Purpose: Cancer survivors are at an increased risk for fractures, but lack of effective and economical biomarkers limits quantitative assessments of marrow fat (MF), bone mineral density (BMD) and their relation in response to cytotoxic cancer treatment. We report dual energy CT (DECT) imaging, commonly used for cancer diagnosis, treatment and surveillance, as a novel biomarker of MF and BMD. Methods: We validated DECT in pre-clinical and phase I clinical trials and verified with water-fat MRI (WF-MRI), quantitative CT (QCT) and dual-energy X-ray absorptiometry (DXA). Basis material composition framework was validated using water and small-chain alcohols simulating different components of bone marrow. Histologic validation was achieved by measuring percent adipocyte in the cadaver vertebrae and compared with DECT and WF-MRI. For a phase I trial, sixteen patients with gynecologic malignancies (treated with oophorectomy, radiotherapy or chemotherapy) underwent DECT, QCT, WF-MRI and DXA before and 12. months after treatment. BMD and MF percent and distribution were quantified in the lumbar vertebrae and the right femoral neck. Results: Measured precision (3mg/cm3) was sufficient to distinguish test solutions. Adiposity in cadaver bone histology was highly correlated with MF measured using DECT and WF-MRI (r=0.80 and 0.77, respectively). In the clinical trial, DECT showed high overall correlation (r=0.77, 95% CI: 0.69, 0.83) with WF-MRI. MF increased significantly after treatment (p<0.002). Chemotherapy and radiation caused greater increases in MF than oophorectomy (p<0.032). L4 BMD decreased 14% by DECT, 20% by QCT, but only 5% by DXA (p<0.002 for all). At baseline, we observed a statistically significant inverse association between MF and BMD which was dramatically attenuated after treatment. Conclusion: Our study demonstrated that DECT, similar to WF-MRI, can accurately measure marrow adiposity. Both imaging modalities show rapid increase in MF following cancer treatment. Our results suggest that MF and BMD cannot be used interchangeably to monitor skeletal health following cancer therapy.
Bibliographical noteFunding Information:
This work was supported by the NIH ( RO3 AR055333-02 , 1R01CA154491 , 1K12-HD055887-01 , NIH 8UL1TR0001114 , P41 RR008079 , P41 EB015894 , NIH R24 DK092759 , and P30 CA77398 ). Other grant support includes University of Minnesota seed grants (the Minnesota Medical Foundation, Academic Health Center, Grant in Aid, Breast Cancer Research). We acknowledge Matthew H Gerber for supporting recruitment.
© 2014 Elsevier Inc.
Copyright 2020 Elsevier B.V., All rights reserved.
- Dual energy CT
- Quantification and visualization of bone marrow
- Water-fat MRI