruli by MRI during the development of CKD using two mouse models: a congenital reduction in nephron number and a glomerulosclerosis model of CKD. We will compare the changes in glomerular microstructure to the vascular and tubular compartments and to traditional biomarkers of renal disease. 2) We will determine the time course of tubulointerstitial pathology using MRI in mouse model representing the transition from acute kidney injury to chronic kidney disease. 3) We will determine the effect of ACE inhibition of the microstructure of the kidney in a mouse model of essential hypertension. At the conclusion of this project, we will have the first comprehensive, integrated MRI-based evaluation of the kidney, powerful data to inform the translation of these MRI-based biomarkers for future studies to predict kidney disease progression.