Quantitative Magnetization Transfer Detects Renal Fibrosis in Murine Kidneys With Renal Artery Stenosis.

BACKGROUND: Renal fibrosis is a common pathway in tubulointerstitial injury and a major determinant of renal insufficiency. Collagen deposition, a key feature of renal fibrosis, may serve as an imaging biomarker to differentiate scarred from healthy kidneys.

PURPOSE: To test the feasibility of using quantitative magnetization transfer (qMT), which assesses tissue macromolecule content, to measure renal fibrosis.

STUDY TYPE: Prospective.

ANIMAL MODEL: Fifteen 129S1 mice were studied 4 weeks after either sham (n = 7) or unilateral renal artery stenosis (RAS, n = 8) surgeries.

FIELD STRENGTH/SEQUENCE: Magnetization transfer (MT)-weighted images were acquired at 16.4T using an MT-prepared fast-low-angle-shot sequence. Renal B0 , B1 , and T1 maps were also acquired, using a dual-echo gradient echo, an actual flip angle, and inversion recovery method, respectively.

ASSESSMENT: A two-pool model was used to estimate the bound water fraction (f) and other tissue imaging biomarkers. Masson's trichrome staining was subsequently performed ex vivo to evaluate renal fibrosis.

STATISTICAL TESTS: Comparisons of renal parameters between sham and RAS were performed using independent samples t-tests. Pearson's correlation was conducted to investigate the relationship between renal fibrosis by histology and the qMT-derived bound pool fraction f.

RESULTS: The two-pool model provided accurate fittings of measured MT signal. The qMT-derived f of RAS kidneys was significantly increased compared to sham in all kidney zones (renal cortex [CO], 7.6 ± 2.4% vs. 4.6 ± 0.6%; outer medulla [OM], 8.2 ± 4.2% vs. 4.2 ± 0.9%; inner medulla [IM] + P, 5.8 ± 1.6% vs. 2.9 ± 0.6%, all P < 0.05). Measured f correlated well with histological fibrosis in all kidney zones (CO, Pearson's correlation coefficient r = 0.95; OM, r = 0.93; IM + P, r = 0.94, all P < 0.05).

DATA CONCLUSION: The bound pool fraction f can be quantified using qMT at 16.4T in murine kidneys, increases significantly in fibrotic RAS kidneys, and correlates well with fibrosis by histology. Therefore, qMT may constitute a valuable tool for measuring renal fibrosis in RAS.

LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 3.