Ghimire Hemendra, Malekzadeh Malakeh, Lim Ji Eun, Madabushi Srideshikan Sargur, Zampini Marco Andrea, Camacho Angela, Hu Weidong, Baran Natalia, Storme Guy, Al Malki Monzr M, Hui Susanta K
Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA 91010, USA.
MR Solutions Ltd., Ashbourne House, Guildford GU3 1LR, UK.
Bioengineering (Basel). 2025 Mar 28;12(4):349. doi: 10.3390/bioengineering12040349.
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.
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.
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.
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.
骨髓脂肪细胞在实体瘤转移进展以及从儿科到老年人群各个年龄段血液系统恶性肿瘤的扩展过程中发挥着关键作用。单点活检仍然是监测骨髓疾病（包括血液系统恶性肿瘤）的金标准，但在捕捉局部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）、计算机断层扫描（CT）和正电子发射断层扫描（PET）等非侵入性成像技术可为临床前转化研究和临床研究中的实时评估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，用于定量评估骨髓组成，重点关注小鼠股骨内的脂肪分数（FF）。与年轻对照小鼠相比，我们使用衰老小鼠和接受10 Gy X射线照射的年轻小鼠对该方法进行了验证。使用具有不同脂肪百分比（0%至100%）的水脂体模优化成像序列，并用苏木精和伊红（H&E）进行免疫组织化学（IHC）染色，验证股骨骨髓区域中相当的脂肪含量。
在各年龄组之间（组织学分析P = 0.001，PDFF分析P < 0.001）以及照射小鼠与对照小鼠之间（组织学分析P = 0.005，PDFF分析P = 0.002）观察到FF存在显著差异。PDFF-MRI的FF值与组织学分析之间存在强相关性（R~0.84），验证了该技术的准确性。
这些发现突出了PDFF-MRI作为一种非侵入性、实时、体内生物标志物在临床前研究中定量评估骨髓脂肪分数的潜力，特别是在评估衰老、疾病进展以及细胞毒性癌症治疗（包括化疗和放疗）效果的研究中。
