Abstract
Cardiotoxicity is a major complication of chemotherapy, which leads in time to progressive electro-mechanical dysfunction, irreversible myocardial tissue remodeling and eventual heart failure. In this pilot study, we seek to find key biomarkers of early cardiotoxic effects. For this, a weekly dose of doxorubicin, DXO was injected in swine during a four-week treatment. Longitudinal MR imaging was performed pre- and post-DXO (at: 1, 5 and 9 weeks after ending the DXO-therapy) using a scanning protocol at 3T that included: functional CINE imaging; T2 and T1 mapping, and 3D late gadolinium enhancement (LGE) for tissue characterization. Our results showed that, compared to the mean baseline values pre-DXO, ejection fraction gradually decreased from a mean 47% to ~34% post-DXO, indicating that the cardiac biomechanical function started to deteriorate within weeks post-DXO. The initially increased T2-derived edema appeared to resolve by week 5. Furthermore, a gradual deposition of diffuse fibrosis post-DXO was identified by T1 values and LGE, and confirmed by collagen-sensitive histological stains. Our preliminary results will help establish MR imaging protocols and models that predict early DXO-induced cardiotoxicity, which could be used by clinicians to develop cardioprotective strategies for preventing heart failure progression post-chemotherapy.
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Acknowledgment
This work was financially supported by a CIHR project grant (PJT 153212) awarded to Dr. Mihaela Pop. The authors would like to thank Mr. Adebayo Adeeko (Biomarker Imaging Lab, Sunnybrook Research Institute, Toronto, CA) for processing and staining the histopathological slices.
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Lin, P. et al. (2022). Novel Imaging Biomarkers to Evaluate Heart Dysfunction Post-chemotherapy: A Preclinical MRI Feasibility Study. In: Puyol Antón, E., et al. Statistical Atlases and Computational Models of the Heart. Multi-Disease, Multi-View, and Multi-Center Right Ventricular Segmentation in Cardiac MRI Challenge. STACOM 2021. Lecture Notes in Computer Science(), vol 13131. Springer, Cham. https://doi.org/10.1007/978-3-030-93722-5_4
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