Measurements of Liver and Bone Marrow Proton Density Fat Fraction in the Setting of Ferumoxytol-Enhanced MRI.

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.