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ELASTICITY OF CARDIOTOXICITY: ESTIMATING LEFT VENTRICLE ELASTICITY CHANGES AS A BIOMARKER FOR ANTI-CANCER THERAPY-INDUCED CARDIOTOXICITY

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title
ELASTICITY OF CARDIOTOXICITY: ESTIMATING LEFT VENTRICLE ELASTICITY CHANGES AS A BIOMARKER FOR ANTI-CANCER THERAPY-INDUCED CARDIOTOXICITY
author
Miller, Caroline Elizabeth
abstract
Cardiotoxicity due to anti-neoplastic therapies threatens to attenuate recent significant gains in cancer survivability. Cardiac disease has surpassed cancer recurrence as the leading cause of death in breast cancer patients. Breast cancer therapeutics such as anthracycline-based chemotherapeutic agents, radiation therapy, and hormonal therapy have been shown to cause cardiac damage and subsequent heart failure. Clinical image-based metrics to diagnose cancer therapy induced cardiotoxicity consist of left ventricle ejection fraction and myocardial strain imaging metrics while novel methodologies include late gadolinium enhancement, T1 and T2 mapping, and elastography. Limitations to current diagnostic methods include lack of sensitivity to subclinical disease and ability to integrate novel methodologies within standard clinical practice. A clinically relevant method for diagnosing subclinical cardiotoxicity represents a major clinical oncology need. Because of tissue response to anti-neoplastic therapies, myocardial stiffness could be utilized as a functional biomarker for cardiotoxicity. We developed a non-invasive biomechanical elasticity imaging methodology (BEIM) to estimate regional left ventricle (LV) mechanical stiffness to assess myocardial stiffness change in breast cancer patients undergoing anti-neoplastic therapies. BEIM was developed for CINE cardiac magnetic resonance imaging inputs and validated utilizing a non-human primate model with matching histopathological data. To further assess BEIM, elasticity maps were estimated in a healthy cohort undergoing serial imaging to calculate expected variability and methodological reproducibility. Finally, BEIM was used to estimate LV elasticity changes in a clinical cohort of breast cancer patients either undergoing hormonal therapy for hormone-receptor positive breast cancer, or after completion of therapy for triple negative breast cancer. In this study, BEIM was developed, tested, and utilized in a clinical cohort to assess LV elasticity changes due to cardiotoxicity effects of anti-neoplastic therapies in breast cancer patients and represents a promising potential new strategy for assessing subclinical cardiotoxicity utilizing myocardial stiffness as a biomarker.
subject
Biomechanical Model
Breast Cancer
Cardiotoxicity
contributor
Weis, Jared A (advisor)
Jordan, Jennifer H (committee member)
Thomas, Alexandra (committee member)
Zhao, Dawen (committee member)
Hamilton, Craig (committee member)
date
2023-01-24T09:35:43Z (accessioned)
2024-01-23T09:30:06Z (available)
2023 (issued)
degree
Biomedical Engineering (discipline)
embargo
2024-01-23 (terms)
identifier
http://hdl.handle.net/10339/101774 (uri)
language
en (iso)
publisher
Wake Forest University
type
Dissertation

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