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

• Published in: NMR in biomedicine Vol. 34; no. 8; pp. e4539 - n/a
• Main Authors: Wang, Feng, Otsuka, Tadashi, Takahashi, Keiko, Narui, Chikage, Colvin, Daniel C., Harris, Raymond C., Takahashi, Takamune, Gore, John C.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.08.2021
• Subjects: Amides; Animals; Biological products; Collagen; Dilatation; Dilation; Disease Progression; Dispersion; Enlargement; Evaluation; Fibrosis; Histology; Kidney diseases; Kidney Tubules - diagnostic imaging; Kidney Tubules - pathology; Kidneys; Locking; Magnetic Resonance Imaging; Male; Mathematical models; Mice, Inbred BALB C; Mice, Inbred C57BL; MRI; Neuroimaging; Nitric oxide; Parameter sensitivity; relaxation; renal fibrosis; Sensitivity analysis; Spin Labels; spin‐lock R1ρ dispersion; Surgery; tubular dilation; unilateral ureter obstruction; Ureter; Ureteral Obstruction - diagnostic imaging; Ureteral Obstruction - pathology; spin-lock R1ρ dispersion; tubular dilation; renal fibrosis; MRI; unilateral ureter obstruction; relaxation
• ISSN: 0952-3480; 1099-1492; 1099-1492
• DOI: 10.1002/nbm.4539

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. Assessing the severity and progression of tubular dilation and fibrosis in kidneys are important clinical challenges. Here, we evaluate relaxometry and spin‐lock MRI with different locking fields for detecting tubular dilation and fibrosis in a mouse model of unilateral ureter obstruction. We 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.