Intravoxel Incoherent Motion Diffusion Weighted MR Study In Rabbit Liver Fibrosis Model

Objective: To evaluate(Diffusion Coefficient, D),(Perfusion-related Coefficient, D*), and(Perfusion Fraction, f) values that determined from diffusion-weighted imaging(DWI) on the basis of the intravoxel incoherent motion(IVIM) theory in experimental rabbits model of liver fibrosis and evaluate the applicability of these parameters in the differential and grading of liver fibrosis.Methods: Liver fibrosis was induced in rabbits by repetitive dosing of carbon tetrachloride(CCl4). All rabbits were divided into four groups based on the grade of fibrosis. The respiratory gated diffusion-weighted images were acquired using single-shot spin-echo EPI(SE-EPI) with single b-value for common DWI and 8 b-values for IVIM. The diffusion coefficient(D), perfusion-related coefficient,(D*), and perfusion fraction(f) in four stages were measured. Histology was performed with hematoxylineosin and Masson’s trichrome staining.Results: 43 rabbits model of liver fibrosis of different grade were successfully established. Mean ADC values were significantly higher than D in the control group(ADC 1.42±0.34 vs D 1.01±0.44, P<0.05) and in the fibrosis group(ADC 1.32±0.37 vs D 0.78±0.32, P<0.05). Compare to control group, a significant decrease of ADC value was found on fibrosis model(1.42±0.34, 1.32±0.37, respectively; P<0.05). However, there was no significant difference of ADC value between control group and fibrosis stage 1 group(1.42±0.34, 1.38±0.41, respectively; P=0.2). In bi-exponential IVIM model, D value showed significant lower in fibrosis stage 1 group compare with control group(1.01±0.44, 0.89±0.32, respectively; P<0.05), but there were no difference of D*(82.5±24.2, 76.5±34.8, respectively; P=0.23) and f(29.3±6.8, 31.3±8.8, respectively; P=0.6). With the progression of liver fibrosis, the ADC value decreased gradually, D, D* and f value were also showed the similar trend. Meanwhile, ADC values showed no significant differences in stage 2 and stage 3 fibrosis groups(1.36±0.44, 1.32±0.62, respectively; P=0.15), so were D(0.82±0.34, 0.74±0.56, respectively; P=0.27)and f value(27.3±11.2, 24.1±7.3, respectively; P=0.32). However, D* showed significant differences in these two fibrosis groups(65.6±35.1, 52.6±22.2, respectively; P<0.05). Liver histology showed collagen deposition, the presence of intracellular fat vacuoles, and cell necrosis/apoptosis in livers with CCl4 insult.Conclusions: Both molecular water diffusion and blood microcirculation contribute to the alteration in apparent diffusion changes in liver fibrosis. Reduction in Dtrue and Dpseudo 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.