| Anthracycline chemotherapies induce nonfocal cardiac injury to the left ventricular (LV) myocardium. This damage, chemotherapy induced cardiotoxicity, is difficult to detect noninvasively prior to the advancement of injury to an irreversible state with decrements in left ventricular ejection fraction (LVEF). As cancer survival rates increase, the occurrence of chemotherapy induced cardiotoxicity is also increasing with reports of chronic heart failure rates of 3-36%, dependent on total dosage of chemotherapy. The recognition of the need to better manage the cardiovascular care of oncology patients and survivors of cancer has necessitated an emerging field, cardiooncology, to bring the two areas of clinical practice together. The current noninvasive method of detecting cardiotoxicity, a decrement in LVEF, may occur before the extent of myocardial injury is irreversible. Safe, noninvasive methods for accurately detecting early evidence of myocardial injury are critically needed to prevent irreversible cardiotoxicity.;Cardiovascular magnetic resonance (CMR) has successfully imaged both structural and functional properties of focal and non-focal cardiovascular diseases, making it a practical tool for translation to chemotherapy induced cardiotoxicity imaging. Delayed enhancement CMR imaging was used in this study to detect structural changes in LV myocardium in the form of necrosis, inflammation, and edema. This technique, however, is not a quantitative imaging technique and has many disadvantages that may be addressed with quantitative mapping of magnetic relaxation values (T1 and T2). MOLLI T1 mapping, recently developed by Siemens, and a method we developed, TrueFISP T1 and T2 mapping, were used to measure LV T1 and T2 in this study. A functional CMR measurement, myocardial strain, was quantified using tagged CMR imaging, and is known to increase in the presence of LV dysfunction. The pathology of chemotherapy induced cardiotoxicity includes both structural and functional changes to the myocardium as the disease progresses, and CMR has the ability to identify changes in these measurements in a targeted manner. This study investigated the association of structural and functional changes with LVEF and determined that they may serve as subclinical markers of chemotherapy induced cardiotoxicity.;An early detection methodology has been developed that can quantify structural properties (delayed enhancement CMR, T1, and T2) and functional properties (strain) of the myocardial tissue. This comprehensive approach to noninvasive, longitudinal imaging of the LV myocardium has shown that changes in structural and functional CMR measurements occur in patients who may not yet have a decrement in LVEF. The early detection of these changes has implications on the future treatment of patients undergoing cardiotoxic chemotherapy and may serve as an important tool in the emerging field of cardio-oncology.;The structure of the dissertation is as follows: (1) Chapter 1 – Gives an introduction to the project aims as well as an overview of the following topics: cardiovascular structure and function, magnetic resonance imaging, and chemotherapy induced cardiotoxicity. (2) Chapter 2 – Discusses studies in delayed enhancement CMR applied in an experiment rodent model and a patient population undergoing anthracycline chemotherapy to identify subclinical structural damage to the myocardium. (3) Chapter 3 – Discusses two methods of quantitative imaging (MOLLI T1 mapping and TrueFISP T1 and T 2 mapping) used to identify subclinical structural damage to the myocardium. (4) Chapter 4 – Explains analyses of functional subclinical damage (Eulerian strain) measured with CMR. (5) Chapter 5 – Contains multivariate analyses of structural and functional measures used together to model changes in LVEF using CMR. (6) Chapter 6 – Concludes the dissertation work and explores contributions, applications, and future directions of the research. |
