Liver Fat Quantification Research Articles

Abbreviated Multiparametric MR Solution (the “Liver Triple Screen”), the Future of Non-Invasive MR Quantification of Liver Fat, Iron, and Fibrosis

Background/Objectives: To review the findings of a multiparametric MRI (the “liver triple screen”) solution for the non-invasive assessment of liver fat, iron, and fibrosis in patients with chronic liver disease (CLD). Methods: A retrospective evaluation of all consecutive triple screen MRI cases was performed at our institution over the last 32 months. Relevant clinical, laboratory, and radiologic data were analyzed using descriptive statistics. Results: There were 268 patients, including 162 (60.4%) males and 106 (39.6%) females. The mean age was 54 ± 15.2 years (range 16 to 71 years). The most common cause of CLD was metabolic dysfunction-associated steatotic liver disease (MASLD) at 45.5%. The most common referring physician group was Gastroenterology at 62.7%. In 23.9% of cases, the reason for ordering the MRI was a pre-existing failed or unreliable US elastography. There were 17 cases (6.3%) of MRI technical failure. Our analysis revealed liver fibrosis in 66% of patients, steatosis in 68.3%, and iron overload in 22.1%. Combined fibrosis and steatosis were seen in 28.7%, steatosis and iron overload in 16.8%, fibrosis and iron overload in 6%, and combined fibrosis, steatosis, and iron overload in 4.1%. A positive MEFIB index, a predictor of liver-related outcomes, was found in 57 (27.5%) of 207 patients. Incidental findings were found in 14.9% of all MRIs. Conclusions: The liver triple screen MRI is an effective tool for evaluating liver fat, iron, and fibrosis in patients with CLD. It provides essential clinical information and can help identify MASLD patients at risk for liver-related outcomes.

Interobserver Reproducibility of Ultrasound Attenuation Imaging Technology in Liver Fat Quantification.

This study aims to investigate the interobserver variability in the quantitative assessment of liver fat content using ultrasound attenuation imaging technology (USAT). This prospective, single-center study included 96 adult patients who were either diagnosed with or suspected of having metabolic dysfunction-associated steatotic liver disease. Independent observers, blinded to each other's assessments, evaluated hepatic steatosis visually and through USAT measurements. Separate measurements were taken at five intercostal and subcostal sites, and the median values of these measurements were recorded. The correlation between USAT measurements and visual steatosis grades was examined using Spearman's correlation test. Intraclass correlation coefficient (ICC) and Bland-Altman analysis were used to evaluate the interobserver variability of USAT measurements. Interobserver agreement for USAT measurements was excellent for the intercostal examination and good for the subcostal examination (p < 0.001). Body mass index did not significantly affect the level of interobserver agreement. Interobserver variability in Bland-Altman plots of USAT measurements was within the 95% limits of agreement. USAT measurements correlated very strongly with the visual degree of hepatic steatosis, both intercostal and subcostal (p < 0.001). USAT measurements were also significantly different between different visual degrees of hepatic steatosis (p < 0.001). In the assessment of hepatic steatosis, USAT measurements obtained from the intercostal space showed excellent agreement in terms of interobserver reproducibility.

Association of liver multi-parameter quantitative metrics determined by dual-layer spectral detector computed tomography (SDCT) with coronary plaque scores.

Hepatic steatosis is closely related to the occurrence and development of coronary plaques. Spectral detector computed tomography (SDCT) can provide more precise multiparameter quantitative parameters for hepatic steatosis. Hence, the purpose of this cross-sectional study was to explore the effect of quantitative liver metrics measured using SDCT on the extent and severity of coronary plaques. In patients who underwent upper abdomen unenhanced SDCT and coronary computed tomography angiography, plaque extent and severity were assessed using segmental involvement score (SIS) and segmental stenosis score (SSS). Liver fat quantification was evaluated by polychromatic and virtual mono-energetic images at 40 and 70 kev, spectral attenuation curve slope, and effective atomic number (CT40 keV, CT70 kev, λHU, and Zeff, respectively). A logistic regression model evaluated the factors influencing high SIS and SSS. Enrolled patients (n=644) were divided into groups: low SIS (<5) (n=451), high SIS (≥5) (n=193), low SSS (<5) (n=461), and high SSS (≥5) (n=183). Zeff was more closely correlated with SIS (standard partial regression coefficient =-0.422, P<0.001) and SSS (standard partial regression coefficient =-0.346, P<0.001). Zeff was divided into four groups using interquartile intervals. Compared with the patients in the lowest quartile, those in the second [odds ratio (OR) =2.116, 95% confidence interval (CI): 1.134-3.949, P=0.018], third (OR =2.832, 95% CI: 1.461-5.491, P=0.002), and fourth (OR =3.584, 95% CI: 1.857-6.918, P<0.001) quartiles showed higher risk for high SIS. And correspondingly, the second (OR =1.933, 95% CI: 1.040-3.592, P=0.037), third (OR =2.900, 95% CI: 1.499-5.609, P=0.002), and fourth (OR =3.368, 95% CI: 1.743-6.510, P<0.001) quartiles showed higher risk for high SSS, especially in those who were <60 years old, male and had visceral adipose tissue/subcutaneous adipose tissue <1.18. The SDCT-Zeff was an independent factor associated with high SIS and SSS. The quantification of liver fat may be useful for evaluating the risk and prognosis of coronary atherosclerosis.

Assessing Quality of Ultrasound Attenuation Coefficient Results for Liver Fat Quantification.

Algorithms for quantifying liver fat content based on the ultrasound attenuation coefficient (AC) are currently available; however, little is known about whether their accuracy increases by applying quality criteria such as the interquartile range-to-median ratio (IQR/M) or whether the median or average AC value should be used. AC measurements were performed with the Aplio i800 ultrasound system using the attenuation imaging (ATI) algorithm (Canon Medical Systems, Otawara, Tochigi, Japan). Magnetic resonance imaging proton density fat fraction (MRI-PDFF) was the reference standard. The diagnostic performance of the AC median value of 5 measurements (AC-M) was compared to that of AC average value (AC-A) of 5 or 3 acquisitions and different levels of IQR/M for median values or standard deviation/average (SD/A) for average values were also analyzed. Concordance between AC-5M, AC-5A, and AC3A was evaluated with concordance correlation coefficient (CCC). A total of 182 individuals (94 females; mean age, 51.2y [SD: 15]) were evaluated. A total of 77 (42.3%) individuals had S0 steatosis (MRI-PDFF < 6%), 75 (41.2%) S1 (MRI-PDFF 6-17%), 10 (5.5%) S2 (MRI-PDFF 17.1-22%), and 20 (11%) S3 (MRI-PDFF ≥ 22.1%). Concordance of AC-5A and AC-3A with AC-5M was excellent (CCC: 0.99 and 0.96, respectively). The correlation with MRI-PDFF was almost perfect. Diagnostic accuracy of AC-5M, AC-5A, and AC3A was not significantly affected by different levels of IQR/M or SD/A. The accuracy of AC in quantifying liver fat content was not affected by reducing the number of acquisitions (from five to three), by using the mean instead of the median, or by reducing the IQR/M or SD/A to ≤5%.

Potential of Raman-Reflectance Combination in Quantifying Liver Steatosis and Fat Droplet Size: Evidence From Monte Carlo Simulations and Phantom Studies.

This study explores a combined strategy of Raman and reflectance spectroscopy for quantifying liver fat content and fat droplet size, crucial in assessing donor livers. By using Monte Carlo simulations and experimental setups with oil-in-water phantoms, our findings indicate that Raman scattering can solely differentiate between varying fat contents. At the same time, reflectance intensity is influenced by both fat content and oil droplet size, with a more pronounced sensitivity to fat droplet size. This study demonstrates the efficacy of combined Raman and reflectance spectroscopy in assessing liver steatosis and fat droplet size, potentially aiding in assessing donor livers for transplantation.

Ultrasound-estimated hepatorenal index: diagnostic performance and interobserver agreement for pediatric liver fat quantification.

Semiquantitative and quantitative sonographic techniques have the potential for screening and surveillance of children at risk of nonalcoholic fatty liver disease. To determine diagnostic performance and interobserver agreement of hepatorenal index (HRI) for pediatric ultrasound-based liver fat quantification. In an institutional review board (IRB)-approved retrospective study (April 2014 to April 2023), children (< 18years) with clinically performed magnetic resonance imaging (MRI) scans for liver fat quantification were assessed. Inclusion criteria required availability of abdominal ultrasound within 3months of quantitative MRI. Three blinded readers subjectively assessed for sonographic hepatic steatosis and calculated HRI. MRI proton density fat fraction (PDFF) was the reference standard. Interobserver agreement, correlation with PDFF, and optimal HRI (using ROC analysis) values were analyzed. The significance level was set at p < 0.05. A total of 41 patients (25 male) with median (interquartile range (IQR)) age of 13 (10-15) years were included. Median (IQR) MRI PDFF was 11.30% (2.70-17.95%). Hepatic steatosis distribution by MRI PDFF included grade 0 (34%), grade 1 (15%), grade 2 (22%), and grade 3 (29%) patients. Intraclass correlation coefficient for HRI among the three readers was 0.61 (95% CI 0.43-0.75) (p < 0.001). Moderate correlation was observed between manually estimated HRI and PDFF for each reader (r = 0.62, 0.67, and 0.67; p < 0.001). Optimal HRI cutoff was found to be 1.99 to diagnose hepatic steatosis (sensitivity 89%, specificity 93%). Median (IQR) HRI for each MRI grade of hepatic steatosis (0-4) was as follows: 1.2 (1.1-1.5), 2.6 (1.1-3.3), 3.6 (2.6-5.4), 5.6 (2.6-10.9), respectively (p < 0.001). Ultrasound-estimated HRI has moderate interobserver agreement and moderate correlation with MRI-derived PDFF. HRI of 1.99 maximizes accuracy for identifying pediatric liver fat.

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.

An ultrasound multiparametric method to quantify liver fat using magnetic resonance as standard reference.

There is an unmet need for a reliable and reproducible non-invasive measure of fatty liver content (FLC) for monitoring steatotic liver disease in clinical practice. Sonographic FLC assessment is qualitative and operator-dependent, and the dynamic quantification range of algorithms based on a single ultrasound (US) parameter is unsatisfactory. This study aims to develop and validate a new multiparametric algorithm based on B-mode images to quantify FLC using Magnetic Resonance (MR) values as standard reference. Patients with elevated liver enzymes and/or bright liver at US (N = 195) underwent FLC evaluation by MR and by US. Five US-derived quantitative features [attenuation rate(AR), hepatic renal-ratio(HR), diaphragm visualization(DV), hepatic-portal-vein-ratio(HPV), portal-vein-wall(PVW)] were combined by mixed linear/exponential regression in a multiparametric model (Steatoscore2.0). One hundred and thirty-four subjects were used for training and 61 for independent validations; score-computation underwent an inter-operator reproducibility analysis. The model is based on a mixed linear/exponential combination of 3 US parameters (AR, HR, DV), modelled by 2 equations according to AR values. The computation of FLC by Steatoscore2.0 (mean ± std, 7.91% ± 8.69) and MR (mean ± std, 8.10% ± 10.31) is highly correlated with a low root mean square error in both training/validation cohorts, respectively (R = 0.92/0.86 and RMSE = 5.15/4.62, p < .001). Steatoscore2.0 identified patients with MR-FLC≥5%/≥10% with sensitivity = 93.2%/89.4%, specificity = 86.1%/95.8%, AUROC = 0.958/0.975, respectively and correlated with MR (R = 0.92) significantly (p < .001) better than CAP (R = 0.73). Multiparametric Steatoscore2.0 measures FLC providing values highly comparable with MR. It is reliable, inexpensive, easy to use with any US equipment and qualifies to be tested in larger, prospective studies as new tool for the non-invasive screening and monitoring of FLC.

Quantification of liver fat using non-invasive MRI-PDFF technique versus guided biopsy in potential liver donor

IntroductionSignificant hepatic steatosis affects the outcome of surgery when living donors are transplanted. The gold standard for diagnosing and evaluating hepatic steatosis is hepatic imaging-guided biopsy. Hepatic steatosis assessment using MR spectroscopy and the proton density fat fraction (MR-PDFF) method has produced positive findings.ObjectivesIs to compare the pre-operative assessment of liver fat quantification using MRI-PDFF methods, a non-invasive method, with histopathology.Subjects and methodsA 42 potential donors were then operated surgically for liver transplantation, consequently, were available for the assessment of the efficiency and sensitivity of the radiological findings MRI-PDFF procedures and imaging-guided liver biopsy. This radiological workup of these donors was done through a period of 7 months.ResultsIn many liver transplantations centers, liver imaging-guided biopsy histopathological examination is the gold standard. The study examined the MR proton density fat fraction modality, a recently developed test for hepatic steatosis measurement. The findings indicate 86.8% sensitivity, 50% specificity, 94.2% PDV, 28.5% NPV, 83.3% accuracy, and 0.684 AUC. On analyzing the fat percent, we found that the recorded fat percent using liver imaging-guided biopsy ranges between 1 and 10% with a median of 3. On the other hand, the recorded fat percent using MRI ranged between 2 and 15% with a median of 5.ConclusionThe non-invasive magnetic resonance hepatic proton density fat fraction approach using IDEAL sequence is a reliable and accurate means of quantitatively evaluating hepatic steatosis with excellent sensitivity, specificity, and accuracy.

Free-breathing MRI techniques for fat and R2* quantification in the liver.

To review the recent advancements in free-breathing MRI techniques for proton-density fat fraction (PDFF) and R2* quantification in the liver, and discuss the current challenges and future opportunities. This work focused on recent developments of different MRI pulse sequences, motion management strategies, and reconstruction approaches that enable free-breathing liver PDFF and R2* quantification. Different free-breathing liver PDFF and R2* quantification techniques have been evaluated in various cohorts, including healthy volunteers and patients with liver diseases, both in adults and children. Initial results demonstrate promising performance with respect to reference measurements. These techniques have a high potential impact on providing a solution to the clinical need of accurate liver fat and iron quantification in populations with limited breath-holding capacity. As these free-breathing techniques progress toward clinical translation, studies of the linearity, bias, and repeatability of free-breathing PDFF and R2* quantification in a larger cohort are important. Scan acceleration and improved motion management also hold potential for further enhancement.

Perspective article: determinants and assessment of cardiovascular risk in steatotic liver disease owing to metabolic dysfunction-addressing the challenge

Metabolic dysfunction-associated steatotic liver disease (MASLD) stands as an independent risk factor for cardiovascular disease (CVD), which is the leading cause of mortality among MASLD patients. The diverse spectrum of cardio-nephro-metabolic and vascular manifestations inherent in MASLD highlights the complex profile of CVD risk associated with this condition. However, current approaches to assessing CVD risk in MASLD lack specificity, predominantly relying on traditional markers. Although it is widely accepted that patients with advanced fibrosis are more prone to CVD risk, recent evidence suggests that this isolated focus may overlook the remarkable phenotypic variability of this CVD risk across the entire MASLD population. Emerging data indicate a progressive escalation of CVD risk in parallel with the severity of MASLD, highlighting the need for precise disease staging to inform accurate risk assessment. To address this challenge, we propose a novel sequential approach to CVD risk assessment in MASLD. While traditional CVD risk factors remain essential, incorporating liver-specific parameters enhances risk stratification and guides targeted interventions to mitigate the substantial burden of cardiovascular disease in this vulnerable population. This approach involves initial screening using FIB-4 and NAFLD fibrosis score, followed by assessment of liver fibrosis with imaging-based non-invasive techniques in individuals at intermediate-high risk for advanced fibrosis and liver fat quantification in low-risk individuals. Future prospective investigations should focus on the simultaneous use of liver biomarkers and imaging modalities to evaluate, in a sex-specific manner, the efficacy of the proposed approach and to determine optimal thresholds of liver fibrosis and steatosis for optimal CVD risk assessment.

Four hepatic steatosis indices in predicting quantitative computed tomography-based metabolic dysfunction-associated fatty liver disease

Aim: To evaluate the prediction ability for quantitative computed tomography (QCT)-based metabolic dysfunction-associated fatty liver disease (MAFLD) of four widely known hepatic steatosis algorithms, namely the fatty liver index (FLI), the hepatic steatosis index (HSI), the Framingham Steatosis index (FSI) and the Zhejiang University index (ZJU index). Methods: From July 2020 to June 2022, health checkup subjects who accepted liver fat quantification with QCT at the Health Management Center of the Second Affiliated Hospital of Chongqing Medical University were recruited in this study. MAFLD was diagnosed by using QCT-based liver fat quantification. The prediction performance of FLI, HSI, FSI, and ZJU index on MAFLD was evaluated using the area under the receiver operating characteristic curve (AUC). Results: Of a total of 4,566 subjects enrolled in this study, 48.7% were diagnosed with MAFLD. The AUC values of FLI, HSI, FSI, and ZJU index were 0.819, 0.792, 0.822 and 0.826, respectively. FLI exhibited the highest sensitivity (SN) of 79.42%, while the ZJU index demonstrated the highest specificity (SP) of 75.35%. Conclusions: All four indices (FLI, HSI, FSI, and ZJU index) have acceptable predictive performance for patients with QCT-based MAFLD. Our study suggests that the above indices have a stable ability for detecting MAFLD.

Update on Imaging-based Noninvasive Methods for Assessing Hepatic Steatosis in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD), among the most common chronic liver diseases worldwide, affects approximately 25% of the global population. Its incidence is increasing owing to various risk factors, including genetic variation, metabolic health, dietary habits, and microbiota. Hepatic steatosis is a critical histological characteristic of NAFLD. Evaluating liver fat content is vital for identifying and following up with patients at risk of developing NAFLD. NAFLD includes simple liver steatosis and more severe forms such as inflammation, nonalcoholic steatohepatitis, fibrosis, and cirrhosis. The early assessment of fatty liver is important for reversing liver disease progression. Metabolic (dysfunction)-associated fatty liver disease recently replaced NAFLD as the most common hepatic disease worldwide. This article reviews the current state of noninvasive imaging, especially ultrasound, for liver fat quantification.

IATT liver fat quantification for steatosis grading by referring to MRI proton density fat fraction: a multicenter study.

Several preliminary reports have suggested the utility of ultrasound attenuation coefficient measurements based on B-mode ultrasound, such as iATT, for diagnosing steatotic liver disease. Nonetheless, evidence supporting such utility is lacking. This prospective study aimed to investigate whether iATT is highly concordant with magnetic resonance imaging (MRI)-based proton density fat fraction (MRI-PDFF) and could well distinguish between steatosis grades. A cohort of 846 individuals underwent both iATT and MRI-PDFF assessments. Steatosis grade was defined as grade 0 with MRI-PDFF < 5.2%, grade 1 with 5.2% MRI-PDFF < 11.3%, grade 2 with 11.3% MRI-PDFF < 17.1%, and grade 3 with MRI-PDFF of 17.1%. The reproducibility of iATT and MRI-PDFF was evaluated using the Bland-Altman analysis and intraclass correlation coefficients, whereas the diagnostic performance of each steatosis grade was examined using receiver operating characteristic analysis. The Bland-Altman analysis indicated excellent reproducibility with minimal fixed bias between iATT and MRI-PDFF. The area under the curve for distinguishing steatosis grades 1, 2, and 3 were 0.887, 0.882, and 0.867, respectively. A skin-to-capsula distance of ≥ 25mm was identified as the only significant factor causing the discrepancy. No interaction between MRI-logPDFF and MRE-LSM on iATT values was observed. Compared to MRI-PDFF, iATT showed excellent diagnostic accuracy in grading steatosis. iATT could be used as a diagnostic tool instead of MRI in clinical practice and trials. Trial registration This study was registered in the UMIN Clinical Trials Registry (UMIN000047411).

Correlation between magnetic resonance imaging proton density fat fraction (MRI-PDFF) and liver biopsy to assess hepatic steatosis in obesity

Obesity is highly associated with Non-alcoholic fatty liver disease (NAFLD) and increased risk of liver cirrhosis and liver cancer-related death. We determined the diagnostic performance of the complex-based chemical shift technique MRI-PDFF for quantifying liver fat and its correlation with histopathologic findings in an obese population within 24 h before bariatric surgery. This was a prospective, cross-sectional, Institutional Review Board-approved study of PDFF-MRI of the liver and MRI-DIXON image volume before bariatric surgery. Liver tissues were obtained during bariatric surgery. The prevalence of NAFLD in the investigated cohort was as high as 94%. Histologic hepatic steatosis grades 0, 1, 2, and 3 were observed in 3 (6%), 25 (50%), 14 (28%), and 8 (16%) of 50 obese patients, respectively. The mean percentages of MRI-PDFF from the anterior and posterior right hepatic lobe and left lobe vs. isolate left hepatic lobe were 15.6% (standard deviation [SD], 9.28%) vs. 16.29% (SD, 9.25%). There was a strong correlation between the percentage of steatotic hepatocytes and MRI-PDFF in the left hepatic lobe (r = 0.82, p < 0.001) and the mean value (r = 0.78, p < 0.001). There was a strong correlation between MRI-derived subcutaneous adipose tissue volume and total body fat mass by dual-energy X-ray absorptiometry, especially at the L2–3 and L4 level (r = 0.85, p < 0.001). MRI-PDFF showed good performance in assessing hepatic steatosis and was an excellent noninvasive technique for monitoring hepatic steatosis in an obese population.

Recent advances in noninvasive assessment of liver steatosis.

Due to the steatosis epidemic, noninvasive quantification of liver fat content is of great interest. Magnetic resonance (MR) techniques, including proton MR spectroscopy (MRS) and MR chemical shift imaging can quantify liver fat by measuring, directly or indirectly (the latter), the proton density fat fraction (PDFF). They have shown excellent diagnostic accuracy and are currently the reference standard for the noninvasive assessment of liver steatosis and are used in clinical trials for evaluating the change in liver fat over time. Using ultrasound (US), three different quantitative parameters can be obtained to estimate liver fat: attenuation coefficient, backscatter coefficient, and speed of sound. Controlled attenuation parameter (CAP), which estimates the attenuation of the US beam, was the first algorithm available and is performed with a non-imaging system. Currently, several other algorithms are available on B-mode imaging ultrasound systems, and they have shown an accuracy similar to or higher than the CAP. This article reports the current knowledge about their application in patients with metabolic dysfunction-associated steatotic liver disease.

Quantifying the effect of nutritional interventions on metabolic resilience using personalized computational models

The manifestation of metabolic deteriorations that accompany overweight and obesity can differ greatly between individuals, giving rise to a highly heterogeneous population. This inter-individual variation can impede both the provision and assessment of nutritional interventions as multiple aspects of metabolic health should be considered at once. Here, we apply the Mixed Meal Model, a physiology-based computational model, to characterize an individual's metabolic health in silico. A population of 342 personalized models were generated using data for individuals with overweight and obesity from three independent intervention studies, demonstrating a strong relationship between the model-derived metric of insulin resistance (ρ= 0.67, p<0.05) and the gold-standard hyperinsulinemic-euglycemic clamp. The model is also shown to quantify liver fat accumulation and β-cell functionality. Moreover, we show that personalized Mixed Meal Models can be used to evaluate the impact of a dietary intervention on multiple aspects of metabolic health at the individual level.

Liver fat volume fraction measurements based on multi-material decomposition algorithm in patients with nonalcoholic fatty liver disease: the influences of blood vessel, location, and iodine contrast

BackgroundIn recent years, spectral CT-derived liver fat quantification method named multi-material decomposition (MMD) is playing an increasingly important role as an imaging biomarker of hepatic steatosis. However, there are various measurement ways with various results among different researches, and the impact of measurement methods on the research results is unknown. The aim of this study is to evaluate the reproducibility of liver fat volume fraction (FVF) using MMD algorithm in nonalcoholic fatty liver disease (NAFLD) patients when taking blood vessel, location, and iodine contrast into account during measurement.MethodsThis retrospective study was approved by the institutional ethics committee, and the requirement for informed consent was waived because of the retrospective nature of the study. 101 patients with NAFLD were enrolled in this study. Participants underwent non-contrast phase (NCP) and two-phase enhanced CT scanning (late arterial phase (LAP) and portal vein phase (PVP)) with spectral mode. Regions of interest (ROIs) were placed at right posterior lobe (RPL), right anterior lobe (RAL) and left lateral lobe (LLL) to obtain FVF values on liver fat images without and with the reference of enhanced CT images. The differences of FVF values measured under different conditions (ROI locations, with/without enhancement reference, NCP and enhanced phases) were compared. Friedman test was used to compare FVF values among three phases for each lobe, while the consistency of FVF values was assessed between each two phases using Bland–Altman analysis.ResultsSignificant difference was found between FVF values obtained without and with the reference of enhanced CT images. There was no significant difference about FVF values obtained from NCP images under the reference of enhanced CT images between any two lobes or among three lobes. The FVF value increased after the contrast injection, and there were significant differences in the FVF values among three scanning phases. Poor consistencies of FVF values between each two phases were found in each lobe by Bland–Altman analysis.ConclusionMMD algorithm quantifying hepatic fat was reproducible among different lobes, while was influenced by blood vessel and iodine contrast.

Development and evaluation of emulsified reference materials for magnetic resonance imaging

Hepatic steatosis is characterized by an abnormal accumulation of lipids within hepatocytes. Magnetic resonance imaging (MRI) is a widely used noninvasive method that can accurately and objectively quantify liver fat. To evaluate the accuracy of the quantitatively measured fat fraction, stable and homogenous qualified material is needed as a reference. Surfactant-free micro-emulsions of three fat fractions I, II, and III, corresponding to (9.12 ± 0.02)%, (18.32 ± 0.04)%, and (27.86 ± 0.05)%, respectively, were prepared using a high-intensity focused ultrasonic emulsification technique. The targeted fat fraction of 10%–30% covers the range of grade I moderate non-alcoholic fatty liver disease, which occurs in the early stages that require early detection. Water contents as the main component of the emulsified reference materials (RMs) were determined using the Karl Fisher titration method to evaluate the stability and homogeneity of the RMs. The water contents of fat fraction I, II, and III were (89.12 ± 1.08)%, (79.87 ± 0.81)%, and (72.71 ± 1.29)%, respectively. The RMs were stable for six months and showed good homogeneity with both standard deviations between and within units in the range of 0.3%–0.6%. The physical phantom consisted of nine vials of RMs surrounded by agarose gel. The phantom was scanned on 3 T MRI (Siemens MAGNETOM Vida, Siemens Healthineers, Erlangen, Germany). The correlation between the measured proton density fat fraction values and the fabricated fat fraction values was evaluated using linear regression analysis. The slope of the linear fitting was 0.99, and the intercept was −0.88%. These results show that the developed RMs can provide a reference value for the measured fat fraction from a medical imaging system to evaluate the effectiveness of a measurement procedure. It is also expected that the developed RMs can be utilized to harmonize the measured values across multi-site.

Systematic review with meta-analysis: Steatosis severity and subclinical atherosclerosis in metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent liver condition recognised as an independent risk factor for cardiovascular disease (CVD). However, there is ongoing debate regarding the effective strategy for cardiovascular risk assessment in MASLD. To investigate the relationship between liver imaging, specifically focusing on the severity of steatosis and subclinical atherosclerosis. We conducted a thorough search across four databases, from 1950 to April 2023, to identify eligible studies employing imaging to explore the relationship between different degrees of steatosis and subclinical atherosclerosis among MASLD. Additionally, we conducted a quality assessment using the Newcastle Ottawa Scale, performed a meta-analysis employing the DerSimonian-Liard random-effects model, and conducted subgroup analyses for validation. In total, 19 studies, encompassing 147,411 middle-aged individuals without previous CVD (74.94% male; mean age 45.53 years [SD 10.69]; mean BMI 24.3 kg/m2 [SD 3.35]), were included. The pooled odds ratio for subclinical atherosclerosis was 1.27 (95% CI: 1.13-1.41, I2 = 76.68%) in mild steatosis and significantly increased to 1.68 (95% CI: 1.41-2.00, I2 = 89.02%) in moderate to severe steatosis. Sensitivity analysis, focusing on high-quality studies, consistently supported this finding and the results remained robust across subgroup analyses. Furthermore, meta-regression revealed that a higher mean AST and ALT, alongside a lower mean HDL, were significant moderators of this association. Even mild steatosis is associated with CVD risk, and steatosis severity further intensifies this association. These findings suggest that liver fat quantification enhances CVD risk stratification in patients with MASLD.