Multiparametric MRI detects longitudinal evolution of folic acid-induced nephropathy in mice
Multiparametric MRI detects longitudinal evolution of folic acid-induced nephropathy in mice
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DOI：
10.1152/ajprenal.00128.2018
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发表时间：
2018-11-01
影响因子：
4.2
通讯作者：
Lerman, Lilach O.
中科院分区：
文献类型：
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作者：
Jiang, Kai;Ponzo, Tristan A.;Lerman, Lilach O.
叶酸（FA）诱导的急性肾损伤（AKI）啮齿动物模型为研究人类AKI提供了一个有用的模型，但对肾脏血流动力学的纵向变化和体内肾纤维化的演变知之甚少。在这项工作中，我们旨在利用多参数磁共振成像（MRI）纵向评估肾脏结构和功能的变化。10只成年小鼠注射FA后，于治疗后2周采用多参数MRI测量肾脏体积、缺氧指数R-2*、磁化传递比（MTR）、灌注、T-1和肾小球滤过率（GFR）。5只小鼠安乐死后进行组织学检查，其余5只小鼠在4周后再次进行MRI检查。对照组小鼠（n=5）注射载药，2周后进行MRI研究。三色染色、血红素染色和伊红染色评估fa诱导的组织损伤。虽然肾脏大小和氧合表现出进行性恶化，但肾灌注的一过性损伤和正常化GFR在4周后略有改善。肾液含量，如T-1所反映的，在2周时显著，在4周时趋于下降，与观察到的肾小管扩张一致。三色染色显示2周时斑片状坏死和轻度间质纤维化，4周时加重。4周时MTR检测到纤维化增加。总之，多参数MRI捕获了叶酸治疗后第一个月内肾脏损伤的纵向进展，并可能为评估治疗策略提供有用的工具。
The rodent model of folic acid (FA)-induced acute kidney injury (AKI) provides a useful model for studying human AKI, but little is known about longitudinal changes in renal hemodynamics and evolution of renal fibrosis in vivo. In this work, we aimed to longitudinally assess renal structural and functional changes using multi-parametric magnetic resonance imaging (MRI). Ten adult mice were injected with FA, after which multi-parametric MRI was used to measure kidney volume, hypoxia index R-2*, magnetization transfer ratio (MTR), perfusion, T-1, and glomerular filtration rate (GFR) at 2 weeks post-treatment. Then five mice were euthanized for histology and the other five underwent MRI again at 4 weeks followed by histology. Control mice (n=5) were injected with vehicle and studied with MRI at 2 weeks. Trichrome and hemotoxylin and eosin staining were performed to assess FA-induced tissue injuries. While kidney size and oxygenation showed progressive deterioration, a transient impairment in renal perfusion and normalized GFR slightly improved by 4 weeks. Kidney fluid content, as reflected by T-1, was prominent at 2 weeks and tended to regress at 4 weeks, consistent with observed tubular dilation. Trichrome staining revealed patchy necrosis and mild interstitial fibrosis at 2 weeks, which exacerbated at 4 weeks. MTR detected increased fibrosis at 4 weeks. In conclusion, multi-parametric MRI captured the longitudinal progression in kidney damage evolving within the first month after treatment with folic acid, and may provide a useful tool for assessment of therapeutic strategies.