MRI-based glomerular morphology and pathology in whole human kidneys

MRI-based glomerular morphology and pathology in whole human kidneys
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DOI:
10.1152/ajprenal.00092.2014
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发表时间:
2014-06-01
影响因子:
4.2
通讯作者:
Bennett, Kevin M.
Bennett, Kevin M.
中科院分区:
医学2区
文献类型:
--
作者:
Beeman, Scott C.;Cullen-McEwen, Luise A.;Bennett, Kevin M.

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肾单位数量(N-glom)和大小(V-glom)与慢性心血管和肾脏疾病的风险相关,并可预测肾移植物的存活率。不幸的是,没有技术来评估完整肾脏中的Nglom和Vglom。这项工作证明了使用阳离子化铁蛋白(CF)作为磁共振成像(MRI)造影剂来测量捐赠给科学的人类肾脏中的N-glom和V-glom。肾脏来自患有不同程度心血管和肾脏疾病的患者。将CF静脉注射到三个活的人肾中。用盐水灌注第四个对照肾脏。固定后,免疫荧光和电子显微镜证实结合CF的肾小球。完整的肾脏用三维MRI成像,CF标记的肾小球呈点状。定制软件识别、计数和测量CF标记的肾小球的表观体积,假阳性率接近6%。这些测量值与体视学估计值相当。基于MRI的技术产生了一种新的肾小球体积的全肾分布。组织学研究表明,CF标记肾小球的分布可能是肾小球和血管疾病的预测。使用图像纹理分析量化CF分布的变化,这是肾小球硬化的有用标记。这是第一个直接测量完整人肾肾小球数量和体积的报告。
Nephron number (N-glom) and size (V-glom) are correlated with risk for chronic cardiovascular and kidney disease and may be predictive of renal allograft viability. Unfortunately, there are no techniques to assess Nglom and Vglom in intact kidneys. This work demonstrates the use of cationized ferritin (CF) as a magnetic resonance imaging (MRI) contrast agent to measure N-glom and V-glom in viable human kidneys donated to science. The kidneys were obtained from patients with varying levels of cardiovascular and renal disease. CF was intravenously injected into three viable human kidneys. A fourth control kidney was perfused with saline. After fixation, immunofluorescence and electron microscopy confirmed binding of CF to the glomerulus. The intact kidneys were imaged with three-dimensional MRI and CF-labeled glomeruli appeared as punctate spots. Custom software identified, counted, and measured the apparent volumes of CF-labeled glomeruli, with an similar to 6% false positive rate. These measurements were comparable to stereological estimates. The MRI-based technique yielded a novel whole kidney distribution of glomerular volumes. Histopathology demonstrated that the distribution of CF-labeled glomeruli may be predictive of glomerular and vascular disease. Variations in CF distribution were quantified using image texture analyses, which be a useful marker of glomerular sclerosis. This is the first report of direct measurement of glomerular number and volume in intact human kidneys.