Multi-Parametric MRI Detects Longitudinal Evolution of Folic Acid-Induced Nephropathy in Mice.

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 R2*, magnetization transfer ratio (MTR), perfusion, T1, 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 T1, 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.