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Updated: Sep 4, 2026
Quantitative Magnetic Resonance Imaging of Skeletal Muscle Disease
Published on: December 18, 2016
MRI Proton Density Fat Fraction as a Biomarker of Marrow Recovery Following Organ-Sparing Total Marrow Irradiation in
Malakeh Malekzadeh1,2, Hemendra Ghimire1,2, Ji Eun Lim1,2
1Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California, USA.
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.
