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

Abstract

PURPOSE:

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-EGFTg/Tg mouse model.

METHODS:

Male hHB-EGFTg/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 R1ρ 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.

RESULTS:

Histology detected extensive fibrosis in the hHB-EGFTg/Tg mice, in which collagen deposition and reductions in capillary density were observed in the fibrotic regions of kidneys. R2 and R1ρ 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 R1ρ∞ between the groups. The exchange parameter Sρ and the inflection frequency ωinfl changed by larger factors.

CONCLUSION:

Both Sρ and ωinfl 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.

• Authors: Feng Wang, Daniel C Colvin, Suwan Wang, Hua Li, Zhongliang Zu, Raymond C Harris, Ming-Zhi Zhang, John C Gore
• Journal: Magnetic resonance in medicine (Magn Reson Med) Vol. 84 Issue 4 Pg. 2074-2087 (10 2020) ISSN: 1522-2594 [Electronic] United States
• PMID: 32141646 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2020 International Society for Magnetic Resonance in Medicine.

Chemical References

• Amides

Topics

• Amides
• Animals
• Disease Models, Animal
• Fibrosis
• Kidney (diagnostic imaging)
• Magnetic Resonance Imaging
• Male
• Mice