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.