Renal tubular dilation and fibrosis after unilateral ureter obstruction revealed by relaxometry and spin‐lock exchange MRI

Abstract

We evaluated the use of quantitative MRI relaxometry, including the dispersion of spin‐lock relaxation with different locking fields, for detecting and assessing tubular dilation and fibrosis in a mouse model of unilateral ureter obstruction (UUO). C57BL/6 J and BALB/c mice that exhibit different levels of tubular dilation and renal fibrosis after UUO were subjected to MR imaging at 7 T. Mice were imaged before UUO surgery, and at 5, 10 and 15 days after surgery. We acquired maps of relaxation rates and fit the dispersion of spin‐lock relaxation rates R1ρ at different locking fields (frequencies) to a model of exchanging water pools, and assessed the sensitivity of the derived quantities for detecting tubular dilation and fibrosis in kidney. Histological scores for tubular dilation and fibrosis, based on luminal space and positive fibrotic areas in sections, were obtained for comparison. Histology detected extensive tubular dilation and mild to moderate fibrosis in the UUO kidneys, in which enlargement of luminal space, deposition of collagen, and reductions in capillary density were observed in the cortex and outer stripe of the outer medulla. Relaxation rates R1, R2 and R1ρ clearly decreased in these regions of UUO kidneys longitudinally. While R1 showed the highest detectability to tubular dilation and overall changes in UUO kidneys, Sρ, a parameter derived from R1ρ dispersion data, showed the highest correlation with renal fibrosis in UUO. While relaxation parameters are sensitive to tubular dilation in UUO kidneys, Sρ depends primarily on the average exchange rate between water and other chemically shifted resonances such as hydroxyls and amides, and provides additional specific information for evaluating fibrosis in kidney disease.

Multiparametric magnetic resonance imaging in diagnosis of long‐term renal atrophy and fibrosis after ischemia reperfusion induced acute kidney injury in mice

“…R 1obs showed quite low detectability for IRI-induced abnormal changes, lower than its detectability for abnormal changes induced by unilateral ureter obstruction (UUO). 33 S ρ showed a large AUC, but lower than the AUC observed in a transgenic murine model whose kidneys show only fibrosis. 32 The sensitivity and AUC of R 2 Ã for detected abnormal tissues (Table 1) were much higher in ISOM than those in the CR + OSOM region (Table 1).…”

“…This is consistent with the previous PSR changes in a fibrotic transgenic model in which fibrosis is predominant, 36 and in a UUO model in which tubular dilation is predominant. 33 R 2 Ã and S ρ could be more specific to a single pathological event than other MRI measures because only R 2 Ã increased and S ρ decreased consistently when either fibrosis or TA dominated (Figures 6 and 7), and their correlations with FS were higher than other MRI measures (Figure S2).…”

“…Spin-lock prepared images were collected 32,33 using a rapid acquisition with relaxation enhancement (RARE). We collected spin-lock data using nine locking frequencies from 200 to 3000 Hz, as detailed in the supporting information.…”

“…Fibrosis was assessed by picrosirius red stains (Figure S1A,B). The positive red area was measured in different region as described previously 33,35 and used as a fibrosis score (FS).…”

“…Indeed, we have shown that tubular dilation, atrophy, and fibrosis largely affect MRI measurements in the UUO model. 33,37 In the IRI-induced AKI model, several processes such as cell swelling, interstitial edema, TA, fibrosis, hypoperfusion, and hypoxia, could all contribute to changes in MRI measurements.…”