Ghimire Hemendra, Malekzadeh Malakeh, Lim Ji Eun, Madabushi Srideshikan Sargur, Zampini Marco Andrea, Camacho Angela, Hu Weidong, Storme Guy, Malki Monzr M Al, Hui Susanta K
bioRxiv. 2025 Jan 4:2025.01.03.631267. doi: 10.1101/2025.01.03.631267.
BACKGROUND/OBJECTIVES: Bone marrow (BM) adipocytes are critical in progressing solid tumor metastases and hematological malignancies across pediatric to aging populations. Single-point biopsies remain the gold standard for monitoring BM diseases, including hematologic malignancies, but are limited in capturing the full complexity of loco-regional and global BM microenvironments. Non-invasive imaging techniques like Magnetic Resonance Imaging (MRI), could offer valuable alternatives for real-time evaluation of BM diseases in both preclinical translational and clinical studies.
We developed a preclinical proton density fat fraction (PDFF) MRI technique for quantitative BM composition assessment, focusing on fat fraction (FF) within mouse femurs. We validated this method using aging mice and young mice subjected to 10 Gy X-ray irradiation, compared with young unirradiated mice as controls. Water-fat phantoms (0% to 100% fat content) were used to optimize the imaging sequence, and immunohistochemical (IHC) staining with H&E validates equivalent adipose content in the femur BM regions.
Significant differences in FF were observed across age groups (p = 0.001 for histology and p = 0.0002 for PDFF) and between irradiated and control mice (p = 0.005 for histology and p = 0.002 for PDFF). A strong correlation (R ∼ 0.84) between FF values from PDFF and histology validates the accuracy of the technique.
These findings demonstrate the potential of PDFF MRI as a non-invasive real-time imaging biomarker for quantifying BM fat fraction in preclinical mice model studies, particularly in evaluating the effects of aging, disease progression, and irradiation therapy in pediatric and translational oncology research.
背景/目的：骨髓脂肪细胞在实体瘤转移进展以及从儿科到老年人群的血液系统恶性肿瘤中起着关键作用。单点活检仍然是监测包括血液系统恶性肿瘤在内的骨髓疾病的金标准，但在捕捉局部区域和整体骨髓微环境的全部复杂性方面存在局限性。磁共振成像（MRI）等非侵入性成像技术可为临床前转化研究和临床研究中实时评估骨髓疾病提供有价值的替代方法。
我们开发了一种临床前质子密度脂肪分数（PDFF）MRI技术，用于定量评估骨髓成分，重点关注小鼠股骨内的脂肪分数（FF）。我们使用衰老小鼠和接受10 Gy X射线照射的年轻小鼠，并与未照射的年轻小鼠作为对照来验证该方法。使用水脂体模（脂肪含量为0%至100%）来优化成像序列，并用苏木精和伊红（H&E）进行免疫组织化学（IHC）染色以验证股骨骨髓区域中相当的脂肪含量。
在各年龄组之间（组织学p = 0.001，PDFF p = 0.0002）以及照射小鼠和对照小鼠之间（组织学p = 0.005，PDFF p = 0.002）观察到FF有显著差异。PDFF的FF值与组织学之间有很强的相关性（R ∼ 0.84），验证了该技术的准确性。
这些发现表明，PDFF MRI作为一种非侵入性实时成像生物标志物，在临床前小鼠模型研究中用于定量骨髓脂肪分数具有潜力，特别是在评估儿科和转化肿瘤学研究中衰老、疾病进展和放射治疗的影响方面。
