Metabolic liver imaging: What you need to know.

Prior work has shown that MRI-derived proton density fat fraction (PDFF) can diagnose metabolic dysfunction-associated steatotic liver disease (MASLD) noninvasively, but there is a paucity of data on the performance of PDFF to classify more advanced forms of the MASLD spectrum. The purpose of this study was to assess the diagnostic performance of PDFF for the diagnoses of MASLD, metabolic dysfunction-associated steatohepatitis (MASH), and fibrotic MASH in adults with obesity undergoing bariatric surgery, using contemporaneous intraoperative liver biopsy as a reference. PDFF was evaluated alone and with other potential classifiers (imaging, serum and anthropometric), using Bayesian Information Criterion-based stepwise logistic regression models. Areas under the receiver operating characteristic (ROC) curves (AUC) were computed for all models and single classifiers. Cross-validated sensitivity and specificity were calculated at Youden-based PDFF classification thresholds. Data analysis from 140 patients demonstrated that PDFF was the most accurate single classifier, with high AUC for MASLD (0.95), MASH (0.85), and fibrotic MASH (0.82) (all p <0.001). Multivariable models, including PDFF, outperformed those without PDFF. The Youden-based threshold for PDFF was 4.4% for MASLD (sensitivity: 87%, specificity: 86%), 6.9% for MASH (sensitivity: 77%, specificity: 66%), and 13.5% for fibrotic MASH (sensitivity: 67%, specificity: 85%). PDFF was the most accurate single classifier for diagnosing MASLD, MASH, and fibrotic MASH. The most accurate multivariable classification models for MASLD, MASH, and fibrotic MASH included PDFF, demonstrating the central importance of PDFF for noninvasive assessment of the MASLD spectrum.

Background Traditional energy-integrating detector CT has limited utility in accurately quantifying liver fat due to protocol-induced CT value shifts, but this limitation can be addressed by using photon-counting detector (PCD) CT, which allows for a standardized CT value. Purpose To develop and validate a universal CT to MRI fat conversion formula to enhance fat quantification accuracy across various PCD CT protocols relative to MRI proton density fat fraction (PDFF). Materials and Methods In this prospective study, the feasibility of fat quantification was evaluated in phantoms with various nominal fat fractions. Five hundred asymptomatic participants and 157 participants with suspected metabolic dysfunction-associated steatotic liver disease (MASLD) were enrolled between September 2023 and March 2024. Participants were randomly assigned to six groups with different CT protocols regarding tube voltage (90, 120, or 140 kVp) and radiation dose (standard or low). Of the participants in the 120-kVp standard-dose asymptomatic group, 51% (53 of 104) were designated as the training cohort, with the rest of the asymptomatic group serving as the validation cohort. A CT to MRI fat quantification formula was derived from the training cohort to estimate the CT-derived fat fraction (CTFF). CTFF agreement with PDFF and its error were evaluated in the asymptomatic validation cohort and subcohorts stratified by tube voltage, radiation dose, and body mass index, and in the MASLD cohort. The factors influencing CTFF error were further evaluated. Results In the phantoms, CTFF showed excellent agreement with nominal fat fraction (intraclass correlation coefficient, 0.98; mean bias, 0.2%). A total of 412 asymptomatic participants and 122 participants with MASLD were included. A CT to MRI fat conversion formula was derived as follows: MRI PDFF (%) = -0.58 · CT (HU) + 43.1. Across all comparisons, CTFF demonstrated excellent agreement with PDFF (mean bias values < 1%). CTFF error was not influenced by tube voltage, radiation dose, body mass index, or PDFF. Agreement between CTFF and PDFF was also found in the MASLD cohort (mean bias, -0.2%). Conclusion Standardized CT value from PCD CT showed a robust and remarkable agreement with MRI PDFF across various protocols and may serve as a precise alternative for liver fat quantification. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Wildman-Tobriner in this issue.

Acquired over a breath hold, multi-echo Dixon (mDixon) magnetic resonance imaging (MRI) of the liver can be used to quantify proton density fat fraction (PDFF) and iron-related signal decay. However, young, obese, and co-morbid patients may have limited breath holding capacity and could benefit from a motion-robust mDixon acquisition. The purpose of this study was to compare hepatic PDFF and R2* values between navigator-gated and breath-held mDixon MRI acquisition techniques in children and young adults with suspected liver disease. This retrospective study was institutional review board-approved with a waiver of informed consent. Patients who underwent liver MRI with breath-held and navigator-gated mDixon sequences between January 2017 and July 2018 were included. One reviewer, blinded to sequence, measured PDFF and R2* on four images from each sequence. Another blinded reviewer graded respiratory motion (5-point Likert scale). Pearson correlation (r), Lin's concordance coefficients (rc), and Bland-Altman analyses were used to assess agreement between techniques. Frequency of clinically limiting motion (score ≥ 3) was compared with Fisher's exact test. Forty-two patients were included (15 female, 27 male; mean age: 15.7 ± 4.6years). Mean PDFF and R2* were 16.6 ± 13.1% and 29.3 ± 4.7s-1 (breath-held) versus 17.0 ± 13.2% and 29.6 ± 5.2s-1 (navigator-gated). PDFF agreed almost perfectly between sequences (rc = 0.997, 95% CI 0.994-0.998; mean bias: 0.3%; 95% limits of agreement: - 2.4 to +1.7%), while R2* values correlated very strongly but with poor agreement (r = 0.837, rc = 0.832, 95% CI 0.716-0.910). Navigator-gated images exhibited significantly higher frequency of clinically limiting respiratory motion (88% vs. 48%, p = 0.0001). Despite greater respiratory motion artifact, a free-breathing navigator-gated mDixon sequence produces PDFF values with almost perfect agreement to a breath-held sequence.

Metabolic dysfunction-associated steatotic liver disease is increasingly affecting younger populations. Ultrasound-derived fat fraction is a technique used in ultrasound to quantify liver fat content. The diagnostic performance of ultrasound-derived fat fraction in pediatric patients with metabolic dysfunction-associated steatotic liver disease is yet to be evaluated. To evaluate the diagnostic performance of ultrasound-derived fat fraction measurement in detecting and grading hepatic steatosis in pediatric patients with metabolic dysfunction-associated steatotic liver disease. In this prospective study, pediatric patients diagnosed with metabolic dysfunction-associated steatotic liver disease were enrolled. Six acquisitions of ultrasound-derived fat fraction were obtained. Taking magnetic resonance imaging (MRI)-proton density fat fraction as a reference standard, the area under the receiver operating characteristic curve (AUC) was performed to evaluate the diagnostic performance of ultrasound-derived fat fraction. Youden index was used to determine the cutoff value of ultrasound-derived fat fraction. Correlation coefficient and Bland-Altman plot were performed. From April 2024 to March 2025, 32 patients (median age, 12years; median body mass index, 29.7kg/m2) were included. The ultrasound-derived fat fraction values showed a positive correlation with MRI-proton density fat fraction (r = 0.72). The ultrasound-derived fat fraction values and MRI-proton density fat fraction had a mean bias of 3.3% (95% limits of agreement: -16.4, 23.1). Using MRI-proton density fat fractions ≥ 5%, ≥ 15%, and ≥ 25% as the reference standard for diagnosing hepatic steatosis grade ≥ S1, ≥ S2, and S3, the AUCs of ultrasound-derived fat fraction were 0.84, 0.88, and 0.88, with the cutoff values of 9.5%, 10.5%, and 12.8%, respectively. Ultrasound-derived fat fraction demonstrates promising diagnostic performance for detecting and grading hepatic steatosis in pediatric patients with metabolic dysfunction-associated steatotic liver disease within this cohort.

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. 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*. 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). 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.

Is it time to advance pediatric NAFLD diagnosis to the magnetic resonance imaging era?

To assess feasibility of and agreement between magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) for estimating hepatic proton density fat fraction (PDFF) in children with known or suspected nonalcoholic fatty liver disease (NAFLD). Children were included in this study from two previous research studies in each of which three MRI and three MRS acquisitions were obtained. Sequence acceptability, and MRI- and MRS-estimated PDFF were evaluated. Agreement of MRI- with MRS-estimated hepatic PDFF was assessed by linear regression and Bland-Altman analysis. Age, sex, BMI-Z score, acquisition time, and artifact score effects on MRI- and MRS-estimated PDFF agreement were assessed by multiple linear regression. Eighty-six children (61 boys and 25 girls) were included in this study. Slope and intercept from regressing MRS-PDFF on MRI-PDFF were 0.969 and 1.591%, respectively, and the Bland-Altman bias and 95% limits of agreement were 1.17% ± 2.61%. MRI motion artifact score was higher in boys than girls (by 0.21, p = 0.021). Higher BMI-Z score was associated with lower agreement between MRS and MRI (p = 0.045). Hepatic PDFF estimation by both MRI and MRS is feasible, and MRI- and MRS-estimated PDFF agree closely in children with known or suspected NAFLD.

BackgroundThe application of quantitative magnetic resonance imaging (MRI) in skeletal muscle is crucial in rehabilitation medicine and competitive sports training.PurposeTo explore the feasibility of evaluating T2 value, proton density fat fraction (PDFF), and cross-sectional area (CSA) of the quadriceps femoris before and after countermovement jump (CMJ) based on T2 mapping and Fat Analysis and Calculation Technique (FACT).Material and MethodsA total of 32 healthy volunteers were recruited and underwent MRI examination of the thigh muscles, including axial T2 mapping and FACT sequence. The T2 value, PDFF, and CSA of the quadriceps femoris, adductor magnus, and gracilis were measured. The peak torque (PT) of the quadriceps femoris was measured using an isokinetic muscle strength system. The differences in MRI parameters before and after CMJ were compared, as well as the differences between sexes.ResultsThe T2 value and CSA of the quadriceps femoris and adductor magnus increased and PDFF decreased after CMJ (P <0.01). The PDFF of the gracilis was significantly higher than that of the vastus lateralis, and the vastus lateralis had a significantly higher PDFF than the other muscles (P <0.01). PT was highly correlated with the CSA of the quadriceps femoris (P <0.001, r = 0.906). CSA and PT of men were higher than those of women (P <0.001).ConclusionT2 mapping and FACT can quantitatively evaluate the differences of T2 value, PDFF, and CSA of different muscles before and after CMJ, which is an important evaluation method for competitive sports training and disease rehabilitation.

Evaluation of Hematopoiesis and Disease Status in Patients with Hematologic Malignancies Using Whole-Body Bone Marrow Imaging with 18 F-FLT PET/MRI

<title>Abstract</title> Objective To investigate the diagnostic value of magnetic resonance imaging (MRI) 3D multi-echo-Dixon (ME-Dixon) and High-Speed T2-Corrected Multiecho Acquisition at 1H MR Spectroscopy (HISTO) sequences for lumbar spine osteoporosis. Method A total of 138 participants (aged 41–70) were enrolled in this study, including 75 females and 63 males. Perform MRI and quantitative computed tomography (QCT) examinations and record the body mass index (BMI), proton density fat fraction (PDFF) of lumbar spine L1-L4, and bone mineral density (BMD) measured by QCT. Analyze the correlation between PDFF and BMD, as well as the relationship between BMI and PDFF, BMD. Use receiver operating characteristic (ROC) curve to test the diagnostic efficacy of PDFF for osteoporosis. Analyze the differences in BMD and PDFF between the upper lumbar spine (L_{1 − 2}) and lower lumbar spine (L_{3 − 4}) in three different age groups: 41–50 years old, 51–60 years old, and 61–70 years old. Result The mean ME-Dixon-PDFF, HISTO-PDFF, and BMD of the lumbar spine were highly negatively correlated (r=-0.681, r=-0.557, p &lt; 0.01); The area under the curve (AUC) of ME-Dixon-PDFF is 0.833, with a diagnostic threshold of 55.1% for osteoporosis, sensitivity of 88.0%, and specificity of 70.8%. The AUC of HISTO-PDFF is 0.819, with a diagnostic threshold of 61.4%, sensitivity of 84.0%, and specificity of 77.9% for osteoporosis. The correlation p values between BMI and lumbar spine ME-Dixon-PDFF mean, HISTO-PDFF mean, and BMD mean are 0.858, 0.399, and 0.363, respectively. The two PDFF values of L1-L4 showed an increasing trend, with the upper lumbar spine having lower PDFF values than the lower lumbar spine in the same age group, and no difference in BMD. Conclusion ME-Dixon-PDFF, HISTO-PDFF are significantly negatively correlated with BMD, and MRI fat quantification sequence is an effective complementary tool for diagnosing osteoporosis. Compared to the upper lumbar spine, the lower lumbar spine can better reflect bone mass.

Quantitative MRI Identifies Heterogeneous Bone Marrow Treatment Responses in a Mouse Model of Myelofibrosis

The main pathologies in the muscles of patients with neuromuscular diseases (NMD) are fatty infiltration and edema. Recently, quantitative magnetic resonance (MR) imaging for determination of the MR biomarkers proton density fat fraction (PDFF) and water T2 (T2w ) has been advanced. Biophysical effects or pathology can have different effects on MR biomarkers. Thus, for heterogeneously affected muscles, the routinely performed mean or median value analyses of MR biomarkers are questionable. Our work presents a voxel-based histogram analysis of PDFF and T2w images to point out potential quantification errors. In 12 patients with NMD, chemical-shift encoding-based water-fat imaging for PDFF and T2 mapping with spectral adiabatic inversion recovery (SPAIR) for T2w determination was performed. Segmentation of nine thigh muscles was performed bilaterally (n = 216). PDFF and T2 maps were coregistered. A voxel-based comparison of PDFF and T2w showed a decreased T2w with increasing PDFF. Mean T2w and mean T2w without fatty voxels (PDFF < 10%) show good agreement, whereas standard deviation (σ) T2w and σ T2w without fatty voxels show increasing difference with increasing values of σ. Thereby two subgroups can be observed, referring to muscles in which the exclusion of fatty voxels has a negligible influence versus muscles in which a strong dependency of the T2w value distribution on the exclusion of fatty voxels is present. Because of the two opposite effects that influence T2w in a voxel, namely, (i) a pathophysiologically increased water mobility leading to T2w elevation, and (ii) a dependency of T2w on the PDFF leading to decreased T2w , the T2w distribution within a muscle might be heterogenous andthe routine mean or median analysis can lead to a misinterpretation of the muscle health. It was concluded that muscle T2w mean values can wrongly suggest healthy muscle tissue. A deeper analysis of the underlying value distribution is necessary. Therefore, a quantitative analysis of T2w histograms is a potential alternative.

To determine the relationship between pancreatic fat content and type 2 diabetes and prediabetes. From the prospective population-based Study of Health in Pomerania (SHIP), 1367 volunteers (563 men, 678 women; median age, 50 years) underwent whole-body magnetic resonance (MR) imaging at 1.5 T, which included multiecho chemical shift-encoded acquisition of the abdomen. SHIP was approved by the institutional review board, and written informed consent was obtained from all participants. The proton density fat fraction (PDFF) was calculated after correction for T1 bias, T2* bias, multipeak spectral complexity of fat, and noise bias. On the basis of oral glucose tolerance test results, participants were grouped into those with normal glucose tolerance (n = 740), those with prediabetes (n = 431), and those with confirmed type 2 diabetes but without medication (n = 70). PDFF was assessed in the pancreatic head, body, and tail. Multivariable regression analysis was conducted to investigate possible relationships of PDFF with demographic factors, behavioral factors, and laboratory data associated with the metabolic syndrome. In all subjects, the mean unadjusted pancreatic fat content was 4.4% (head, 4.6%; body, 4.9%; tail, 3.9%; being unequally distributed, P < .001). There was no significant difference in pancreatic PDFF among subjects with normal glucose tolerance, prediabetes, and type 2 diabetes (P = .980). Pancreatic PDFF showed a positive association with age and body mass index and a negative association with serum lipase activity (P < .001). The presence of pancreatic fat is not related to prediabetes or diabetes, which suggests that it has little clinical relevance for an individual's glycemic status.

PurposeTo determine whether high signal-to-noise ratio (SNR) acquisitions improve the repeatability of liver proton density fat fraction (PDFF) measurements using confounder-corrected chemical shift-encoded magnetic resonance (MR) imaging (CSE-MRI).Materials and MethodsEleven fat-water phantoms were scanned with 8 different protocols with varying SNR. After repositioning the phantoms, the same scans were repeated to evaluate the test-retest repeatability. Next, an in vivo study was performed with 20 volunteers and 28 patients scheduled for liver magnetic resonance imaging (MRI). Two CSE-MRI protocols with standard- and high-SNR were repeated to assess test-retest repeatability. MR spectroscopy (MRS)-based PDFF was acquired as a standard of reference. The standard deviation (SD) of the difference (Δ) of PDFF measured in the two repeated scans was defined to ascertain repeatability. The correlation between PDFF of CSE-MRI and MRS was calculated to assess accuracy. The SD of Δ and correlation coefficients of the two protocols (standard- and high-SNR) were compared using F-test and t-test, respectively. Two reconstruction algorithms (complex-based and magnitude-based) were used for both the phantom and in vivo experiments.ResultsThe phantom study demonstrated that higher SNR improved the repeatability for both complex- and magnitude-based reconstruction. Similarly, the in vivo study demonstrated that the repeatability of the high-SNR protocol (SD of Δ = 0.53 for complex- and = 0.85 for magnitude-based fit) was significantly higher than using the standard-SNR protocol (0.77 for complex, P < 0.001; and 0.94 for magnitude-based fit, P = 0.003). No significant difference was observed in the accuracy between standard- and high-SNR protocols.ConclusionHigher SNR improves the repeatability of fat quantification using confounder-corrected CSE-MRI.

ObjectiveSince the introduction of enzyme replacement therapy (ERT) with alglucosidase alfa, there has been increased survival in patients with Pompe disease. It is essential to characterize and quantify the burden of disease in these patients. Here, we report a measure of muscle fat infiltration in children with infantile and pediatric late‐onset Pompe disease (IPD and LOPD, respectively) to better understand the extent of muscle involvement.MethodsEleven pediatric patients with Pompe disease (five IPD, six LOPD), ages 7‐17 years, received whole‐body magnetic resonance imaging (WBMRI), muscle strength testing using the modified Medical Research Council (mMRC) scale, functional assessment using gait, stairs, gowers, chair (GSGC), and urine glucose tetrasaccharide (Glc4) testing. The intramuscular fat seen on WBMRI was quantified using proton density fat fraction (PDFF) and correlated to appropriate muscle strength and functional tests, and urine Glc4.ResultsPatients with IPD, although younger, had higher mean PDFF values than LOPD patients (11.61% vs 8.52%). Significant correlation existed between PDFF and the GSGC assessment (r = .9273, P = .0003). Moderate correlation existed between PDFF and mMRC (r = −.667, P = .0831), and PDFF and urine Glc4 (r = .6121, P = .0667). Anterior tibialis was in the top quartile of muscle involvement for patients with LOPD.ConclusionIn the past, physical therapy assessments alone have been used to track disease progression. Here, we show the clinical utility of WBMRI in quantifying muscle involvement in children with Pompe disease, especially regarding the novel involvement of anterior tibialis in children with LOPD, to better assess baseline muscle burden and mapping disease progression in children treated with ERT.