Magnetic resonance diffusion tensor imaging applied to rat model of contrast-induced acute kidney injury

Abstract

Objectives: In this preclinical investigation, the feasibility of using diffusion tensor imaging (DTI) to study contrast-induced acute kidney injury (CIAKI) is explored, comparing radiographic outcomes with histopathologic and immunohistochemical findings after repeated animal exposures to iodinated contrast agent.

Materials and methods: Forty-five male wistar rats were allocated to three groups (n = 15 each), each receiving two separate injections 1 day apart: group 1 (iodixanol then saline); group 2 (iodixanol twice); and control group (saline twice). Five rats were then randomly selected from each group at three separate time points (1 h, 24 h, and 120 h) for magnetic resonance imaging (MRI). Upon MRI completion, the animals were sacrificed, examining renal tissue and serum creatinine level. DTI data served to calculate fractional anisotropy (FA) and apparent diffusion coefficient (ADC).

Results: FA values were significantly lower in group 2 than in the others. Compared with controls, FA assessments at 1 h, 24 h, and 120 h after injections commenced were significantly lower in group 2; and ADC was significantly more pronounced at 24 h. Serum creatinine levels at 24 h were markedly elevated in both groups 1 and 2. Pearson correlation analysis revealed significant negative correlations between FA (r = -0.730; p < 0.05) or ADC (r = -0.827; p < 0.05) and tubular injury and between FA (r = -0.563; p < 0.05) or ADC (r = -0.805; p < 0.05) and hypoxia-inducible factor-1α.

Conclusions: Analytic approaches to DTI with better reproducibility should aid in monitoring the early pathophysiologic derangements of CIAKI, thus facilitating timely reversal of the detrimental effects.

Keywords: Contrast-induced acute kidney injury; Chronic kidney disease; Diffusion tensor imaging; Hypoxia-inducible factor-1α.

Figure 1. Morphologic MR images with representative cortical and medullary ROI segmentations.

(A) ROIs traced on DTI of kidney and (B) ROIs traced on DTI pseudocolor map. DTI, diffusion tensor image; ROI, region of interest; CO, cortex; OM, outer medulla.

Figure 2. Sample diffusion maps of animal groups, shown chronologically.

The lower fractional anisotropy (FA) values of DTI maps indicating higher diffusion anisotropy in group 2 (D–F), compared with group 1 (A–C) and control group (G–I) (note: all maps displayed in same window). DTI, diffusion tensor imaging.

Figure 3. Histologic features of renal cortex over time, shown by animal group (200×).

(A–I) H&E-stained tissue sections revealing vacuolar change of renal tubules in contrast-treated rats, with inflammatory cell influx, cellular casts, and glomerular atrophy; and (J) Cortical damage scores by group. ^#p < 0.05 vs control group.

Figure 4. Histologic features of renal medulla over time, shown by animal group (200×).

(A–I) H&E-stained tissue sections showing tubular necrosis, tubular vacuolization, tubulointerstitial fibrosis, and proteinaceous casts in contrast-treated rats; and (J) Medullary damage scores by group. *p < 0.05 vs group 1; ^#p < 0.05 vs control group.

Figure 5. Chronologic views of renal medullary HIF-1α immunostaining in three animal groups (400×).

(A–I) HIF-1α expressed primarily in group 2 surpassing others; and (J) Relative quantitation shown as percentage of cells displaying HIF-1α positivity in high-power field (Image J). HIF-1α, hypoxia-inducible factor-1α; *p < 0.05 vs group 1; ^#p < 0.05 vs control group.

Figure 6. Correlating FA and ADC values with histopathologic scores and HIF-1α expression levels in three animal groups.

(A) FA and histopathologic scores; (B) ADC and histopathologic scores; (C) FA and HIF-1α expression; and (D) ADC and HIF-1α expression FA, fractional anisotropy; ADC, apparent diffusion coefficient; HIF-1α, hypoxia-inducible factor-1α.