Our study found that the rADC value was negatively related to hepatic fibrosis and necroinflammatory activity, but not related to steatosis. FA value had a positive correlation with fibrosis degree, but had no correlation with necroinflammatory activity and steatosis. The FA value of F4 was statistically different from F0 ~ F3, while there were no significant differences among F0 ~ F3, suggesting that liver FA value can distinguish early cirrhosis(F4), but it had little significance in differentiating normal, mild and moderate liver fibrosis(F0 ~ F3).
DTI can effectively detect the free diffusion rate of water molecules with different structures in vivo and can more accurately reflect the changes in the direction of water molecules dispersion, providing both functional and microstructural information in liver by means of water diffusivity and diffusion anisotropy quantitation, and thus may contribute to evaluating liver fibrosis(11).The reduction of rADC value with fibrosis observed in our study was in accordance with most prior researches(14–16). However, both our and previous studies (9, 15) found that rADC value lacked the ability of differentiating the fibrotic grades. The relationship between FA value and liver fibrosis and the evaluation of FA value for fibrosis staging were reported differently. Cheung et al(11) found that FA value of rats at 2 weeks after CCl4 insult was both significantly lower than that before and 4 weeks after the insult, while FA value at 4 weeks after CCl4 insult was not significantly different from that before insult, which suggesting that FA value can reveal the progression of liver fibrosis, especially early cirrhosis. Another animal research used C57BL/6 mice (10) reported that FA was negatively correlated with hepatic fibrosis and the model group(n = 20) had a lower FA than control group(n = 16). But the data in this study was relatively small (F1 = 4, F2 = 11, F3 = 5) and missing value contained in F4. On the contrary, Tosun M et al (9) found that FA values showed a trend toward higher values with increasing fibrotic stage, but there were no statistically significant differences between the FA values at different fibrotic stages. Our study also found a positive correlation between FA value and fibrosis degree. Meanwhile, our study showed FA value of F4(early cirrhosis) was significantly different from F0 ~ F3. Liver cirrhosis is the end stage of liver fibrosis which has small chance to reverse and high risk of develop into complications and hepatocellular carcinoma. Yet radiologists can’t diagnose early cirrhosis rely on conventional medical imaging because the morphological changes are not obvious. Our study results found that FA value of DTI could distinguish early cirrhosis, which may help physicians to take measures early. The explanation for our study results probably was that with the increasing degree of liver fibrosis, the free movement of water molecules in the liver was affected by the presence of the fiber composition, and the movement direction tended to be consistent or opposite, which increased the FA value. FA value of F0-F3 was not significantly different because that in the early stages of liver fibrosis, the distribution of collagen fibers was not regular and directional, which resulted in the restricted diffusion of water molecules in all directions, leading to the direction of the main axis of water molecules movement less obvious. As a result, the FA value changed not so remarkably. With the progress of fibrosis, the fibrous bundles increased, joined into strips, flakes, and rearranged, which made the main axis of water molecule diffusion more obvious so the FA value was increased significantly in F4(early cirrhosis).
There was limited data about the relationship between liver necroinflammatory grade and DTI measurements. In general, studies (8, 9) found that liver ADC values was inversely correlated with inflammation. But the rADC cannot discriminate different inflammation grades. Both our and Tosun M’s (9) study demonstrated that FA value was not related to inflammation grades. The explanation for rADC decreased with increasing inflammation grades may be a large number of inflammatory cells and factors helped to restrict the free movement ability of water molecule. But it didn’t influence the movement direction of water molecule, so the FA value had no means with inflammation.
Because the clinical therapy depends on the fibrotic stage and inflammatory grade, in prior studies there were mainly about DTI for liver fibrosis and inflammation (8, 9). But some scholars emphasized that ADC (17–20) and FA value (10) in the liver need to be carefully interpreted in the presence of hepatic steatosis. Besheer T (17) demonstrated that hepatic steatosis should always be considered when assessing hepatic fibrosis and their study found that detected hepatic steatosis would underestimate ADC value in patients with chronic hepatitis C. Accordingly, our study took steatosis into consideration. However, our study results did not find the relationship between steatosis and both rADC and FA value, which disaccorded with some of previous research (17, 20–22). There were other studies (13, 23) demonstrated no significant relationship between ADC value and steatosis, which were similar to ours. The inconsistent relationship reported by researchers between MR measurements and steatosis cannot be accurately explained. Maybe different MR machines and parameters or different group standards could affect the results.
There were limitations in our study. First, the main deficiency was that the echo-planar imaging sequence of DTI had a lower signal-to-noise ratio and artifactual interference. Second, the distribution of pathological groups was uneven. Different rats had individual difference in sensitivity to the induction of chronic hepatitis after injection of the same dose of drugs, which made the number of some groups relatively small. Future studies are needed to adopt a high signal-to-noise ratio sequence. Chronic liver disease patients who were performed hepatectomy could enrolled in future study.