gadoxetic-acid-disodium and Non-alcoholic-Fatty-Liver-Disease

Relative enhancement (RE) in gadoxetate disodium (Gd-EOB-DTPA)-enhanced MRI is a reliable, non-invasive method for the evaluation and differentiation between simple steatosis and non-alcoholic steatohepatitis in adults. This study evaluated the diagnostic accuracy of RE in Gd-EOB-DTPA-enhanced liver MRI and hepatic fat fraction (HFF) in unenhanced liver MRI and ultrasound (US) for non-alcoholic fatty liver disease (NAFLD) screening in pediatric obesity. Seventy-four liver US and MRIs from 68 pediatric patients (13.07 ± 2.95 years) with obesity (BMI > BMI-for-age + 2SD) were reviewed with regard to imaging biomarkers (liver size, volume, echogenicity, HFF, and RE in Gd-EOB-DTPA-enhanced MRIs, and spleen size), blood biomarkers, and BMI. The agreement between the steatosis grade, according to HFF in MRI and the echogenicity in US, was moderate. Alanine aminotransferase correlated better with the imaging biomarkers in MRI than with those in US. BMI correlated better with liver size and volume on MRI than in US. In patients with RE < 1, blood biomarkers correlated better with RE than those in the whole sample, with a significant association between gamma-glutamyltransferase and RE (

Topics: Adolescent; Biomarkers; Child; Contrast Media; Humans; Liver; Magnetic Resonance Imaging; Non-alcoholic Fatty Liver Disease; Pediatric Obesity

To compare unsupervised deep clustering (UDC) to fat fraction (FF) and relative liver enhancement (RLE) on Gd-EOB-DTPA-enhanced MRI to distinguish simple steatosis from non-alcoholic steatohepatitis (NASH), using histology as the gold standard.. A derivation group of 46 non-alcoholic fatty liver disease (NAFLD) patients underwent 3-T MRI. Histology assessed steatosis, inflammation, ballooning, and fibrosis. UDC was trained to group different texture patterns from MR data into 10 distinct clusters per sequence on unenhanced T1- and Gd-EOB-DTPA-enhanced T1-weighted hepatobiliary phase (T1-Gd-EOB-DTPA-HBP), then on T1 in- and opposed-phase images. RLE and FF were quantified on identical sequences. Differences of these parameters between NASH and simple steatosis were evaluated with χ. For the derivation group, UDC-derived features from unenhanced and T1-Gd-EOB-DTPA-HBP, plus from T1 in- and opposed-phase, distinguished NASH from simple steatosis (p ≤ 0.001 and p = 0.02, respectively) with 85% and 80% accuracy, respectively, while RLE and FF distinguished NASH from simple steatosis (p ≤ 0.001 and p = 0.004, respectively), with 83% and 78% accuracy, respectively. On multivariate regression analysis, RLE and FF correlated only with fibrosis (p = 0.040) and steatosis (p ≤ 0.001), respectively. Conversely, UDC features, using Random Forest classifier predictors, correlated with all histologic NAFLD components. The validation group confirmed these results for both approaches.. UDC, RLE, and FF could independently separate NASH from simple steatosis. UDC may predict all histologic NAFLD components.. Using gadoxetic acid-enhanced MR, fat fraction (FF > 5%) can diagnose NAFLD, and relative liver enhancement can distinguish NASH from simple steatosis. Adding AI may let us non-invasively estimate the histologic components, i.e., fat, ballooning, inflammation, and fibrosis, the latter the main prognosticator.. • Unsupervised deep clustering (UDC) and MR-based parameters (FF and RLE) could independently distinguish simple steatosis from NASH in the derivation group. • On multivariate analysis, RLE could predict only fibrosis, and FF could predict only steatosis; however, UDC could predict all histologic NAFLD components in the derivation group. • The validation cohort confirmed the findings for the derivation group.

Topics: Artificial Intelligence; Contrast Media; Fibrosis; Gadolinium DTPA; Humans; Inflammation; Liver; Magnetic Resonance Imaging; Non-alcoholic Fatty Liver Disease

Melanocortin 4 receptor-deficient (MC4R-KO) mice fed a high-fat diet (HFD) develop liver pathology similar to human nonalcoholic steatohepatitis (NASH). However, although liver histology and blood biochemistry have been reported, hepatic function has not been evaluated. In the present study, we evaluated hepatic function in MC4R-KO mice fed an HFD using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with gadolinium‑ethoxybenzyl‑diethylenetriamine pentaacetic acid (Gd-EOB-DTPA).. Wild type (WT) mice and MC4R-KO mice were fed a standard diet (SD) or an HFD for 20 weeks. The hepatic signal intensity was obtained from DCE-MRI images, and relative enhancement (RE), the time to maximum RE (T. Histological analysis with nonalcoholic fatty liver disease activity score (NAS) revealed that MC4R-KO mice fed an HFD achieved the NAS of 5. There was moderate fibrosis in MC4R-KO mice fed an HFD. DCE-MRI with Gd-EOB-DTPA showed that T. MC4R-KO mice fed an HFD developed obesity and NASH. The liver kinetics of Gd-EOB-DTPA were significantly different in MC4R-KO mice fed an HFD from WT mice, and correlated with the histopathologic score. These results suggest that MC4R-KO mice fed an HFD mimic the hepatic pathology and liver function of human NASH, and therefore might be useful for the study of hepatic dysfunction during the fibrotic stage of NASH.

Topics: Animals; Contrast Media; Disease Models, Animal; Gadolinium DTPA; Image Enhancement; Liver; Magnetic Resonance Imaging; Mice; Non-alcoholic Fatty Liver Disease; Receptor, Melanocortin, Type 4

To assess the value of T1ρ,T1ρ on hepatobiliary phase (HBP) and diffusion metrics in staging of Non-alcoholic fatty liver disease (NAFLD) activity scores, inflammation, fibrosis in NASH rabbits model. Non-alcoholic steatohepatitis (NASH) rabbits model was induced by feeding a varied duration of high-fat, high-cholesterol diet. T1ρ,T1ρ (HBP) 20min after administration of Gd-EOB-DTPA, and Intravoxel incoherent motion imaging (IVIM) diffusion-weighted imaging were performed on a 3.0T magnetic resonance (MR) imaging unit. The diagnostic value of each parameter for NAS, inflammation and fibrosis severity were determined. T1ρ (r=0.658) and T1ρ (HBP) (r=0.750) have strong association with NASH overall activity, T1ρ (HBP) is strongly relevant to inflammation stage (r=0.812). There was negative association between f and inflammation (r=-0.480), whilst no significant relation between other three parameters (apparent diffusion coefficient (ADC), pseudo-diffusion coefficient (D*) and true diffusion coefficient (D)) and inflammation or overall activity. The areas under the receiver operating characteristic curves (AUCs) of f, ADC, T1ρ and T1ρ-HBP were 0.871, 0.728, 0.849 and 0.949 for differentiating NASH; 0.731, 0.552, 0.925 and 0.922 for G2-3 inflammation; and 0.767, 0.625, 0.816, and 0.882 for S1-2 fibrosis. Comparison of ROC curve showed T1ρ (HBP) had an optimal diagnostic performance for NASH [T1ρ (HBP) vs ADC, AUC:0.949 vs 0.728, P=0.043], inflammation [T1ρ (HBP) vs ADC, AUC:0.922 vs 0.552, P=0.003], fibrosis [T1ρ (HBP) vs ADC, AUC:0.882 vs 0.625, P=0.046]. The combination of T1ρ (HBP)+perfusion fraction (f) showed highest diagnostic value for NASH (AUC:0.971), inflammation (AUC:0.935). Among T1ρ imaging and IVIM diffusion metrics, combination of T1rho (HBP)+f was found to be superior noninvasive imaging biomarker for NASH activity assessment.

Topics: Animals; Area Under Curve; Diffusion Magnetic Resonance Imaging; Disease Models, Animal; Gadolinium DTPA; Humans; Image Enhancement; Inflammation; Liver; Magnetic Resonance Imaging; Male; Non-alcoholic Fatty Liver Disease; Rabbits; ROC Curve

Noninvasive liver fibrosis evaluation was performed in patients with nonalcoholic fatty liver disease (NAFLD). We used a quantitative method based on the hepatic volume acquired from gadoxetate disodium-enhanced (Gd-EOB-DTPA-enhanced) magnetic resonance imaging (MRI) for diagnosing advanced fibrosis in patients with NAFLD.. A total of 130 patients who were diagnosed with NAFLD and underwent Gd-EOB-DTPA-enhanced MRI were retrospectively included. Histological data were available for 118 patients. Hepatic volumetric parameters, including the left hepatic lobe to right hepatic lobe volume ratio (L/R ratio), were measured. The usefulness of the L/R ratio for diagnosing fibrosis ≥F3-4 and F4 was assessed using the area under the receiver operating characteristic (AUROC) curve. Multiple regression analysis was performed to identify variables (age, body mass index, serum fibrosis markers, and histological features) that were associated with the L/R ratio.. The L/R ratio demonstrated good performance in differentiating advanced fibrosis (AUROC, 0.80; 95% confidence interval, 0.72 to 0.88) from cirrhosis (AUROC, 0.87; 95% confidence interval, 0.75 to 0.99). Multiple regression analysis showed that only fibrosis was significantly associated with the L/R ratio (coefficient, 0.121; p<0.0001).. The L/R ratio, which is not influenced by pathological parameters other than fibrosis, is useful for diagnosing cirrhosis in patients with NAFLD.

Topics: Aged; Area Under Curve; Contrast Media; Female; Gadolinium DTPA; Humans; Liver; Liver Cirrhosis; Logistic Models; Magnetic Resonance Imaging; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Organ Size; Predictive Value of Tests; Retrospective Studies; ROC Curve; Sensitivity and Specificity; Severity of Illness Index

To 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).. All 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.. All 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.. Development 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.

Topics: Animals; Animals, Newborn; Carcinoma, Hepatocellular; Contrast Media; Disease Models, Animal; Female; Gadolinium DTPA; Liver; Liver Neoplasms; Magnetic Resonance Imaging; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Streptozocin

The purpose of this study is to investigate the correlation between the liver kinetics of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) and liver histopathology in a mouse model of NASH by using dynamic contrast-enhanced MRI.. Twenty male C57/BL6 mice aged 8weeks were fed a methionine-choline-deficient (MCD) diet for 2, 4 and 6weeks (MCD groups: MCD 2w, 4w, or 6w). Gd-EOB-DTPA-enhanced MR imaging of the liver was performed at 2, 4 and 6weeks after the MCD feeding. The signal intensity of the liver was obtained from dynamic MR images and relative enhancement (RE), and the time to maximum RE (Tmax) and half-life of elimination RE (T1/2) were calculated. After MRI scan, histopathological scores of hepatic steatosis and inflammation and blood biochemistry data, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, were obtained.. Plasma AST and ALT levels were significantly increased in mice fed MCD. Histopathological scores indicated that steatohepatitis progressed with the MCD feeding period from 2 to 6weeks, but significant fibrosis was observed only in mice fed MCD for 6weeks. Gd-EOB-DTPA-enhanced MRI showed that Tmax was significantly prolonged in the livers of the 6-week group compared to the control group (control, 4.0±0.7min; MCD 6w, 12.1±1.6min), although there was no alteration in the 2- and 4-week groups. T1/2 was significantly prolonged in mice fed MCD for 4 and 6weeks compared to the control group (control, 19.9±2.0min; MCD 4w, 46.7±8.7min; MCD 6w, 65.4±8.8min). The parameters of Gd-EOB-DTPA kinetics (Tmax and T1/2) in the liver were positively correlated with the liver histopathological score (steatosis vs Tmax, rho=0.69, P=0.0007; inflammation vs Tmax, rho=0.66, P=0.00155; steatosis vs T1/2, rho=0.77, P<0.0001; inflammation vs T1/2, rho=0.73, P=0.0003).. The liver kinetics of Gd-EOB-DTPA correlated well with the inflammation score in the mouse model of NASH, suggesting the possibility of detecting the steatohepatitis stage without fibrosis by Gd-EOB-DTPA-enhanced MR imaging.

Topics: Animals; Contrast Media; Disease Models, Animal; Gadolinium DTPA; Image Enhancement; Inflammation; Liver; Magnetic Resonance Imaging; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease

Topics: Gadolinium DTPA; Humans; Magnetic Resonance Imaging; Non-alcoholic Fatty Liver Disease

This study evaluates the value of Gd-EOB-DTPA-enhanced MRI for diagnosis and staging of non-alcoholic fatty liver disease (NAFLD) in an animal model by T1 relaxation time measurement.. Thirty-four rabbits were divided into the control group (n = 10) and NAFLD group, which was split into four groups (n = 6) with a high-fat diet for an interval of 3 weeks. A dual flip angle was performed before and at the hepatobiliary phase (HBP). T1 relaxation times of the liver parenchyma and the decrease rate (∆%) were calculated. Histological findings according to semi-quantitative scoring of steatosis, activity and fibrosis were the standard of reference.. HBP and ∆% T1 relaxation time measurement showed significant differences between normal and NAFLD groups, between non-alcoholic steatohepatitis (NASH) and NAFLD without NASH (p = 0.000-0.049), between fibrosis groups (p = 0.000-0.019), but no difference between F1 and F2 (p = 0.834). The areas under the receiver operating characteristic curves (AUCs) of T1 relaxation time for HBP and ∆% were 0.86-0.93 for the selection of NASH and activity score ≥2, and 0.86-0.95 for the selection of F ≥ 1, 2, 3. No significant difference was found for diagnostic performance between HBP and ∆% T1 relaxation time.. HBP T1 relaxation time measurement of Gd-EOB-DTPA-enhanced MRI was useful to evaluate NAFLD according to the SAF score. HBP T1 relaxation time measurement was as accurate as ∆% T1 relaxation time.. • Gd-EOB-DTPA-enhanced MRI could give useful information on NAFLD. •HBP T 1 relaxation time measurement was useful for the evaluation of NAFLD. • HBP T 1 relaxation time measurement was as accurate as ∆%.

Topics: Animals; Contrast Media; Diagnosis, Differential; Fatty Liver; Gadolinium DTPA; Liver; Liver Cirrhosis; Magnetic Resonance Imaging; Non-alcoholic Fatty Liver Disease; Rabbits

We used rabbits to investigate the possibility of differentiating between nonalcoholic steatohepatitis (NASH) and fatty liver (FL) on scans acquired by open-type‒ and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)‒enhanced magnetic resonance imaging (MRI).. We divided 15 adult rabbits into three equal groups; they received standard (control group), high-fat (FL) content (FL group), or choline-deficient chow (NASH group). With the animals under general anesthesia we acquired scans on an open 0.3-Tesla MRI system. Signal intensity (SI) was measured before and after contrast administration and defined as SI-pre and SI-post, respectively. Relative SI enhancement (Sr) was calculated using the equation: Sr = (average of three SI-post- minus average of three SI values in no-signal fields)/(average of three SI-pre- minus average of three SI values in no-signal fields) × 100. Maximum Sr (Srmax), the time (in seconds) required to reach Srmax (Tmax), and the difference between Srmax and Sr at 30 minutes (Sr(30m)R) were analyzed.. Srmax was significantly higher in the NASH rabbits than the other two groups (P < .05).. In rabbits, the Srmax value made it possible to differentiate NASH from normal and fatty liver.

Topics: Animals; Contrast Media; Diagnosis, Differential; Fatty Liver; Fatty Liver, Alcoholic; Feasibility Studies; Female; Gadolinium DTPA; Image Enhancement; Magnetic Resonance Imaging; Non-alcoholic Fatty Liver Disease; Rabbits; Reproducibility of Results; Sensitivity and Specificity

Non-invasive MR imaging is expected to be used for accurate diagnosis and quantification of non-alcoholic steatohepatitis (NASH), because NASH is a progressive fatty liver disease. New MR techniques, such as fat fraction ratio (FFR) and T2* value measurement, have attracted an increasing attention, because those techniques can measure quantitative parameters of fibrosis, fat and iron deposition in the liver.. To investigate the potential of FFR and T2* value in NASH with pre-enhancement, gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) or super-paramagnetic iron oxide (SPIO)-enhanced MRI.. Twenty-eight rats were divided equally into four groups (one control group and three NASH groups). All rats underwent unenhanced, Gd-EOB-DTPA, and SPIO-enhanced MRI. The T2* value of the liver was measured for each image sequence, and then changes in T2* values before and after each injection were analyzed using Dunnett's test. The reduction rate of T2* value before and 13 min after injection of Gd-EOB-DTPA or SPIO was analyzed using Mann-Whitney's U test. Moreover, FFR of the liver was measured before enhancement, and the relationship between fat fraction and the calculated fat area percentage on a pathological specimen was examined using Spearman's correlation test.. On pre-enhancement, FFR and T2* value were 26.0% ± 12.0% and 21.5 ± 4.2 ms for all NASH groups, and 0.9% ± 0.5% and 30.8 ±-5.5 ms for control, respectively. Both FFR and T2* values were significantly different between the NASH and control groups. The reduction rate of T2* value was significantly lower in the NASH groups than in the control group on SPIO-enhanced MRI, though there was no significant difference on Gd-EOB-DTPA-enhanced MRI. FFR was correlated with the calculated fat area percentage for the pathological specimen.. Pre-enhancement FFR, T2* value measurement and reduction rate of T2* value on SPIO-enhanced MRI may help estimate the progress of liver fat deposition and fibrosis in NASH.

Topics: Animals; Contrast Media; Dextrans; Disease Models, Animal; Fatty Liver; Gadolinium DTPA; Image Enhancement; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Magnetite Nanoparticles; Male; Non-alcoholic Fatty Liver Disease; Rats; Rats, Sprague-Dawley; Statistics, Nonparametric

To compare the transporter expression and signal profile on Gd-EOB-DTPA-enhanced MRI between non-alcoholic steatohepatitis (NASH) and cirrhotic liver induced in rats, and investigate the correlation of the transporter expression and fibrosis rate in both diseases.. Forty-eight rats were divided into four groups of 12: TAA (cirrhosis), NASH 7- and 10-week, and control groups. Each group was divided into two subgroups: Group 1 for MRI and Group 2 for transporter examinations.. The relative enhancement of the TAA group was significantly lower than those of other groups (p < 0.01). The T(max) and T(1/2) of the NASH 10-week group was significantly prolonged in comparison with the TAA group (p < 0.01). There was no significant difference in the oatp1 expression, whereas the mrp2 expression of the TAA group was significantly higher than those of other groups (p < 0.01). There was no significant correlation between the fibrosis rate and oatp1 expression, whereas a paradoxical correlation was found between the fibrosis rate and mrp2 expression (NASH: negative correlation, r = 0.91, p < 0.01; TAA: positive correlation, r = 0.85, p < 0.01).. Our findings showed that the mrp2 expression in cirrhosis increases in comparison with NASH, and there was a paradoxical correlation between the fibrosis rate and mrp2 expression.

Topics: Animals; ATP-Binding Cassette Transporters; Contrast Media; Fatty Liver; Gadolinium DTPA; Image Processing, Computer-Assisted; Liver Cirrhosis, Experimental; Magnetic Resonance Imaging; Male; Non-alcoholic Fatty Liver Disease; Organic Anion Transporters, Sodium-Independent; Rats; Rats, Wistar