Proton Density Fat Fraction Measurements Research Articles

Influence of Gd-EOB-DTPA on proton-density fat fraction in the liver using chemical shift-encoded magnetic resonance imaging at 3-T.

Non-alcoholic fatty liver disease (NAFLD) and its advanced stage, non-alcoholic steatohepatitis (NASH), have become increasingly prevalent owing to the rise in metabolic syndromes. Accurate assessment of hepatic fat deposition and inflammation is crucial for diagnosing and managing NAFLD/NASH. We investigated the influence of Gd-EOB-DTPA, (EOB) on proton-density fat fraction (PDFF) measurements using chemical shift-encoded magnetic resonance imaging (CSE-MRI) at 3-T. In total, 431 patients who underwent EOB contrast-enhanced MRI were included. PDFF measurements were obtained from pre- and post-contrast CSE-MRI. Linear regression and Bland-Altman analyses were performed to assess the correlation and agreement between pre- and post-EOB PDFF measurements. Relative enhancement (RE) of the liver was calculated as an EOB uptake index. There was a significant decrease in PDFF following EOB administration compared with the pre-contrast values (P < 0.0001), which was observed across all PDFF ranges (< 10% and ≥ 10%). Linear regression analysis revealed high correlation between pre- and post-EOB PDFF measurements. Bland-Altman analysis indicated a small bias between pre- and post-EOB PDFF values. Subgroup analysis based on RE showed a significant difference in ΔPDFF between patients with high RE (> 120%) and those with lower RE levels. EOB administration resulted in a slight decrease in PDFF measurements obtained using CSE-MRI at 3-T. We were able to generalize and clarify that the PDFF of the liver on 3D CSE-MRI at 3-T was slightly decreased after EOB administration as we used a larger group of patients compared to previous studies.

Chemical shift-encoded MRI with compressed sensing combined with parallel imaging for proton density fat fraction measurement of the lumbar vertebral bone marrow.

We aimed to investigate the accuracy of proton density fat fraction (PDFF) measurement of the lumbar vertebral bone marrow using chemical shift-encoded magnetic resonance imaging (CSE-MRI) with compressed sensing combined with parallel imaging (CSPI). This study recruited a commercially available phantom, and 43 patients. Fully sampled data without CSPI and under-sampled data with CSPI acceleration factors of 2.4, 3.6, and 4.8 were acquired using a 1.5T imaging system. The relationships between PDFF measurements obtained with the no-CSPI acquisition and those obtained with each CSPI acquisition were assessed using Pearson correlation coefficient (r), linear regression analyses, and Bland-Altman analysis. The intra- and inter-observer variabilities of the PDFF measurements were evaluated using the intraclass correlation coefficient. PDFF measurements obtained with all acquisitions showed a significant correlation and strong agreement with the reference PDFF measurement of the phantom. PDFF measurements obtained using CSE-MRI with and without CSPI were positively correlated (all acquisitions: r = 0.99; P < .001). The mean bias was -0.31% to -0.17% with 95% limits of agreement within ±2.02%. The intra- and inter-observer agreements were excellent (intraclass correlation coefficient: 0.988 and 0.981, respectively). A strong agreement and positive correlation were observed between the PDFF measurements obtained using CSE-MRI with and without CSPI. PDFF measurement of the lumbar vertebral bone marrow using CSE-MRI with CSPI can be acquired with a maximum reduction of approximately 75% in the acquisition time compared with a fully sampled acquisition.

Marked difference in liver fat measured by histology vs. magnetic resonance-proton density fat fraction: A meta-analysis

Pathologists quantify liver steatosis as the fraction of lipid droplet-containing hepatocytes out of all hepatocytes, whereas the magnetic resonance-determined proton density fat fraction (PDFF) reflects the tissue triacylglycerol concentration. We investigated the linearity, agreement, and correspondence thresholds between histological steatosis and PDFF across the full clinical spectrum of liver fat content associated with non-alcoholic fatty liver disease. Using individual patient-level measurements, we conducted a systematic review and meta-analysis of studies comparing histological steatosis with PDFF determined by magnetic resonance spectroscopy or imaging in adults with suspected non-alcoholic fatty liver disease. Linearity was assessed by meta-analysis of correlation coefficients and by linear mixed modelling of pooled data, agreement by Bland-Altman analysis, and thresholds by receiver operating characteristic analysis. To explain observed differences between the methods, we used RNA-seq to determine the fraction of hepatocytes in human liver biopsies. Eligible studies numbered 9 (N= 597). The relationship between PDFF and histology was predominantly linear (r= 0.85 [95% CI, 0.80-0.89]), and their values approximately coincided at 5% steatosis. Above 5% and towards higher levels of steatosis, absolute values of the methods diverged markedly, with histology exceeding PDFF by up to 3.4-fold. On average, 100% histological steatosis corresponded to a PDFF of 33.0% (29.5-36.7%). Targeting at a specificity of 90%, optimal PDFF thresholds to predict histological steatosis grades were ≥5.75% for ≥S1, ≥15.50% for ≥S2, and ≥21.35% for S3. Hepatocytes comprised 58 ± 5% of liver cells, which may partly explain the lower values of PDFF vs. histology. Histological steatosis and PDFF have non-perfect linearity and fundamentally different scales of measurement. Liver fat values obtained using these methods may be rendered comparable by conversion equations or threshold values. Magnetic resonance-proton density fat fraction (PDFF) is increasingly being used to measure liver fat in place of the invasive liver biopsy. Understanding the relationship between PDFF and histological steatosis fraction is important for preventing misjudgement of clinical status or treatment effects in patient care. Our analysis revealed that histological steatosis fraction is often significantly higher than PDFF, and their association varies across the spectrum of fatty liver severity. These findings are particularly important for physicians and clinical researchers, who may use these data to interpret PDFF measurements in the context of histologically evaluated liver fat content.

Harmonized Multisite MRI-Based Quantification of Human Liver Fat and Stiffness: A Pilot Study.

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of end-stage liver disease. NAFLD diagnosis and follow-up relies on a combination of clinical data, liver imaging, and/or liver biopsy. However, intersite imaging differences impede diagnostic consistency and reduce the repeatability of the multisite clinical trials necessary to develop effective treatments. The goal of this pilot study was to harmonize commercially available 3 T magnetic resonance imaging (MRI) measurements of liver fat and stiffness in human participants across academic sites and MRI vendors. Cohort. Four community-dwelling adults with obesity. 1.5 and 3 T, multiecho 3D imaging, PRESS, and GRE. Harmonized proton density fat fraction (PDFF) and magnetic resonance spectroscopy (MRS) protocols were used to quantify the FF of synthetic phantoms and human participants with obesity using standard acquisition parameters at four sites that had four different 3 T MRI instruments. In addition, a harmonized magnetic resonance elastography (MRE) protocol was used to quantify liver stiffness among participants at two different sites at 1.5 and 3 T field strengths. Data were sent to a single data coordinating site for postprocessing. Linear regression in MATLAB, ICC analyses using SAS 9.4, one-sided 95% confidence intervals for the ICC. PDFF and MRS FF measurements were highly repeatable among sites in both humans and phantoms. MRE measurements of liver stiffness in three individuals at two sites using one 1.5 T and one 3 T instrument showed repeatability that was high although lower than that of MRS and PDFF. We demonstrated harmonization of PDFF, MRS, and MRE-based quantification of liver fat and stiffness through synthetic phantoms, traveling participants, and standardization of postprocessing analysis. Multisite MRI harmonization could contribute to multisite clinical trials assessing the efficacy of interventions and therapy for NAFLD. 2 TECHNICAL EFFICACY STAGE: 2.

Bone Marrow Adiposity and Fragility Fractures in Postmenopausal Women: The ADIMOS Case-Control Study.

Noninvasive assessment of proton density fat fraction (PDFF) by MRI may improve the prediction of fractures. To determine if an association exists between PDFF and fractures. A case-control study with 2 groups of postmenopausal women: one with recent osteoporotic fractures, and the other with no fractures. Lille University Hospital, Lille, France. Lumbar spine and proximal femur (femoral head, neck, and diaphysis) PDFF, determined using chemical shift-based water-fat separation MRI (WFI) and DXA scans of the lumbar spine and hip. Our primary objective was to determine the relationship between lumbar spine PDFF and osteoporotic fractures in postmenopausal women. Analysis of covariance (ANCOVA) was used to compare PDFF measurements between cases (overall and according to the type of fracture) and controls, after adjusting for age, Charlson comorbidity index (CCI) and BMD. In 199 participants, controls (n = 99) were significantly younger (p < 0.001) and had significantly higher BMD (p < 0.001 for all sites) than cases (n = 100). 52 women with clinical vertebral fractures and 48 with nonvertebral fractures were included. When PDFFs in cases and controls were compared, after adjustment on age, CCI and BMD, no significant differences between the groups were found at lumbar spine or proximal femur. When PDFFs in participants with clinical vertebral fractures (n = 52) and controls were compared, femoral neck PDFF and femoral diaphysis PDFF were detected to be lower in participants with clinical vertebral fractures than in controls (adjusted mean (standard error) 79.3% (1.2) vs 83.0% (0.8), p = 0.020, and 77.7% (1.4) vs. 81.6% (0.9), p = 0.029, respectively). No difference in lumbar spine PDFF was found between those with osteoporotic fractures and controls. However, imaging-based proximal femur PDFF may discriminate between postmenopausal women with and without clinical vertebral fractures, independently of age, CCI and BMD.

Impact of Hepatic Iron Overload in the Evaluation of Steatosis and Fibrosis in Patients with Nonalcoholic Fatty Liver Disease Using Vibration-Controlled Transient Elastography (VCTE) and MR Imaging Techniques: A Clinical Study

PurposeThree main non-invasive imaging methods are routinely used for the assessment of liver fibrosis and steatosis in patients with nonalcoholic fatty liver disease (NAFLD): the vibration-controlled transient elastography (VCTE) using the FibroScan device, the magnetic resonance imaging (MRI) based on proton density fat fraction (PDFF), and the magnetic resonance elastography (MRE). The purpose of our study is to evaluate the efficiency of the VCTE findings compared to the two others methods, and to analyze the impact of hepatic iron overload on these comparisons. MethodsA clinical study was performed on 94 patients with NAFLD in the radiology department of ACRIM-Polyclinic Saint-Côme (France). The study also included 17 patients with hemochromatosis, measured from T2⁎ MRI. The liver tissues of all the patients were evaluated with 1) VCTE (including the controlled attenuation (CAP) and stiffness parameters), 2) MRI (fat fraction parameter), and 3) MRE (stiffness parameter) techniques. The performance of VCTE was assessed by estimating the area under the ROC curve (AUC) for patients without or with hemochromatosis. Spearman's correlation was used for the comparison of VCTE measurements to MRI and MRE. ResultsVCTE-based stiffness and CAP were significantly correlated with PDFF and MRE measurements (P<0.01) for the subgroup without hemochromatosis. The correlations failed for the subgroup with hemochromatosis. ConclusionVCTE and CAP measurements were not correlated with those from MR PDFF and MRE for patients with hemochromatosis. VCTE, PDFF and MRE modalities don't give concordant results for patients with hemochromatosis.

Associations of incidental vertebral fractures and longitudinal changes of MR-based proton density fat fraction and T2* measurements of vertebral bone marrow.

Quantitative magnetic resonance imaging (MRI) techniques such as chemical shift encoding-based water-fat separation techniques (CSE-MRI) are increasingly applied as noninvasive biomarkers to assess the biochemical composition of vertebrae. This study aims to investigate the longitudinal change of proton density fat fraction (PDFF) and T2* derived from CSE-MRI of the thoracolumbar vertebral bone marrow in patients that develop incidental vertebral compression fractures (VCFs), and whether PDFF and T2* enable the prediction of an incidental VCF. In this study we included 48 patients with CT-derived bone mineral density (BMD) measurements at baseline. Patients that presented an incidental VCF at follow up (N=12, mean age 70.5 ± 7.4 years, 5 female) were compared to controls without incidental VCF at follow up (N=36, mean age 71.1 ± 8.6 years, 15 females). All patients underwent 3T MRI, containing a significant part of the thoracolumbar spine (Th11-L4), at baseline, 6-month and 12 month follow up, including a gradient echo sequence for chemical shift encoding-based water-fat separation, from which PDFF and T2* maps were obtained. Associations between changes in PDFF, T2* and BMD measurements over 12 months and the group (incidental VCF vs. no VCF) were assessed using multivariable regression models. Mixed-effect regression models were used to test if there is a difference in the rate of change in PDFF, T2* and BMD between patients with and without incidental VCF. Prior to the occurrence of an incidental VCF, PDFF in vertebrae increased in the VCF group (ΔPDFF=6.3 ± 3.1%) and was significantly higher than the change of PDFF in the group without VCF (ΔPDFF=2.1 ± 2.5%, P=0.03). There was no significant change in T2* (ΔT2*=1.7 ± 1.1ms vs. ΔT2*=1.1 ± 1.3ms, P=0.31) and BMD (ΔBMD=-1.2 ± 11.3mg/cm3 vs. ΔBMD=-11.4 ± 24.1mg/cm3, P= 0.37) between the two groups over 12 months. At baseline, no significant differences were detected in the average PDFF, T2* and BMD of all measured vertebrae (Th11-L4) between the VCF group and the group without VCF (P=0.66, P=0.35 and P= 0.21, respectively). When assessing the differences in rates of change, there was a significant change in slope for PDFF (2.32 per 6 months, 95% confidence interval (CI) 0.31-4.32; P=0.03) but not for T2* (0.02 per 6 months, CI -0.98-0.95; P=0.90) or BMD (-4.84 per 6 months, CI -23.4-13.7; P=0.60). In our study population, the average change of PDFF over 12 months is significantly higher in patients that develop incidental fractures at 12-month follow up compared to patients without incidental VCF, while T2* and BMD show no significant changes prior to the occurrence of the incidental vertebral fractures. Therefore, a longitudinal increase in bone marrow PDFF may be predictive for vertebral compression fractures.

Impact of arm position on vertebral bone marrow proton density fat fraction in chemical-shift-encoded magnetic resonance imaging: a preliminary study.

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.

Proton density fat fraction (PDFF) maps aid fat metaplasia evaluation in the sacroiliac joints in additional to T1WI: Improved diagnostic accuracy in axial spondyloarthritis

PurposeTo evaluate the added value of qualitative and quantitative fat metaplasia analysis using proton-density fat fraction (PDFF) map in additional to T1-weighted imaging (T1WI) of the sacroiliac joints (SIJ) for diagnosis of axial spondyloarthritis (axSpA). MethodPatients aged 18–45 years with axSpA were enrolled. Non-SpA patients and healthy volunteers were included as controls. All participants underwent 3.0T MRI of the SIJs including semi-coronal T1WI and semi-coronal chemical-shift encoded MRI sequence for generating PDFF map. Each joint was divided into four quadrants for analysis. Two independent readers scored fat metaplasia on T1WI alone or with additional PDFF map and measured PDFF values in different reading sessions. Using clinical diagnosis as the reference, diagnostic accuracy of visual scores and PDFF measurements was evaluated by area under the receiver operating characteristic curve (AUC). Inter-reader agreement was evaluated by the intra-class correlation coefficient (ICC). ResultsForty-nine patients with axSpA and thirty-six controls were included. Qualitative fat metaplasia scores using additional PDFF map performed better than using T1WI alone (AUC: Reader 1, 0.847 vs 0.795, p = 0.082; Reader 2, 0.785 vs 0.719, p = 0.048). AUCs of quantitative analysis using number of quadrants with PDFF value ≥75 % were higher than qualitative analysis using T1WI alone (Reader 1, 0.863 vs 0.795, p = 0.046; Reader 2, 0.823 vs 0.785, p = 0.011). ICCs were 0.854 to 0.922 for qualitative analysis and 0.935 for quantitative analysis. ConclusionsAdditional PDFF map can increase the diagnostic accuracy for axSpA by qualitative and quantitative fat metaplasia analysis, in comparison to using T1WI alone.

Clinical significance of hepatic fat loss in chronic liver disease: a study using MRI proton density fat fractionation.

The liver plays a central role in the fatty acid metabolism. Therefore, cirrhosis is prone to energy malnutrition and is associated with a poor prognosis. On the other hand, proton density fat fraction (PDFF) measured by magnetic resonance imaging (MRI) is a noninvasive and highly accurate method to quantify liver fat. In this study, we aimed to investigate the relationship between hepatic fat loss (HFL) and malnutrition by PDFF measurement in chronic liver disease (CLD). In this retrospective single-center study of 485 patients with CLD, hepatic fat content was measured by MRI-PDFF, and CT-measured body composition and CONUT (Controlling Nutritional Status) score were used as nutritional assessment methods, respectively. In the overall cohort, MRI-PDFF was positively correlated with body fat mass, muscle mass and respectively. The HFL defined by PDFF ≤ 2.7% is 25%, and in multivariate analysis, decreased body fat mass and Triglyceride, and increased CONUT score were independent associated factors of HFL (p < 0.05, for all). Additionally, 35% of patients with cirrhosis (n = 107) had HFL, and the Cox proportional hazards model showed that Child-Pugh score and HFL were independent prognostic factors (p < 0.01, for both). MRI-PDFF was shown to be a useful indicator of malnutrition in cirrhosis reflecting body composition. Preservation of liver fat content in nutritional therapy may improve the prognosis of cirrhotic patients.

Quantification of Hepatic Steatosis by Ultrasound: Prospective Comparison With MRI Proton Density Fat Fraction as Reference Standard.

BACKGROUND. Multiple ultrasound platforms now provide quantitative measures of hepatic steatosis. One such measure is the ultrasound-derived fat fraction (UDFF), which combines attenuation and backscatter quantification. OBJECTIVE. The purpose of this study was to characterize agreement between UDFF and MRI proton-density fat fraction (PDFF) measurements. METHODS. This prospective cross-sectional study enrolled 56 overweight and obese adolescents and adults (age ≥ 16 years) who underwent investigational ultrasound (deep abdominal transducer) and MRI examinations of the liver during a single visit from August 2020 to October 2020. Ultrasound examinations included three UDFF acquisitions of five measurements each (15 measurements total), and an overall median of medians was computed (UDFFoverall). MRI examinations included three PDFF acquisitions with calculation of an overall median PDFF. Spearman rank-order correlation was computed between UDFF and MRI PDFF measurements. Intraclass correlation coefficients and Bland-Altman difference plots were used to assess agreement. ROC curves were used to assess diagnostic performance of UDFF for detecting MRI PDFF of 5.5% or more. RESULTS. Median participant age was 32.5 years (IQR, 24.0-39.0 years); 40 participants were female, and 16 were male. A total of 34 (60.7%) participants had an MRI PDFF of 5.5% or more. UDFFoverall was 10.5% (IQR, 5.0-20.0%); median MRI PDFF was 6.1% (IQR, 3.4-13.7%). UDFFoverall was positively associated with MRI PDFF (ρ, 0.82; p < .001; intraclass correlation coefficient, 0.84 [95% CI, 0.59-0.93]). Mean bias between UDFF and PDFF was 4.0% (95% limits of agreement, -7.9% to 15.9%), with similar bias if summarizing UDFF by the first five measurements (4.4%), first three measurements (4.4%), or first measurement (4.6%). UDFFoverall AUC was 0.90 (95% CI, 0.79-0.96) for MRI PDFF of 5.5% or more; AUC was not significantly different when it was based on the number of UDFF measurements (p = .11-.97 for all pairwise AUC comparisons). UDFFoverall cutoff of more than 5% had sensitivity of 94.1% and specificity of 63.6% for diagnosing MRI PDFF of 5.5% or more. CONCLUSION. Measurements of hepatic steatosis using UDFF show strong agreement with measurements by MRI PDFF. A UDFFoverall cutoff of more than 5% provides high AUC and sensitivity, albeit low specificity, for detection of MRI PDFF of 5.5% or more. CLINICAL IMPACT. UDFF may have a clinical role in detection of hepatic steatosis. A reduced number of individual measurements is likely sufficient for determining an overall UDFF value. TRIAL REGISTRATION. ClinicalTrials.gov: NCT04523584.

Novel metabolic classification for extrahepatic complication of metabolic associated fatty liver disease: A data-driven cluster analysis with international validation

BackgroundTraditional classification systems of metabolic-associated fatty liver disease (MAFLD) do not account for the high rate of extrahepatic complications. To create a new classification of MAFLD using metabolic parameters to identify risks of complications more accurately. MethodsThe retrospective study included MAFLD patients from the First Affiliated Hospital of Sun Yat-sen University for model development, and the model was validated respectively using Chinese cohort and UK Biobank database. Cluster analysis with k-means cluster was built using age, body mass index (BMI), glycosylated hemoglobin (HbA1c), total cholesterol/high density lipoprotein cholesterol (HDL-C) ratio, triglyceride, and lipoprotein(a) [Lp(a)] levels. Cox regression models were used to compare the risk of type 2 diabetes (T2DM), chronic heart disease (CHD), stroke and mortality between the clusters. Results1038 MAFLD patients from cross-sectional population were recruited for the model derivation, with 10,451 cases (33.4 % of MAFLD) from Chinese cohort and 304,141 cases (34.9 % of MAFLD, 1010 cases with magnetic resonance imaging proton density fat fraction measurement [MRI-PDFF]) from the international cohort validated. Five replicable clusters of MAFLD patients were identified: Cluster 1(mild obesity and dyslipidemia-related), Cluster 2 (age related), Cluster 3 (severe insulin resistance-related), Cluster 4[high Lp(a)-related], and Cluster 5 (severe mixed hyperlipidemia-related). Patients in different clusters exhibited differences in the development of T2DM, CHD, stroke and all-causes mortality. Patients in Cluster 3 had significantly worst survival outcomes and higher risks of T2DM and CVD than those in other clusters. ConclusionThe novel classification offers improved discrimination of new-onset MAFLD patients with different metabolic complications.

Association of Paraspinal Muscle CSA and PDFF Measurements With Lumbar Intervertebral Disk Degeneration in Patients With Chronic Low Back Pain.

There is an interaction between the lumbar spine and paraspinal muscles, which may play a role in the development of intervertebral disc (IVD) degeneration and may affect CLBP. The study aims to assess the relationship between IVD degeneration and paraspinal muscle fat infiltration in CLBP patients by quantitative MR imaging, and to evaluate the influence of sex and age on CLBP muscle fat infiltration. Sixty CLBP patients (46.3 years ±17.0) and thirty-two healthy subjects (44.9 years ±17.6) were recruited for this study. 3.0 T MRI was used to perform the sagittal and axial T1, T2 of the lumbar spine, and axial paraspinal muscle IDEAL imaging at the L4/5 and L5/S1 levels. Proton density fat fraction (PDFF) of the multifidus and erector spinae at two IVD levels were measured. The Pfirrmann grades of IVD degeneration, Oswestry Disability Index (ODI), and Visual Analog Scale (VAS) were also evaluated. Compare the cross-sectional area (CSA) and PDFF of the paraspinal muscles between CLBP patients and healthy subjects, and analyze the relationship between the muscle PDFF and Pfirrmann grades, gender, and age of CLBP patients. Compared with healthy subjects, the CSA of the multifidus muscle in CLBP patients decreased (1320.2±188.1mm2 vs. 1228.7±191.0 mm2, p<0.05) at the L4/5 level, the average PDFF increased, (7.7±2.6% vs. 14.79±5.3%, 8.8±4.2% vs. 16.03±5.3%, all p<0.05) at both L4/5 and L5/S1 levels. The PDFF of paraspinal muscles were correlated with adjacent IVD degeneration, ODI and VSA in CLBP patients (all p<0.05). After using age and body mass index (BMI) as control variables, significance was retained (all p<0.05). Multiple regression analysis revealed sex and age also were significantly associated with multifidus PDFF (all p < 0.05). This study confirmed that the CSA decreased and the PDFF increased of the paraspinal muscles in CLBP patients. It reveals a significant correlation between the PDFF of CLBP paraspinal muscles and the grade of IVD degeneration. Sex and age are also important factors influencing CLBP paraspinal muscle infiltration.

Adding liver R2* quantification to proton density fat fraction MRI of vertebral bone marrow improves the prediction of osteoporosis.

To assess the predictive value of the combination of bone marrow (BM) proton density fat fraction (PDFF) and liver R2* for osteopenia and osteoporosis and the additional role of liver R2*. A total of 107 healthy women were included between June 2019 and January 2021. Each participant underwent dual-energy X-ray absorptiometry (DXA) and chemical shift-encoded 3.0-T MRI. PDFF measurements were performed for each lumbar vertebral body, and R2* measurements were performed in liver segments. Agreement among measurements was assessed by Bland-Altman analysis. Receiver operating characteristic (ROC) curves were generated to select optimised cut-offs for BM PDFF and liver R2*. Univariable and multivariable logistic regressions were performed. The C statistic and continuous net reclassification improvement (NRI) were adopted to explore the incremental predictive ability of liver R2*. Bone mass decreased in 42 cases (39.3%) and nonbone mass decreased in 65 cases (60.7%). There were significant differences among the age groups, menopausal status groups, PDFF > 45.0% groups, and R2* > 67.7 groups. Each measurement had good reproducibility. The odds ratios (95% CIs) were 4.05 (1.22-13.43) for PDFF and 4.34 (1.41-13.35) for R2*. The C statistic (95% CI) without R2* was 0.888 (0.827-0.950), and with R2* was 0.900 (0.841-0.960). The NRI resulting from the combination of PDFF and R2* was 75.6% (p < 0.01). The predictive improvement over the use of BM PDFF and other traditional risk factors demonstrates the potential of liver R2* as a biomarker for osteopenia and osteoporosis in healthy women. • Liver R2* is a biomarker for the assessment of osteopenia and osteoporosis. • Liver R2* improved the ability to predict osteopenia and osteoporosis. • The intra- and interobserver measurements showed high agreement.

Proton density fat fraction measurements of rotator cuff muscles: Accuracy, repeatability, and reproducibility across readers and scanners

PurposeTo determine the accuracy, repeatability, and reproducibility of magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) measurements of rotator cuff muscles between two readers and three different scanners. MethodsTwenty-seven volunteers underwent serial shoulder MRI examinations of both left and right sides on one 1.5-T MRI scanner and two 3.0-T MRI scanners. Two independent readers measured muscular PDFF of the supraspinatus, infraspinatus/teres minor muscle, and subscapularis. MR spectroscopy-based proton density fat fraction (MRS-PDFF) was regarded as the reference standard for assessing accuracy. A “coffee break” examination method was used to test the repeatability of each scanner. Bland-Altman plots, Pearson correlation, and linear regression analysis were used to assess bias and linearity. The Wilcoxon signed-rank test and Friedman test were applied to evaluate repeatability and reproducibility. ResultsMRI-PDFF measurements indicated strong linearity (R2 = 0.749) and small bias (−0.18%) in comparison with the MRS-PDFF measurements. A very strong positive Pearson correlation (r = 0.955–0.986) between the PDFF estimates of the two repeat scans indicated excellent repeatability. The PDFF measurements showed high reproducibility, with a strong positive Pearson correlation (r = 0.668–0.698) and a small mean bias (−0.04 to −0.10%) across different scanners. ConclusionMRI-PDFF measurements of rotator cuff muscles were highly accurate, repeatable, and reproducible across different readers and scanners, leading us to the conclusion that PDFF can be a reliable and robust quantitative imaging biomarker for longitudinal or multi-center studies.

Comparison of reader agreement, correlation with liver biopsy, and time-burden sampling strategies for liver proton density fat fraction measured using magnetic resonance imaging in patients with obesity: a secondary cross-sectional study

BackgroundThe magnetic resonance imaging (MRI)-based proton density fat fraction (PDFF) has become popular for quantifying liver fat content. However, the variability of the region-of-interest (ROI) sampling strategy may result in a lack of standardisation of this technology. In an effort to establish an accurate and effective PDFF measurement scheme, this study assessed the pathological correlation, the reader agreement, and time-burden of different sampling strategies with variable ROI size, location, and number.MethodsSix-echo spoiled gradient-recalled-echo magnitude-based fat quantification was performed for 50 patients with obesity, using a 3.0-T MRI scanner. Two readers used different ROI sampling strategies to measure liver PDFF, three times. Intra-reader and inter-reader agreement was evaluated using intra-class correlation coefficients and Bland‒Altman analysis. Pearson correlations were used to assess the correlation between PDFFs and liver biopsy. Time-burden was recorded.ResultsFor pathological correlations, the correlations for the strategy of using three large ROIs in Couinaud segment 3 (S3 3L-ROI) were significantly greater than those for all sampling strategies at the whole-liver level (P < 0.05). For inter-reader agreement, the sampling strategies at the segmental level for S3 3L-ROI and using three large ROIs in Couinaud segment 6 (S6 3L-ROI) and the sampling strategies at the whole-liver level for three small ROIs per Couinaud segment (27S-ROI), one large ROI per Couinaud segment (9L-ROI), and three large ROIs per Couinaud segment (27S-ROI) had limits of agreement (LOA) < 1.5%. For intra-reader agreement, the sampling strategies at the whole-liver level for 27S-ROI, 9L-ROI, and 27L-ROI had both intraclass coefficients > 0.995 and LOAs < 1.5%. The change in the time-burden was the largest (100.80 s) when 9L-ROI was changed to 27L-ROI.ConclusionsFor hepatic PDFF measurement without liver puncture biopsy as the gold standard, and for general hepatic PDFF assessment, 9L-ROI sampling strategy at the whole-liver level should be used preferentially. For hepatic PDFF with liver puncture biopsy as the gold standard, 3L-ROI sampling strategy at the puncture site segment is recommended.

Hepatic Steatosis: CT-Based Prevalence in Adults in China and the United States and Associations With Age, Sex, and Body Mass Index.

BACKGROUND. Calibrated CT fat fraction (FFCT) measurements derived from un-enhanced abdominal CT reliably reflect liver fat content, allowing large-scale population-level investigations of steatosis prevalence and associations. OBJECTIVE. The purpose of this study was to compare the prevalence of hepatic steatosis, as assessed by calibrated CT measurements, between population-based Chinese and U.S. cohorts, and to investigate in these populations the relationship of steatosis with age, sex, and body mass index (BMI). METHODS. This retrospective study included 3176 adults (1985 women and 1191 men) from seven Chinese provinces and 8748 adults (4834 women and 3914 men) from a single U.S. medical center, all drawn from previous studies. All participants were at least 40 years old and had undergone unenhanced abdominal CT in previous studies. Liver fat content measurements on CT were cross-calibrated to MRI proton density fat fraction measurements using phantoms and expressed as adjusted FFCT measurements. Mild, moderate, and severe steatosis were defined as adjusted FFCT of 5.0-14.9%, 15.0-24.9%, and 25.0% or more, respectively. The two cohorts were compared. RESULTS. In the Chinese and U.S. cohorts, the median adjusted FFCT for women was 4.7% and 4.8%, respectively, and that for men was 5.8% and 6.2%, respectively. In the Chinese and U.S. cohorts, steatosis prevalence for women was 46.3% and 48.7%, respectively, whereas that for men was 58.9% and 61.9%, respectively. Severe steatosis prevalence was 0.9% and 1.8% for women and 0.2% and 2.6% for men in the Chinese and U.S. cohorts, respectively. Adjusted FFCT did not vary across age decades among women or men in the Chinese cohort, although it increased across age decades among women and men in the U.S. cohort. Adjusted FFCT and BMI exhibited weak correlation (r = 0.312-0.431). Among participants with normal BMI, 36.8% and 38.5% of those in the Chinese and U.S. cohorts, respectively, had mild steatosis, and 3.0% and 1.5% of those in the Chinese and U.S. cohorts, respectively, had moderate or severe steatosis. Among U.S. participants with a BMI of 40.0 or greater, 17.7% had normal liver content. CONCLUSION. Steatosis and severe steatosis had higher prevalence in the U.S. cohort than in the Chinese cohort in both women and men. BMI did not reliably predict steatosis. CLINICAL IMPACT. The findings provide new information on the dependence of hepatic steatosis on age, sex, and BMI.

Direct Comparison of Quantitative US versus Controlled Attenuation Parameter for Liver Fat Assessment Using MRI Proton Density Fat Fraction as the Reference Standard in Patients Suspected of Having NAFLD.

Background MRI-derived proton density fat fraction (PDFF) is an accurate, reliable, and safe biologic marker for use in the noninvasive diagnosis of hepatic steatosis in patients with nonalcoholic fatty liver disease (NAFLD). Because of the cost and limited availability of MRI, it is necessary to develop an accurate method to diagnose NAFLD with potential point-of-care access. Purpose To compare the diagnostic accuracy of the quantitative US (QUS) fat fraction (FF) estimator with that of the controlled attenuation parameter (CAP) in the diagnosis of NAFLD using contemporaneous MRI-derived PDFF as the reference standard. Materials and Methods Participants with or suspected of having NAFLD were prospectively recruited at the NAFLD Research Center between July 2015 and July 2019. All participants underwent MRI-derived PDFF measurement, transient elastography with CAP measurement, and QUS. QUS FF was derived using computed QUS parameters from the acquired radiofrequency US data using a calibrated reference phantom. The area under the receiver operating characteristic curve (AUC) was calculated to assess the accuracy of QUS FF and CAP in the diagnosis of hepatic steatosis (defined as MRI-derived PDFF ≥ 5%). AUCs were compared using the DeLong test. Results A total of 123 participants were included (mean age, 52 years ± 13 [SD]; 67 [54%] women). Of these participants, 100 (81%) had MRI-derived PDFF of 5% or more. QUS FF had a significantly higher AUC for diagnosis of NAFLD than did CAP (0.92 [95% CI: 0.87, 0.98] vs 0.79 [95% CI: 0.67, 0.90], P = .03). QUS FF had a sensitivity of 98% (98 of 100) and a specificity of 48% (11 of 23). CAP had a sensitivity of 87% (87 of 100) and a specificity of 57% (13 of 23). Conclusion The quantitative US fat fraction estimator is more accurate than the controlled attenuation parameter in the diagnosis of hepatic steatosis in patients with or suspected of having nonalcoholic fatty liver disease. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Ito in this issue.

Role of Advanced MRI Techniques in the Quantitative Assessment of Liver Fat—A Multimodality-Based Comparative Study of Diagnostic Performance in a Tertiary Care Institute

Abstract Objective To evaluate the accuracy of noninvasive imaging methods including gray-scale ultrasound, ultrasound shear wave elastography, unenhanced computed tomography (CT), and proton density fat fraction (PDFF) on magnetic resonance imaging (MRI) using three-dimensional (3D) multiecho multipoint chemical shift–encoded spoiled gradient echo (q-DIXON) sequence in the quantification of hepatic steatosis, with proton MR spectroscopy (H1-MRS) as the reference standard in Indian population. Methods Our study included 100 consecutive adult patients referred to the department of radiology in our hospital for imaging of liver. Fat content of liver was recorded using MRI (H1-MRS and q-DIXON), unenhanced CT (average liver attenuation [ALI] and liver attenuation index [LAI]) and ultrasonography (USG) (gray-scale grading and shear wave elastography [SWE]). Data were analyzed by linear regression and Bland–Altman analysis for each technique compared with H1-MRS. The diagnostic performances of all the methods were compared using DeLong test, for detection of mild and moderate-to-severe hepatic steatosis, separately. Results MRI q-DIXON PDFF showed excellent correlation (r = 0.917, r2 = 0.840) and strong agreement (1.48 ±3.01) with H1-MRS-derived PDFF measurements. Unenhanced CT-based methods showed moderate correlation with modest agreement (r = −0.826, r2 = 0.681, −40.18 ± 16.05 for ALI and r = −0.858, r2 = 0.735, 13.4 ± 15.3 for LAI) whereas USG gray-scale assessment showed low correlation (weighted Kappa value 0.366) with H1-MRS PDFF. No correlation was found between USG-SWE results and PDFF measured with H1-MRS. Comparison of areas under curve (AUCs) using DeLong test revealed that MRI q-DIXON method performed the best for diagnosis of hepatic steatosis compared with rest. For moderate to severe steatosis, MRI q-DIXON and unenhanced CT-based methods had comparable diagnostic performance with AUCs not showing statistically significant differences. Conclusion MRI q-DIXON shows strongest correlation with MRS and should be preferred for estimation of hepatic fat, especially when MRS is not available. Unenhanced CT shows limited diagnostic performance in detecting mild steatosis; however, it certainly has a role in diagnosing moderate-to-severe hepatic steatosis, such as evaluating donor candidates for living donor liver transplantation. USG, using both the traditional four-grade visual assessment and elastography in the present form, appears to have limited role in liver fat quantification.

Varied Relationship of Lipid and Lipoprotein Profiles to Liver Fat Content in Phenotypes of Metabolic Associated Fatty Liver Disease.

BackgroundProgressive overloads of intrahepatic triglycerides are related to metabolic dysregulation of multiple lipid and lipoprotein profiles, but whether similar dose effects are found in each subtype of metabolic associated fatty liver disease (MAFLD) remains unclear. We aimed to characterize the lipid profiles associated with liver fat content (LFC) in MAFLD patients who were overweight, lean/normal weight, or had diabetes.MethodsWe conducted a cross-sectional study enrolling 1,182 consecutive participants (144 non-MAFLD and 1,038 MAFLD) who underwent MRI proton density fat fraction measurement (MRI-PDFF) from 2011 to 2020. Lipid and apolipoprotein profiles, free fatty acid (FFA), liver and metabolism parameters, and anthropometric measurements were also assessed.ResultsMAFLD patients with type 2 diabetes or overweight/obesity had a higher proportion of abnormal lipid and lipoprotein profiles than those who were lean/normal weight. The degree of LFC had a positive correlation with total cholesterol, triglyceride, ApoB, and ApoE in patients with overweight/obesity and type 2 diabetes. In those with overweight/obesity, there were dose–response relationships between moderate-to-severe steatosis and total cholesterol, triglyceride, HDL-c, LDL-c, ApoB, ApoE, and Lp(a). A similar trend was observed for triglyceride in those with type 2 diabetes and for HDL-c in patients who were lean/normal weight (all p for trend <0.05). The combined model of relative lipid-related markers performed well in the prediction of moderate-to-severe steatosis (AUC: 0.762 for overweight/obesity; 0.742 for lean/normal weight).ConclusionLFC was associated with lipid profiles, including triglyceride, LDL-c, ApoB, ApoE, and FFA. These relationships were varied by the phenotype of MAFLD according to its diagnostic flow.