Published online Mar 21, 2019. doi: 10.3748/wjg.v25.i11.1355
Peer-review started: December 21, 2018
First decision: January 23, 2019
Revised: January 31, 2019
Accepted: February 22, 2019
Article in press: February 22, 2019
Published online: March 21, 2019
Despite the high incidence of fatty liver, there was no specific diagnosis and treatment. And the study of morphological and medical physics changes in fatty liver have been ignored for many years. It has been reported that hemodynamic changes occur in steatosis stage, which might be caused by the compression of the liver microcirculation and changes in the hemorheology characteristics.
Re-examining steatosis from a new perspective - hemodynamics - may enhance our understanding of fatty liver and provide a new idea of treatment.
We mainly focused on the microcirculation of the liver in steatosis stage, which cannot be detected by clinical imaging technique. By the two-photon fluorescence microscopy imaging technique, we observed the structure and hemodynamic characteristics of the liver sinusoids, which linked microscopic morphology with hemodynamics and complemented laboratory imaging to fill gaps in clinical imaging.
A hepatic steatosis model was established by subcutaneous injection of carbon tetrachloride in mice. After establishing the model, liver tissue from mice was stained with hematoxylin and eosin (HE) and oil red O stains. Blood was collected from the angular vein, and hemorheological parameters were estimated. A two-photon fluorescence microscope was used to examine the flow properties of red blood cells in the hepatic sinusoids. All result values are presented on graphs as the mean ± SEM. The comparison between multiple groups was performed by one-way ANOVA followed by Dunnett's multiple comparison Test. P-values < 0.05 were considered statistically significant.
Oil red O staining indicated lipid accumulation in the liver after CCl4 treatment. HE staining indicated narrowing of the hepatic sinusoidal vessels. No significant difference was observed between the 2-wk and 4-wk groups of mice on morphological examination. Hemorheological tests revealed pathological changes in plasma components and red blood cells of hepatic steatosis. Assessment of blood flow velocity in the hepatic sinusoids revealed that as the modeling time increased, the blood flow velocity in the hepatic sinusoids decreased gradually; meanwhile, the diameter of the hepatic sinusoids became smaller.
These results revealed that hemodynamic changes occurring during steatosis stage (at least in the early stage) were more likely caused by sinusoidal deformation, but the mechanism of these phenomena remains to be solved.
We used two-photon fluorescence microscopy imaging technique to study hemodynamic changes in fatty liver. And we observed that hemorheological change occurred in hepatic steatosis stage, and manifested as changes in blood flow velocity. We found that this change may be mainly caused by sinusoidal deformation, although it is related to hemorheology characteristics, but there was no statistical difference.
Two-photon fluorescence microscopy imaging technique provides us with another way to observe microcirculation in addition to electron microscopy, and can be used to display stereoscopic blood vessel morphology through 3D reconstruction. In the future, it can be combined with magnetic resonance imaging and other fine imaging techniques to completely reconstruct the liver circulation through 3D printing, which will be a major breakthrough in the development of liver hemodynamics.