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Keywords = proton-density fat fraction

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11 pages, 856 KB  
Article
MRI-Based Assessment of Etiology-Specific Sarcopenia Phenotypes in Chronic Liver Disease: A Comparative Study of MASH and Viral Hepatitis
by Mika Yasutomi, Kazuhiro Saito, Yoichi Araki, Katsutoshi Sugimoto, Daisuke Yoshimaru, Shuhei Shibukawa and Masanori Ishida
Diagnostics 2026, 16(2), 306; https://doi.org/10.3390/diagnostics16020306 (registering DOI) - 17 Jan 2026
Abstract
Background: Sarcopenia is a clinically important complication of chronic liver disease (CLD), but its underlying mechanisms may differ according to disease etiology. Quantitative MRI biomarkers, including proton density fat fraction (PDFF) and magnetic resonance elastography (MRE), may help characterize etiology-specific patterns of muscle [...] Read more.
Background: Sarcopenia is a clinically important complication of chronic liver disease (CLD), but its underlying mechanisms may differ according to disease etiology. Quantitative MRI biomarkers, including proton density fat fraction (PDFF) and magnetic resonance elastography (MRE), may help characterize etiology-specific patterns of muscle loss. This study aimed to explore etiology-specific associations between MRI-derived biomarkers and sarcopenia, with a particular focus on metabolic dysfunction-associated steatohepatitis (MASH) and viral hepatitis. Methods: This retrospective single-center study included 131 CLD patients (77 with MASH, 54 with viral hepatitis) who underwent MRI, including PDFF and MRE. Sarcopenia was defined by L2 skeletal muscle index thresholds (<42 cm2/m2 for men, <38 cm2/m2 for women). Muscle identification was performed by automatic threshold-based segmentation by a single observer. Multivariable logistic regression analyses incorporating interaction terms were performed to evaluate whether associations between MRI biomarkers and sarcopenia differed by etiology. Results: Sarcopenia was present in 56% of patients. In the overall cohort, older age (OR = 1.05, p = 0.01), lower PDFF (OR = 0.93, p = 0.03), and lower liver stiffness (OR = 0.51, p = 0.006) were independently associated with sarcopenia. A significant interaction between BMI and disease etiology was observed (p = 0.02). Subgroup analyses suggested that in MASH, sarcopenia was associated with aging, hepatic fat depletion, and lower stiffness. In contrast, in viral hepatitis, it tended to be associated with higher stiffness and lower BMI. Conclusion: MRI-derived hepatic fat and stiffness reflect distinct etiologic patterns of sarcopenia in CLD—metabolically depleted in MASH and fibrosis-related in viral hepatitis. These findings suggest that sarcopenia in MASH and viral hepatitis may reflect different underlying phenotypic patterns, highlighting the importance of considering disease etiology in imaging-based sarcopenia assessment. The results should be interpreted as hypothesis-generating and warrant validation in prospective studies. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
21 pages, 7325 KB  
Article
Choline Deficiency Drives the Inflammation–Fibrosis Cascade: A Spatiotemporal Atlas of Hepatic Injury from Weeks 6 to 10
by Shang Li, Guoqiang Zhang, Xiaohong Li, Xu Zhao, Axi Shi, Qingmin Dong, Changpeng Chai, Xiaojing Song, Yuhui Wei and Xun Li
Antioxidants 2026, 15(1), 110; https://doi.org/10.3390/antiox15010110 - 15 Jan 2026
Viewed by 63
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly linked to systemic metabolic disturbances and features a lipid-driven cascade that promotes hepatic inflammation and fibrosis. Choline insufficiency contributes to disease advancement by altering phospholipid turnover and redox homeostasis; however, its spatial and temporal regulatory [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly linked to systemic metabolic disturbances and features a lipid-driven cascade that promotes hepatic inflammation and fibrosis. Choline insufficiency contributes to disease advancement by altering phospholipid turnover and redox homeostasis; however, its spatial and temporal regulatory roles throughout MASLD progression remain insufficiently defined. A 10-week high-fat, choline-deficient (HFCD) mouse model was established, and liver pathology was evaluated at weeks 6, 8, and 10. Time-resolved assessments combined untargeted metabolomics, magnetic resonance imaging–proton density fat fraction (MRI-PDFF), serum biochemistry, histological staining, immunofluorescence, and transmission electron microscopy to characterize dynamic alterations in lipid metabolism, redox status, inflammation, and fibrogenesis. The HFCD diet produced a clear temporal sequence of liver injury. Steatosis, phosphatidylcholine depletion, and early antioxidant loss appeared by week 6. By week 8, mitochondrial structural damage and pronounced cytokine elevation were evident. At week 10, collagen deposition and α-SMA activation signaled fibrotic progression. Metabolomics indicated significant disruptions in pathways related to ATP-binding cassette (ABC) transporters, one-carbon metabolism, and the tricarboxylic acid (TCA) cycle. Using integrated analytical strategies, this study suggests that choline deficiency may be associated with a time-dependent pathological cascade in MASLD, beginning with phospholipid destabilization and extending to altered mitochondria–endoplasmic reticulum crosstalk at mitochondria-associated membranes, alongside amplified oxidative–inflammatory responses, which collectively may contribute to progressive fibrogenesis as the disease advances. Full article
(This article belongs to the Topic Oxidative Stress and Inflammation, 3rd Edition)
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12 pages, 3355 KB  
Article
Fat Content Quantification with US Attenuation Coefficient: Phantom Correlation with MRI Proton Density Fat Fraction
by Rongying Chen, Genglin Zhang, Jie Zeng, Yin Zhang, Haixin Chen, Jie Ren, Xin Chen, Manli Wu, Haoming Lin and Ting Zhang
Diagnostics 2026, 16(1), 80; https://doi.org/10.3390/diagnostics16010080 - 25 Dec 2025
Viewed by 261
Abstract
Objective: The aim of this study was to evaluate the consistency and reproducibility of attenuation coefficient (AC) measurements using different commercial ultrasound (US) across via a phantom experiment to investigate the relationship between the AC and MRI-derived proton density fat fraction (MRI-PDFF) values [...] Read more.
Objective: The aim of this study was to evaluate the consistency and reproducibility of attenuation coefficient (AC) measurements using different commercial ultrasound (US) across via a phantom experiment to investigate the relationship between the AC and MRI-derived proton density fat fraction (MRI-PDFF) values and the conversion equation. Methods: Twelve phantoms containing varying fat proportions (0–100%) were constructed. Phantom ACs were estimated via three US attenuation systems, including attenuation imaging (ATI), ultrasound attenuation analysis (USAT), and the US-guided attenuation parameter (UGAP), along with MRI-PDFF. Agreement among the AC values from the three ultrasonic attenuation systems was evaluated. Linear correlation analysis was used to explore the ACs, fat concentrations of the phantom, and MRI-PDFF measurements, from which a linear conversion formula between the ultrasonic attenuation parameters and the MRI-PDFF was derived. Results: MRI-PDFF and phantom fat concentration measurements appeared with a strong linear correlation (R2 = 0.996, p < 0.001). For the three US attenuation parameters, both inter-operator and intra-operator intraclass correlation coefficients (ICCs) ranged from 0.990 to 0.995 and 0.989 to 0.995, respectively. Bland–Altman analysis revealed no significant differences between the above three (all p > 0.05). Significant linear relationships were demonstrated between ultrasound attenuation parameters and phantom fat concentration (r = 0.938–0.986; all p < 0.001), as well as between ultrasound attenuation parameters and MRI-PDFF values (r = 0.922–0.982; all p < 0.001). A conversion formula (fat proportions ≤ 50%) was derived: US (dB/cm/MHz) = 0.501 + 0.012 MRI-PDFF (%). Conclusions: AC across different commercial ultrasound devices demonstrated significant diagnostic value in fat concentrations that appeared good consistency in measuring phantom fat concentration both between and within groups. The linear relationship between AC and MRI-PDFF enables the application of a conversion formula. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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19 pages, 3623 KB  
Article
An Invisible Early Steatosis Phenotype Defined for a Large Population-Based Cohort
by Thierry Poynard, Olivier Deckmyn, Valentina Peta, Raluca Pais, Bernard Van Beers, Laurent Castera, Frederic Charlotte, Valerie Paradis, Pierre Bedossa and Dominique Valla
Biomedicines 2025, 13(12), 3045; https://doi.org/10.3390/biomedicines13123045 - 11 Dec 2025
Viewed by 353
Abstract
Background: The current definition of metabolic dysfunction-associated steatotic liver disease (MASLD) relies on a classical assessment of steatosis via liver biopsy, with grades S0–S3 (5–100% fat) potentially underestimating low-grade steatosis. We propose a new, more sensitive classification based on magnetic resonance imaging–proton-density fat [...] Read more.
Background: The current definition of metabolic dysfunction-associated steatotic liver disease (MASLD) relies on a classical assessment of steatosis via liver biopsy, with grades S0–S3 (5–100% fat) potentially underestimating low-grade steatosis. We propose a new, more sensitive classification based on magnetic resonance imaging–proton-density fat fraction (MRI-PDFF), splitting the existing S0 and S1 grades into three classes: new-S0, very early S1 (S1A), and later S1 (S1B). We aimed to determine whether these early S1A/S1B phenotypes differed clinically or biologically from the new-S0 grade using large population cohorts. Methods: We assessed the prevalence of the new MRI-PDFF—based grades in 29,252 healthy participants from the UK Biobank discovery cohort, 286 outpatients with type 2 diabetes, and in six previously published databases (N = 149,212) using SteatoTest-2 or a proxy. We performed a multimodal assessment of steatosis using longitudinal MRI-PDFF and liver biopsy data (N = 286). Models were used to adjust for phenotypes and overall mortality, controlling for age, sex, and cardiometabolic factors. Results: In the UK Biobank cohort, the prevalences of the new-S0, S1A, and S1B grades were 54%, 26%, and 17%, respectively. Grades S1A and new-S0 were most discriminated by triglycerides (odds ratio [OR]: 2.40, 95% confidence interval [CI]: 2.07–2.77, p < 0.00001) and body mass index (BMI; OR: 1.30, 95% CI: 1.27–1.33, p < 0.00001), and grades S1A and S1B were most discriminated by triglycerides, BMI, systolic blood pressure (SBP), and glycated hemoglobin (HbA1c). Adjusting for age, sex, SBP, BMI, HbA1c, triglycerides, and high-density lipoprotein–cholesterol) revealed significantly lower 15-year survival in the high-risk group (97.2%, 95% CI: 96.9–97.7) versus the low-risk (99.4%, 95% CI: 99.2–99.6) group (p < 0.00001). Conclusions: The early trajectory of liver steatosis is undetectable in 26% of middle-aged adults. This early steatosis phenotype differs clinically and biologically from the new-S0 grade in large population cohorts. Full article
(This article belongs to the Section Endocrinology and Metabolism Research)
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16 pages, 1158 KB  
Article
Plasma Extracellular Vesicles Contain Protein Biomarkers for Capturing Stages of Metabolic Dysfunction-Associated Steatotic Liver Disease: A Preliminary Exploratory Study
by Yakun Li, Koen C. van Son, Sandra Serna-Salas, Justina C. Wolters, Nienke P. M. Wassenaar, Stan Driessen, Anne Linde Mak, Anne-Marieke van Dijk, Veera A. T. Houttu, Julia J. Witjes, Diona Zwirs, Michail Doukas, Joanne Verheij, Robin P. F. Dullaart, Hans Blokzijl, Adriaan G. Holleboom and Han Moshage
Biomolecules 2025, 15(11), 1596; https://doi.org/10.3390/biom15111596 - 14 Nov 2025
Viewed by 933
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing in both prevalence and severity, highlighting the need for non-invasive biomarkers to assess disease activity. Extracellular vesicles (EVs), which carry molecular cargo from their cells of origin, hold promise as accessible biomarkers. We performed proteomic [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing in both prevalence and severity, highlighting the need for non-invasive biomarkers to assess disease activity. Extracellular vesicles (EVs), which carry molecular cargo from their cells of origin, hold promise as accessible biomarkers. We performed proteomic profiling of plasma-derived EVs from 70 patients with MASLD to identify protein signatures associated with key histological features (steatosis, metabolic dysfunction-associated steatohepatitis (MASH), and fibrosis). These proteins were subsequently correlated with magnetic resonance (MR)-based liver imaging. Plasma EV protein profile differed between mild (S1) and advanced steatosis (S3). H4C1, OIT3, and ANPEP were elevated in S3, while CCDC25 and KLHL41 were decreased (|log2 fold change| > 1, p < 0.05). KLHL41 had a weak-to-moderate correlation with proton density fat fraction (PDFF) (R = −0.34, p = 0.016). GP1BA was upregulated in MASH (log2 fold change = 1.13, p = 0.03) but showed weak correlation with cT1, an imaging parameter for steatohepatitis (R = 0.22, p = 0.173). In fibrosis, complement component 7 (C7) was elevated in advanced (≥F3) vs. mild fibrosis (<F2) (log2 fold change = 0.95, adjusted p = 0.002) and correlated with MR elastography-derived liver stiffness (R = 0.38, p = 0.004). The AUC of C7 for differentiating <F2 vs. ≥F2 and <F3 vs. ≥F3 was 0.80 (95% CI: 0.69–0.91) and 0.83 (95% CI: 0.72–0.93), respectively. In conclusion, plasma EVs contain distinct protein signatures associated with steatosis, steatohepatitis, and fibrosis in MASLD. These preliminary findings support the potential utility of plasma EVs as non-invasive biomarkers and provide insights into disease pathophysiology. However, further validation in larger, independent cohorts is necessary to confirm these associations and establish their clinical relevance. Full article
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13 pages, 1130 KB  
Article
Magnetic Resonance Imaging-Based Assessment of Bone Marrow Fat and T2 Relaxation in Adolescents with Obesity and Liver Steatosis: A Feasibility Pilot Study
by Camille Letissier, Kenza El Ghomari, Sylvie Gervais, Léna Ahmarani and Ramy El Jalbout
J. Clin. Med. 2025, 14(21), 7594; https://doi.org/10.3390/jcm14217594 - 26 Oct 2025
Viewed by 717
Abstract
Background: Adolescents suffering from obesity are at higher risk of bone fragility due to hepatic steatosis, which may lead to an inflammatory microenvironment in the bone marrow. We therefore aimed to assess the reliability of measuring the bone marrow fat fraction (BMFF) and [...] Read more.
Background: Adolescents suffering from obesity are at higher risk of bone fragility due to hepatic steatosis, which may lead to an inflammatory microenvironment in the bone marrow. We therefore aimed to assess the reliability of measuring the bone marrow fat fraction (BMFF) and T2* of the lumbar vertebral marrow using the proton density fat fraction (PDFF) sequence for adolescents with obesity and liver steatosis. Method: This was an observational feasibility pilot study on adolescents living with obesity and liver steatosis. Anthropometric measurements were obtained. Participants underwent abdominal MRI, MR elastography and dual-energy X-ray absorptiometry (DXA). Regions of interest were drawn using the radiology interface from the central L1 to L4 vertebrae on fat and T2* maps from the PDFF sequence. ImageJ was used to measure abdominal compartment fat areas. Descriptive analyses, the intraclass correlation coefficient, and correlation results were obtained from anthropometric, adiposity, BMFF, and T2* measurements. Results: We recruited 23 adolescents with a body mass index > 85th percentile and mean age = 14.7 years (interval 12–17 years), and n = 18 (78%) were boys. BMFF and T2* measurements were successful in 100% of cases. The intra-operator reproducibility of the BMFF and T2* measurements was excellent: ICC = 0.99 (95% confidence interval (CI) [0.986; 0.999]) and ICC = 0.99 (95% CI [0.992; 0.999]), respectively. The inter-operator ICC was good for BMFF (ICC = 0.89; 95% CI [0.705; 0.963]) and moderate for T2* (ICC = 0.66; 95% CI [0.239; 0.873]). Only BMFF was inversely correlated with vertebral-bone mineral density (r = −0.67; p = 0.0009). However, T2* measurements showed a positive linear relationship with the total body fat tissue percentage measured by DXA (r = 0.48; p = 0.03) and the total abdominal fat area (r = 0.45; p = 0.04). Conclusions: PDFF could be a reliable imaging biomarker for bone health assessment in adolescents living with obesity. Full article
(This article belongs to the Special Issue Pediatric Obesity: Causes, Prevention and Treatment)
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17 pages, 1926 KB  
Systematic Review
Quantitative Ultrasound for Hepatic Steatosis: A Systematic Review Highlighting the Diagnostic Performance of Ultrasound-Derived Fat Fraction
by Dimitrios Kavvadas, Vasileios Rafailidis, Aris Liakos, Emmanouil Sinakos, Sasan Partovi, Theodora Papamitsou and Panos Prassopoulos
Diagnostics 2025, 15(20), 2640; https://doi.org/10.3390/diagnostics15202640 - 20 Oct 2025
Cited by 1 | Viewed by 4119
Abstract
Background/Objectives: Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease worldwide, requiring accurate and accessible diagnostic tools. Methods: A systematic review evaluated the diagnostic performance of Ultrasound-Derived Fat Fraction (UDFF), with a primary focus on prospective studies [...] Read more.
Background/Objectives: Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease worldwide, requiring accurate and accessible diagnostic tools. Methods: A systematic review evaluated the diagnostic performance of Ultrasound-Derived Fat Fraction (UDFF), with a primary focus on prospective studies comparing UDFF to MRI Proton Density Fat Fraction (MRI-PDFF) as the reference standard and a secondary appraisal of its performance against other modalities. Additional parameters, such as technical feasibility, inter-observer agreement, and proposed thresholds, were summarized to support clinical applicability. Results: Seven prospective MRI-based studies (n = 862) demonstrated excellent correlation (average r = 0.848) and reproducibility (inter-observer intraclass correlation coefficient ICC = 0.978, intra-observer ICC = 0.980) of UDFF, with high diagnostic accuracy across steatosis grades (AUCs ≥ 0.89). Additional studies comparing UDFF with Controlled Attenuation Parameter (CAP), histology, and other quantitative ultrasound techniques (attenuation- or backscatter-based methods) confirmed high sensitivity and specificity, particularly for advanced steatosis, and emphasized the potential of UDFF as a comprehensive quantitative biomarker. Proposed UDFF cut-offs for mild, moderate, and severe steatosis ranged from 5% to 23%, demonstrating high sensitivity and specificity. Factors like body position, probe pressure, and visceral fat influenced measurements, underscoring the need for standardized protocols. Conclusions: UDFF seems to offer a reliable and cost-effective quantitative ultrasound modality. So far, it correlates strongly with MRI-PDFF and accurately grades steatosis, especially for S2–S3. Given cut-off variability and protocol sensitivity, broad routine adoption may be premature. Therefore, we recommend further studies focusing on standardized acquisition and cut-off calibration to MRI-PDFF. Full article
(This article belongs to the Special Issue Diagnostic Imaging in Gastrointestinal and Liver Diseases)
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16 pages, 842 KB  
Review
Endoscopic Bariatric Therapies for Metabolic Dysfunction-Associated Steatotic Liver Disease: Mechanistic Insights and Metabolic Implications
by Wissam Ghusn, Mira Sridharan, Rachel Fromer, Muhammet Ozdemir, Madeleine G. Haff and Eric J. Vargas
Biomedicines 2025, 13(10), 2437; https://doi.org/10.3390/biomedicines13102437 - 7 Oct 2025
Viewed by 1343
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly emerging as the leading cause of chronic liver disease, closely tied to rising global obesity rates. Endoscopic bariatric therapies (EBTs), including endoscopic sleeve gastroplasty (ESG), intragastric balloons (IGB), duodenal-jejunal bypass liners (DJBL), and duodenal mucosal [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly emerging as the leading cause of chronic liver disease, closely tied to rising global obesity rates. Endoscopic bariatric therapies (EBTs), including endoscopic sleeve gastroplasty (ESG), intragastric balloons (IGB), duodenal-jejunal bypass liners (DJBL), and duodenal mucosal resurfacing (DMR), offer minimally invasive interventions that target metabolic dysfunction and weight loss. This review synthesizes current evidence on the mechanisms and hepatic outcomes of EBTs in MASLD, highlighting improvements in hepatic steatosis, liver stiffness, and fibrosis biomarkers across multiple modalities. ESG is consistently associated with reductions in hepatic steatosis and fibrosis scores across multiple studies. IGB therapy improves liver stiffness and reduces hepatic fat as assessed by imaging modalities such as MRI- Proton Density Fat Fraction and ultrasound. DJBL lowers liver enzymes and improves non-invasive markers of steatohepatitis like the Fibroscan-AST score, although its effect on fibrosis appears limited. DMR demonstrates reductions in liver fat, particularly in patients with type 2 diabetes, but evidence for histological improvement in MASLD remains inconsistent. Despite their promise, most EBT studies remain limited by small sample sizes and short follow-up. Further randomized trials are needed to validate long-term efficacy and position EBTs alongside or as alternatives to surgical interventions for MASLD. Full article
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17 pages, 2753 KB  
Article
Relationship Between Liver Steatosis, Pancreas Steatosis, Metabolic Comorbidities, and Subclinical Vascular Markers in Children with Obesity: An Imaging-Based Study
by Kenza El Ghomari, Anna Voia, Jean-Baptiste Moretti, Anik Cloutier, Guy Cloutier and Ramy El Jalbout
J. Clin. Med. 2025, 14(19), 7048; https://doi.org/10.3390/jcm14197048 - 6 Oct 2025
Viewed by 1143
Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is prevalent in adolescents with obesity and is linked to insulin resistance and cardiovascular disease (CVD). Pancreas steatosis might be associated with MASLD and early CVD. Imaging-based analyses of these associations have not been studied [...] Read more.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is prevalent in adolescents with obesity and is linked to insulin resistance and cardiovascular disease (CVD). Pancreas steatosis might be associated with MASLD and early CVD. Imaging-based analyses of these associations have not been studied extensively in children. Objectives: To assess the reproducibility of liver and pancreatic steatosis and volume measurement on MRI in adolescents with obesity and MASLD and their association with homeostatic model assessment of insulin resistance (HOMA-IR) and subclinical vascular changes on ultrasound. Methods: This is an observational study on adolescents with MASLD and obesity. Hepatic and pancreatic steatosis, volume, and abdominal fat were assessed using magnetic resonance spectroscopy and proton density fat fraction. Reproducibility of these measurements was performed. Vascular markers included non-invasive vascular elastography (NIVE), carotid artery intima-media thickness (IMT), and pericardial fat thickness. Fasting blood tests measured the HOMA-IR. Bivariate correlation and simple linear regression were performed using SPSS. Results: We obtained 23 participants aged 12 to 17 years (78.3% male). Measurements were reproducible [ICC 0.807–0.998]. Liver steatosis was positively correlated with HOMA-IR (p = 0.015). Pancreas steatosis was positively correlated with HOMA-IR (p = 0.02), IMT/diameter (p = 0.002), and pericardial fat (p = 0.03). Liver steatosis was not significantly correlated with pancreas steatosis nor vascular markers. There were negative associations between NIVE metrics and visceral abdominal fat (p = 0.009) and intraperitoneal fat (p = 0.047). Conclusions: Liver and pancreas steatosis measurements on MRI are reproducible. In this exploratory study, adolescents with obesity and MASLD, pancreas steatosis, and pancreas volume show association with subclinical CVD markers. Visceral and intraperitoneal abdominal fat show association with increased vascular stiffness, suggesting a potential role of imaging-based cardiovascular risk assessment in this population if validated. These preliminary findings require validation in larger, diverse prospective cohorts. Full article
(This article belongs to the Special Issue Pediatric Obesity: Causes, Prevention and Treatment)
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11 pages, 542 KB  
Article
Cumulative Effect of Metabolic Factors on Hepatic Steatosis
by Anna Egresi, Brigitta Kozma, Márton Karácsony, Aladár Rónaszéki, Klára Werling, Barbara Csongrády, Pál Kaposi Novák, Anikó Folhoffer, Attila Szijártó and Krisztina Hagymási
Diagnostics 2025, 15(18), 2406; https://doi.org/10.3390/diagnostics15182406 - 22 Sep 2025
Cited by 1 | Viewed by 1044
Abstract
Background/Objectives: Hepatic steatosis, a hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD), is closely associated with systemic metabolic dysfunction. However, the cumulative impact of metabolic risk factors on liver fat content remains underexplored. To evaluate the association between metabolic risk factors and hepatic [...] Read more.
Background/Objectives: Hepatic steatosis, a hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD), is closely associated with systemic metabolic dysfunction. However, the cumulative impact of metabolic risk factors on liver fat content remains underexplored. To evaluate the association between metabolic risk factors and hepatic steatosis severity using magnetic resonance imaging proton density fat fraction (MR-PDFF) measurement, and to assess the cumulative effect of multiple metabolic abnormalities. Methods: In this cross-sectional study, MASLD patients (n = 132, aged ≥ 18 years, age: 61.3 ± 10.3, male: 54, female: 78) underwent metabolic risk assessment and MR-PDFF liver fat content measurement. The association between certain metabolic risk scores (obesity/overweight, hypertension, hypercholesterolemia, hypertriglyceridemia, impaired fasting glucose or type 2 diabetes mellitus) both continuous and categorized, as well as liver fat content was analyzed using linear regression models. The cumulative effect of increasing metabolic risk was further explored with subgroup comparisons. Results: A significant positive association was observed between continuous metabolic risk scores and MR-PDFF values (β = 0.021, p < 0.001). Participants with higher cumulative metabolic risk (4 and 5 risk factors group) showed significantly higher liver fat content compared to the reference group (p < 0.01) (MetfO0 = 5.7 ± 5.9%; MetfO1 = 11.6 ± 9.5%; MetfO2 = 7.9 ± 5.6%; MetfO3 = 10.2 ± 7.9%; MetfO4 = 16.4 ± 11.0%; MetfO5 = 17.8 ± 9.5%). Intermediate metabolic risk categories showed a trend toward increased steatosis but did not reach statistical significance. Conclusions: Cumulative metabolic risk is strongly associated with increased hepatic fat accumulation. These findings underscore the need for early identification and management of metabolic risk factors to prevent the development and progression of hepatic steatosis. Full article
(This article belongs to the Special Issue Diagnostic and Prognostic Markers in Liver Diseases)
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15 pages, 2487 KB  
Article
Feasibility of Sodium and Amide Proton Transfer-Weighted Magnetic Resonance Imaging Methods in Mild Steatotic Liver Disease
by Diana M. Lindquist, Mary Kate Manhard, Joel Levoy and Jonathan R. Dillman
Tomography 2025, 11(8), 89; https://doi.org/10.3390/tomography11080089 - 6 Aug 2025
Viewed by 800
Abstract
Background/Objectives: Fat and inflammation confound current magnetic resonance imaging (MRI) methods for assessing fibrosis in liver disease. Sodium or amide proton transfer-weighted MRI methods may be more specific for assessing liver fibrosis. The purpose of this study was to determine the feasibility [...] Read more.
Background/Objectives: Fat and inflammation confound current magnetic resonance imaging (MRI) methods for assessing fibrosis in liver disease. Sodium or amide proton transfer-weighted MRI methods may be more specific for assessing liver fibrosis. The purpose of this study was to determine the feasibility of sodium and amide proton transfer-weighted MRI in individuals with liver disease and to determine if either method correlated with clinical markers of fibrosis. Methods: T1 and T2 relaxation maps, proton density fat fraction maps, liver shear stiffness maps, amide proton transfer-weighted (APTw) images, and sodium images were acquired at 3T. Image data were extracted from regions of interest placed in the liver. ANOVA tests were run with disease status, age, and body mass index as independent factors; significance was set to p < 0.05. Post-hoc t-tests were run when the ANOVA showed significance. Results: A total of 36 participants were enrolled, 34 of whom were included in the final APTw analysis and 24 in the sodium analysis. Estimated liver tissue sodium concentration differentiated participants with liver disease from those without, whereas amide proton transfer-weighted MRI did not. Estimated liver tissue sodium concentration negatively correlated with the Fibrosis-4 score, but amide proton transfer-weighted MRI did not correlate with any clinical marker of disease. Conclusions: Amide proton-weighted imaging was not different between groups. Estimated liver tissue sodium concentrations did differ between groups but did not provide additional information over conventional methods. Full article
(This article belongs to the Section Abdominal Imaging)
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16 pages, 3424 KB  
Article
Fat Fraction MRI for Longitudinal Assessment of Bone Marrow Heterogeneity in a Mouse Model of Myelofibrosis
by Lauren Brenner, Tanner H. Robison, Timothy D. Johnson, Kristen Pettit, Moshe Talpaz, Thomas L. Chenevert, Brian D. Ross and Gary D. Luker
Tomography 2025, 11(8), 82; https://doi.org/10.3390/tomography11080082 - 28 Jul 2025
Viewed by 1459
Abstract
Background/Objectives: Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by the replacement of healthy bone marrow (BM) with malignant and fibrotic tissue. In a healthy state, bone marrow is composed of approximately 60–70% fat cells, which are replaced as disease progresses. Proton density fat [...] Read more.
Background/Objectives: Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by the replacement of healthy bone marrow (BM) with malignant and fibrotic tissue. In a healthy state, bone marrow is composed of approximately 60–70% fat cells, which are replaced as disease progresses. Proton density fat fraction (PDFF), a non-invasive and quantitative MRI metric, enables analysis of BM architecture by measuring the percentage of fat versus cells in the environment. Our objective is to investigate variance in quantitative PDFF-MRI values over time as a marker of disease progression and response to treatment. Methods: We analyzed existing data from three cohorts of mice: two groups with MF that failed to respond to therapy with approved drugs for MF (ruxolitinib, fedratinib), investigational compounds (navitoclax, balixafortide), or vehicle and monitored over time by MRI; the third group consisted of healthy controls imaged at a single time point. Using in-house MATLAB programs, we performed a voxel-wise analysis of PDFF values in lower extremity bone marrow, specifically comparing the variance of each voxel within and among mice. Results: Our findings revealed a significant difference in PDFF values between healthy and diseased BM. With progressive disease non-responsive to therapy, the expansion of hematopoietic cells in BM nearly completely replaced normal fat, as determined by a markedly reduced PDFF and notable reduction in the variance in PDFF values in bone marrow over time. Conclusions: This study validated our hypothesis that the variance in PDFF in BM decreases with disease progression, indicating pathologic expansion of hematopoietic cells. We can conclude that disease progression can be tracked by a decrease in PDFF values. Analyzing variance in PDFF may improve the assessment of disease progression in pre-clinical models and ultimately patients with MF. Full article
(This article belongs to the Section Cancer Imaging)
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14 pages, 2237 KB  
Article
Proton Density Fat Fraction Micro-MRI for Non-Invasive Quantification of Bone Marrow Aging and Radiation Effects in Mice
by Hemendra Ghimire, Malakeh Malekzadeh, Ji Eun Lim, Srideshikan Sargur Madabushi, Marco Andrea Zampini, Angela Camacho, Weidong Hu, Natalia Baran, Guy Storme, Monzr M. Al Malki and Susanta K. Hui
Bioengineering 2025, 12(4), 349; https://doi.org/10.3390/bioengineering12040349 - 28 Mar 2025
Cited by 1 | Viewed by 1646
Abstract
Background: Bone marrow (BM) adipocytes play a critical role in the progression of both solid tumor metastases and expansion of hematological malignancies across a spectrum of ages, from pediatric to aging populations. Single-point biopsies remain the gold standard for monitoring BM diseases, including [...] Read more.
Background: Bone marrow (BM) adipocytes play a critical role in the progression of both solid tumor metastases and expansion of hematological malignancies across a spectrum of ages, from pediatric to aging populations. Single-point biopsies remain the gold standard for monitoring BM diseases, including hematologic malignancies, but these are limited in capturing the full complexity of loco-regional and global BM microenvironments. Non-invasive imaging techniques such as Magnetic Resonance Imaging (MRI), Computed Tomography (CT), and Positron Emission Tomography (PET) could provide valuable alternatives for real-time evaluation in both preclinical translational and clinical studies. Methods: We developed a preclinical proton density fat fraction (PDFF) MRI technique for the quantitative assessment of BM composition, focusing on the fat fraction (FF) within mouse femurs. We validated this method using aging mice and young mice subjected to 10 Gy X-ray irradiation, compared to young control mice. Water–fat phantoms with varying fat percentages (0% to 100%) were used to optimize the imaging sequence, and immunohistochemical (IHC) staining with H&E validated equivalent adipose content in the femur BM region. Results: Significant differences in FF were observed across age groups (p = 0.001 for histology and p < 0.001 for PDFF) and between irradiated and control mice (p = 0.005 for histology and p = 0.002 for PDFF). A strong correlation (R2~0.84) between FF values from PDFF-MRI and histology validated the accuracy of the technique. Conclusions: These findings highlight PDFF-MRI’s potential as a non-invasive, real-time, in vivo biomarker for quantitatively assessing the BM fat fraction in preclinical studies, particularly in studies evaluating the effects of aging, disease progression, and cytotoxic cancer therapies, including chemotherapy and radiation. Full article
(This article belongs to the Section Regenerative Engineering)
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15 pages, 5248 KB  
Article
Multiparametric Magnetic Resonance Imaging Findings of the Pancreas: A Comparison in Patients with Type 1 and 2 Diabetes
by Mayumi Higashi, Masahiro Tanabe, Katsuya Tanabe, Shigeru Okuya, Koumei Takeda, Yuko Nagao and Katsuyoshi Ito
Tomography 2025, 11(2), 16; https://doi.org/10.3390/tomography11020016 - 7 Feb 2025
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Abstract
Background/Objectives: Diabetes-related pancreatic changes on MRI remain unclear. Thus, we evaluated the pancreatic changes on MRI in patients with both type 1 diabetes (T1D) and type 2 diabetes (T2D) using multiparametric MRI. Methods: This prospective study involved patients with T1D or T2D who [...] Read more.
Background/Objectives: Diabetes-related pancreatic changes on MRI remain unclear. Thus, we evaluated the pancreatic changes on MRI in patients with both type 1 diabetes (T1D) and type 2 diabetes (T2D) using multiparametric MRI. Methods: This prospective study involved patients with T1D or T2D who underwent upper abdominal 3-T MRI. Additionally, patients without impaired glucose metabolism were retrospectively included as a control. The imaging data included pancreatic anteroposterior (AP) diameter, pancreas-to-muscle signal intensity ratio (SIR) on fat-suppressed T1-weighted image (FS-T1WI), apparent diffusion coefficient (ADC) value, T1 value on T1 map, proton density fat fraction (PDFF), and mean secretion grade of pancreatic juice flow on cine-dynamic magnetic resonance cholangiopancreatography (MRCP). The MR measurements were compared using one-way analysis of variance and the Kruskal–Wallis test. Results: Sixty-one patients with T1D (n = 7) or T2D (n = 54) and 21 control patients were evaluated. The pancreatic AP diameters were significantly smaller in patients with T1D than in patients with T2D (p < 0.05). The average SIR on FS-T1WI was significantly lower in patients with T1D than in controls (p < 0.001). The average ADC and T1 values of the pancreas were significantly higher in patients with T1D than in patients with T2D (p < 0.01) and controls (p < 0.05). The mean secretion grade of pancreatic juice flow was significantly lower in patients with T1D than in controls (p = 0.019). The average PDFF of the pancreas was significantly higher in patients with T2D than in controls (p = 0.029). Conclusions: Patients with T1D had reduced pancreas size, increased pancreatic T1 and ADC values, and decreased pancreatic juice flow on cine-dynamic MRCP, whereas patients with T2D had increased pancreatic fat content. Full article
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19 pages, 319 KB  
Review
Evaluating Pediatric NAFLD with Controlled Attenuation Parameter: A Comprehensive Narrative Review
by Ingrid Arteaga, Carla Chacón, Alba Martínez-Escudé, Irene Ruiz Rojano, Galadriel Diez-Fadrique, Meritxell Carmona-Cervelló and Pere Torán-Monserrat
Diagnostics 2025, 15(3), 299; https://doi.org/10.3390/diagnostics15030299 - 27 Jan 2025
Cited by 1 | Viewed by 2617
Abstract
Non-alcoholic fatty liver disease (NAFLD) in the pediatric population has emerged as a significant health concern due to its alarming rise in prevalence. In children, the characteristics of the disease differ from those seen in adults. NAFLD may progress to more severe liver [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) in the pediatric population has emerged as a significant health concern due to its alarming rise in prevalence. In children, the characteristics of the disease differ from those seen in adults. NAFLD may progress to more severe liver disease in children compared to adults with similar profiles. Liver biopsy remains the gold standard for diagnosis; its invasive nature and high cost limit its use as a first-line tool. Alternatively, magnetic resonance imaging (MRI) techniques, such as magnetic resonance imaging-estimated liver proton density fat fraction (MRI-PDFF), have shown a good correlation with the degree of histological steatosis, although their use is limited by high costs and limited accessibility. Controlled attenuation parameter (CAP), integrated with vibration-controlled transient elastography (VCTE) (FibroScan®), is a novel non-invasive, accessible, and effective method for diagnosing hepatic steatosis. In this article, we reviewed the existing literature on the diagnostic accuracy of CAP in pediatric NAFLD. The PubMed and EMBASE databases were searched. Seven relevant studies were identified, conducted in pediatric hospital populations with specific demographic characteristics. Two of these studies compared CAP with liver biopsy, one compared CAP with liver biopsy and MRI-PDFF, and the remaining four compared CAP with MRI. Overall, CAP proved to be accurate in detecting the presence or absence of fatty infiltration, positioning it as a promising tool to simplify the diagnosis of NAFLD in children. However, further studies in larger populations are needed to confirm these findings and facilitate its implementation in routine clinical practice. Full article
(This article belongs to the Special Issue Pathology of Hepatobiliary Diseases)
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