Hepatic Enhancement Research Articles

Amelioration of nonalcoholic fatty liver disease by swertiamarin in fructose-fed mice

BackgroundNonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease. Swertia bimaculata (Sieb. et Zucc.) Hook. Thoms.ex Clarke, a glabrous or procumbent perennial herb, is a traditional herb medicine. Swertiamarin, a secoiridoid glycoside, is a representative ingredient in this medical plant crude extract and shows antidiabetic and antihyperlipidaemic activities and protective effect against hepatic injury. PurposeThe present study aimed to determine whether swertiamarin can attenuate NAFLD in fructose-fed mice. MethodsHealthy male mice freely drank water containing 10% fructose for 12 consecutive weeks, whereas animals in those swertiamarin tested groups received different doses of swertiamarin (25, 50 and 100 mg/kg) by intragastric administration once a day from the ninth week to the twelfth week. ResultsAt the end of the experiment, fructose-fed mice administrated with swertiamarin showed low levels of serum glucose, triglycerides, uric acid, alanine aminotransferase and aspartate transaminase. Histological examinations suggested the alleviation of hepatic ballooning degeneration and steatosis by swertiamarin treatment. Moreover, swertiamarin administration mitigated hepatic oxidative stress along with decreases of hepatic pro-inflammation cytokines, which was associated with decrease of hepatic xanthine oxidase (XO) activity and enhancements of anti-oxidant defense system enzymes, as well as activation of nuclear factor E2-related factor 2 (Nrf2) in fructose-fed mice. In addition, swertiamarin down-regulated expression of sterol-regulatory element-binding protein-1 (SREBP-1), fatty acid synthase (FAS) and acetyl-CoA carboxylase 1 (ACC1) in liver of fructose-fed mice. ConclusionThe present study demonstrates that swertiamarin alleviates NAFLD and metabolic alterations in fructose-fed mice.

Contrast-enhanced ultrasonography is a feasible technique for quantifying hepatic microvascular perfusion in dogs with extrahepatic congenital portosystemic shunts.

Extrahepatic-congenital portosystemic shunt is a vascular anomaly that connects the portal vein to the systemic circulation and leads to a change in hepatic microvascular perfusion. However, an assessment of hepatic microvascular perfusion is limited by conventional diagnostic modalities. The aim of this prospective, exploratory study was to assess hepatic microvascular perfusion in dogs with extrahepatic-congenital portosystemic shunt using contrast-enhanced ultrasonography (CEUS) using perfluorobutane (Sonazoid® ). A total of 17 dogs were included, eight healthy dogs and nine with extrahepatic-congenital portosystemic shunt. The time-to-peak (TTP), rising time (RT), and rising rate (RR) in the hepatic artery, portal vein, and hepatic parenchyma, as well as the portal vein-to-hepatic parenchyma transit time (ΔHP-PV) measured from time-intensity curve on CEUS were compared between healthy and extrahepatic-congenital portosystemic shunt dogs. The RT of the hepatic artery in extrahepatic-congenital portosystemic shunt dogs was significantly earlier than in healthy dogs (P=0.0153). The TTP and RT of the hepatic parenchyma were significantly earlier in extrahepatic-congenital portosystemic shunt dogs than in healthy dogs (P=0.0018 and P=0.0024, respectively). ΔHP-PV was significantly shorter in extrahepatic-congenital portosystemic shunt dogs than in healthy dogs (P=0.0018). CEUS effectively revealed changes in hepatic microvascular perfusion including hepatic artery, portal vein, and hepatic parenchyma simultaneously in extrahepatic-congenital portosystemic shunt dogs. Rapid hepatic artery and hepatic parenchyma enhancements may reflect a compensatory increase in hepatic artery blood flow (arterialization) caused by a decrease in portal vein blood flow and may be used as an additional diagnostic test to distinguish extrahepatic-congenital portosystemic shunt dogs from healthy dogs.

Pathological Hepatic Contrast-Enhanced Ultrasound (CEUS) Pattern in Patients Undergoing Allogeneic Stem Cell Transplantation (allo-SCT)

Purpose:Veno-occlusive disease (VOD) is a severe complication of allogenic stem cell transplantation (allo-SCT). The diagnosis of VOD is often difficult and relies on clinical assessment and clinical chemistry. B-mode ultrasound (B-US) and color doppler sonography (CDS) are only of limited additional diagnostic value. We recently observed a patient with VOD, who revealed a pathologic hepatic CEUS pattern (reduced portal venous and parenchymal enhancement). Because CEUS is a measure of perfusion, this suggested that CEUS could potentially be a novel diagnostic tool of VOD (Trenker et al. Bone Marrow Transplantation, 2018). The aim of the present study was to prospectively analyze the hepatic CEUS pattern prior and post allo-SCT and correlate these results with the pre allo-SCT VOD-risk-score, clinical findings suggestive of VOD, as well as with standard B-US and CDS findings.Patient/ Material/ Methods:From April to July 2018 13 consecutive patients, who underwent allo-SCT (n=6 AML, n=5 ALL, n=1 MDS, n=1 NHL) and had at least one VOD risk factor (Bu/Cy therapy, TBI, mismatched/haplo donor, prior liver damage, re-allo-SCT) were included. All patients received VOD prophylaxes with 300 IU unfractionated heparin /h. Elevated transaminases, bilirubin, g-GT, ascites, hepatomegaly, splenomegaly, reduced portal flow, weight gain >5 KG, as well as abdominal pain were considered as clinical signs of VOD and assessed prior and during allo-SCT. B-US and CEUS were performed at defined times before and after allo-SCT (day (d) +10 and at leucocyte engraftment (LE). The one-minute hepatic enhancement (OMHE) in CEUS (Fig. 1A, 1B) was standardized to splenic enhancement as in vivo reference by two independent investigators and retrospectively quantitated using optical density (OD) measurements software (QuantityOne) (Fig. 1C). A hypo-OMHE in CEUS was arbitrarily defined as pathological (PE), if the optical density of the liver was less than 90% compared to mean optical density of the spleen.Results:Eight of 13 (61.5%) patients had a pathological OMHE in CEUS (1 patient only prior-, 1 patient prior and post, and 6 only post-allo-SCT), suggestive of malperfusion. The median optical density in the pathological OMHE-group was 56.46% (range 34.5-81.4) and thus significantly lower than in the non- pathological group (105.6%, range 90.2-125.9) (p<0.0001) (Fig. 1D). Interestingly, a pathological OD in OMHE was significantly associated with a higher median number of variables indicating clinical signs of VOD (3.25; range 1 to 6 signs) vs. non-pathological OD (0.6; range 0 to 1 signs) (p=0.013). Patients with a pathological OD had also a significantly higher number of VOD-associated B-US and CDS findings when compared to patients with a non-pathological OD (1.5 vs 0.4 signs, p=0.0241). However, the number of pre-treatment VOD-risk factors in the pathological vs. non-pathological OD group was not significantly different.Conclusion:Patients undergoing allo-SCT frequently show a pathological hepatic CEUS pattern, which can be quantified by OD measurement and is suggestive of preclinical VOD or yet undefined hepatic pathologies. Further studies to evaluate the clinical significance of a PE with regard to VOD development and risk of GvHD are ongoing. [Display omitted] DisclosuresBurchert:Pfizer: Honoraria; Bayer: Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; AOP Orphan: Honoraria, Research Funding; Novartis: Research Funding. Görg:Bracco imaging: Other: Bracco imaging supports workshop for contrast enhanced ultrasound for education at the university hospital in Marburg.

Continuous Hepatic Arterial Multiphase Magnetic Resonance Imaging During Free-Breathing.

The aim of this study was to evaluate the feasibility of a prototype volume-interpolated breath-hold examination (VIBE) sequence using compressed sensing (VIBECS) for rapid multiphase arterial magnetic resonance imaging (MRI) at different temporal resolution during free-breathing in comparison with a conventional breath-hold approach (VIBESTD). A total of 40 patients with liver malignancies were prospectively included in this study and underwent contrast-enhanced liver MRI at 1.5 T to evaluate the performance of VIBECS for rapid arterial multiphase imaging. An additional 40 patients examined with a VIBESTD were included serving as standard of reference. The VIBECS study cohort was subdivided into 2 groups (each n = 20). In both groups, VIBECS was continuously acquired for 60 seconds starting with the contrast agent administration (group A, temporal resolution 4 seconds; group B, temporal resolution 8 seconds). Subsequently, the time point with the subjectively best image quality was selected and defined as hepatic arterial dominant (HAD) phase. Overall image quality, lesion conspicuity, vessel contrast, and artifacts of HAD phase were assessed by 2 radiologists independently on a 5-point Likert scale (5 = excellent) and compared with arterial phase images of VIBESTD. In addition, signal attenuation/time curves of VIBECS were plotted for each patient to quantify the hepatic arterial enhancement. No patients were excluded and all HAD phases were reliably recorded in the investigated VIBECS cohort. Most commonly, HAD was observed at the ninth time point (36 seconds after intravenous contrast injection) in group A and at the fifth time point (40 seconds after intravenous contrast injection) in group B. Timing with VIBESTD was only adequate in 65% (26/40). Image quality, lesion conspicuity, and vessel contrast were good to excellent without significant differences between both VIBECS groups (P ≥ 0.2) and with significantly higher reading scores as compared with VIBESTD with respect to lesion conspicuity (P ≤ 0.006) and image quality (group B; P < 0.001). VIBECS showed reconstruction artifacts, which were significantly higher in group A (P = 0.001). Mean peak arterial enhancement was observed at the ninth time point (36 seconds) in group A and at the sixth (48 seconds) in group B. VIBECS allows for robust multiphase arterial imaging during free-breathing at high spatial and temporal resolution (preferably 8 seconds) with improved image quality and lesion conspicuity as compared with VIBESTD.

An Uncommon Cause of Ascites: A Combination of Budd Chiari Syndrome and Secondary Bacterial Peritonitis in a Postpartum Patient

Acute Budd Chiari syndrome usually presents with new onset ascites and hepatic dysfunction, at times acute liver failure. Here we present an interesting case of secondary bacterial peritonitis and recurrent Budd Chiari syndrome in a patient with Paroxysmal Nocturnal Hemoglobinuria (PNH) in immediate post partum period. Our patient is 26 year old, diagnosed with Budd Chiari syndrome and PNH, 9 years ago who is post partum after a vaginal delivery. Post partum hemorrhage (PPH) complicated her course requiring Bakri balloon tamponade. Few days post partum she developed abdominal distention, fever, new onset ascites, hepatomegaly, and diffuse abdominal tenderness. There was no purulent vaginal discharge. Lab work showed leukocytosis (5.4 K/CUMM), elevated from her normal baseline of 2-3(secondary to aplastic anemia/PNH). Liver enzymes were normal except ALP of 140 IU/L. Paracentesis revealed bacterial peritonitis with absolute neutrophil count of 3273. She was started on appropriate empiric antibiotics. CT scan showed new onset marked hepatomegaly and moderate ascites. In the setting of PNH (pro-coagulant state), suspicion for a recurrent Budd Chiari syndrome was high. Even though the Doppler ultrasound was negative for hepatic/portal vein thrombosis, CT abdomen with contrast in venous phase revealed heterogeneous hepatic enhancement, predominant left hepatic lobe enlargement and non visualization of the hepatic veins; consistent with Budd Chiari Syndrome. We ruled out chronic Budd Chiari Syndrome, although we acknowledge that this can't be done with 100% certainty (Magnetic Resonance angiogram in 2011 did not reveal any features of Budd Chiari syndrome, nor did the periodic obstetric ultrasounds reveal any ascites prepartum). In patients with new onset ascites and hepatomegaly, Budd Chiari syndrome is an important differential in setting of PNH. This patient was at risk for post partum endometritis (in setting of balloon tamponade) which could lead to bacterial peritonitis due to micro-perforations. Considering the purulent ascites with absolute neutrophil count of 3273, we believe a combination of the above two pathologies resulted in this clinical presentation. For Budd Chiari syndrome, duplex imaging studies may not be conclusive, and in cases with high suspicion CT done in venous phase maybe helpful. The ascitic fluid cultures may remain negative as in our case, requiring empiric antibiotic coverage.

Improving hepatic mitochondrial biogenesis as a postulated mechanism for the antidiabetic effect of Spirulina platensis in comparison with metformin.

Various nutritional and medicinal potencies have been accredited to metabolites from the cyanobacteria, Spirulina platensis (Arthrospira platensis) sp. Hence, our study was designed to examine whether the Spirulina supplementation would possess beneficial effects in type 2 diabetes mellitus (T2DM) in comparison with metformin. High-fat diet/low-dose streptozotocin (HFD/STZ) model was adopted and the diabetic rats were orally treated with metformin (200 mg/kg) or Spirulina (250 or 500 or 750 mg/kg) for 30 days. Spirulina ameliorated the HFD/STZ-induced elevation of fasting blood glucose, insulin, and hepatic enzymes. Moreover, Spirulina successfully rectified disrupted serum lipid profile and exhibited an anti-inflammatory effect via tumor necrosis factor-α and adiponectin modulation. On the molecular level, Spirulina reduced the expression of hepatic sterol regulatory element binding protein-1c (SREBP-1c), confirming its lipotropic effect. Furthermore, Spirulina amended compromised hepatic mitochondrial biogenesis signaling by significantly increasing peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), mitochondrial transcription factor A (Tfam), and mitochondrial DNA (mtDNA) copy number. On almost all parameters, the highest dose of Spirulina showed the best effects, which were comparable to that of metformin. To our knowledge, our study is the first to attribute the various aspects of the effect of Spirulina to the SREBP-1c and PGC-1α/Tfam/mtDNA pathways in liver. The present results clearly proved that Spirulina modulated glucose/lipid profile and exhibited prominent anti-inflammatory properties through SREBP-1c inhibition and hepatic mitochondrial biogenesis enhancement. Thus, Spirulina can be considered as an add-on to conventional antidiabetic agents and might influence the whole dynamics of the therapeutic approaches in T2DM.

Gadoxetic acid-enhanced MRI of transient hepatic enhancement differences: Another cause of hypointense observation on hepatobiliary phase

PurposeTo retrospectively determine the frequency, natural history and factors associated with the presence of transient hepatic enhancement difference showing hypointensity on hepatobiliary phase images of gadoxetic acid-enhanced MRI. Materials and methodsGadoxetic acid-enhanced MRI of 125 patients (91 men; 34 women) with transient hepatic enhancement difference were retrospectively reviewed. Three readers qualitatively and quantitatively evaluated MR imaging features and evolution at follow up. The Chi-square test, Fisher’s exact test and Kruskall-Wallis rank test were used for statistical analysis. ResultsTransient hepatic enhancement difference were hypointense on hepatobiliary phase images in 20 of 125 cases (16%). At univariate analysis there was association with wedge-shape morphology (p < 0.001), size ≥21 mm (p < 0.001), hyperintensity on T2-weighted imaging (p < 0.001), restricted diffusion (p < 0.001) and previous treatment (p < 0.005). At multivariate analysis, the following factors were associated: previous treatment (p < 0.05), hyperintensity on T2-weighted imaging (p < 0.001) and size ≥21 mm (p < 0.001). Of 12 patients with hypointense transient hepatic enhancement difference on hepatobiliary phase images who had follow-up MRI, nine showed reduction in size. ConclusionTransient hepatic enhancement difference observations showing hypointensity on hepatobiliary phase images of gadoxetic acid-enhanced MRI are not infrequent and may shrink at follow-up. They are more likely associated with size ≥21 mm, hyperintensity on T2-weighted images and previous treatment of adjacent tumor.

A New Model for MR Evaluation of Liver Function with Gadoxetic Acid, Including Both Uptake and Excretion.

Most existing models that are in use to model hepatic function through assessment of hepatic gadoxetic acid enhancement kinetics do not consider quantitative measures of gadoxetic excretion. We developed a model that allows a simultaneous quantitation of uptake and excretion of liver specific contrast agents. The aim was to improve the assessment of hepatic synthetic function, and provide quantitative measures of hepatic excretion function. Sixteen patients underwent dynamic T1-weighted turbo gradient echo imaging at 1.5 T prior and after bolus injection of gadoxetic acid at 0.1 ml/kg. DCE-images were obtained for 30 min after injection. A dual-inlet two-compartment model was then used to fit the measured liver signal values. Four tissue parameters (extracellular volume fraction, arterial flow fraction, uptake rate and excretion half-time) were extracted for each liver segment. The proposed model provided a good fit to acquired data. Mean values for arterial flow fraction (0.08+-0.04), extracellular volume (0.20±0.08) and uptake rate (4.02 ±1.32 /100 ml/min) were comparable to those obtained with the conventional model (0.08±0.05, 0.21±0.12, and 4.93±1.74), but exhibited significantly less variation and improved fit quality. The proposed model is more accurate than existing conventional models and provides an additional excretion parameter. • Models of hepatic contrast agent uptake can be extended to include excretion. • Including an additional excretion parameter improves accuracy of the model. • Standard diagnostic sequences can be extended to incorporate the model.

Intrauterine programming mechanism for hypercholesterolemia in prenatal caffeine‐exposed female adult rat offspring

Clinical and animal studies have indicated that hypercholesterolemia and its associated diseases have intrauterine developmental origins. Our previous studies showed that prenatal caffeine exposure (PCE) led to fetal overexposure to maternal glucocorticoids (GCs) and increased serum total cholesterol levels in adult rat offspring. This study further confirms the intrauterine programming of PCE-induced hypercholesterolemia in female adult rat offspring. Pregnant Wistar rats were intragastrically administered caffeine (30, 60, and 120 mg/kg/d) from gestational day (GD)9 to 20. Female rat offspring were euthanized at GD20 and postnatal wk 12; several adult rat offspring were additionally subjected to ice-water swimming stimulation to induce chronic stress prior to death. The effects of GCs on cholesterol metabolism and epigenetic regulation were verified using the L02 cell line. The results showed that PCE induced hypercholesterolemia in adult offspring, which manifested as significantly higher levels of serum total cholesterol and LDL cholesterol (LDL-C) as well as higher ratios of LDL-C/HDL cholesterol. We further found that the cholesterol levels were increased in fetal livers but were decreased in fetal blood, accompanied by increased maternal blood cholesterol levels and reduced placental cholesterol transport. Furthermore, analysis of PCE offspring in the uterus and in a postnatal basal/chronic stress state and the results of in vitro experiments showed that hepatic cholesterol metabolism underwent GC-dependent changes and was associated with cholesterol synthase via abnormalities in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) histone acetylation. We concluded that, to compensate for intrauterine placentally derived decreases in fetal blood cholesterol levels, high intrauterine GC levels activated fetal hepatic CCAAT enhancer binding protein α signaling and down-regulated Sirtuin1 expression, which mediated the high levels of histone acetylation ( via H3K9ac and H3K14ac) and expression of HMGCR. This GC-dependent cholesterol metabolism programming effect was sustained through adulthood, leading to the occurrence of hypercholesterolemia.-Xu, D., Luo, H. W., Hu, W., Hu, S. W., Yuan, C., Wang, G. H., Zhang, L., Yu, H., Magdalou, J., Chen, L. B., Wang, H. Intrauterine programming mechanism for hypercholesterolemia in prenatal caffeine-exposed female adult rat offspring.

Best Protocol for Combined Contrast-Enhanced Thoracic and Abdominal CT for Lung Cancer: A Single-Institution Randomized Crossover Clinical Trial.

The purpose of this study was to evaluate the superiority of either of two protocols for combined contrast-enhanced thoracic and abdominal CT of patients with lung cancer by comparing contrast enhancement, contrast-related artifacts, image quality, and radiation dose. In this randomized controlled crossover clinical trial, 77 patients who underwent 203 CT examinations were enrolled. All patients underwent at least two examinations performed with both protocols. Protocol A consisted of two acquisitions: one 35-second delayed CT acquisition for the chest followed by a 70-second delayed abdominal acquisition. Protocol B was a single 60-second delayed acquisition covering the chest and the abdomen. Attenuation and noise of the aorta, pulmonary artery, and liver were measured. Contrast-related artifacts, mediastinal lymph node visualization, liver enhancement, and noise were visually scored. Dose-length product was recorded. Statistical analysis was performed by t and chi-square tests and kappa statistics. Contrast-related artifacts were more severe at all evaluated levels, and visualization of lymph node regions was statistically significantly worse with protocol A. There were no differences in enhancement or noise score of the liver. Tumor delineation and pleural findings were better evaluated with delayed phase images. Dose-length product was significantly higher with protocol A (645.0 vs 521.5 mGy · cm; p < 0.0001). A single 60-second delayed acquisition for thoracic and abdominal contrast-enhanced CT is associated with less contrast artifact and affords better visualization of lymph nodes at a lower radiation dose while acceptable vascular and hepatic contrast enhancement is maintained.

Contrast-enhanced computed tomography of the liver, gall bladder and urogenital tract in female red-eared terrapins (Trachemys scripta elegans)

The aim of the present study was to evaluate the feasibility of contrast-enhanced computed tomography for organ morphology and perfusion in five captive terrapins. Native scans were performed and afterwards an iodinated non-ionic contrast media was manually administered through the jugular vein catheter. Post-contrast CT scans were taken 20 (T&lt;sub&gt;20&lt;/sub&gt;), 60 (T&lt;sub&gt;60&lt;/sub&gt;) and 180 (T&lt;sub&gt;180&lt;/sub&gt;) seconds after the contrast medium administration. Maximum contrast enhancement of the kidneys and the liver was detected at T&lt;sub&gt;20&lt;/sub&gt; and T&lt;sub&gt;60&lt;/sub&gt;, respectively. The gall bladder content, the urinary bladder content and ovarian follicles were all without contrast enhancement in all five terrapins. Gall bladder wall thickness was 0.9 mm in all terrapins. Enhancement of the gall bladder wall in post-contrast studies was considered excellent, good or poor in two terrapins, two terrapins and one terrapin, respectively, with a mean score of 1.8 ± 0.84 over all contrast studies. Enhancement of the ureters in post-contrast studies was considered excellent in all terrapins in all contrast studies. Peak aortic enhancement was reached 20 seconds after contrast medium administration with the peak enhancement of 213.5 ± 41 HU in four terrapins and 560 HU in one terrapin. Peak hepatic vein enhancement after contrast medium administration was recorded 20 and 60 seconds in two and three terrapins, respectively. In conclusion, contrast-enhanced computed tomography proved to be a valuable method for clinical examination of the liver, gall bladder, kidneys, ureters, urinary bladder and ovarian follicles in red-eared terrapins.

Effect of catheter size and injection rate of contrast agent on enhancement and image quality for triple-phase helical computed tomography of the liver in small dogs.

Rapid contrast injection is recommended for triple-phase helical computed tomography (CT) of the liver. However, a large-gauge catheter is needed for faster contrast injection and this is not practical for small breed dogs or cats. The purpose of this crossover group study was to evaluate applicability of a lower injection rate with a small-gauge (G) catheter for triple-phase hepatic CT in small dogs. Triple-phase CT images were acquired for six beagle dogs using three protocols: an injection rate of 1.5 ml/s with a 24 G catheter, 3.0 ml/s with a 22 G catheter, and 4.5 ml/s with a 20 G catheter. Enhancement of the aorta, portal vein, and hepatic parenchyma was measured in each phase (arterial, portal, and delayed) and image quality was scored subjectively by two observers. Injection duration, time to scan delay, and time to peak enhancement were also recorded. Contrast injection duration decreased with a higher injection rate (n = 6, P ≤ 0.01), but time to peak enhancement and time to scan delay were not significantly affected by injection rates and catheter sizes. Contrast injection rate did not significantly affect aortic, portal, and hepatic enhancement. In addition, separation between each phase and quality of images was subjectively scored as good regardless of injection rate. Findings from the current study supported using an injection rate of 1.5 ml/s with a catheter size of 24 G for triple-phase hepatic CT in small dogs (weight < 12 kg).

Assessment of Cirrhotic Liver Enhancement With Multiphasic Computed Tomography Using a Faster Injection Rate, Late Arterial Phase, and Weight-Based Contrast Dosing

PurposeThis study aimed to update our liver computed tomography (CT) protocol according to published guidelines, and to quantitatively evaluate the effect of these modifications. MethodsThe modified liver CT protocol employed a faster injection rate (5 vs 3 mL/s), later arterial phase (20-second vs 10-second postbolus trigger), and weight-based dosing of iodinated contrast (1.7 mL/kg vs 100 mL fixed dose). Liver and vascular attenuation values were measured on CTs of patients with cirrhosis from January to September 2015 (old protocol, n = 49) and from October to December 2015 (modified protocol, n = 31). CTs were considered adequate if liver enhancement exceeded 50 Hounsfield units (HU) in portal venous phase, or when the unenhanced phase was unavailable, if a minimum iodine concentration of 500 mg I/kg was achieved. Attenuations and iodine concentrations were compared using the t test and the number of suboptimal studies was compared with Fisher's exact test. ResultsCTs acquired with the modified protocol demonstrated higher aortic (P = .001) and portal vein (P < .0001) attenuations in the arterial phase as well as greater hepatic attenuation on all postcontrast phases (P = .0006, .002, and .003 for arterial, venous, and equilibrium phases, respectively). Hepatic enhancement in the portal venous phase (61 ± 15 HU vs 51 ± 16 HU; P = .0282) and iodine concentrations (595 ± 88 mg I/kg vs 456 ± 112 mg I/kg; P < .0001) were improved, and the number of suboptimal studies was reduced from 57% to 23% (P = .01). ConclusionsA liver CT protocol with later arterial phase, faster injection rate, and weight-based dosing of intravenous contrast significantly improves liver enhancement and iodine concentrations in patients with cirrhosis, resulting in significantly fewer suboptimal studies.

Anti-obesogenic effects of WY14643 (PPAR-alpha agonist): Hepatic mitochondrial enhancement and suppressed lipogenic pathway in diet-induced obese mice

Non-alcoholic fatty liver disease (NAFLD) presents with growing prevalence worldwide, though its pharmacological treatment remains to be established. This study aimed to evaluate the effects of a PPAR-alpha agonist on liver tissue structure, ultrastructure, and metabolism, focusing on gene and protein expression of de novo lipogenesis and gluconeogenesis pathways, in diet-induced obese mice. Male C57BL/6 mice (three months old) received a control diet (C, 10% of lipids, n = 10) or a high-fat diet (HFD, 50% of lipids, n = 10) for ten weeks. These groups were subdivided to receive the treatment (n = 5 per group): C, C-alpha (PPAR-alpha agonist, 2.5 mg/kg/day mixed in the control diet), HFD and HFD-alpha group (PPAR-alpha agonist, 2.5 mg/kg/day mixed in the HFD). The effects were compared with biometrical, biochemical, molecular biology and transmission electron microscopy (TEM) analyses. HFD showed greater body mass (BM) and insulinemia than C, both of which were tackled by the treatment in the HFD-alpha group. Increased hepatic protein expression of glucose-6-phosphatase, CHREBP and gene expression of PEPCK in HFD points to increased gluconeogenesis. Treatment rescued these parameters in the HFD-alpha group, eliciting a reduced hepatic glucose output, confirmed by the smaller GLUT2 expression in HFD-alpha than in HFD. Conversely, favored de novo lipogenesis was found in the HFD group by the increased expression of PPAR-gamma, and its target gene SREBP-1, FAS and GK when compared to C. The treatment yielded a marked reduction in the expression of all lipogenic factors. TEM analyses showed a greater numerical density of mitochondria per area of tissue in treated than in untreated groups, suggesting an increase in beta-oxidation and the consequent NAFLD control. PPAR-alpha activation reduced BM and treated insulin resistance (IR) and NAFLD by increasing the number of mitochondria and reducing hepatic gluconeogenesis and de novo lipogenesis protein and gene expressions in a murine obesity model.

Self-gated 4D-MRI of the liver: Initial clinical results of continuous multiphase imaging of hepatic enhancement.

To evaluate the feasibility of a self-gated free-breathing volume-interpolated breath-hold examination (VIBE) sequence using compressed sensing (CS) for contrast-enhanced multiphase liver MRI. We identified 23 patients who underwent multiphase gadobutrol-enhanced liver magnetic resonance imaging (MRI) using 1) a prototype free-breathing VIBE sequence with respiratory self-gating and CS (VIBECS ), and 2) a standard breath-hold VIBE (VIBESTD ) on the same 1.5T scanner at two timepoints. VIBECS was continuously acquired for 128 seconds and a time-series of 16 timepoints was jointly reconstructed from the dataset. The unenhanced, arterial, portal-venous, and venous timepoints with the best image quality were selected and compared to the corresponding VIBESTD series serving as reference. Image quality was assessed qualitatively (image quality, sharpness, lesion conspicuity, vessel contrast, noise, motion/other artifacts; two readers independently; 5-point Likert scale; 5 = excellent) and quantitatively (vessel contrast [VC], coefficient-of-variation [CV]) Statistics were performed using Wilcoxon-sign-rank (ordinal) and paired t-test (continuous variables). Image quality and lesion conspicuity revealed no significant differences between the sequences (P ≥ 0.3). VIBESTD showed a tendency to higher motion artifacts (P ≥ 0.07). Image sharpness significantly increased in VIBECS as compared to VIBESTD (P ≤ 0.03). Arterial phase vessel contrast appeared significantly lower in VIBECS than in VIBESTD (P = 0.04). VIBECS showed reconstruction artifacts not present in VIBESTD (P = 0.001). Image noise was significantly lower in VIBECS than in VIBESTD (P ≤ 0.004). Arterial phase VC was significantly lower in VIBECS than in VIBESTD (P = 0.01). CV revealed no differences between sequences (P = 0.7). VIBECS is feasible for continuous free-breathing contrast-enhanced multiphase liver MRI, providing similar image quality and lesion conspicuity as VIBESTD . 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:459-467.

Budd Chiari syndrome presenting with hepatic transient mosaic enhancement pattern and treated with early transjugular intrahepatic portosystemic shunt

Budd Chiari syndrome (BCS) can present with ascites and with the so-called hepatic mosaic enhancement pattern (MEP) on CT and MR imaging, as well as other different diseases. However, no previously cases of transient MEP and BCS were reported. Transjugular intrahepatic portosystemic shunt (TIPS) is an established interventional treatment of BCS, whose timing is a debated issue. We report a case of BCS presenting with ascites and transient MEP and treated with early TIPS. We report the case of a 73-year-old man who presented with ascites and MEP on CT imaging. Anticoagulant therapy resulted in disappearance of MEP, despite persistence of ascites. However, liver biopsy was performed confirming a picture of BCS. Despite clinical albeit suboptimal response to medical therapy, TIPS was performed. Subsequently, ascites disappeared and the clinical outcome was favourable after 30 months. Transient hepatic MEP on CT imaging may be indicative of BCS. Furthermore, early interventional treatment for of BCS could challenge the step-wise strategy.

Plasma Paraoxonase, Sphingosine-1-phosphate, Total Sialic Acid, and Heat Shock Protein-27 in the Liver of the Sheep Naturally Infected with Cysticercus Tenuicollis: Evidence on Pathological Changes.

The present study aimed to investigate whether sphingosine 1 phosphate (S1P), paraoxonase (PON), total sialic acid (TSA), and heat shock protein-27 (HSP27) are altered in the sheep during infection of the liver with Cysticercus tenuicollis. This study was conducted on40 healthy sheep and40 sheep with Cysticercus tenuicollis infection. The infected and non-infected animals were selected based on the observation of severe Cysticercus tenuicollis infection in the liver and absence of any hepatic cysts, respectively. All parameters were measured in serum and plasma. The results revealed a significant decrease (P&amp;lt;0.01) in PON, TSA, and albumin (Alb) in the infected group, compared with those in the healthy one. Furthermore, the infected sheep had a significant increase (P&amp;lt;0.01) in S1P, HSP-27, malondialdehyde (MDA), total bilirubin, and unconjugated bilirubin as compared with those in their non-infected counterparts. Moreover, no significant change was observed in total plasma protein level in the infected animals in comparison to that in the healthy ones. The low levels of TSA and Alb revealed liver damage in the infected sheep. Moreover, the PON reduction might have resulted from hepatic steatosis and MDA enhancement. Meanwhile, S1P elevation could be attributed to the activation of platelets. In addition, HSP-27 increase was ascribed to the disease-induced stress conditions.

The Effect of Contrast Material on Radiation Dose at CT: Part I. Incorporation of Contrast Material Dynamics in Anthropomorphic Phantoms.

Purpose To develop a method to incorporate the propagation of contrast material into computational anthropomorphic phantoms for estimation of organ dose at computed tomography (CT). Materials and Methods A patient-specific physiologically based pharmacokinetic (PBPK) model of the human cardiovascular system was incorporated into 58 extended cardiac-torso (XCAT) patient phantoms. The PBPK model comprised compartmental models of vessels and organs unique to each XCAT model. For typical injection protocols, the dynamics of the contrast material in the body were described according to a series of patient-specific iodine mass-balance differential equations, the solutions to which provided the contrast material concentration time curves for each compartment. Each organ was assigned to a corresponding time-varying iodinated contrast agent to create the contrast material-enhanced five-dimensional XCAT models, in which the fifth dimension represents the dynamics of contrast material. To validate the accuracy of the models, simulated aortic and hepatic contrast-enhancement results throughout the models were compared with previously published clinical data by using the percentage of discrepancy in the mean, time to 90% peak, peak value, and slope of enhancement in a paired t test at the 95% significance level. Results The PBPK model allowed effective prediction of the time-varying concentration curves of various contrast material administrations in each organ for different patient models. The contrast-enhancement results were in agreement with results of previously published clinical data, with mean percentage, time to 90% peak, peak value, and slope of less than 10% (P > .74), 4%, 7%, and 14% for uniphasic and 12% (P > .56), 4%, 12%, and 14% for biphasic injection protocols, respectively. The exception was hepatic enhancement results calculated for a uniphasic injection protocol for which the discrepancy was less than 25%. Conclusion A technique to model the propagation of contrast material in XCAT human models was developed. The models with added contrast material propagation can be applied to simulate contrast-enhanced CT examinations. © RSNA, 2017 Online supplemental material is available for this article.

High fat diet-induced changes of mouse hepatic transcription and enhancer activity can be reversed by subsequent weight loss

Epigenetic factors have been suggested to play an important role in metabolic memory by trapping and maintaining initial metabolic changes within the transcriptional regulatory machinery. In this study we fed mice a high fat diet (HFD) for seven weeks followed by additional five weeks of chow, to identify HFD-mediated changes to the hepatic transcriptional program that may persist after weight loss. Mice fed a HFD displayed increased fasting insulin levels, hepatosteatosis and major changes in hepatic gene transcription associated with modulation of H3K27Ac at enhancers, but no significant changes in chromatin accessibility, indicating that HFD-regulated gene transcription is primarily controlled by modulating the activity of pre-established enhancers. After return to the same body weight as chow fed control mice, the fasting insulin, glucose, and hepatic triglyceride levels were fully restored to normal levels. Moreover, HFD-regulated H3K27Ac and mRNA levels returned to similar levels as control mice. These data demonstrates that the transcription regulatory landscape in the liver induced by HFD is highly dynamic and can be reversed by weight loss. This provides hope for efficient treatment of early obesity-associated changes to hepatic complications by simple weight loss intervention without persistent reprograming of the liver transcriptome.

The natural history of streptozotocin-stimulated non-alcoholic steatohepatitis mice followed by Gd-EOB-DTPA-enhanced MRI: Comparison with simple steatosis mice

PurposeTo clarify the development of HCC, temporal change of steatosis and Gd-EOB-DTPA enhancement of non-alcoholic steatohepatitis (NASH) model mice by magnetic resonance imaging (MRI). Materials and methodsAll animal experiments were approved by the institution's Animal Research Committee. MRI was performed on six NASH and six simple steatosis (SS) model mice every 2weeks from the ages of 8weeks to 16weeks. The sequential changes in the number and size of the focal liver lesions detected on Gd-EOB-DTPA-enhanced MRI were evaluated. Additionally, the hepatic fat fraction (HFF), contrast-to-noise ratio (CNR) and relative enhancement (RE) were calculated at each time point. The temporal changes and correlations in these parameters were evaluated. ResultsAll alive NASH model mice demonstrated focal liver lesions from week 10, at the latest. Number of the lesions increased with time, and all the lesion enlarged with time. All the lesions larger than 1mm were confirmed as hepatocellular carcinoma (HCC) pathologically. While the HFF remained constant in NASH model mice, HFF in SS model mice dramatically increased with time. CNR of the NASH model mice remained constant through the study period, while CNR in SS model mice decreased with time. Although no correlation was seen in NASH model mice, the HFF showed a negative correlation against CNR and RE in SS model mice. ConclusionDevelopment of HCC was observed using Gd-EOB-DTPA-enhanced MRI only in NASH model mice. Degree of steatosis and hepatic enhancement by Gd-EOB-DTPA was both constant in NASH model mice, while steatosis increased and hepatic enhancement decreased with time in SS model mice.