Quantitative Magnetization EXchange MRI Measurement of Liver Fibrosis Model in Rodents

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 T-1 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 T-1, 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 T-1 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). T-1 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