Evaluation of the uptake function of liver in rats with obstructive jaundice before and after relief from obstruction by superparamagnetic iron oxide-enhanced magnetic resonance imaging

Abstract

Abstract. The aim of this study was to investigate the changes in the uptake function of the liver in rats with obstructive jaundice prior to and following relief from obstructive jaundice, and to investigate whether superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) could be used to assess liver uptake function. In total, 40 male Sprague Dawley rats were randomly assigned into four groups: Obstructive jaundice, internal drainage, external drainage and sham surgery. The common bile ducts in the obstructive jaundice group were ligated. Internal drainage (ID) and external drainage (ED) groups were ligated, followed by internal drainage or external drainage, respectively. The T2 and T2* values of the liver parenchyma were measured. Liver sections were stained with Perls' Prussian blue, and hematoxylin and eosin. The number of SPIO-nanoparticle clusters was counted manually using a microscope. Total bilirubin of the blood was measured. Results showed that the T2 and T2* values and total bilirubin of the obstructive jaundice group were significantly higher compared to the other three groups. The number of SPIO-nanoparticle clusters in the obstructive jaundice group was significantly lower compared to the other three groups. In conclusion, obstructive jaundice suppresses liver uptake function in rats, which may be reversed by internal and external biliary drainage. However, no significant difference was found between the therapeutic effect of ID and ED on liver uptake function. Thus, SPIO-enhanced MRI may be used to evaluate the uptake function of the liver.

Monitoring of impaired phagocytic function of Kupffer cells in an obstructive cholangitis rat model using superparamagnetic iron oxide MRI and contrast-enhanced ultrasound

“…Second, we did not perform tissue harvest at every time point in order to evaluate the KC and KC fraction. However, pathologic findings on the four-week follow-up showed a prominent increase of KC in the CBDL group compared to that of the control group, which are similar results to those of previous studies (10,12,14,23). Third, we could not directly compare the KC phagocytic function between the CBDL group and the control rats in vitro.…”

“…This paradoxical temporary increase of the parenchymal enhancement could be explained by the fact that obstructive cholangitis causes bacterial translocation to bile-duct and portal bacteremia so that KC’s immune activation arises and the number and phagocytic activity of KCs initially increase (2,5,7,8). Eventually, both the mean RSL values and the KPE values of the CBDL group markedly decreased than those of the period-matched control group at four weeks, which is similar to the results in the previous studies that evaluated SPIO-MRI (10,12,23) or CEUS (13–15). As disease aggravates bacterial clearance by bile flow is nearly stopped, inflammatory cytokines and lipopolysaccharides are accumulated in bile fluid and immune-regulatory effects of bile acid are blunted, thus causing severe impairment of KC’s both phagocytic and intracellular killing functions (2,5,7,8,25).…”

“…Kupffer cells (KC) are tissue resident macrophages of the liver, having phagocytic ability to remove foreign materials such as bacteria, viruses, apoptotic cell debris, and cytokines (6)(7)(8). Although the pathophysiological mechanism is not fully understood, recent research suggested that KC have an important role in the host defense in cholangitis (4,5,(8)(9)(10). Previous studies have postulated that cholangitis is caused by increased biliary pressure, increased bacterial translocation, and impaired KC function (4,(6)(7)(8)11).…”

“…More specifically, phagocytic clearance and killing efficiency of KC are decreased in cholangitis, and thus promoting bacterial translocation and the progression of bacteremia (5,11). In animal obstructive cholangitis or non-alcoholic fatty liver disease models, KC seem to have an impaired phagocytic function which leads to a defective clearance of toxic substances such as bacteria, microbial debris, and various types of endotoxin (10,(12)(13)(14)(15).…”

“…Phagocytosis of ultrasound contrast agent by KC are key mechanism of delayed ultrasonic enhancement of liver parenchyma, which enables non-invasive monitoring of KC function by contrast-enhanced ultrasonography (CEUS) (13,(20)(21)(22). There have been several studies which depicted the impaired phagocytic function of KC using SPIO-MRI (10,12,23) or CEUS (13,15). However, to the best of our knowledge, there have been no studies comparing two independent imaging modalities at the same time.…”