Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, Missouri.
Department of Physics, University of Hawai'i at Mānoa, Honolulu, Hawaii.
Am J Physiol Renal Physiol. 2019 Oct 1;317(4):F865-F873. doi: 10.1152/ajprenal.00078.2019. Epub 2019 Jul 24.
The development of chronic kidney disease (CKD) is associated with the loss of functional nephrons. However, there are no methods to directly measure nephron number in living subjects. Thus, there are no methods to track the early stages of progressive CKD before changes in total renal function. In this work, we used cationic ferritin-enhanced magnetic resonance imaging (CFE-MRI) to enable measurements of glomerular number () and apparent glomerular volume (aV) in vivo in healthy wild-type (WT) mice ( = 4) and mice with oligosyndactylism (Os; = 4), a model of congenital renal hypoplasia leading to nephron reduction. We validated in vivo measurements of and aV by high-resolution ex vivo MRI. CFE-MRI measured a mean of 12,220 ± 2,028 and 6,848 ± 1,676 (means ± SD) for WT and Os mouse kidneys in vivo, respectively. measured in all mice in vivo using CFE-MRI varied by an average 15% from measured ex vivo in the same kidney (α = 0.05, = 0.67). To confirm that CFE-MRI can also be used to track nephron endowment longitudinally, a WT mouse was imaged three times by CFE-MRI over 2 wk. Values of measured in vivo in the same kidney varied within 3%. Values of aV calculated from CFE-MRI in vivo were significantly different (15% on average, < 0.01) from those measured ex vivo, warranting further investigation. This is the first report of direct measurements of and aV in healthy and diseased mice in vivo.
慢性肾脏病(CKD)的发展与功能性肾单位的丧失有关。然而,目前没有直接测量活体肾单位数量的方法。因此,在总肾功能发生变化之前,无法跟踪进行性 CKD 的早期阶段。在这项工作中,我们使用阳离子铁蛋白增强磁共振成像(CFE-MRI)来实现在健康野生型(WT)小鼠(n = 4)和多指畸形(Os;n = 4)小鼠体内肾小球数量()和表观肾小球体积(aV)的活体测量,Os 是一种导致肾单位减少的先天性肾发育不全的模型。我们通过高分辨率离体 MRI 验证了体内测量的和 aV 的准确性。CFE-MRI 分别测量到 WT 和 Os 小鼠肾脏的平均和 aV 分别为 12220±2028 和 6848±1676(平均值±标准差)。在所有小鼠体内使用 CFE-MRI 测量的,与同一肾脏离体测量的相差平均 15%(α=0.05,=0.67)。为了证实 CFE-MRI 也可用于跟踪肾单位的纵向分配,我们对一只 WT 小鼠进行了 CFE-MRI 三次成像,时间跨度为 2 周。同一肾脏体内测量的 值在3%范围内波动。从 CFE-MRI 体内计算的 aV 值与离体测量的显著不同(平均15%,<0.01),这需要进一步研究。这是首次直接在健康和患病小鼠体内测量和 aV 的报道。