Proton Density Fat Fraction Micro-MRI for Non-Invasive Quantification of Bone Marrow Aging and Radiation Effects in Mice.

Background: Bone marrow (BM) adipocytes play a critical role in the progression of both solid tumor metastases and expansion of hematological malignancies across a spectrum of ages, from pediatric to aging populations. Single-point biopsies remain the gold standard for monitoring BM diseases, including hematologic malignancies, but these are limited in capturing the full complexity of loco-regional and global BM microenvironments. Non-invasive imaging techniques such as Magnetic Resonance Imaging (MRI), Computed Tomography (CT), and Positron Emission Tomography (PET) could provide valuable alternatives for real-time evaluation in both preclinical translational and clinical studies.

Methods: We developed a preclinical proton density fat fraction (PDFF) MRI technique for the quantitative assessment of BM composition, focusing on the fat fraction (FF) within mouse femurs. We validated this method using aging mice and young mice subjected to 10 Gy X-ray irradiation, compared to young control mice. Water-fat phantoms with varying fat percentages (0% to 100%) were used to optimize the imaging sequence, and immunohistochemical (IHC) staining with H&E validated equivalent adipose content in the femur BM region.

Results: Significant differences in FF were observed across age groups ( = 0.001 for histology and < 0.001 for PDFF) and between irradiated and control mice ( = 0.005 for histology and = 0.002 for PDFF). A strong correlation (R~0.84) between FF values from PDFF-MRI and histology validated the accuracy of the technique.

Conclusions: These findings highlight PDFF-MRI's potential as a non-invasive, real-time, in vivo biomarker for quantitatively assessing the BM fat fraction in preclinical studies, particularly in studies evaluating the effects of aging, disease progression, and cytotoxic cancer therapies, including chemotherapy and radiation.