Quantitative Magnetization EXchange MRI Measurement of Liver Fibrosis Model in Rodents

Abstract

Background: Quantitative MRI can elucidate the complex microstructural changes in liver disease. The Magnetization EXchange (MEX) method estimates macromolecular fraction, such as collagen, and can potentially aid in this task.

Hypothesis: MEX sequence, and its derived quantitative macromolecular fraction, should correlate with collagen deposition in rodents liver fibrosis model.

Study type: Prospective.

Animal model: Sixteen adults Sprague-Dawley rats and 13 adults C57BL/6 strain mice given carbon tetrachloride (CCl₄ ) twice weekly for 6 or 8 weeks.

Field strength/sequence: A 7 T scanner. MEX sequence (selective suppression and magnetization exchange), spin-echo and gradient-echo scans.

Assessment: Macromolecular fraction (F) and T₁ were extracted for each voxel and for livers' regions of interest, additional to calculating the percentage of F > 0.1 pixels in F maps (high-F). Histology included staining with hematoxylin and eosin, picrosirius red and Masson trichrome, and inflammation scoring. Quantitative collagen percentage calculated using automatic spectral-segmentation of the staining.

Statistical tests: Comparing CCl₄ -treated groups and controls using Welch's t-test and paired t-test between different time points. Pearson's correlation used between ROI MEX parameters or high-F fraction, and quantitative histology. F or T₁ , and inflammation scores were tested with one-sided t-test. P < 0.05 was deemed significant.

Results: Rats: F values were significantly different after 6 weeks of treatment (0.10 ± 0.02) compared to controls (0.080 ± 0.003). After 8 weeks, F significantly increased (0.11 ± 0.02) in treated animals, while controls are not significant (0.0814 ± 0.0008, P = 0.079). F correlated with quantitative histology (R = 0.87), and T₁ was significantly different between inflammation scores (1: 1332 ± 224 msec, 2: 2007 ± 464 msec). Mice: F was significantly higher (0.062 ± 0.006) in treatment group compared to controls (0.042 ± 0.006). F and high-F fraction correlated with quantitative histology (R = 0.88; R = 0.84). T₁ was significantly different between inflammation scores (1:1366 ± 99 msec; 2:1648 ± 45 msec).

Data conclusion: MEX extracted parameters are sensitive to collagen deposition and inflammation and are correlated with histology results of mouse and rat liver fibrosis model.

Evidence level: 1 TECHNICAL EFFICACY: Stage 3.

Keywords: MEX MRI; animal model; collagen fraction; liver fibrosis.