Noninvasive Assessment of Renal Fibrosis with Magnetization Transfer MR Imaging: Validation and Evaluation in Murine Renal Artery Stenosis

Abstract

Purpose To test the utility of magnetization transfer imaging (MTI) in detection and monitoring the progression of renal fibrosis in mice with unilateral renal artery stenosis (RAS). Materials and Methods This prospective study was approved by the Institutional Animal Care and Use Committee. RAS (n=10) or sham surgery (n=5) was performed, and the stenotic and contralateral kidneys were studied longitudinally in-vivo at baseline and 2, 4 and 6 weeks post-surgery. Following a 16.4T MRI exam, magnetization transfer ratio (MTR) was measured as an index of fibrosis (guided by parameters selected in preliminary phantom studies). In addition, renal volume, perfusion, blood flow and oxygenation were assessed. Fibrosis was subsequently measured ex-vivo by histology and hydroxyproline assay. The Wilcoxon rank-sum or signed-rank test was used for statistical comparisons between or within groups, and Pearson’s and Spearman’s rank correlation to compare fibrosis measured in-vivo and ex-vivo. Results In the stenotic kidney, the median MTR showed progressive increases from baseline to 6 weeks post-surgery (by 13.7% [P=0.0006] and 21.3% [P=0.0005] in cortex and medulla, respectively), which were accompanied by a progressive loss in renal volume, perfusion, blood flow, and oxygenation. The 6-week MTR map showed good correlation with fibrosis measured ex-vivo (Pearson’s r=0.9038 and Spearman’s ρ=0.8107, P=0.0002 vs. trichrome staining; r=0.9540 and ρ=0.8821, P<0.0001 vs. Sirius red staining; r=0.8429 and ρ=0.7607, P=0.001 vs. hydroxyproline assay). Conclusion MT successfully measured and longitudinally monitored the progression of renal fibrosis in mice with unilateral RAS.

A rapid T1 mapping method for assessment of murine kidney viability using dynamic manganese‐enhanced magnetic resonance imaging

“…At baseline, CO and OSOM in the stenotic kidneys showed elevated T 1 values (P ¼ 0.031 and 0.0075, respectively) compared to the control kidneys (Fig. 5c), possibly because of edema (21). In control kidneys, R 1 showed an approximately linear increase during Mn 2þ infusion and reached a steady state during washout in CO and OSOM, but a slight decrease in ISOM (Fig.…”

Magnetization Transfer Magnetic Resonance Imaging Noninvasively Detects Renal Fibrosis in Swine Atherosclerotic Renal Artery Stenosis at 3.0 T

“…With a high offset-frequency, a larger flip angle is required to maintain MT contrast-to-noise ratio, but when too low, direct saturation of free water signal causes imaging artifacts. Previously, an optimal offset frequency at 1500Hz has been identified for collagen detection at 16.4T (23). Given the field dependence of the optimal offset frequency, a collagen phantom study was first performed in this study at 3.0T.…”

“…MT parameters for collagen detection in murine RAS at 16.4T were recently identified, and the applicability of MT-MRI in measuring and monitoring longitudinal progression of renal fibrosis demonstrated (23). However, its capability for detecting renal fibrosis at clinical field-strength remains unknown.…”

Longitudinal assessment of rabbit renal fibrosis induced by unilateral ureteral obstruction using two‐dimensional susceptibility weighted imaging

“…[31][32][33] The significant differences between the cortical r values and the medullary r values suggested that the severity of fibrosis was different in the two regions. However, this study demonstrated the cortical and medullary r values elevated when obvious fibrosis appeared at week 2.…”