Dynamic Contrast-Enhanced MRI Assessing Antifibrotic Therapeutic Effects of Pancreatic Fibrosis with Curcumin – An Experimental Study at 11.7 T

Abstract

Pancreatic fibrosis is the hallmark of chronic pancreatitis (CP), which is associated with microcirculatory disturbance. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can assess the perfusion and permeability of the pancreas by providing information about microcirculation. We hypothesize that DCE-MRI parameters can be utilized to assess pancreatic fibrosis and may furthermore provide an opportunity to evaluate response to antifibrotic treatment with curcumin. Our study was to evaluate the feasibility of quantitative DCE-MRI in assessing pancreatic fibrosis and the antifibrotic effect of curcumin in a rat model of CP. Pancreatic fibrosis was induced by injecting dibutyltin dichloride (DBTC). Seventy rats were randomized to five groups: the control group (n=10); DBTC for 2 weeks (n=15); DBTC for 4 weeks (n=15); DBTC+curcumin for 2 weeks (n=15); DBTC+curcumin for 4 weeks (n=15). DCE-MRI was performed at an 11.7T MR scanner. DCE-MRI quantitative parameters (Ktrans, Ve, and Vp) were derived from an extended Tofts model. Fibrosis content and DCE-MRI parameters were compared among the above groups (one-way analysis of variance). The correlations between DCE-MRI parameters and pancreatic fibrosis content as well as the expression of α-SMA were computed by Spearman correlation coefficients. Fifty-three rats survived and underwent MR imaging. Ktrans in rats 4 weeks after DBTC injection was significantly lower than DBTC 2 weeks rats and control rats (0.30±0.06min vs 0.49±0.09 vs 0.62±0.09, respectively). Vp in DBTC 4 weeks rats was also significantly lower than control rats (0.048±0.010min-1 vs 0.065±0.011min-1, respectively). Ktrans and Vp significantly correlated with fibrosis content of pancreas (r=-0.619 and -0.450, all P<0.001), and the expression of α-SMA (r=-0.688 and -0.402, all P<0.01). Ktrans and Vp in rats with daily curcumin treatment for 4 weeks were significantly higher than DBTC 4 weeks rats (Ktrans, 0.51±0.09 vs 0.30±0.06; Vp, 0.064±0.015 vs 0.048±0.010). DCE-MRI parameters (Ktrans and Vp) have the potential to noninvasively assess pancreatic fibrosis and the antifibrotic treatment response of curcumin.