Abstract
To characterize longitudinal changes in molecular water diffusion, blood microcirculation, and their contributions to the apparent diffusion changes using intravoxel incoherent motion (IVIM) analysis in an experimental mouse model of liver fibrosis. Liver fibrosis was induced in male adult C57BL/6N mice (22-25 g; n = 12) by repetitive dosing of carbon tetrachloride (CCl(4) ). The respiratory-gated diffusion-weighted (DW) images were acquired using single-shot spin-echo EPI (SE-EPI) with 8 b-values and single diffusion gradient direction. True diffusion coefficient (D(true) ), blood pseudodiffusion coefficient (D(pseudo) ), and perfusion fraction (P(fraction) ) were measured. Diffusion tensor imaging (DTI) was also performed for comparison. Histology was performed with hematoxylin-eosin and Masson's trichrome staining. A significant decrease in D(true) was found at 2 weeks and 4 weeks following CCl(4) insult, as compared with that before insult. Similarly, D(pseudo) values before injury was significantly higher than those at 2 weeks and 4 weeks after CCl(4) insult. Meanwhile, P(fraction) values showed no significant differences over different timepoints. For DTI, significant decrease in ADC was observed following CCl(4) administration. Fractional anisotropy at 2 weeks after CCl(4) insult was significantly lower than that before insult, and subsequently normalized at 4 weeks after the insult. Liver histology showed collagen deposition, the presence of intracellular fat vacuoles, and cell necrosis/apoptosis in livers with CCl(4) insult. Both molecular water diffusion and blood microcirculation contribute to the alteration in apparent diffusion changes in liver fibrosis. Reduction in D(true) and D(pseudo) values resulted from diffusion and perfusion changes, respectively, during the progression of liver fibrosis. IVIM analysis may serve as valuable and robust tool in detecting and characterizing liver fibrosis at early stages, monitoring its progression in a noninvasive manner.
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