PURPOSE:To introduce and evaluate the feasibility of a novel RF-phase modulated gradient echo (GRE) method for quantitative diffusion MRI, aimed at mitigating geometric distortion and enabling high-resolution 3D quantitative diffusion/T2 mapping as a complementary alternative to conventional DWI. THEORY AND METHODS:The proposed phase-based diffusion (PBD) method employs RF phase modulation to encode both diffusion and T2 information into the GRE signal phase. A closed-form analytical model enables joint apparent diffusion coefficient (ADC) and T2 mapping via iterative reconstruction. The method's feasibility was evaluated via Bloch equation simulations, phantom experiments, and preliminary in vivo imaging studies. RESULTS:Monte Carlo simulations revealed that PBD provides more accurate median ADC estimates at low signal-to-noise ratios (SNRs) compared to conventional single-shot echo-planar imaging (SS-EPI), although PBD exhibited greater variability. Phantom studies demonstrated good agreement for PBD-derived ADC values (e.g., R2 = 0.99) with reference methods and strong correlation for PBD-derived T2 values (e.g., R2 = 0.89), though the latter showed some systematic bias in phantoms. In vivo results from patients with benign or malignant prostate disease demonstrated the feasibility of the PBD method to provide high-resolution ADC and T2 maps with minimal geometric distortions relative to conventional SS-EPI. CONCLUSION:PBD provides ADC and T2 maps with improved geometric fidelity in phantoms and in vivo, and offers robust median ADC estimates from noisy data based on simulations. This combination of spatial precision and noise characteristics makes PBD promising for applications such as high-resolution DWI for prostate MRI.

BACKGROUND:Access to MRI is limited by lengthy exam times and inefficient utilization. Focused protocols can reduce exam times, but workflow variability and inefficient room turnaround contribute to conservative scheduling with long exam slots. PURPOSE:To develop and evaluate a high-throughput clinical MRI suite architecture and workflow, using an AI-prescribed free-breathing chemical shift-encoded (CSE) MRI exam to quantify liver proton density fat fraction (PDFF) in under 5 min of total MRI room time. STUDY TYPE:Prospective. SUBJECTS:24 healthy volunteers in two cohorts: 12 research staff (7 women/5 men; age 26.8 ± 5.8 years) and 12 community volunteers (6 women/6 men; age 41.3 ± 13.5 years). FIELD STRENGTH/SEQUENCE:1.5 T; free-breathing 2D multi-echo gradient echo CSE-MRI. ASSESSMENT:Each participant underwent three nonconsecutive CSE-MRI exams in a continuously queued workflow to characterize timing and PDFF repeatability. Workflow intervals were recorded from timestamped video review and image metadata. Staff cohort exams included two CSE-MRI acquisitions to assess within-exam repeatability, while community cohort exams included one to simulate clinical practice. Three radiologists (8/13/14 years of experience) independently evaluated AI-automated prescriptions for complete liver coverage and rated CSE-MRI image quality (five-point Likert scale). STATISTICAL TESTS:Student's t-tests; Gwet's AC2; repeatability coefficients (RCs) with bootstrap 95% confidence intervals; Bland-Altman analysis. p < 0.05 was significant. RESULTS:Diagnostic image quality was achieved in all 72 exams (median PDFF Likert score 5/5, inter-rater AC2 ≥ 0.86). Total MRI room times averaged 4:09 ± 0:14 min (staff) and 3:35 ± 0:34 min (community). Turnaround times averaged under 2 min, enabling throughput of 16.1 exams per hour in the community cohort. Automated prescription achieved complete liver coverage in all exams. PDFF RCs were 0.78% (staff within-exam), 0.99% (staff between-exam), and 1.21% (community between-exam) absolute PDFF. DATA CONCLUSION:The proposed high-throughput MRI workflow achieved over 16 exams per hour with highly repeatable liver fat quantification, demonstrating a framework for improving MRI utilization and access. EVIDENCE LEVEL:1. STAGE OF TECHNICAL EFFICACY:2.

PURPOSE:To calibrate the effect of hepatic steatosis on diffusion parameters, including ADC and pure diffusion coefficient ( D ), by Monte Carlo simulation and phantom studies. METHODS:In the simulation study, four types of virtual liver models were constructed by incorporating size, nearest neighbor distance and regional anisotropy of fat droplets. By simulating magnetic field, proton movement and phase accrual, DWI signals were synthesized and analyzed to predict ADC and D . Correlation analyses were performed to investigate relationships between fat fraction (FF) and diffusion parameters predictions. Bland Altman analysis was conducted to evaluate the effects of virtual liver model, fat susceptibility and proton diffusivity on these predictions. In the phantom study, a fat-water phantom was scanned to investigate the relationships between proton density fat fraction (PDFF) and diffusion parameters. RESULTS:The simulation study demonstrated that ADC and D predictions were linearly and negatively correlated with FFs ( r ≤ - 0.924 ), unaffected by virtual liver model and fat susceptibility ( p ≥ 0.756 ). Additionally, proton diffusivity posed positive effects on these predictions. Compared with in vivo calibration, simulations with the virtual liver model incorporating all criteria, fat susceptibility of 0.2 ppm and proton diffusivity of 0.96 μm2/ms can accurately predict the diffusion parameters. The phantom study indicated that ADC and D measurements were linearly and negatively correlated with PDFF ( r ≤ - 0.895 ). CONCLUSION:Hepatic steatosis decreases both diffusion parameters and should be calibrated in the DWI-based assessment of liver fibrosis.

BACKGROUND:In chronic liver disease, fat and fibroinflammatory changes often coexist. However, their biomarkers, proton density fat fraction (PDFF) and T1, are typically assessed separately. Their reproducibility under mutual confounding remains unclear. PURPOSE:To assess multicenter, multi-vendor reproducibility of confounder-corrected chemical shift-encoded (CSE)-MRI-based PDFF mapping and MOLLI-based T1 mapping using a combined PDFF-T1 phantom. STUDY TYPE:Prospective phantom study. PHANTOM:Commercial PDFF-T1 Phantom (Model 725) with varying PDFF (0%-30%) and T1 (200-1400 ms) values. FIELD STRENGTH/SEQUENCE:1.5 T and 3 T multi-echo, three-dimensional spoiled-gradient-echo (SGRE) sequence for PDFF mapping, and MOLLI sequence (5(3)3 acquisition scheme) using two-dimensional SGRE readouts for T1 mapping across four centers and vendors. ASSESSMENT:PDFF and T1 maps were acquired using standardized protocols. PDFF maps were reconstructed locally, while T1 maps were generated using a centralized algorithm. All maps were quantitatively analyzed by a single radiologist using standardized region-of-interest placement. Phantom temporal stability was assessed at one center across five sessions over 9 months (baseline, retest, 1 week, 6 and 9 months). STATISTICAL TESTS:Intraclass correlation coefficients (ICC), reproducibility coefficients (RDC), and linear regression analysis were used. A p value < 0.05 was considered statistically significant. RESULTS:PDFF showed overall excellent reproducibility (ICC = 0.987, RDC = 3.7%), with increased variability at higher T1 values (RDC up to 7.9% at T1 = 1400 ms). T1 mapping showed good reproducibility in the absence of fat (RDC 16-161 ms at PDFF = 0%), but moderate to poor reproducibility in the presence of fat, with RDC increasing up to 1553 ms at PDFF 30%. Temporal stability was excellent ICC ≥ 0.998 for both PDFF and T1, and RDC of 1.1%-1.3% for PDFF and 52-57 ms for T1. DATA CONCLUSION:This phantom study demonstrated high reproducibility of PDFF, whereas T1 reproducibility deteriorated at higher fat and T1 levels, underscoring the need for fat-corrected T1 mapping for reliable assessment of fibroinflammatory changes. EVIDENCE LEVEL:N/A. TECHNICAL EFFICACY:Stage 1.

Patellar tendinopathy and bone-patellar tendon-bone autograft harvest for anterior cruciate ligament reconstruction are tendon injuries that impact long-term knee health. Diffusion tensor imaging (DTI) is a non-invasive magnetic resonance imaging (MRI) based approach with the potential to assess tendon microstructure. This study aimed to determine the inter-rater reliability of segmentations and test-retest repeatability of DTI metrics in pathological and contralateral patellar tendons. Ten participants received two bilateral knee MRI scans within a 7-day period. 3D CUBE proton density weighted images and DTI were acquired. Two raters segmented each of the first scans, and one rater segmented the second scans. Tendon masks were then bisected into proximal and distal regions of equal length and trisected into medial, lateral, and central regions of equal width. From the DTI acquisition, diffusivities and fractional anisotropy averages were extracted. Intraclass correlations (ICCs) for inter-rater reliability and test-retest repeatability were calculated for each metric separated by limb (pathological vs contralateral tendon). Excellent inter-rater reliability was observed for all DTI scalar metrics in all regions (ICCs from 0.920 to 0.994). Repeatability was poor to moderate in pathological tendons (0.164 to 0.709) and moderate to good in contralateral tendons (0.566 to 0.842).Statement of Clinical Significance: While clinical implications of altered DTI scalar metrics in pathological tendons require further investigation, findings from this study provide clinicians and researchers with a reliable method for capturing patellar tendon microstructure.

Intravoxel incoherent motion (IVIM) MRI allows for simultaneous assessment of tissue microcirculation (perfusion) and diffusion of water. In single-center studies, IVIM has shown great potential for diagnosis, treatment outcome prediction, and treatment monitoring for many different diseases and organs. However, heterogeneity in data acquisition protocols, pre-processing pipelines, and post-processing routines yields differences in reported IVIM parameters, which has constrained large-scale deployment of IVIM. Moreover, deploying IVIM protocols and analysis typically requires technical expertise, further challenging wider use, especially for clinicians. In this consensus paper, to accelerate the deployment of IVIM, we provide recommendations and harmonize protocols for brain, breast, kidney, liver, muscle, and pancreas IVIM studies. For this goal we organized multiple questionnaires and held a dedicated workshop. To ensure a level of standardized, reproducible results, without restricting innovation, we suggest a small subset of b-values to always be measured and analyzed separately, and to which more extensive b-value sampling can be added for advanced investigations. We further introduce detailed recommendations on acquisition protocols and analysis pipelines. To increase consistency, repeatability, and reproducibility, we highly recommend that these protocols and pipelines be deployed by scientists and clinicians for IVIM studies. For advanced users who desire different protocols or analysis approaches, we suggest adding results from our suggested protocols and analysis pipeline in the supplemental part of their paper to enable retrospective studies.

BACKGROUND:Proton density fat fraction (PDFF) is typically measured using confounder-corrected, multi-echo, gradient-recalled-echo chemical-shift-encoded (CSE)-MRI. Ferumoxytol, an iron-based MRI contrast agent, increases liver and bone marrow (BM) R2*, a major confounder of PDFF. PURPOSE:To assess the impact of ferumoxytol-induced R2* increase on BM and liver PDFF. STUDY TYPE:Retrospective. POPULATION:Eleven healthy volunteers (6 female) imaged before and 1, 2, 4, 7, and 30 days after ferumoxytol; 25 patients (10 female) imaged before and 2-3 days after ferumoxytol. FIELD STRENGTH/SEQUENCE:1.5-T and 3.0-T; 3D GRE-CSE-MRI. ASSESSMENT:Regions of interest were placed on liver and spinal BM to measure PDFF and R2* before and after ferumoxytol. Dual-R2* simulations evaluated the effect of differential water and fat R2* relaxation on PDFF. STATISTICAL TESTS:Liver and BM PDFF and R2* were compared before and after ferumoxytol using regression analyses and F-tests. Changes from baseline were assessed with Wilcoxon signed-rank tests; p < 0.05 was considered significant. RESULTS:Among volunteers, BM R2* increased significantly after ferumoxytol, peaking at Day 1, 222 (84) s-1 at 1.5-T and 328 (106) s-1 at 3.0-T (baseline 72 [26] s-1 and 182 [64] s-1, respectively). BM PDFF increased significantly after ferumoxytol: 49.7 (11.3) % at 1.5-T and 47.5 (12.9) % at 3.0-T (baseline 41.1 [13.2] % and 38.4 [11.0] %, respectively). Post-ferumoxytol liver R2* also increased, yet liver PDFF did not significantly change (p range 0.579-0.983). Among patients, post-ferumoxytol BM PDFF demonstrated a systematic positive bias relative to baseline, yet this effect was not observed in liver. Simulations confirmed that a differential increase in water relative to fat R2* results in PDFF bias when a single-R2* model is fitted. DATA CONCLUSION:BM PDFF demonstrates a systematic bias in the presence of ferumoxytol-induced R2* increase and should be interpreted with caution. This bias was not observed in the liver. EVIDENCE LEVEL:3. TECHNICAL EFFICACY:Stage 1.

PURPOSE:Quantitative MRI biomarkers are increasingly used to assess liver health; however, athlete-specific normative values are lacking. This study aimed to establish liver-specific normative values for proton density fat fraction (PDFF), R2*-based liver iron concentration (LIC), and T1 and T2 relaxation times in collegiate athletes. METHODS:In this retrospective single-center study, collegiate athletes undergoing return-to-play cardiac MRI (1.5 T/3.0 T) following Coronavirus Disease 2019 recovery were identified. Whole-liver PDFF and R2* were obtained from chemical shift-encoded MRI, T1 and T2 relaxation times were derived from cardiac mapping with partial liver coverage. LIC was calculated from R2*. PDFF and LIC were considered field-strength-independent, whereas R2*, T1, and T2 were analyzed by field strength. Biomarkers are reported as median (interquartile range). RESULTS:A total of 211 athletes (64.0% males; median age 19.9 years) were included. PDFF and LIC were 2.2% (1.7, 2.8) and 0.67 mg/g (0.58, 0.74) in males and 1.8% (1.5, 2.3) and 0.57 mg/g (0.50, 0.67) in females. At 1.5 T, R2*, T1 and T2 were 34.0 s-1 (31.9, 36.4), 571 ms (552, 593), and 45.4 ms (43.3, 47.0) in males and 32.0 s-1 (29.5, 34.6), 588 ms (577, 600), and 49.4 ms (46.4, 52.2) in females. At 3.0 T, values were 44.1 s-1 (41.8, 48.8), 755 ms (727, 783), and 40.9 ms (38.3, 43.4) in males and 41.6 s-1 (37.7, 44.0), 806 ms (791, 822), and 42.8 ms (38.9, 44.3) in females. CONCLUSIONS:We established sex- and field strength-specific normative values for quantitative liver MRI biomarkers in collegiate athletes, providing a foundation for baseline clinical interpretation and longitudinal monitoring of liver health.

PURPOSE:To evaluate diffusion-weighted imaging (DWI) and MR Elastography (MRE) performance over a clinically relevant stiffness range for liver fibrosis with and without the presence of compressive motion using an in vitro phantom pipeline. METHODS:Five anthropomorphic liver phantoms were created using polyacrylamide (PAA) hydrogels. Phantom stiffness ranged from approximately 1.5-11 kPa. Phantoms were connected to a pulsatile flow circuit to induce compressive motion. Imaging was performed on a 3T MRI system. MRE, conventional DWI, and M1-motion optimized DWI (MODI) were assessed at varying pulsatile flow states (mean flow = 0, 0.5, 1, 1.5 L/min). Conventional and MODI DWI apparent diffusion coefficients (ADC) were correlated to MRE stiffness. RESULTS:Stiffness and ADC maps were obtained for all phantoms and flow states. Conventional and MODI DWI under static conditions exhibited an inverse relationship with MRE stiffness (R2 = 0.94 and R2 = 0.95, respectively). MODI-DWI exhibited reduced motion-induced signal dropout, minimizing ADC bias under motion conditions compared to conventional DWI. Mean MRE stiffness was largely unaffected by motion, except for the lowest and highest stiffness phantoms at the highest flow rate. CONCLUSION:Anthropomorphic liver phantoms were used to systemically investigate the effects of stiffness and motion on the performance of MRE and DWI. MRE and MODI-DWI demonstrated strong insensitivity to motion across stiffness and motion level.

PURPOSE:To develop and validate a vendor-agnostic, motion-insensitive proton-density fat-fraction (PDFF) quantification method. METHODS:Flip-angle-modulated (FAM) 2D chemical-shift-encoded (CSE) MRI for PDFF quantification was implemented in both the vendor-agnostic platform Pulseq ("Pulseq-FAM") and one vendor-specific platform ("GE-specific FAM"). These implementations were distributed to four sites with twelve MR systems of three vendors (Siemens/GE/Philips) and field strengths (0.55T/1.5T/3T). A sequentially-shipped 16-vial phantom (PDFF = 0%-30%/T1water = 200-1400 ms) underwent confounder-corrected PDFF mapping with commercial 3D-CSE methods and GE-specific FAM as available on each system, and Pulseq-FAM on every system. To assess bias, phantom PDFF measurements were compared to reference. Between-system variance was evaluated with linear mixed-effects modeling. Different volunteers were also imaged at each site to assess free-breathing PDFF mapping feasibility. A prospective single-site volunteer study was also conducted. Adult patients and children were imaged with breath-held 3D-CSE and free-breathing GE-specific and Pulseq-FAM. Radiologists evaluated images for overall quality and motion artifacts. To assess bias, Pulseq-FAM PDFF measurements were compared to 3D-CSE and GE-specific FAM. Test-retest repeatability was assessed by re-imaging after repositioning. Between-field-strength reproducibility was assessed at 1.5T and 3.0T. RESULTS:In the multi-center study, Pulseq-FAM showed reduced T1-bias and between-system variability versus 3D-CSE in phantom PDFF measurements, and free-breathing feasibility in volunteers. In the single-site volunteer study (N = 57), Pulseq-FAM improved image quality and motion artifacts versus 3D-CSE (p < 0.01). Pulseq-FAM showed excellent agreement with 3D-CSE (95% limits-of-agreement (LoA) = 3.4% PDFF) and GE-specific FAM (LoA = 2.0%). Pulseq-FAM showed excellent repeatability (repeatability coefficient (RC) = 1.6% PDFF) and between-field-strength reproducibility (reproducibility coefficient (RDC) = 2.4%) versus 3D-CSE (RC = 2.7%/RDC = 3.4%; differences p < 0.05). CONCLUSION:Pulseq-FAM enables accurate, reproducible, vendor-agnostic, and motion-insensitive PDFF quantification in adults and children.

PURPOSE:Phase-contrast MRI (2D PC-MRI) and Dixon techniques share the characteristic that the difference in frequency between water and fat, as well as the velocity, are encoded in the phase of the MR signal. We propose to take advantage of this characteristic to obtain both sets of images simultaneously. Such an acquisition will improve efficiency by obtaining both types of images in the same scan and will provide co-registered images of water-fat species and velocity images. This, in turn, will correct fat artifacts due to chemical shift in PC-MRI based measurements. METHODS:This study presents a novel PC multi-echo (PCME-MRI) sequence jointly with a 3-point (3p-) Dixon pipeline that enables reconstruction of water, fat, and velocity images simultaneously. The proposed 3p-Dixon approach preserves the phase information of water-fat images, while velocity images are obtained from the resulting water components. RESULTS:Numerical phantom tests and 2D MR axial images of the neck acquired in 12 healthy volunteers demonstrated the feasibility of the PC 3p-Dixon method, showing comparable performance to standard techniques. In volunteers the median and range MAE comparing PC 3p-Dixon, and standard 3p-Dixon fat fraction were 0.06 and [0.03, 0.09]. The median and range of velocity for PC 3p-Dixon were 6.15 ml and [3.86, 7.21]ml, compared to 6.43 ml and [4.62, 8.27]ml obtained by 2D PC-MRI. CONCLUSION:Numerical phantom experiments and acquisitions from healthy volunteers showed promising results in fat fraction and velocity estimation of PC 3p-Dixon compared with standard 3p-Dixon and 2D PC-MRI, obtaining both data sets in similar times as standard 3p Dixon.

PURPOSE:Evaluate the feasibility of using perfused explanted human livers for validating intravoxel incoherent motion (IVIM). METHODS:Eight (n = 8) explanted livers from deceased donors were obtained. The portal vein and hepatic artery of each explanted liver were connected to a perfusion system. IVIM data were acquired at four total volumetric flow rates (0, 0.6, 0.9, and 1.2 L/min). For each IVIM dataset, diffusion coefficient (D), relaxation-corrected perfusion signal fraction (Fc), blood velocity SD (Vb), and/or pseudo-diffusion coefficient (D*) were estimated. Linear mixed-effects modeling was performed to determine if the effect of applied flow, flow rate, and fibrosis stage on the estimated IVIM parameters was significant (F-tests), while correcting for temporal effect(s). Liver fibrosis stages were obtained from clinical histology. RESULTS:D was independent of applied flow and total volumetric flow rate (p ≥ 0.30). Fc was approximately zero when no flow was applied and a positive, non-negligible value that was independent of flow rate with applied flow (p < 0.001 and ≥ 0.58 for applied flow and flow rate effects, respectively). Vb and D* were dependent on applied flow and flow rate (p ≤ 0.04 with flow rate effect size ≥ 0.69 mm/s per L/min and 25.7 × 10-3 mm2/s per L/min for Vb and D*, respectively). Significantly lower (p ≤ 0.01) Fc, Vb, and D* estimates were observed for livers with moderate-to-advanced fibrosis (stages F2-4) compared to no-to-mild fibrosis (stages F0-1) (effect sizes = -0.74%, -0.60 mm/s, and -19.8 × 10-3 mm2/s, respectively). CONCLUSION:Perfused explanted human livers from deceased donors may serve as biologically accurate systems for validation of quantitative IVIM techniques.

PURPOSE:Gadoxetic acid-enhanced hepatobiliary phase T1-weighted (T1w) MRI is effective for the detection of focal liver lesions but lacks sufficient T1 contrast to distinguish benign from malignant lesions. Although the addition of T2, diffusion, and dynamic contrast-enhanced T1w imaging improves lesion characterization, these methods often do not provide adequate spatial resolution to identify subcentimeter lesions. This work proposes a high-resolution, volumetric, free-breathing liver MRI method that produces colocalized fat-suppressed, variable T1w images from a single acquisition, thereby improving both lesion detection and characterization. THEORY AND METHODS:This method combines stack-of-stars radial sampling, magnetization preparation, and chemical shift encoding to enable free-breathing, T1w imaging with water/fat separation. A model-based image reconstruction algorithm reconstructs images from highly undersampled k-space data. Pseudo-T1 relaxation maps are calculated from the variable T1w images. The feasibility of this method was investigated in patients undergoing clinical contrast-enhanced MRI examinations for detection and characterization of focal liver lesions at both 1.5 and 3.0 T. An expert reader study was conducted to evaluate the method's performance, compared with the hepatobiliary phase-navigated T1w MRI based on image quality and lesion conspicuity. RESULTS:Expert readers found that at shorter inversion times (TIs) (˜500 ms), the proposed method had superior liver-lesion contrast for characterizing simple cysts and metastases, compared with navigated T1w images. CONCLUSION:The proposed method produces colocalized fat-suppressed, variable T1w images from a single acquisition that may improve focal liver lesion detection and characterization.

OBJECTIVE:18 F-fluorodeoxyglucose positron-emission tomography (FDG PET) and whole-body (WB) MRI with diffusion weighted imaging (DWI) are complementary in assessment of multiple myeloma. However, WB DWI suffers from prolonged acquisition times and artifacts. Alternatively, rapid T2-weighted MRI with 2-point Dixon fat-suppression (T2-FS) has demonstrated promise in detection of bone lesions in exam times shorter than DWI. This study evaluated (1) the accuracy of rapid WB T2-FS for multiple myeloma lesion detection and (2) the incremental impact of adding DWI and FDG PET to T2-FS on diagnostic accuracy and patient care management. METHODS:This retrospective single-center study included patients with clinical WB PET/MRI exams obtained for multiple myeloma. T2-FS, DWI, and PET were reviewed in consensus by 2 readers, each technique reviewed blinded to the other 2 and to other imaging/clinical information. Focal lesions and nonfocal bone marrow disease were recorded. Per-lesion sensitivity and per-patient sensitivity and specificity for each technique were compared with a composite reference standard using McNemar exact test; 95% confidence intervals were calculated, and P <0.05 was considered significant. The incremental impact of adding DWI and PET to T2-FS on diagnostic accuracy and patient care management was recorded. RESULTS:From 34 PET/MRI exams from 34 patients, 3 incomplete exams were excluded. Among the 31 included exams, T2-FS demonstrated a significantly higher per-lesion sensitivity than DWI and PET, at 91.9%, 66.7%, and 44.4%, respectively ( P <0.001). T2-FS identified all 21 patients with disease, compared with 85.7% for both DWI and PET; this difference did not reach statistical significance ( P >0.050). Adding DWI to T2-FS did not change management in any patient; adding PET to T2-FS changed management in 3 patients. CONCLUSION:T2-FS was more rapid and more sensitive than DWI for assessment of multiple myeloma. Unlike FDG PET, addition of DWI did not impact clinical management. Larger prospective studies for further validation are needed.

BACKGROUND:Fat and iron deposition confound measurements of R2* and proton density fat fraction (PDFF), respectively, yet their combined impact on reproducibility is poorly understood. PURPOSE:To evaluate the multi-center, multi-vendor reproducibility of PDFF and R2* quantification using a PDFF-R2* phantom. STUDY TYPE:Prospective multi-center, phantom study. PHANTOM:Commercial PDFF-R2* phantom with simultaneously controlled combination of PDFF (0%-30%) and R2* (50-600 s-1) values. FIELD STRENGTH/SEQUENCE:1.5-T and 3-T, three-dimensional (3D) multi-echo, spoiled-gradient-echo sequences, in four different centers, each with a different vendor. ASSESSMENT:Two acquisition protocols were used, optimized for moderate R2* (Protocol 1) and high R2* (Protocol 2), respectively. The phantom was imaged multiple times at one of the centers to assess its stability. STATISTICAL TESTS:Intraclass correlation coefficient (ICC), linear regression analysis, reproducibility coefficient (RDC) and repeatability coefficient (RC). RESULTS:Excellent agreement was observed for PDFF measurements between centers, vendors, field strengths, and protocols (ICC = 0.97). Stratified by protocol, excellent agreement was observed, with ICC = 0.96 (RDC = 6.2%) for Protocol 1 and ICC = 0.99 (RDC = 3.8%) for Protocol 2. Increased variability in PDFF measurements was observed with increasing PDFF and especially with higher R2*. Excellent agreement was observed for R2* between centers, vendors, field strengths, and protocols (ICC = 0.99). Stratified by protocol, strong agreement was observed, with ICC = 0.988 (RDC = 66.7 s-1) for Protocol 1 and ICC = 0.99 (RDC = 57.7 s-1) for Protocol 2. Higher variability in R2* measurements was observed in vials with higher PDFF or R2*. Stability tests demonstrated an ICC = 1.0 for PDFF and R2*, and RC of 0.4% for PDFF and 12 s-1 for R2*. DATA CONCLUSION:Excellent PDFF and R2* reproducibility was observed across centers, vendors, field strengths, and acquisition protocols. Reproducibility decreased slightly with increasing PDFF and R2*, especially for PDFF measurements in vials with high R2*. EVIDENCE LEVEL:N/A. TECHNICAL EFFICACY:Stage 1.

BACKGROUND:Steatotic liver disease (SLD) is the most common liver disease worldwide, affecting 30% of the global population. It is strongly associated with the interplay of genetic and lifestyle-related risk factors. The genetic variant accounting for the largest fraction of SLD heritability is PNPLA3 I148M, which is carried by 23% of the western population and increases the risk of SLD two to three-fold. However, identification of variant carriers is not part of routine clinical care and prevents patients from receiving personalised care. METHODS:We analysed MRI images and common genetic variants in PNPLA3, TM6SF2, MTARC1, HSD17B13 and GCKR from a cohort of 45 603 individuals from the UK Biobank. Proton density fat fraction (PDFF) maps were generated using a water-fat separation toolbox, applied to the magnitude and phase MRI data. The liver region was segmented using a U-Net model trained on 600 manually segmented ground truth images. The resulting liver masks and PDFF maps were subsequently used to calculate liver PDFF values. Individuals with (PDFF ≥ 5%) and without SLD (PDFF < 5%) were selected as the study cohort and used to train and test a Vision Transformer classification model with five-fold cross validation. We aimed to differentiate individuals who are homozygous for the PNPLA3 I148M variant from non-carriers, as evaluated by the area under the receiver operating characteristic curve (AUROC). To ensure a clear genetic contrast, all heterozygous individuals were excluded. To interpret our model, we generated attention maps that highlight the regions that are most predictive of the outcomes. RESULTS:Homozygosity for the PNPLA3 I148M variant demonstrated the best predictive performance among five variants with AUROC of 0.68 (95% CI: 0.64-0.73) in SLD patients and 0.57 (95% CI: 0.52-0.61) in non-SLD patients. The AUROCs for the other SNPs ranged from 0.54 to 0.57 in SLD patients and from 0.52 to 0.54 in non-SLD patients. The predictive performance was generally higher in SLD patients compared to non-SLD patients. Attention maps for PNPLA3 I148M carriers showed that fat deposition in regions adjacent to the hepatic vessels, near the liver hilum, plays an important role in predicting the presence of the I148M variant. CONCLUSION:Our study marks novel progress in the non-invasive detection of homozygosity for PNPLA3 I148M through the application of deep learning models on MRI images. Our findings suggest that PNPLA3 I148M might affect the liver fat distribution and could be used to predict the presence of PNPLA3 variants in patients with fatty liver. The findings of this research have the potential to be integrated into standard clinical practice, particularly when combined with clinical and biochemical data from other modalities to increase accuracy, enabling easier identification of at-risk individuals and facilitating the development of tailored interventions for PNPLA3 I148M-associated liver disease.

PURPOSE:To implement, optimize, and validate parallel imaging (PI)-accelerated, 2D, flip angle modulated (FAM) chemical shift-encoded quantification of liver proton-density fat fraction (PDFF), with motion insensitivity. METHODS:The optimization cost function that determines flip angles in FAM was generalized for PI. Phantom studies and prospective studies in volunteers with varying liver fat levels were performed. Free-breathing FAM was acquired in the axial, sagittal, and coronal planes, with varying nominal PI acceleration factors (R) of 1.0 to 3.0. A breath-held, commercially available 3D chemical shift-encoded method was acquired as reference for PDFF. Overall image quality, qualitative SNR, and motion artifacts for all methods were Likert-scale rated. PDFF measured by FAM was compared to reference to assess bias. Test-retest repeatability was assessed for all methods by repeating acquisitions after volunteer repositioning. Noise performance was assessed with standard deviation of PDFF maps as R increased. RESULTS:The reader study (N = 3 readers/10 subjects) demonstrated excellent image quality for FAM during free-breathing, with reduced motion artifacts compared to breath-held reference (p < 0.01). PI-accelerated FAM shows fewer motion artifacts than unaccelerated FAM (p < 0.01). In all planes and accelerations, PDFF measured by FAM showed good agreement with reference PDFF measurements (mean bias: -0.4% to 2.0% PDFF; 95% limits of agreement: 2.8% to 4.0% PDFF). FAM in axial and coronal planes showed similar or improved repeatability (repeatability coefficient = 1.7% to 2.6% PDFF) compared to the reference (2.7%). Sagittal FAM shows similar or worse repeatability (repeatability coefficient = 3.0% to 3.6%). FAM with R = 2.0 has good noise performance and high SNR efficiency. CONCLUSION:FAM, in axial or coronal planes with R = 2.0, is optimal for motion-insensitive liver PDFF quantification.

OBJECTIVE:Changes in bone marrow fat content measured through relative fat fraction (rFF) obtained from dual-echo gradient-recalled echo (GRE) in- and opposed-phase (IOP) MRI have been proposed to evaluate treatment response for multiple myeloma. However, rFF suffers from several significant limitations that lead to inaccurate fat fraction measurements. In contrast, proton density fat fraction (PDFF) is the most objective and validated MRI metric of tissue fat content, and it is measured through confounder-corrected, multiecho, chemical-shift-encoded (CSE) MRI. The purpose of this study was to evaluate the linearity and bias of bone marrow rFF compared with PDFF. METHODS:This single-center, retrospective study included 100 patients who underwent clinical MRI for liver fat/iron quantification at 1.5T and 3.0T (50 exams/patients for each field strength), which included dual-echo GRE IOP and commercial multiecho CSE MRI (IDEAL-IQ). One region of interest (ROI) was placed in each of the T12, L1, and L2 vertebral bodies. Per-ROI rFF was calculated using (S IP and S OP = signal intensities on IP and OP images, respectively). rFF was correlated with PDFF using linear regression and coefficient of determination ( R2 ). Bland-Altman analysis evaluated rFF bias across the observed range for R2* and PDFF; mean bias and 95% limits of agreement (LOA) were reported. RESULTS:Bone marrow rFF demonstrated no linearity against PDFF at 1.5T or at 3.0T ( R2 = 0.032 and 0.057, respectively). Moreover, bone marrow rFF demonstrated significant bias with respect to PDFF at 1.5T and 3.0T, with significant bias that increases directly with bone marrow fat fraction. CONCLUSIONS:Bone marrow rFF is nonlinear and variably biased compared with PDFF and should not be used in research or clinical settings.