University of Hawaii at Manoa, Department of Physics , Honolulu, Hawaii.
University of Virginia , Department of Pediatrics, Charlottesville, Virginia.
Am J Physiol Renal Physiol. 2018 Mar 1;314(3):F399-F406. doi: 10.1152/ajprenal.00399.2017. Epub 2017 Nov 1.
number is highly variable in humans and is thought to play an important role in renal health. Chronic kidney disease (CKD) is the result of too few nephrons to maintain homeostasis. Currently, nephron number can only be determined invasively or as a terminal assessment. Due to a lack of tools to measure and track nephron number in the living, the early stages of CKD often go unrecognized, preventing early intervention that might halt the progression of CKD. In this work, we present a technique to directly measure glomerular number ( N) and volume in vivo in the rat kidney ( n = 8) using MRI enhanced with the novel contrast agent cationized ferritin (CFE-MRI). Adult male rats were administered intravenous cationized ferritin (CF) and imaged in vivo with MRI. Glomerular number was measured and each glomerulus was spatially mapped in 3D in the image. Mean apparent glomerular volume (a V) and intrarenal distribution of the individual glomerular volume (IGV), were also measured. These metrics were compared between images of the same kidneys scanned in vivo and ex vivo with CFE-MRI. In vivo N and a V correlated to ex vivo metrics within the same kidneys and were within 10% of N and a V previously validated by stereologic methods. This is the first report of direct in vivo measurements of N and a V, introducing an opportunity to investigate mechanisms of renal disease progression and therapeutic response over time.
数量在人类中高度可变,被认为在肾脏健康中发挥重要作用。慢性肾脏病 (CKD) 是由于肾小球数量不足以维持体内平衡而导致的。目前,肾小球数量只能通过侵入性手段或作为终末评估来确定。由于缺乏在活体中测量和跟踪肾小球数量的工具,CKD 的早期阶段经常被忽视,从而无法进行早期干预以阻止 CKD 的进展。在这项工作中,我们提出了一种使用新型造影剂正铁蛋白(CFE-MRI)增强 MRI 直接测量活体大鼠肾脏肾小球数量(N)和体积的技术(n = 8)。成年雄性大鼠给予静脉内正铁蛋白(CF)并进行 MRI 活体成像。测量肾小球数量,并在图像中以 3D 方式对每个肾小球进行空间映射。还测量了平均表观肾小球体积(aV)和单个肾小球体积(IGV)的肾内分布。这些指标在体内用 CFE-MRI 扫描的相同肾脏的图像与离体的图像之间进行了比较。体内 N 和 aV 与同一肾脏的离体指标相关,与通过体视学法验证的 N 和 aV 相差 10%以内。这是首次直接活体测量 N 和 aV 的报道,为研究肾脏疾病进展和治疗反应的机制提供了机会。