J Magn Reson Imaging. 2026 Sep 3. doi: 10.1002/jmri.70510. Online ahead of print.
ABSTRACT
BACKGROUND: Noninvasive quantitative assessment of marrow recovery after curative therapies such as total marrow irradiation (TMI) and bone marrow transplantation (BMT) remain poorly defined, particularly in sickle cell disease (SCD).
PURPOSE: To evaluate MRI-derived proton density fat fraction (PDFF) as a biomarker of marrow recovery following organ-sparing total marrow irradiation-based transplantation (OS-TMI/BMT) in an SCD mouse model and to assess initial clinical feasibility in patients.
STUDY TYPE: Exploratory preclinical study with descriptive pilot feasibility analysis in humans.
SUBJECTS: Townes SCD mice (n = 10 controls, n = 8 treated) and 2 adults (male, 24 ± 1 years old) with SCD.
FIELD STRENGTH/SEQUENCE: Preclinical 7-T small-bore MRI used a spoiled gradient echo (GRE) multi-echo sequence for PDFF and R2* mapping, while clinical 3-T MRI employed a spoiled GRE-based sequence.
ASSESSMENT: Marrow recovery in an animal study was assessed using MRI-derived PDFF with ROI analysis, complemented by micro-CT and histologic evaluation. Translational feasibility was assessed with longitudinal PDFF MRI in 2 adults with severe SCD undergoing marrow transplantation.
STATISTICAL TESTS: Parametric data were analyzed using t-tests and Pearson correlation, nonparametric data using Mann-Whitney U and Spearman correlation, and two-way ANOVA assessed group, region, and interaction effects, with significance set at p < 0.05.
RESULTS: Right femur MRI showed partial restoration of adipose-rich marrow in the OS-TMI/BMT group versus controls, higher PDFF in the proximal metaphysis (42.5 ± 2.7 vs. 34.8 ± 6.5), midshaft diaphysis (44.8 ± 3.0 vs. 26.9 ± 7.0), and distal metaphysis (45.1 ± 2.6 vs. 36.2 ± 4.9). OS-TMI/BMT also improved trabecular structure, with increased trabecular thickness, reduced bone surface-to-volume ratio, lower structure model index and anisotropy, and increased distal bone volume density. In 2 patients, PDFF increased post-transplant, and 1-year biopsy showed trilineage hematopoiesis without fibrosis.
DATA CONCLUSION: Marrow-selective transplantation was associated with partial normalization of the marrow and skeletal microenvironment in SCD. PDFF may provide a practical noninvasive approach for monitoring post-transplant marrow recovery.
TECHNICAL EFFICACY: Stage 2.
PMID:42689386 | DOI:10.1002/jmri.70510
