Spin-lock relaxation rate dispersion reveals spatiotemporal changes associated with tubulointerstitial fibrosis in...

To develop and evaluate a reliable non-invasive means for assessing the severity and progression of fibrosis in kidneys. We used spin-lock MR imaging with different locking fields to detect and characterize progressive renal fibrosis in an hHB-EGF^Tg/Tg mouse model.

Male hHB-EGF^Tg/Tg mice, a well-established model of progressive fibrosis, and age-matched normal wild type (WT) mice, were imaged at 7T at ages 5-7, 11-13, and 30-40 weeks. Spin-lock relaxation rates R_1ρ were measured at different locking fields (frequencies) and the resultant dispersion curves were fit to a model of exchanging water pools. The obtained MRI parameters were evaluated as potential indicators of tubulointerstitial fibrosis in kidney. Histological examinations of renal fibrosis were also carried out post-mortem after MRI.

Histology detected extensive fibrosis in the hHB-EGF^Tg/Tg mice, in which collagen deposition and reductions in capillary density were observed in the fibrotic regions of kidneys. R₂ and R_1ρ values at different spin-lock powers clearly dropped in the fibrotic region as fibrosis progressed. There was less variation in the asymptotic locking field relaxation rate $$ between the groups. The exchange parameter S_ρ and the inflection frequency ω_infl changed by larger factors.

Both S_ρ and ω_infl depend primarily on the average exchange rate between water and other chemically shifted resonances such as hydroxyls and amides. Spin-lock relaxation rate dispersion, rather than single measurements of relaxation rates, provides more comprehensive and specific information on spatiotemporal changes associated with tubulointerstitial fibrosis in murine kidney.