Combination of Functional Magnetic Resonance Imaging and Histopathologic Analysis to Evaluate Interstitial Fibrosis in Kidney Allografts

Abstract

Background and objectives: Recent developments indicated that functional magnetic resonance imaging (MRI) could potentially provide noninvasive assessment of kidney interstitial fibrosis in patients with kidney diseases, but direct evidence from histopathology is scarce. We aimed to explore the diagnostic utilities of functional MRI for the evaluation of kidney allograft interstitial fibrosis.

Design, setting, participants, & measurements: We prospectively examined 103 kidney transplant recipients who underwent for-cause biopsies and 20 biopsy-proven normal subjects with functional MRI. Histomorphometric analyses of interstitial fibrosis and peritubular capillary densities were performed on digitally scanned Masson's trichrome- and CD34-stained slides, respectively. The performances of functional MRI to discriminate interstitial fibrosis were assessed by calculating the area under the curve using receiver-operating characteristic curve.

Results: Main pathologic findings in this single-center cohort were representative of common diagnostic entities in the kidney allografts, with rejection (32%) and glomerulonephritides (31%) accounting for the majority of diagnoses. Apparent diffusion coefficient from diffusion-weighted imaging correlated with interstitial fibrosis (ρ=-0.77; P<0.001). Additionally, decreased arterial spin labelings were accompanied by peritubular capillary density reductions (r=0.77; P<0.001). Blood oxygen level-dependent (BOLD) imaging demonstrated cortical hypoxia with increasing interstitial fibrosis (ρ=0.61; P<0.001). The area under the curve for the discrimination of ≤25% versus >25% interstitial fibrosis and ≤50% versus >50% interstitial fibrosis were 0.87 (95% confidence interval [95% CI], 0.79 to 0.93) and 0.88 (95% CI, 0.80 to 0.93) by apparent diffusion coefficient, 0.92 (95% CI, 0.85 to 0.97) and 0.94 (95% CI, 0.87 to 0.98) by arterial spin labeling, 0.81 (95% CI, 0.72 to 0.88) and 0.86 (95% CI, 0.78 to 0.92) by perfusion fraction, 0.79 (95% CI, 0.69 to 0.87) and 0.85 (95% CI, 0.76 to 0.92) by BOLD imaging, respectively.

Conclusions: Functional MRI measurements were strongly correlated with kidney allograft interstitial fibrosis. The performances of functional MRI for discriminating ≤50% versus >50% interstitial fibrosis were good to excellent.

Keywords: ROC curve; allografts; area under curve; biopsy; cohort studies; confidence intervals; fibrosis; glomerulonephritis; humans; hypoxia; interstitial fibrosis; kidney biopsy; kidney disease; kidney diseases; kidney transplantation; magnetic resonance imaging; oxygen; renal dysfunction; transplantation; transplantation, homologous.