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September 5, 2026Journal of Magnetic Resonance ImagingOpen Access

MRI Proton Density Fat Fraction as a Biomarker of Marrow Recovery Following Organ‐Sparing Total Marrow Irradiation in Sickle Cell Disease

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Authors

MMMalakeh MalekzadehHGHemendra GhimireJLJi Eun Lim

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Overview

Preclinical and pilot study demonstrates MRI proton density fat fraction detects marrow recovery following transplantation in sickle cell disease, highlighting its potential as a noninvasive...

Key Points

  • To evaluate MRI-derived proton density fat fraction (PDFF) as a noninvasive biomarker of marrow recovery following organ-sparing total marrow irradiation and transplantation in sickle cell disease models and patients.
  • Conducted a preclinical 7-T MRI study in Townes sickle cell disease mice comparing organ-sparing total marrow irradiation-based bone marrow transplantation (OS-TMI/BMT, n = 8) against controls (n = 10) with validation via micro-CT and histology.
  • Assessed translational clinical feasibility using longitudinal 3-T MRI PDFF mapping and one-year bone marrow biopsies in two adult males (24 ± 1 years old) with severe sickle cell disease undergoing marrow transplantation.
  • Mice receiving OS-TMI/BMT exhibited higher PDFF across the right femur compared to controls 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 significantly improved trabecular microarchitecture in mice, increasing trabecular thickness and distal bone volume density while reducing bone surface-to-volume ratio, structure model index, and anisotropy.
  • Both clinical patients demonstrated increased marrow PDFF following transplantation, with one-year bone marrow biopsy confirming trilineage hematopoiesis without marrow fibrosis.

Cite This Study

Malekzadeh et al. (2026) studied this question.

synapsesocial.com/papers/6a9bd3726b95aff0620eaa68https://doi.org/10.1002/jmri.70510
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