Hepatic Fat Quantification Research Articles

Comparative analysis of hepatic fat quantification across 5 T, 3 T and 1.5 T: A study on consistency and feasibility

ObjectivesMagnetic resonance imaging (MRI) is a critical noninvasive technique for evaluating liver steatosis, with efficient and precise fat quantification being essential for diagnosing liver diseases. This study leverages 5 T ultra-high-field MRI to demonstrate the clinical significance of liver fat quantification, and explores the consistency and accuracy of the Proton Density Fat Fraction (PDFF) in the liver across different magnetic field strengths and measurement methodologies. MethodsThe study involved phantoms with lipid contents ranging from 0 % to 30 % and 35 participants (21 females, 14 males; average age 30.17 ± 13.98 years, body mass index 25.84 ± 4.76, waist-hip ratio 0.84 ± 0.09). PDFF measurements were conducted using chemical shift encoded (CSE) MRI at 5 T, 3 T, and 1.5 T, alongside magnetic resonance spectroscopy (MRS) at 5 T and 1.5 T for both liver and phantoms, analyzed using jMRUI software. The MRS-derived PDFF values served as the reference standard. Repeatability of 5 T MRI measurements was assessed through correlation analysis, while accuracy was evaluated using linear regression analysis against the reference standards. ResultsThe CSE-PDFF measurements at 5 T demonstrated strong consistency with those at 3 T and 1.5 T, showing high intraclass correlation coefficients (ICC) of 0.988 and 0.980, respectively (all p < 0.001). There was also significant consistency across ROIs within liver lobes, with ICC values ranging from 0.975 to 0.986 (all p < 0.001). MRS-PDFF measurements for both phantoms and liver at 5 T and 1.5 T exhibited substantial agreement, with ICC values of 0.996 and 0.980, respectively (all p < 0.001). Particularly, ICC values for ROIs in the liver ranged from 0.963 to 0.990 (all p < 0.001). Despite overall agreement, statistically significant differences were noted in specific ROIs within the liver lobes (p = 0.004 and 0.012). The CSE and MRS PDFF measurements at 5 T displayed strong consistency, with an ICC of 0.988 (p < 0.001), and significant agreement was also found between 5 T CSE and 1.5 T MRS PDFF measurements, with an ICC of 0.978 (p < 0.001). Agreement was significant within the ROIs of the liver lobes on the same platform at 5 T, with ICC values ranging from 0.986 to 0.991 (all p < 0.001). ConclusionPDFF measurements at 5 T MR imaging exhibited both accuracy and repeatability, indicating that 5 T imaging provides reliable quantification of liver fat content and shows substantial potential for clinical diagnostic applications.

A functional genomic framework to elucidate novel causal metabolic dysfunction-associated fatty liver disease genes.

Metabolic dysfunction-associated fatty liver disease (MASLD) is the most prevalent chronic liver pathology in western countries, with serious public health consequences. Efforts to identify causal genes for MASLD have been hampered by the relative paucity of human data from gold-standard magnetic resonance quantification of hepatic fat. To overcome insufficient sample size, genome-wide association studies using MASLD surrogate phenotypes have been used, but only a small number of loci have been identified to date. In this study, we combined GWAS of MASLD composite surrogate phenotypes with genetic colocalization studies followed by functional in vitro screens to identify bona fide causal genes for MASLD. We used the UK Biobank to explore the associations of our novel MASLD score, and genetic colocalization to prioritize putative causal genes for in vitro validation. We created a functional genomic framework to study MASLD genes in vitro using CRISPRi. Our data identify VKORC1, TNKS, LYPLAL1 and GPAM as regulators of lipid accumulation in hepatocytes and suggest the involvement of VKORC1 in the lipid storage related to the development of MASLD. Complementary genetic and genomic approaches are useful for the identification of MASLD genes. Our data supports VKORC1 as a bona fide MASLD gene. We have established a functional genomic framework to study at scale putative novel MASLD genes from human genetic association studies.

R2* Impact on Hepatic Fat Quantification With a Commercial Single Voxel Technique at 1.5 and 3.0 T.

Rationale and Objectives: Fat quantification accuracy using a commercial single-voxel high speed T2-corrected multi-echo (HISTO) technique and its robustness to R2* variations at 3.0 T, such as those introduced by iron in liver, has not been fully established. This study evaluated HISTO at 3.0 T and sought to reproduce results at 1.5 T. Methods: Phantoms were prepared with a range of fat content and R2*. Data were acquired at 1.5 T and 3.0 T, using HISTO and a Dixon technique. Fat quantification accuracy was evaluated as a function of R2*. The patient study included 239 consecutive patients. Data were acquired at 1.5 T or 3.0 T, using HISTO and Dixon techniques. The techniques were compared using Bland-Altman plots. Bias significance was evaluated using a one-sample t-test. Results: In phantoms, HISTO was accurate within 10% up to a R2* of 100 s-1 at both field strengths, while Dixon was accurate within 10% where R2* was accurately quantified (up to 350 s-1 at 1.5 T, and 550 s-1 at 3.0 T). In patients, where R2* was <100 s-1, fat quantification from both techniques agreed at 1.5 T (P = .71), but not at 3.0 T (P = .007), with a bias <1%. Conclusion: Results suggest that HISTO is reliable when R2* is <100 s-1, corresponding to patients with at most mild liver iron overload, and that it should be used with caution when R2* is >100 s-1. Dixon should be preferred for hepatic fat quantification due to its robustness to R2* variations.

Quantification of hepatic fat: evaluation of different magnetic resonance imaging measurement strategies in cases of homogeneous and heterogeneous distribution.

To evaluate three different measurements strategies to quantify hepatic steatosis and to investigate the differences between homogeneous and heterogeneous forms of hepatic steatosis. Retrospective study conducted by magnetic resonance imaging review. We evaluated three different strategies measures for quantification of hepatic steatosis in two matched groups: homogeneous and heterogeneous steatosis. We considered p < 0.05 significance level in all made tests. In heterogeneous steatosis group, the strategy with a region of interest (ROI) of 1 cm2 to measure the signal intensity in the most altered area showed significant variations in the quantification, while the average of four ROIs of 1 cm2 or representative target area in axial section did not vary significant. In diffuse hepatic steatosis, any strategy used showed no significant difference. The intraclass correlation coefficient ranged between 0.96 and 0.99, with 95% confidence interval of 0.93-0.99. The quantification of fat liver by magnetic resonance imaging using only one ROI is less representative, especially in heterogeneous steatosis. There was no significant difference between the average of four ROIs strategy and the strategy of representative segmentation area of parenchyma.

Non-invasive hepatic fat quantification: Can multi-echo Dixon help?

To evaluate the diagnostic accuracy of multi-echo Dixon magnetic resonance imaging (MRI) in hepatic fat quantification, in comparison with that of magnetic resonance spectroscopy (MRS), on 3.0-T MRI. Fifty-five adults with no known liver disease underwent MRI in a 3.0-T scanner for determination of the hepatic fat fraction, with two techniques: multi-echo Dixon, in a manually drawn region of interest (ROI) and in the entire liver parenchyma (automated segmentation); and MRS. The diagnostic accuracy and cutoff value for multi-echo Dixon were determined, with MRS being used as the reference standard. The mean fat fraction obtained by multi-echo Dixon in the manually drawn ROI and in the entire liver was 5.2 ± 5.8% and 6.6 ± 5.2%, respectively, whereas the mean hepatic fat fraction obtained by MRS was 5.7 ± 6.4%. A very strong positive correlation and good agreement were observed between MRS and multi-echo Dixon, for the ROI (r = 0.988, r2 = 0.978, p < 0.001) and for the entire liver parenchyma (r = 0.960, r2 = 0.922, p < 0.001). A moderate positive correlation was observed between the hepatic fat fraction and body mass index of the participants, regardless of the fat estimation technique employed. For hepatic fat quantification, multi-echo Dixon MRI demonstrated a very strong positive correlation and good agreement with MRS (often considered the gold-standard noninvasive technique). Because multi-echo Dixon MRI is more readily available than is MRS, it can be used as a rapid tool for hepatic fat quantification, especially when the hepatic fat distribution is not homogeneous.

Hepatic fat quantification in dual-layer computed tomography using a three-material decomposition algorithm.

The purpose of this study was to evaluate a three-material decomposition algorithm for hepatic fat quantification using a dual-layer computed tomography (DL-CT) and MRI as reference standard on a large patient cohort. A total of 104 patients were retrospectively included in our study, i.e., each patient had an MRI exam and a DL-CT exam in our institution within a maximum of 31days. Four regions of interest (ROIs) were positioned blindly and similarly in the liver, by two independent readers on DL-CT and MRI images. For DL-CT exams, all imaging phases were included. Fat fraction agreement between CT and MRI was performed using intraclass correlation coefficients (ICC), determination coefficients R2, and Bland-Altman plots. Diagnostic performance was determined using sensitivity, specificity, and positive and negative predictive values. The cutoff for steatosis was 5%. Correlation between MRI and CT data was excellent for all perfusion phases with ICC calculated at 0.99 for each phase. Determination coefficients R2 were also good for all perfusion phases (about 0.95 for all phases). Performance of DL-CT in the diagnosis of hepatic steatosis was good with sensitivity between 89 and 91% and specificity ranging from 75 to 80%, depending on the perfusion phase. The positive predictive value was ranging from 78 to 93% and the negative predictive value from 82 to 86%. Multi-material decomposition in DL-CT allows quantification of hepatic fat fraction with a good correlation to MRI data. The use of DL-CT allows for detection of hepatic steatosis. This is especially interesting as an opportunistic finding CT performed for other reasons, as early detection can help prevent or slowdown the development of liver metabolic disease. • Hepatic fat fractions provided by the dual-layer CT algorithm is strongly correlated with that measured on MRI. • Dual-layer CT is accurate to detect hepatic steatosis ≥ 5%. • Dual-layer CT allows opportunistic detection of steatosis, on CT scan performed for various indications.

Deep Learning for Inference of Hepatic Proton Density Fat Fraction From T1-Weighted In-Phase and Opposed-Phase MRI: Retrospective Analysis of Population-Based Trial Data.

BACKGROUND. The confounder-corrected chemical shift-encoded MRI (CSE-MRI) sequence used to determine proton density fat fraction (PDFF) for hepatic fat quantification is not widely available. As an alternative, hepatic fat can be assessed by a two-point Dixon method to calculate signal fat fraction (FF) from conventional T1-weighted in- and opposed-phase (IOP) images, although signal FF is prone to biases, leading to inaccurate quantification. OBJECTIVE. The purpose of this study was to compare hepatic fat quantification by use of PDFF inferred from conventional T1-weighted IOP images and deep-learning convolutional neural networks (CNNs) with quantification by use of two-point Dixon signal FF with CSE-MRI PDFF as the reference standard. METHODS. This study entailed retrospective analysis of data from 292 participants (203 women, 89 men; mean age, 53.7 ± 12.0 [SD] years) enrolled at two sites from September 1, 2017, to December 18, 2019, in the Strong Heart Family Study (a prospective population-based study of American Indian communities). Participants underwent liver MRI (site A, 3 T; site B, 1.5 T) including T1-weighted IOP MRI and CSE-MRI (used to reconstruct CSE PDFF and CSE R2* maps). With CSE PDFF as reference, a CNN was trained in a random sample of 218 (75%) participants to infer voxel-by-voxel PDFF maps from T1-weighted IOP images; testing was performed in the other 74 (25%) participants. Parametric values from the entire liver were automatically extracted. Per-participant median CNN-inferred PDFF and median two-point Dixon signal FF were compared with reference median CSE-MRI PDFF by means of linear regression analysis, intraclass correlation coefficient (ICC), and Bland-Altman analysis. The code is publicly available at github.com/kang927/CNN-inference-of-PDFF-from-T1w-IOP-MR. RESULTS. In the 74 test-set participants, reference CSE PDFF ranged from 1% to 32% (mean, 11.3% ± 8.3% [SD]); reference CSE R2* ranged from 31 to 457 seconds-1 (mean, 62.4 ± 67.3 seconds-1 [SD]). Agreement metrics with reference to CSE PDFF for CNN-inferred PDFF were ICC = 0.99, bias = -0.19%, 95% limits of agreement (LoA) = (-2.80%, 2.71%) and for two-point Dixon signal FF were ICC = 0.93, bias = -1.11%, LoA = (-7.54%, 5.33%). CONCLUSION. Agreement with reference CSE PDFF was better for CNN-inferred PDFF from conventional T1-weighted IOP images than for two-point Dixon signal FF. Further investigation is needed in individuals with moderate-to-severe iron overload. CLINICAL IMPACT. Measurement of CNN-inferred PDFF from widely available T1-weighted IOP images may facilitate adoption of hepatic PDFF as a quantitative bio-marker for liver fat assessment, expanding opportunities to screen for hepatic steatosis and nonalcoholic fatty liver disease.

Hepatic Fat Quantification with the Multi-Material Decomposition Algorithm by Using Low-Dose Non-Contrast Material-Enhanced Dual-Energy Computed Tomography in a Prospectively Enrolled Cohort.

The early diagnosis of hepatic steatosis is important. No study has assessed hepatic fat quantification by using low-dose dual-energy computed tomography (CT). We assessed the accuracy of hepatic fat quantification using the multi-material decomposition (MMD) algorithm with low-dose non-contrast material-enhanced dual-energy CT. We retrospectively reviewed 33 prospectively enrolled patients who had undergone low-dose non-contrast material-enhanced dual-energy CT and magnetic resonance image (MRI) proton density fat fraction (PDFF) on the same day. Percentage fat volume fraction (FVF) images were generated using the MMD algorithm on the low-dose dual-energy CT data. We assessed the correlation between FVFs and MRI-PDFFs by using Spearman’s rank correlation. With a 5% cutoff value of MRI-PDFF for fatty liver, a receiver operating characteristic (ROC) curve analysis was performed to identify the optimal criteria of FVF for diagnosing fatty liver. CTDIvol of CT was 2.94 mGy. FVF showed a strong correlation with MRI-PDFF (r = 0.756). The ROC curve analysis demonstrated that FVF ≥ 4.61% was the optimal cutoff for fatty liver. With this cutoff value for diagnosing the fatty liver on low-dose dual-energy CT, the sensitivity, specificity, and area under the curve were 90%, 100%, and 0.987, respectively. The MMD algorithm using low-dose non-contrast material-enhanced dual-energy CT is feasible for quantifying hepatic fat.

A Standardized Approach for MRI-PDFF is Necessary in the Assessment of Diagnostic Performances of the Ultrasound-Based Hepatic Fat Quantification Tools.

The recently developed ultrasound-based hepatic fat quantification tools have the potential to be implemented in daily practice with wide acceptance due to inherited advantages of ultrasound technology. Researchers intensively focused on this topic and the accumulated evidences that support clinical usefulness of these tools. However, differences in the researcher-dependent factors of the utilized MRI-PDFF technique, the recommended reference standard, may hinder the better understanding of the diagnostic performances of these tools. Therefore, a standardized approach for MRI-PDFF technique, which is established with international consensus may be considered as important.

Hepatic Fat Quantification With Novel Ultrasound Based Techniques: A Diagnostic Performance Study Using Magnetic Resonance Imaging Proton Density Fat Fraction as Reference Standard.

Purpose: To assess the diagnostic performances of novel Tissue attenuation imaging (TAI) and Tissue scatter distribution imaging (TSI) tools in quantification of liver fat content using magnetic resonance imaging proton density fat fraction (MRI PDFF) as reference standard. Methods: Eighty consecutive patients with known or suspected non-alcoholic fatty liver disease (NAFLD) who volunteered to participate in the study comprised the study cohort. All patients underwent MRI PDFF scan and quantitative ultrasound (QUS) imaging using TAI and TSI tools. The cutoff values of ≥5%, ≥16.3% and ≥21.7% on MRI PDFF were used for mild, moderate and severe steatosis, respectively. Area under the Receiver operating characteristic (AUROC) curves were used to assess the diagnostic performance of TAI and TSI in detecting different grades of hepatic steatosis. Results: The AUROCs of TAI and TSI tools in detecting hepatosteatosis (MRI PDFF ≥5%), were 0.95 [95% Confidence Interval (CI): 0.91-0.99] (P < 0.001) and 0.96 (95% CI: 0.93-0.99) (P < 0.001), respectively. In distinguishing between different grades of steatosis, the values of 0.75, 0.86 and 0.96dB/cm/MHz have 88%, 88% and 100% sensitivity, respectively, for TAI tool; and the values of 92.44, 96.64 and 99.45 have 90%, 92% and 91.7% sensitivity, respectively, for TSI tool. Conclusion: TAI and TSI tools accurately quantify liver fat content and can be used for the assessment and grading of hepatosteatosis in patients with known or suspected NAFLD.

Steatosis Grading Comparison Between Qualitative Ultrasonography and Magnetic Resonance Spectroscopy in Patients With Nonalcoholic Fatty Liver Disease

Objective: Assess the correlation between the qualitative sonographic score for detecting hepatic steatosis (HS) and liver fat quantification, using proton magnetic resonance spectroscopy (MRS). Materials and Methods: Sixty-six patients with known or suspected nonalcoholic fatty liver disease (NAFLD) underwent ultrasonography (US) and magnetic resonance imaging (MRI). The qualitative sonographic score and fat quantification, measured by MRS, were the techniques used. A Kappa coefficient was used for agreement calculation, and a Fisher test was used to assess the normality of the variables. The MRS results were the gold standard for US quality assessment. Results: The agreement between MRS and US was 50% (Kappa 0.35). Ultrasonography results were more severe in 42.4% of the cases, and 66.7% of the patients had a body mass index greater than 30 ( P = .017). For diagnosis of HS, US presented 100% sensitivity, 30.8% to 60% specificity, 61.7% to 72.7% accuracy, 40% to 69.2% false-positive rate, 0% false-negative rate, 53.8% positive predictive value, and 100% negative predictive value. Conclusion: Ultrasonography is a reliable exam for detecting HS, although not for grading purposes. Therefore, US is not a good predictor of HS severity for the management and follow-up of NAFLD.

LiverScreen project: study protocol for screening for liver fibrosis in the general population in European countries

BackgroundThe development of liver cirrhosis is usually an asymptomatic process until late stages when complications occur. The potential reversibility of the disease is dependent on early diagnosis of liver fibrosis and timely targeted treatment. Recently, the use of non-invasive tools has been suggested for screening of liver fibrosis, especially in subjects with risk factors for chronic liver disease. Nevertheless, large population-based studies with cost-effectiveness analyses are still lacking to support the widespread use of such tools. The aim of this study is to investigate whether non-invasive liver stiffness measurement in the general population is useful to identify subjects with asymptomatic, advanced chronic liver disease.MethodsThis study aims to include 30,000 subjects from eight European countries. Subjects from the general population aged ≥ 40 years without known liver disease will be invited to participate in the study either through phone calls/letters or through their primary care center. In the first study visit, subjects will undergo bloodwork as well as hepatic fat quantification and liver stiffness measurement (LSM) by vibration-controlled transient elastography. If LSM is ≥ 8 kPa and/or if ALT levels are ≥1.5 x upper limit of normal, subjects will be referred to hospital for further evaluation and consideration of liver biopsy. The primary outcome is the percentage of subjects with LSM ≥ 8kPa. In addition, a health economic evaluation will be performed to assess the cost-effectiveness and budget impact of such an intervention. The project is funded by the European Commission H2020 program.DiscussionThis study comes at an especially important time, as the burden of chronic liver diseases is expected to increase in the coming years. There is consequently an urgent need to change our current approach, from diagnosing the disease late when the impact of interventions may be limited to diagnosing the disease earlier, when the patient is asymptomatic and free of complications, and the disease potentially reversible. Ultimately, the LiverScreen study will serve as a basis from which diagnostic pathways can be developed and adapted to the specific socio-economic and healthcare conditions in each country.Trial registrationThis study is registered on Clinicaltrials.gov (NCT03789825).

Validation of Accuracy of Non-Invasive Imaging Methods (Magnetic Resonance Imaging (MRI) Fat Fraction Calculation and Computed Tomography (CT) Liver Attenuation Index) for Hepatic Graft Fat Quantification in Living Liver Transplant Donors.

BackgroundDiagnosis of significant hepatic graft steatosis remains vital for success of any transplant program as it has an impact on donor morbidity and recipient survival. Even histopathological quantification faces limitations. The present study compared the diagnostic accuracy of CT-LAI and MRI fat fraction imaging with histopathological analysis for donor graft parenchymal fat quantification.Material/MethodsCT-LAI and MR-FF values and histopathological fat quantification results of 273 patients were identified from electronic records of the author’s institutes from September 2015 to April 2020. Data analysis was done using SPSS version 21.0.ResultsMost participants were young with nearly equal sex distribution and significant number of overweight and obese patients. Moderate agreement and significant positive correlation were found between MR fat fraction (%) and biopsy-macrosteatosis (%). Diagnostic accuracy and negative predictive value of MRI for fat fraction calculation was high (95.24% and 98.07% for fat fraction of 10% threshold, respectively), and it further improved for fat fraction threshold of 15%.ConclusionsMRI-based fat quantification calculation displayed near-perfect negative predictive values and very high diagnostic accuracy, suggesting that it can obviate the need for biopsy in patients with graft fat percentage <10% on MRI.

MRI-based fat quantification of the liver: Is it time for commercially available products?

Purpose(1) To assess the clinical applicability of commercially available solutions for MR-based quantification of the hepatic fat fraction (HFF) and (2) to compare their results with clinically established in-phase/oppose-phase (IP/OP) imaging as proposed by Dixon. MethodsTwenty-eight patients underwent MRI examinations using multigradient-echo sequences including multi-peak modeling and T2∗ correction, IP/OP imaging and multi-echo spectroscopy with successive HFF evaluation. Histopathological examination yielded the fraction of adipose hepatocytes (fAH) and the presence of increased liver iron concentration (LIC). We correlated HFF with fAH, and assessed concordance correlations among the MR-based methods with the presence of increased LIC as a control parameter. We investigated the liver segmentation quality and overall workflow of the postprocessing solutions (Philips LiverHealth and Siemens LiverLab). ResultsIP/OP imaging yielded a very strong correlation (r=0.88) with fAH when excluding three cases with increased LIC. Multigradient echo imaging and multiecho spectroscopy quantifications yielded similar correlations (r=0.87…0.93) as IP/OP imaging but were insensitive to increased LIC. Visceral fat, kidney tissue and major vessels were included regularly in the segmentation. Spectroscopic fat quantification was sensitive to the inclusion of visceral fat. ConclusionsIP/OP imaging allows HFF quantification when ruling out hepatic siderosis, whereas dedicated multi-echo imaging sequences and spectroscopy show no bias for increased iron concentration. The segmentation quality and workflow of both postprocessing solutions need to be improved. Nevertheless, all solutions are able to bring MRI-based hepatic fat quantification into the clinical application. We therefore recommend commercial hepatic fat quantification tools for institutions specialised to abdominal imaging.

Hepatic fat quantification of magnetic resonance imaging whole-liver segmentation for assessing the severity of nonalcoholic fatty liver disease: comparison with a region of interest sampling method.

Accurate and early assessment of the hepatic fat content is crucial for patients with nonalcoholic fatty liver disease (NAFLD). For years, magnetic resonance imaging (MRI) has been considered the optimal noninvasive method for the assessment of fat accumulation. To avoid time-consuming manual placement of multiple regions of interest (ROI), the use of whole-liver segmentation has been proposed to measure liver fat, mainly for heterogeneous fat deposition. However, it remains uncertain whether the hepatic mean fat fraction (FF) obtained by whole-liver segmentation with the inclusion of intrahepatic vasculature is consistent with the traditional ROI sampling method. In this study, we assessed the accuracy of hepatic mean FF obtained by whole-liver segmentation in patients of NAFLD with different severities using the ROI sampling method as a reference standard. Hepatic FFs were measured by whole-liver segmentation and the ROI sampling method (reference standard) using MRI scanning with the iterative decomposition of water and fat with echo an asymmetry at least-square estimation-iron quantification (IDEAL-IQ) sequence. SPSS version 25.0 software was used to analyze the correlation and consistency of data between the two methods. There was a strong correlation in hepatic FF between whole-liver segmentation and the ROI sampling method in healthy, mild, and moderate steatosis patients (r = 0.943, 0.990, and 0.961, respectively). Bland-Altman analysis showed a small bias of +0.50±0.27 and +0.05±0.30, which indicated a small overestimation when using whole-liver segmentation in healthy subjects and mild NAFLD patients. The 95% limits of agreement ranged from +1.02 to -0.03, and from +0.65 to -0.55, respectively. However, a small bias of -0.96±0.77 was also evident, which indicated a small underestimation when using whole-liver segmentation in moderate NAFLD patients. The 95% limits of agreement ranged from +0.56 to -2.48. Due to inclusion of the intrahepatic vasculature, whole-liver segmentation has some effects on hepatic FF assessment in patients with different NAFLD severities; yet, it does not significantly affect the assessment of whole-liver FF in MRI FF maps.

Feasibility of Hepatic Fat Quantification Using Proton Density Fat Fraction by Multi-Echo Chemical-Shift-Encoded MRI at 7T.

Fat fraction quantification and assessment of its distribution in the hepatic tissue become more important with the growing epidemic of obesity, and the increasing prevalence of diabetes mellitus type 2 and non-alcoholic fatty liver disease. At 3Tesla, the multi-echo, chemical-shift-encoded magnetic resonance imaging (CSE-MRI)-based acquisition allows the measurement of proton density fat-fraction (PDFF) even in clinical protocols. Further improvements in SNR can be achieved by the use of phased array coils and increased static magnetic field. The purpose of the study is to evaluate the feasibility of PDFF imaging using a multi-echo CSE-MRI technique at ultra-high magnetic field (7Tesla). Thirteen volunteers (M/F) with a broad range of age, body mass index, and hepatic PDFF were measured at 3 and 7T by multi-gradient-echo MRI and single-voxel spectroscopy MRS. All measurements were performed in breath-hold (exhalation); the MRI protocols were optimized for a short measurement time, thus minimizing motion-related problems. 7T data were processed off-line using Matlab® (MRI:multi-gradient-echo) and jMRUI (MRS), respectively. For quantitative validation of the PDFF results, a similar protocol was performed at 3T, including on-line data processing provided by the system manufacturer, and correlation analyses between 7 and 3T data were performed off-line. The multi-echo CSE-MRI measurements at 7T with a phased-array coil configuration and an optimal post-processing yielded liver volume coverage ranging from 30 to 90% for high- and low-BMI subjects, respectively. PDFFs ranged between 1 and 20%. We found significant correlations between 7T MRI and -MRS measurements (R2 ≅ 0.97; p < 0.005), and between MRI-PDFF at 7T and 3T fields (R2 ≅ 0.94; p < 0.005) in the evaluated volumes. Based on the measurements and analyses performed, the multi-echo CSE-MRI method using a 32-channel coil at 7T showed its aptitude for MRI-based quantitation of PDFF in the investigated volumes. The results are the first step toward qMRI of the whole liver at 7T with further improvements in hardware.

Simultaneous hepatic iron and fat quantification with dual-energy CT in a rabbit model of coexisting iron and fat.

Liver iron and fat are often co-deposited, synergistically aggravating the progression of chronic liver disease. Accurate determination of liver iron and fat content is helpful for patient management. To assess the accuracy of hepatic iron/fat decomposition using dual-energy computed tomography (DECT) for simultaneously quantifying hepatic iron and fat when both are present. Sixty-eight New Zealand rabbits on a high-fat/cholesterol diet plus iron injections were used to establish a model of coexisting hepatic iron/fat. Abdominal imaging was performed using dual-source DECT. The iron and fat fractions (Iron-CT and Fat-CT, respectively) were calculated using a 3-material decomposition algorithm. The spectroscopic liver iron concentration (LIC) grading (normal, mild, moderate, severe, and massive iron overload) and the histopathological fat fraction (Fat-ref) grading (normal, mild, moderate, severe steatosis) were used as references. Correlations between the DECT parameters and the references were analyzed. Hepatic iron/fat quantification equations were established and validated. Analysis of covariance was used to assess the influence of fat on iron measurements and vice versa. Iron-CT highly correlated with LIC (r=0.94, P<0.001), and Fat-CT highly correlated with Fat-ref (r=0.88, P<0.001). Both the Iron-CT- and Fat-CT-derived LIC and fat fraction showed good agreement with spectroscopy/histology. The linear relationship between Iron-CT and spectroscopic LIC was not affected by the grade of hepatic fat (F=1.93, P=0.16). The linear relationship between Fat-CT and Fat-ref was unaffected by hepatic iron grades from normal to severe (F=0.18, P=0.91). However, with massive iron overload [>15.0 mg Fe/g (270 µmol/g)] the regression began to deviate, causing fat underestimation (F=5.50, P=0.04). Our DECT-based iron/fat decomposition algorithm accurately measured hepatic iron and fat when both were present in a rabbit model. Hepatic fat may be underestimated when there is massive iron overload.

M84. METFORMIN FOR EARLY CO-MORBID PREDIABETES OR DIABETES IN SCHIZOPHRENIA SPECTRUM DISORDERS: A DOUBLE BLIND RANDOMIZED PILOT STUDY

BackgroundPatients with severe mental illness (SMI) loose 15–20 years of life due to cardiovascular disease. Much of the metabolic risk, including high rates of type 2 diabetes (T2D) is accrued early on in the illness, highlighting the need for early intervention strategies to target modifiable cardiovascular risk factors. Beyond cardiovascular (CV) risk, metabolic complications have wide-ranging detrimental effects on cognitive performance, medication compliance, and quality of life. There is however an astounding paucity of studies in SMI examining metabolic interventions outside of weight loss. Furthermore, patients with SMI are typically systematically excluded from trials investigating anti-diabetic agents resulting in lack of evidence to guide treatment.MethodsThirty participants with schizophrenia spectrum disorders and co-morbid prediabetes or type 2 diabetes were randomly assigned, in a double-blind fashion to 1500mg/ day of metformin or placebo (2:1 ratio; n=21 metformin and n=9 placebo). Patients had to be overweight or obese, within 5 years of psychosis onset or under the age of 40, and receiving a stable dose of antipsychotics. The primary outcome measures were improvements in glycemia (HbA1c, fasting glucose), and insulin resistance index (Matsuda-derived from glucose tolerance tests and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)). Secondary outcome measures included changes in weight, fat mass (MRI quantification of hepatic and visceral fat), improvements in cognition, and hippocampal volume (MRI). Data were analyzed using mixed-models methods, and intention to treat analysis.ResultsTwenty-two patients (n=14 metformin; n=8 placebo) completed the 4-month trial. The metformin group had a significant decrease over time in the HOMA-IR (p=0.043), and fasting blood glucose (p=0.007) vs. placebo. There were no differences between treatment groups in the Matsuda index or HBA1c or any secondary outcome measures. Interestingly, weight loss in both groups correlated significantly with decreases in subcutaneous, but not visceral adipose tissue measured by MRI. Controlling for baseline BMI and fasting blood glucose did not change any study findings. Exploratory correlations between change in metabolic indices and change in clinical and cognitive parameters did not reveal any significant associations.DiscussionIndependently of weight loss, metformin is effective in improving dysglycemia and insulin sensitivity in a young, severely mentally ill population at very high risk for early CV mortality. Our preliminary findings, however, fail to find an effect of metformin on weight reduction or tissue specific adiposity measures (which in themselves represent key CV risk factors). Notably, patients in this study had overt glucose dysregulation, a sample routinely excluded in studies examining weight loss interventions in SMI. Moreover, meta-analyses of metformin studies in SMI note greater efficacy early in the illness; possibly weight loss effects are blunted once patients develop prediabetes/T2D. It is also possible that this subgroup of patients may benefit from alternate or combined antidiabetic/obesity therapies.In conclusion, our findings support glucose lowering effects of metformin in SMI patients with early onset prediabetes/T2D, but raise the issue of treatment initiation before the development of overt glucose dysregulation to obtain maximum benefits on adiposity reduction. Given the extremely high rates of T2D in patients with SMI, future adequately powered trials are required to examine metabolic interventions in relation to CV risk factors, and also other related domains such as cognitive function in this highly under-researched population.

Effect of Daesiho-tang on obesity with non-alcoholic fatty liver disease: a study protocol for a randomised, double-blind, placebo-controlled pilot trial

BackgroundThe high prevalence of obesity and non-alcoholic fatty acid disease has become an important public health problem. Daesiho-tang (DST) is an herbal medicine widely used to treat obesity, metabolic syndrome and liver diseases. This pilot study will assess the feasibility of using DST in obese patients with a non-alcoholic fatty liver disease (NAFLD) prior to undertaking a full-scale clinical trial.Methods/designThis is a study protocol for a randomised, double-blind, parallel-group, stratified, placebo-controlled pilot trial. We will recruit a total of 60 participants with NAFLD who have a body mass index ≥ 25 kg/m2. They will take either DST or placebo (3 g, three times daily) for 12 weeks with a 4-week follow-up period. The effects of DST will be evaluated by the mean change in body weight as the primary measurement and other secondary parameters (body composition, anthropometric measurements, blood tests, hepatic fat quantification through transient elastography and a physical symptoms questionnaire). Faecal samples will be collected before and after the intervention for a gut microbial analysis.DiscussionIn anticipation of conducting further large-scale trials, in this study we will explore the effect of DST on weight loss and obesity-related markers, along with NAFLD-related clinical parameters, in obese patients with NAFLD. Furthermore, it will provide insight into the DST pharmacological mechanism of action through a gut microbiome analysis.Trial registrationKorean Clinical Trial Registry, KCT0003554. Registered on 25 February 2019.

Minimally Invasive Sleeve Gastrectomy as a Surgical Treatment for Nonalcoholic Fatty Liver Disease in Liver Transplant Recipients

BackgroundObesity is a major public health burden that affects the transplant community because of its key role in fatty liver disease and transplantation outcomes. ObjectivesTo evaluate the role of sleeve gastrectomy in treating recurrent and de novo nonalcoholic fatty liver disease (NAFLD) in liver transplant recipients. SettingA university hospital. MethodsWe describe 2 obese liver transplant recipients with recurrent and de novo NAFLD who underwent minimally invasive metabolic and bariatric surgery. ResultsThe surgery was performed successfully, with much of the operative time consumed by enterolysis. There were no intraoperative or postoperative complications. At last follow-up appointment (16 months postoperatively), there was a mean reduction in weight (31.98 kg), body mass index (10.2 kg/m2), glycosylated hemoglobin (1.05%), alanine aminotransferase (38 IU/L), steatosis score (0.34), and fibrosis score (0.05). The mean decrease in 6-month postoperative hepatic fat quantification was 6%. ConclusionsThese cases show that metabolic and bariatric surgery in obese, posttransplant recipients with recurrent and de novo nonalcoholic steatohepatitis lead to improved steatosis and reduced obesity and obesity-associated comorbidities.