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Noninvasive quantitative magnetization transfer MRI reveals tubulointerstitial fibrosis in murine kidney
Author(s) -
Wang Feng,
Wang Suwan,
Zhang Yahua,
Li Ke,
Harris Raymond C.,
Gore John C.,
Zhang MingZhi
Publication year - 2019
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.4128
Subject(s) - fibrosis , magnetization transfer , pathology , staining , chemistry , kidney , renal cortex , nuclear magnetic resonance , magnetic resonance imaging , biology , medicine , endocrinology , physics , radiology
Excessive tissue scarring, or fibrosis, is a critical contributor to end stage renal disease, but current clinical tests are not sufficient for assessing renal fibrosis. Quantitative magnetization transfer (qMT) MRI provides indirect information about the macromolecular composition of tissues. We evaluated measurements of the pool size ratio (PSR, the ratio of immobilized macromolecular to free water protons) obtained by qMT as a biomarker of tubulointerstitial fibrosis in a well‐established murine model with progressive renal disease. MR images were acquired from 16‐week‐old fibrotic hHB‐EGF Tg/Tg mice and normal wild‐type (WT) mice ( N = 12) at 7 T. QMT parameters were derived using a two‐pool five‐parameter fitting model. A normal range of PSR values in the cortex and outer stripe of outer medulla (CR + OSOM) was determined by averaging across voxels within WT kidneys (mean ± 2SD). Regions in diseased mice whose PSR values exceeded the normal range above a threshold value ( t PSR ) were identified and measured. The spatial distribution of fibrosis was confirmed using picrosirius red stains. Compared with normal WT mice, scattered clusters of high PSR regions were observed in the OSOM of hHB‐EGF Tg/Tg mouse kidneys. Moderate increases in mean PSR ( m PSR) of CR + OSOM regions were observed across fibrotic kidneys. The abnormally high PSR regions (% area) detected by the t PSR were significantly increased in hHB‐EGF Tg/Tg mice, and were highly correlated with regions of fibrosis detected by histological fibrosis indices measured from picrosirius red staining. Renal tubulointerstitial fibrosis in OSOM can thus be assessed by qMT MRI using an appropriate analysis of PSR. This technique may be used as an imaging biomarker for chronic kidney diseases.