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The purpose of this study was to compare measurements of hepatic tissue blood flow (TBF) calculated by xenon and perfusion CT. Seven patients with normal liver and eight with chronic liver disease underwent both xenon and perfusion CT. During xenon CT examinations, serial abdominal CT scans were obtained every minute before and during 4 min of nonradioactive 25% (v/v) xenon gas inhalation and 5 min of administration of oxygen-rich air. Hepatic arterial and portal venous TBF were measured separately with a special imaging system using the Kety-Schmidt expression based on the Fick principle (AZ-7000W; Anzai Medical Co.). The hepatic arterial fraction (HAF) was calculated as follows: [hepatic arterial TBF/(hepatic arterial TBF + portal venous TBF)]. During perfusion CT examinations, total hepatic TBF and HAF were also calculated from the enhanced CT cine image data on a workstation using a commercially available software package based on a deconvolution algorithm (CT Perfusion 3 GE Healthcare, USA). Total hepatic TBF measured by xenon and perfusion CT was 82.9+/-15 and 82.8+/-18 ml/min/100 g, respectively. The measured values by the two techniques showed a significant correlation (R (2)= 0.657, P < 0.05). HAF measured by xenon and perfusion CT was 26.6+/-11 and 21.8+/-13%, respectively. The measured values by the two techniques also showed a significant correlation (R (2)= 0.869, P < 0.05). We conclude that there was a good correlation between hepatic TBF quantified by xenon CT and perfusion CT.

Background Although many factors and molecules that are closely associated with non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) have been reported, the role of endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) in the pathogenesis of NAFLD/NASH remains unclear. We therefore investigated the role of eNOS-derived NO in NAFLD pathogenesis using systemic eNOS -knockout mice fed a high-fat diet. Methods eNOS -knockout and wild-type mice were fed a basal diet or a high-fat diet for 12 weeks. Lipid accumulation and inflammation were evaluated in the liver, and various factors that are closely associated with NAFLD/NASH and hepatic tissue blood flow were analyzed. Results Lipid accumulation and inflammation were more extensive in the liver and lipid accumulation was less extensive in the visceral fat tissue in eNOS -knockout mice, compared with wild-type mice, after 12 weeks of being fed a high-fat diet. While systemic insulin resistance was comparable between the eNOS -knockout and wild-type mice fed a high-fat diet, hepatic tissue blood flow was significantly suppressed in the eNOS -knockout mice, compared with the wild-type mice, in mice fed a high-fat diet. The microsomal triglyceride transfer protein activity was down-regulated in eNOS -knockout mice, compared with wild-type mice, in mice fed a high-fat diet. Conclusions A deficiency of eNOS-derived NO may exacerbate the early-stage of NASH pathogenesis by changing the fat distribution in a mouse model via the regulation of hepatic tissue blood flow.

Introduction Effective noninvasive tests that can distinguish early-stage nonalcoholic steatohepatitis (NASH) from simple steatosis (SS) have long been sought. Our aim was to determine the possibility of noninvasively distinguishing early-stage NASH from SS. Materials and methods We used Fick’s principle and the Kety–Schmidt equation to determine the hepatic tissue blood flow (TBF) in 65 NASH patients who underwent xenon computed tomography (Xe-CT). We calculated the lambda value (LV), i.e., Xe gas solubility coefficient, in liver and blood. We assessed the histological severity of fatty changes and fibrosis on the basis of Brunt’s classification. Liver biopsy revealed SS in 9 patients and NASH in 56 patients. NASH stages 1 and 2 were classified as early-stage NASH (Ea-NASH; 38 patients) and stages 3 and 4 as advanced-stage NASH (Ad-NASH; 18 patients). We evaluated the differences in LV and TBF among the 3 groups. Results LV was significantly lower in the Ad-NASH group than in the SS and Ea-NASH groups. Portal venous TBF (PVTBF) was significantly lower in the Ea-NASH group than in the SS group, and PVTBF was lower in the Ad-NASH group than in the Ea-NASH group. Total hepatic TBF (THTBF) was significantly different between the SS and Ea-NASH groups and between the SS and Ad-NASH groups. Conclusions In conclusion, measurements of TBF and LV are useful for evaluating the pathophysiological progression of NASH. In addition, these measurements can facilitate the differential diagnosis of SS and Ea-NASH, which may not be distinguishable by other means.

Background Xenon computed tomography (Xe-CT) provides quantitative information on tissue blood flow (TBF). In the present study, Xe-CT was performed in patients with esophagogastric varices (EGV) before and after endoscopic injection sclerotherapy (EIS) to evaluate hepatic blood flow (HBF), hepatic arterial TBF (HATBF) and portal venous TBF (PVTBF). Methods Subjects comprised of 88 patients with EGV (49 men, 39 women, average age 65.8 ± 11.5 years, median age 68 years, 30–86 years) and liver cirrhosis related to either hepatitis C virus (C) ( n  = 33), hepatitis B virus (B) ( n  = 3), alcohol (AL) ( n  = 22), AL + C ( n  = 7), AL + B ( n  = 1), B + C + AL ( n  = 1), nonalcoholic steatohepatitis (NASH) ( n  = 4), autoimmune hepatitis (AIH) ( n  = 5), primary biliary cirrhosis (PBC) ( n  = 2), or cryptogenic ( n  = 10) were enrolled. All patients, who were enrolled in this study, were performed EIS for prophylaxis. Xe-CT and measurement of the retention rate of indocyanine green 15 min after administration (ICG R15) were performed before and after EIS. Total hepatic TBF (THTBF) and PVTBF/HATBF ratio (P/A) were also calculated. Results PVTBF, HATBF, THTBF, P/A and ICG R15 before EIS were 28.3 ± 8.91, 22.5 ± 14.4 and 50.8 ± 17.6 ml/100 ml/min, 1.62 ± 0.71 and 28.8 ± 12.7 %, respectively and those after EIS were 31.9 ± 10.0, 19.3 ± 11.6, and 51.2 ± 17.0 ml/100 ml/min, 1.92 ± 0.84 and 23.6 ± 11.3 %, respectively. PVTBF and P/A after EIS were significantly higher than those before EIS ( p  = 0.00444, p  = 0.0179, respectively), and HATBF and ICG R15 after EIS were significantly lower than those before EIS ( p  = 0.00129, p  < 0.001, respectively). Conclusions Xenon computed tomography showed that PVTBF increased after EIS for EGV and HATBF decreased in response to an increase in PVTBF.

Aims: The present study evaluated the utility of xenon computed tomography (Xe-CT) as a noninvasive diagnostic procedure for the measurement of hepatic tissue blood flow (TBF) in patients with nonalcoholic fatty liver disease (NAFLD) or chronic hepatitis C (CH-C). Methods: Xe-CT was performed in 93 patients with NAFLD and in 109 patients with CH-C. Subjects were classified into one of three groups, based on fibrosis stage: group 1, no bridging fibrosis; group 2, bridging fibrosis; and group 3, liver cirrhosis. Correlations between hepatic TBFs in each fibrosis stage were examined. Results: In group 1, portal venous TBF (PVTBF), hepatic arterial (HATBF), and total hepatic TBF (THTBF) were significantly lower in patients with in nonalcoholic steatohepatitis (NASH) than in those with CH-C (p < 0.001, p < 0.05, p < 0.001, respectively). In group 2, PVTBF and THTBF were significantly lower in patients with in NASH than in those with CH-C (p < 0.001, p < 0.05, respectively). In group 3, hepatic TBFs were not significantly different when comparing patients with NASH and those with CH-C. Conclusions: PVTBF decreased due to fat infiltration. Therefore, hemodynamic changes occur relatively earlier in NAFLD than in CH-C. Patients with NASH should be monitored carefully for portal hypertensive complications in the early fibrosis stage.

We evaluated the role of magnetic resonance (MR) imaging with gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA), in estimating regional liver function in a rat ischemia-reperfusion model. Ischemic liver damage was induced in the right lobe by vascular clamping for 0 (sham), 30 (I-30), 60 (I-60), and 90 min (I-90 group). The ischemic lobes in the I-60 and I-90 groups was clearly visualized as a high intensity area in the T1 images at late phase of Gd-EOB-DTPA enhancement, Moreover, the T1/2 of signal intensity in ischemic lobes significantly correlated with the duration of vascular clamping. We also observed significant correlation between T1/2 and ATP concentration in the liver tissue (r = -0.719, P = 0.04). Our results indicate that MR imaging with Gd-EOB-DTPA is useful for evaluation of regional liver function in rats.

Background/Aim: Liver regeneration is a finely tuned process that is closely regulated by multiple cell cycle steps. Although the portal blood flow affects liver regeneration, the molecular mechanism by which the blood flow regulates gene expression and liver function is largely unknown. The aim of this study was to investigate the molecular effect of portal blood flow on hepatocyte proliferation and gene regulation during liver regeneration. Materials and Methods: We developed a simple surgical rat model to investigate the relation between portal blood flow and liver regeneration by partially ligating the portal trunk with 8-0 Proline sutures under microscopy to reduce the blood flow by 40%. We investigated recovery of liver volume, DNA synthesis, and gene expression associated with cell cycle regulators, comparing partially hepatectomized (PH) rats without (PH group; n = 30) and with partial portal ligation (PHPL group; n = 30) for 7 days after the operation. Results: The hepatic tissue blood flow and the recovery ratio between liver weight and body weight in the PHPL group were significantly lower than in the PH group after hepatectomy. The peak 5-bromo-2′-deoxyuridine labeling index in the PHPL group was delayed and weak compared with the PH group. The expression of CT-1 and cyclin D, E, and B mRNAs indicated that the liver regeneration in the PHPL group was delayed and weak. In addition, there was reciprocal expression of C/EBPα and C/EBPβ mRNAs, an observation supported by their nuclear protein levels. Furthermore, the cytochrome P-450 protein level in the PHPL group was higher than that in the PH group 1 day after hepatectomy. Conclusion: The portal blood flow regulates the activity of liver regeneration and the gene expression associated with cell cycle regulators, while the functions are maintained.

The purpose of this study was to investigate whether regional liver damage could be detected by means of enhanced MR imaging with a superparamagnetic iron oxide (SH U 555A) in an ischemia-reperfusion model of rat liver. Ischemic liver damage was induced in the right lobe by vascular clamping for 0 (sham), 30 (I-30), 60 (I-60), and 90 minutes (I-90). There was no significant difference in relative enhancement (RE) between the ischemic and nonischemic lobes in the sham, I-30 and I-60 groups, while RE of the ischemic lobe was significantly lower than that of its nonischemic counterpart in the I-90 group as seen on SH U 555A enhanced proton density spin echo images (P < 0.05). Histological examination revealed that iron deposits were significantly smaller in the ischemic than the nonischemic lobe in the I-90 group (P < 0.05), although there was no significant difference in the number of Kupffer cells. Our results indicate that severe regional liver damage can be evaluated by MR imaging with SH U 555A.

Artificial vascular graft (AVG) fistula is widely used for hemodialysis treatment in patients with renal failure. However, it has poor elasticity and compliance, leading to stenosis and thrombosis. The ideal artificial blood vessel for dialysis should replicate the structure and components of a real artery, which is primarily maintained by collagen in the extracellular matrix (ECM) of arterial cells. Studies have revealed that in hepatitis B virus (HBV)-induced liver fibrosis, hepatic stellate cells (HSCs) become hyperactive and produce excessive ECM fibers. Furthermore, mechanical stimulation can encourage ECM secretion and remodeling of a fiber structure. Based on the above factors, we transfected HSCs with the hepatitis B viral X ( HBX ) gene for simulating the process of HBV infection. Subsequently, these HBX -HSCs were implanted into a polycaprolactone-polyurethane (PCL-PU) bilayer scaffold in which the inner layer is dense and the outer layer consists of pores, which was mechanically stimulated to promote the secretion of collagen nanofiber from the HBX -HSCs and to facilitate crosslinking with the scaffold. We obtained an ECM-PCL-PU composite bionic blood vessel that could act as access for dialysis after decellularization. Then, the vessel scaffold was implanted into a rabbit’s neck arteriovenous fistula model. It exhibited strong tensile strength and smooth blood flow and formed autologous blood vessels in the rabbit’s body. Our study demonstrates the use of human cells to create biomimetic dialysis blood vessels, providing a novel approach for creating clinical vascular access for dialysis.

Propagation-based phase-contrast computed micro-tomography (PPCT) dominates the non-destructive, three-dimensional inner-structure measurement in synchrotron-based biomedical research due to its simple experimental setup. To quantitatively visualize tiny density variations in soft tissues and organs closely related to early pathological morphology, an experimental study of synchrotron-based X-ray PPCT combined with generalized phase and attenuation duality (PAD) phase retrieval was implemented with the hepatic echinococcosis (HE) infection rat model at different stages. We quantitatively analyzed and evaluated the different pathological characterizations of hepatic echinococcosis during the development of this disease via our PAD-based PPCT and especially provided evidence that hepatic alveolar echinococcosis invades the liver tissue and spreads through blood flow systems with abundant blood supply in the early stage. Additionally, the infiltration of tiny vesicles in HE lesions can be clearly observed by our PAD-PPCT technique due to the striking contrast-to-noise ratio (CNR) and mass density resolution, which cannot be found by the medical imaging techniques, such as magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound, in hospitals. The results demonstrated that our PAD-PPCT technique has a great potential for indicating the subtle structural information of pathological changes in soft biomedical specimens, especially helpful for the research of early micro-morphology of diseases.