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OBJECTIVES: Magnetic 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. METHODS: The 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. RESULTS: The 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). CONCLUSION: PDFF 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.

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OBJECTIVE: To establish an image acquisition and post-processing workflow for the determination of the proton density fat fraction (PDFF) in calf muscle tissue at 7 T. MATERIALS AND METHODS: Echo times (TEs) of the applied vendor-provided multi-echo gradient echo sequence were optimized based on simulations of the effective number of signal averages (NSA*). The resulting parameters were validated by measurements in phantom and in healthy calf muscle tissue (n = 12). Additionally, methods to reduce phase errors arising at 7 T were evaluated. Finally, PDFF values measured at 7 T in calf muscle tissue of healthy subjects (n = 9) and patients with fatty replacement of muscle tissue (n = 3) were compared to 3 T results. RESULTS: Simulations, phantom and in vivo measurements showed the importance of using optimized TEs for the fat-water separation at 7 T. Fat-water swaps could be mitigated using a phase demodulation with an additional B0 map, or by shifting the TEs to longer values. Muscular PDFF values measured at 7 T were comparable to measurements at 3 T in both healthy subjects and patients with increased fatty replacement. CONCLUSION: PDFF determination in calf muscle tissue is feasible at 7 T using a chemical shift-based approach with optimized acquisition and post-processing parameters.

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Background: Bariatric surgery and lifestyle modification are important treatments for obesity, a risk factor for metabolic dysfunction-associated steatohepatitis (MASH). Studies have related weight reduction with changes in MASH, however, few have used imaging to investigate effects on liver health. We evaluated differences in liver response to obesity treatment using disease activity iron corrected T1 (cT1) and proton density fat fraction (PDFF) in patients with both obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: Thirty-four patients with obesity and MASLD were recruited between March 2019 to February 2022 from a tertiary hospital in this longitudinal study; 13 underwent laparoscopic sleeve gastrectomy (LSG) alongside intraoperative liver biopsy, and 21 underwent a 4-month lifestyle modification program (LMP). All patients had multi-parametric magnetic resonance imaging (MRI) at baseline and 4-months. Diagnostic accuracy to identify MASH was assessed using the area under receiver operating characteristic (AUROC) curve. Results: Four (31%) of patients in the LSG group had MASH [non-alcoholic steatohepatitis (NAS) activity score ≥4] on liver biopsy. PDFF and cT1 correlated with the NAS activity score [r=0.81, 95% confidence interval (CI): 0.453 to 0.943, P<0.001] and (r=0.70, 95% CI: 0.228 to 0.907, P=0.008, respectively). There was good AUROC curve for cT1 (0.89, 95% CI: 0.67 to 1.00, P=0.031) and PDFF (0.83, 95% CI: 0.57 to 1.00, P=0.064) to identify MASH. At follow-up, weight reduction -22.8% (P=0.013) vs. -1.3% (P=0.262) resulted in cT1 reduction of -8.04% (864 ms, P=0.025) vs. -3.87% (907 ms, P=0.083) in the LSG vs. LMP group, respectively. Significant differences between interventions were observed for percentage PDFF decrease (-64.52% vs. -29.16%, P=0.001). Both biomarkers were significantly reduced in the LSG group (cT1 by -8.04%, P=0.025, PDFF by -64.52%, P=0.012), while only PDFF (-29.16%, P=0.012) was significantly reduced in the LMP group. Conclusions: MRI biomarkers may have some utility to monitor MASH following intervention in patients with obesity allowing objective comparison between intervention strategies. Compared to LMP, LSG was more effective in improving liver health.

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(1) Background: Open-source software tools are available to estimate proton density fat fraction (PDFF). (2) Methods: We compared four algorithms: complex-based with graph cut (GC), magnitude-based (MAG), magnitude-only estimation with Rician noise modeling (MAG-R), and multi-scale quadratic pseudo-Boolean optimization with graph cut (QPBO). The accuracy and reliability of the methods were evaluated in phantoms with known fat/water ratios and a patient cohort with various grades (S0-S3) of steatosis. Image acquisitions were performed at 1.5 Tesla (T). (3) Results: The PDFF estimates showed a nearly perfect correlation (Pearson r = 0.999, p < 0.001) and inter-rater agreement (ICC = from 0.995 to 0.999, p < 0.001) with true fat fractions. The absolute bias was low with all methods (0.001-1%), and an ANCOVA detected no significant difference between the algorithms in vitro. The agreement across the methods was very good in the patient cohort (ICC = 0.891, p < 0.001). However, MAG estimates (-2.30% ± 6.11%, p = 0.005) were lower than MAG-R. The field inhomogeneity artifacts were most frequent in MAG-R (70%) and GC (39%) and absent in QPBO images. (4) Conclusions: The tested algorithms all accurately estimate PDFF in vitro. Meanwhile, QPBO is the least affected by field inhomogeneity artifacts in vivo.

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We investigated the associations of low handgrip strength (HGS, i.e., a marker of muscular fitness) with liver fat content (LFC) and serum liver enzymes in a population-based setting. We used data from 2700 participants (51.7% women), aged 21-90 years, from two independent cohorts of the population-based Study of Health in Pomerania (SHIP-START-2 and SHIP-TREND-0). Cross-sectional, multivariable adjusted regression models were performed to examine the associations of HGS with LFC, measured by magnetic resonance imaging and serum liver enzymes. We found significant inverse associations of HGS with both LFC and serum liver enzymes. Specifically, a 10-kg lower HGS was associated with a 0.59% (95% confidence interval [CI]: 0.24-0.94; p = 0.001) higher LFC, a 0.051 µkatal/L (95% CI: 0.005-0.097; p = 0.031) higher gamma-glutamyltransferase (GGT) concentration and a 0.010 µkatal/L (95% CI: 0.001-0.020; p = 0.023) higher aspartate aminotransferase (AST) concentration. The adjusted odds-ratio for prevalent hepatic steatosis (defined by a MRI-PDFF ≥5.1%) per 10-kg lower HGS was 1.21 (95% CI: 1.04-1.40; p = 0.014). When considering only obese individuals, those with low HGS had a 1.58% (95% CI: 0.18-2.98; p = 0.027) higher mean LFC and higher chance of prevalent hepatic steatosis (adjusted OR 1.74, 95% CI: 1.15-2.62; p = 0.009) compared to individuals with high HGS. We found similar associations in individuals with overweight, but not in those with normal weight. Lower HGS was strongly associated with both higher LFC and higher serum GGT and AST concentrations. Future studies might clarify whether these findings reflect adverse effects of a sedentary lifestyle or aging on the liver.

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OBJECTIVES: Controlled attenuation parameter (CAP) is a noninvasive and quantitative method to evaluate hepatic steatosis, which is not well evaluated in children. The aim of this study was to examine the diagnostic value of CAP for hepatic steatosis in children with obesity based on MR proton density fat fraction (PDFF). METHODS: About 108 pediatric patients with nonalcoholic fatty liver disease (NAFLD) who were assessed for PDFF, CAP, and other laboratory results were enrolled. In this study, pediatric patients were separated for the obese group (n=80) and the severe obese group (n=28). Hepatic steatosis grades (0-3) were classified according to PDFF using cutoff values of 6.4 , 17.4, and 22.1 %. RESULTS: There are significant differences in CAP between the obese and severe obese groups (p<0.05). CAP showed a good correlation with PDFF in pediatric patients with NAFLD for diagnosing hepatic steatosis using a cutoff value of 265 dB/m (p<0.001). Meanwhile, ALT significantly outperforms CAP in receiver-operating curve (ROC) analysis for diagnosing hepatic steatosis grades. The diagnostic accuracy of CAP for steatosis is 77.8 %, and the diagnostic accuracy of ALT for steatosis is 83.3 %. CONCLUSIONS: While CAP holds promise as a diagnostic tool for pediatric NAFLD, its diagnostic performance warrants some caution. The potential of CAP is evident; however, ALT emerges as a simpler and more accurate measure for detecting hepatic steatosis in children. Further research is essential to determine the optimal role of CAP in pediatric NAFLD diagnosis and management.

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OBJECTIVE: To study the impact of Gx on quantification of hepatic fat contents under metabolic dysfunction-associated steatotic liver disease (MASLD) imaged on VIBE Dixon in hepatobiliary specific phase. METHODS: Forty-two rabbits were randomly divided into control group (n = 10) and high-fat diet group (n = 32). Imaging was performed before enhancement (Pre-Gx) and at the 13th (Post-Gx13) and 17th (Post-Gx17) min after Gx enhancement with 2E- and 6E-VIBE Dixon to determine hepatic proton density fat fractions (PDFF). PDFFs were compared with vacuole percentage (VP) measured under histopathology. RESULTS: 33 animals were evaluated and including control group (n = 11) and MASLD group (n = 22). Pre-Gx, Post-Gx13, Post-Gx17 PDFFs under 6E-VIBE Dixon had strong correlations with VPs (r2 = 0.8208-0.8536). PDFFs under 2E-VIBE Dixon were reduced significantly (P < 0.001) after enhancement (r2 = 0.7991/0.8014) compared with that before enhancement (r2 = 0.7643). There was no significant difference between PDFFs of Post-Gx13 and Post-Gx17 (P = 0.123) for which the highest consistency being found with 6E-VIBE Dixon before enhancement (r2 = 0.8536). The signal intensity of the precontrast compared with the postcontrast, water image under 2E-VIBE Dixon increased significantly (P < 0.001), fat image showed no significant difference (P = 0.754). CONCLUSION: 2E- and 6E-VIBE Dixon can obtain accurate PDFFs in the hepatobiliary specific phase from 13 to 17th min after Gx enhancement. On 2E-VIBE Dixon (FA = 10°), effective minimization of T1 Bias by the Gx administration markedly improved the accuracy of the hepatic PDFF quantification.

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Background: Early childhood bone development affects that of bone disease in adolescence and adulthood. Many diseases can affect the cancellous bone or bone marrow. Therefore, it is of great significance to quantify the bone development of healthy children. The evaluation methods of bone development include bone age (BA) assessment and dual-energy X-ray bone mineral densitometry (DXA), both of which have strong subjectivity. The present study was conducted to improve our understanding of the bone development of healthy children using the quantitative parameters derived from iterative decomposition of water and fat with echo asymmetry and least squares estimation quantification (IDEAL-IQ) sequence. Methods: Our study enrolled healthy children between January 2022 to December 2022 consecutively in Children's Hospital of Shanxi. The inclusion criteria were as follows: (I) age ≤18 years; (II) no contraindications (surgical and interventional devices for ferromagnetic materials, cardiac implantable electronic devices, cochlear implants, insulin pumps, dental implants containing metal or alloy) to magnetic resonance imaging (MRI) scan. The exclusion criteria were as follows: (I) previous malignant disease, (II) previous chemoradiotherapy, (III) previous spine surgery, (IV) previous or acute vertebral compression fracture, (V) artifacts present in images. Participants underwent MRI scans using IDEAL-IQ sequence in the lumbar vertebrae. The IDEAL-IQ parameters [proton density fat fraction (PDFF), 1/T2* (R2*)] were obtained. The factor analysis of variance was applied to compare the differences of PDFF and R2* in different lumbar vertebral groups. The Kruskal-Wallis H test or Mann-Whitney U test was applied to compare the differences of quantitative data among different gender or age groups. Spearman correlation analysis was applied to study the relationship among the age, PDFF, and R2*. Results: A total of 145 participants (76 males, 69 females) were evaluated. There were no significant differences in PDFF and R2* of different lumbar vertebrae (PPDFF=0.338, PR2*=0.868). The average age was 36 [13-72] months. They were assigned into 4 groups (0-11, 12-35, 36-71, and 72-144 months). As the age increased, the average PDFF and R2* both increased significantly (rPDFF=0.659, rR2*=0.359, P<0.001). There were significant statistical differences in PDFF and R2* between the 4 age groups (ZPDFF=46.651, ZR2*=27.537, P<0.001). Moreover, the PDFF was also positively correlated with R2* (r=0.576, P<0.001). No association was found between the gender and PDFF, R2* (PPDFF=0.949, PR2*=0.177). Conclusions: The quantitative parameters derived from IDEAL-IQ in the lumbar vertebrae of healthy children will improve our understanding of bone development and provide a basis for further exploring the diseases that affect children's bone development.

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Objective: To assess the prevalence of pancreatic steatosis and iron overload in non-alcoholic fatty liver disease (NAFLD) and their correlation with liver histology severity and the risk of cardiometabolic diseases. Method: A prospective, multicenter study including NAFLD patients with biopsy and paired Magnetic Resonance Imaging (MRI) was performed. Liver biopsies were evaluated according to NASH Clinical Research Network, hepatic iron storages were scored, and digital pathology quantified the tissue proportionate areas of fat and iron. MRI-biomarkers of fat fraction (PDFF) and iron accumulation (R2*) were obtained from the liver and pancreas. Different metabolic traits were evaluated, cardiovascular disease (CVD) risk was estimated with the atherosclerotic CVD score, and the severity of iron metabolism alteration was determined by grading metabolic hiperferritinemia (MHF). Associations between CVD, histology and MRI were investigated. Results: In total, 324 patients were included. MRI-determined pancreatic iron overload and moderate-to severe steatosis were present in 45% and 25%, respectively. Liver and pancreatic MRI-biomarkers showed a weak correlation (r=0.32 for PDFF, r=0.17 for R2*). Pancreatic PDFF increased with hepatic histologic steatosis grades and NASH diagnosis (p<0.001). Prevalence of pancreatic steatosis and iron overload increased with the number of metabolic traits (p<0.001). Liver R2* significantly correlated with MHF (AUC=0.77 [0.72-0.82]). MRI-determined pancreatic steatosis (OR=3.15 [1.63-6.09]), and iron overload (OR=2.39 [1.32-4.37]) were independently associated with high-risk CVD. Histologic diagnosis of NASH and advanced fibrosis were also associated with high-risk CVD. Conclusion: Pancreatic steatosis and iron overload could be of utility in clinical decision-making and prognostication of NAFLD.

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Chronic liver disease (CLD) is a common source of morbidity and mortality worldwide. Non-alcoholic fatty liver disease (NAFLD) serves as a major cause of CLD with a rising annual prevalence. Additionally, iron overload can be both a cause and effect of CLD with a negative synergistic effect when combined with NAFLD. The development of state-of-the-art multiparametric MR solutions has led to a change in the diagnostic paradigm in CLD, shifting from traditional liver biopsy to innovative non-invasive methods for providing accurate and reliable detection and quantification of the disease burden. Novel imaging biomarkers such as MRI-PDFF for fat, R2 and R2* for iron, and liver stiffness for fibrosis provide important information for diagnosis, surveillance, risk stratification, and treatment. In this article, we provide a concise overview of the MR concepts and techniques involved in the detection and quantification of liver fat, iron, and fibrosis including their relative strengths and limitations and discuss a practical abbreviated MR protocol for clinical use that integrates these three MR biomarkers into a single simplified MR assessment. Multiparametric MR techniques provide accurate and reliable non-invasive detection and quantification of liver fat, iron, and fibrosis. These techniques can be combined in a single abbreviated MR "Triple Screen" assessment to offer a more complete metabolic imaging profile of CLD.

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Quantitative MRI biomarkers are sought to replace painful and invasive sequential bone-marrow biopsies routinely used for myelofibrosis (MF) cancer monitoring and treatment assessment. Repeatability of MRI-based quantitative imaging biomarker (QIB) measurements was investigated for apparent diffusion coefficient (ADC), proton density fat fraction (PDFF), and magnetization transfer ratio (MTR) in a JAK2 V617F hematopoietic transplant model of MF. Repeatability coefficients (RCs) were determined for three defined tibia bone-marrow sections (2-9 mm; 10-12 mm; and 12.5-13.5 mm from the knee joint) across 15 diseased mice from 20-37 test-retest pairs. Scans were performed on consecutive days every two weeks for a period of 10 weeks starting 3-4 weeks after transplant. The mean RC with (95% confidence interval (CI)) for these sections, respectively, were for ADC: 0.037 (0.031, 0.050), 0.087 (0.069, 0.116), and 0.030 (0.022, 0.044) µm2/ms; for PDFF: 1.6 (1.3, 2.0), 15.5 (12.5, 20.2), and 25.5 (12.0, 33.0)%; and for MTR: 0.16 (0.14, 0.19), 0.11 (0.09, 0.15), and 0.09 (0.08, 0.15). Change-trend analysis of these QIBs identified a dynamic section within the mid-tibial bone marrow in which confident changes (exceeding RC) could be observed after a four-week interval between scans across all measured MRI-based QIBs. Our results demonstrate the capability to derive quantitative imaging metrics from mouse tibia bone marrow for monitoring significant longitudinal MF changes.

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Arm positions employed during magnetic resonance imaging (MRI) can affect magnetic field distribution, which may result in variability in proton density fat fraction (PDFF) measurements. This study evaluated the effect of arm position on lumbar PDFF measured using chemical-shift-encoded MRI (CSE-MRI). Fifteen healthy volunteers from a single-center underwent lumbar CSE-MRI at two different arm positions (side and elevated) using a single 3T scanner. Scans were performed twice in each position. PDFFs of the L1-L5 vertebrae were independently measured by two readers, and reader measurements were compared by calculating intraclass correlation coefficients (ICC). We compared PDFF measurements from two arm positions and from two consecutive scans using the Wilcoxon test and Bland-Altman analysis. Measurements from the two readers were in high agreement [ICC =0.999; 95% confidence interval (CI), 0.998-0.999]. No significant difference was observed between PDFFs from the first and second scans of all vertebrae for each reader (all P>0.05); however, PDFF for the elevated arm position was significantly higher than that for the side arm position (37.9-44.8% vs. 37.0-43.8%; all P<0.05), except at the L2 level by reader 2. The mean differences in PDFF measurements from the first and second scans [0.1%; 95% limits of agreement (LoA), -1.8% to 1.9%] and from the side arm and elevated arm positions (0.8%; 95% LoA, -1.6% to 3.2%) were small. In conclusion, these preliminary data suggest that different arm positions during CSE-MRI can slightly affect lumbar PDFF; however, the mean absolute differences were very small.

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OBJECTIVE: To investigate the clinical, laboratory and genetic features of NAFLD patients based on MRI-PDFF in China. DESIGN: Patients with high ALT and with a diagnosis of fatty liver were included in this cross-sectional study. Fasting blood was collected to test biomarkers and SNPs. A total of 266 patients underwent MRI-PDFF and FibroScan examinations, and 38 underwent liver biopsy. Diagnostic models (decision tree, LASSO, and elastic net) were developed based on the diagnosis from MRI-PDFF reports. RESULTS: Approximately, 1/3 of the patients were found to have NASH and fibrosis. After quantifying liver steatosis by MRI-PDFF (healthy: n = 47; mild NAFLD: n = 136; moderate/severe NAFLD: n = 83; liver fat content (LFC): 3.6% vs. 8.7% vs. 19.0%), most biomarkers showed significant differences among the three groups, and patients without obesity were found to have a similar LFC as those with obesity (11.1% vs. 12.3%). Models including biomarkers showed strong diagnostic ability (accuracy: 0.80-0.91). Variant alleles of PNPLA3, HSD17B13 and MBOAT7 were identified as genetic risk factors causing higher LFC (8.7% vs. 12.3%; 11.0% vs. 14.5%; 8.5% vs. 10.2%, p < 0.05); those with the UQCC1 rs878639 variant allele showed lower LFC (10.4% vs. 8.4%; OR = 0.58, p < 0.05). Patients with more risk alleles had higher LFCs (8.1% vs. 10.7% vs. 11.6% vs. 14.5%). CONCLUSIONS: Based on MRI-PDFF, a combination of several specific biomarkers can accurately predict disease status. When the effects of genes on liver steatosis were first quantified by MRI-PDFF, the UQCC1 rs878639 G allele was identified as a protective factor, and the MBOAT7 T allele was identified as a risk only among nonobese individuals.

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OBJECTIVES: To examine the value of 3-T MRI for evaluating the difference between the pancreatic parenchyma of intraductal papillary mucinous neoplasm with a concomitant invasive carcinoma (IPMN-IC) and the pancreatic parenchyma of patients without an IPMN-IC. METHODS: A total of 132 patients underwent abdominal 3-T MRI. Of the normal pancreatic parenchymal measurements, the pancreas-to-muscle signal intensity ratio in in-phase imaging (SIR-I), SIR in opposed-phase imaging (SIR-O), SIR in T2-weighted imaging (SIR-T2), ADC (×10-3 mm2/s) in DWI, and proton density fat fraction (PDFF [%]) in multi-echo 3D DIXON were calculated. The patients were divided into three groups (normal pancreas group: n = 60, intraductal papillary mucinous neoplasm (IPMN) group: n = 60, IPMN-IC group: n = 12). RESULTS: No significant differences were observed among the three groups in age, sex, body mass index, prevalence of diabetes mellitus, and hemoglobin A1c (p = 0.141 to p = 0.657). In comparisons among the three groups, the PDFF showed a significant difference (p < 0.001), and there were no significant differences among the three groups in SIR-I, SIR-O, SIR-T2, and ADC (p = 0.153 to p = 0.684). The PDFF of the pancreas was significantly higher in the IPMN-IC group than in the normal pancreas group or the IPMN group (p < 0.001 and p < 0.001, respectively), with no significant difference between the normal pancreas group and the IPMN group (p = 0.916). CONCLUSIONS: These observations suggest that the PDFF of the pancreas is associated with the presence of IPMN-IC. KEY POINTS: • The cause and risk factors of IPMN with a concomitant invasive carcinoma have not yet been clarified. • The PDFF of the pancreas was significantly higher in the IPMN-IC group than in the normal pancreas group or the IPMN group. • Pancreatic PDFF may be a potential biomarker for the development of IPMN with a concomitant invasive carcinoma.

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Background: Brown adipose tissue (BAT) activity is triggered by cold exposure resulting in an increased resting energy expenditure, called cold-induced non-shivering thermogenesis (CIT). Magnetic resonance (MR)-based proton density fat fraction (PDFF) of the supraclavicular fossa has been proposed as a surrogate marker of human BAT. The present study investigates supraclavicular PDFF in relation to CIT. Methods: For this prospective cross-sectional study 39 adults were recruited, from a cross-sectional study, exploring energy expenditure after cold exposure compared to thermoneutral conditions. Participants underwent additional MR examination of neck, pelvis, and abdomen. Supraclavicular and subcutaneous gluteal adipose tissue depots were segmented semi-automatically. Mean PDFF was assessed for each compartment and the delta PDFF was calculated as the difference of both. Correlation analysis of supraclavicular PDFF to CIT was performed for the whole cohort and subgroups, sorted by body mass index (BMI) and body fat percentage. Results: Median age of participants (61.5% female) was 27 years. BMI ranged from 19.0 to 38.5 kg/m2, with body fat percentages from 4.6% to 45.3%. Median supraclavicular PDFF of 82.5% and median gluteal PDFF of 91.1%, were significantly different (P<0.0001). Median delta PDFF was 8.8% (3.9-21.9%). Mean CIT was 4.7%±9.0%. No statistically significant correlation of supraclavicular PDFF and CIT was found in the whole cohort and in most of the observed subgroups. Just the subgroup with normal body fat percentage revealed significant correlations between supraclavicular PDFF and CIT (rho =-0.59; P=0.003). Delta PDFF was significantly associated with CIT (rho =0.36; P=0.026). Conclusions: PDFF is influenced by adiposity. Therefore, if supraclavicular PDFF is used as approach to indirectly assess BAT presence, body composition should be considered. Delta PDFF, as the difference between gluteal and supraclavicular PDFF, may be a marker of CIT.

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BACKGROUND: We investigated the association between low cardiorespiratory fitness and liver fat content (LFC) in the general population. MATERIALS AND METHODS: We evaluated data from 2151 adults (51.1% women) from two population-based cohorts of the Study of Health in Pomerania (SHIP-2 and SHIP-TREND-0). We analysed the cross-sectional associations of peak oxygen uptake (VO2peak ) with LFC, assessed by magnetic resonance imaging proton density fat fraction, as well as serum gamma-glutamyltransferase (GGT) and aminotransferase concentrations by multivariable regression models. RESULTS: We observed significant inverse associations of VO2peak with LFC and serum GGT, but not with serum aminotransferase levels. Specifically, a 1 L/min lower VO2peak was associated with a 1.09% (95% confidence interval [CI]: 0.45-1.73; P = .002) higher LFC and a 0.18 µkatal/L (95% CI: 0.09-0.26; P < .001) higher GGT levels. The adjusted odds ratio (OR) for the risk of prevalent hepatic steatosis (HS) by a 1 L/min decrease in VO2peak was 1.61 (95% CI: 1.22-2.13; P = .001). Compared to subjects with high VO2peak , obese and overweight individuals with low VO2peak had 1.78% (95% CI: 0.32-3.25; P = .017) and 0.94% (95% CI: 0.15-1.74; P = .021) higher mean LFC, respectively. Compared to those with high VO2peak , low VO2peak was independently associated with a higher risk of prevalent HS in the obese (adjusted-OR 2.29, 95% CI=1.48-3.56; P < .001) and overweight (adjusted OR 1.57, 95% CI=1.16-2.14; P = .04) groups. CONCLUSIONS: Lower VO2peak was significantly associated with greater LFC and higher serum GGT levels in a population-based cohort of adult individuals. Our results suggest that low VO2peak might be a risk factor for HS.

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PURPOSE: To evaluate the suitability of psoas and erector spinae muscle proton density fat fraction (PDFF) and fat volume as biomarkers for monitoring cachexia severity in an oncological cohort, and to evaluate regional variances in muscle parameters over time. METHODS: In this prospective study, 58 oncological patients were examined by a 3 T MRI receiving between one and five scans. Muscle volume and PDFF were measured, segmentation masks were divided into proximal, middle and distal muscle section. RESULTS: A regional variation of fat distribution in erector spinae muscle at baseline was found (p < 0.01). During follow-ups significant relative change of muscle parameters was observed. Relative maximum change of erector spinae muscle showed a significant regional variation. Correlation testing with age as a covariate revealed significant correlations for baseline psoas fat volume (r = -0.55, p < 0.01) and baseline psoas PDFF (r = -0.52, p = 0.02) with maximum BMI change during the course of the disease. CONCLUSION: In erector spinae muscles, a regional variation of fat distribution at baseline and relative maximum change of muscle parameters was observed. Our results indicate that psoas muscle PDFF and fat volume could serve as MRI-determined biomarkers for early risk stratification and disease monitoring regarding progression and severity of weight loss in cancer cachexia.

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Controlled attenuation parameter (CAP) is a measurement of ultrasound attenuation used to assess liver steatosis non-invasively. However, the standard method has some limitations. This study assessed the performance of a new CAP method by ex vivo and in vivo assessments. The major difference with the new method is that it uses ultrasound data continuously acquired during the imaging phase of the FibroScan examination. Seven reference tissue-mimicking phantoms were used to test the performance. In vivo performance was assessed in two cohorts (in total 195 patients) of patients using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as a reference. The precision of CAP was improved by more than 50% on tissue-mimicking phantoms and 22%-41% in the in vivo cohort studies. The agreement between both methods was excellent, and the correlation between CAP and MRI-PDFF improved in both studies (0.71 to 0.74; 0.70 to 0.76). Using MRI-PDFF as a reference, the diagnostic performance of the new method was at least equal or superior (area under the receiver operating curve 0.889-0.900, 0.835-0.873). This study suggests that the new continuous CAP method can significantly improve the precision of CAP measurements ex vivo and in vivo.

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BACKGROUND: Chemical shift encoding-based water-fat magnetic resonance imaging (CSE-MRI) measures a quantitative biomarker: the proton density fat fraction (PDFF). The aim was to assess regional and proximo-distal PDFF variations at the thigh in patients with myotonic dystrophy type 2 (DM2), limb-girdle muscular dystrophy type 2A (LGMD2A), and late-onset Pompe disease (LOPD) as compared to healthy controls. METHODS: Seven patients (n=2 DM2, n=2 LGMD2A, n=3 LOPD) and 20 controls were recruited. A 3D-spoiled gradient echo sequence was used to scan the thigh musculature. Muscles were manually segmented to generate mean muscle PDFF. RESULTS: In all three disease entities, there was an increase in muscle fat replacement compared to healthy controls. However, within each disease group, there were patients with a shorter time since symptom onset that only showed mild PDFF elevation (range, 10% to 20%) compared to controls (P≤0.05), whereas patients with a longer period since symptom onset showed a more severe grade of fat replacement with a range of 50% to 70% (P<0.01). Increased PDFF of around 5% was observed for vastus medialis, semimembranosus and gracilis muscles in advanced compared to early DM2. LGMD2A_1 showed an early disease stage with predominantly mild PDFF elevations over all muscles and levels (10.9%±7.1%) compared to controls. The quadriceps, gracilis and biceps femoris muscles showed the highest difference between LGMD2A_1 with 5 years since symptom onset (average PDFF 11.1%±6.9%) compared to LGMD2A_2 with 32 years since symptom onset (average PDFF 66.3%±6.3%). For LOPD patients, overall PDFF elevations were observed in all major hip flexors and extensors (range, 25.8% to 30.8%) compared to controls (range, 1.7% to 2.3%, P<0.05). Proximal-to-distal PDFF highly varied within and between diseases and within controls. The intra-reader reliability was high (reproducibility coefficient ≤2.19%). CONCLUSIONS: By quantitatively measuring muscle fat infiltration at the thigh, we identified candidate muscles for disease monitoring due to their gradual PDFF elevation with longer disease duration. Regional variation between proximal, central, and distal muscle PDFF was high and is important to consider when performing longitudinal MRI follow-ups in the clinical setting or in longitudinal studies.