ABSTRACT
A reliable, non-invasive diagnostic method is needed for early detection and serial monitoring of cardiotoxicity, a well-known side effect of chemotherapy. This study aimed to assess the feasibility of T1-mapping cardiac magnetic resonance imaging (CMR) for evaluating subclinical myocardial changes in a doxorubicin-induced cardiotoxicity rabbit model. Adult male New Zealand White rabbits were injected twice-weekly with doxorubicin and subjected to CMR on a clinical 3T MR system before and every 2-4 weeks post-drug administration. Native T1 and extracellular volume (ECV) values were measured at six mid-left ventricle (LV) and specific LV lesions. Histological assessments evaluated myocardial injury and fibrosis. Three pre-model and 11 post-model animals were included. Myocardial injury was observed from 3 weeks. Mean LV myocardium ECV values increased significantly from week 3 before LV ejection fraction decreases (week 6), and ECVs of the RV upper/lower insertion sites and papillary muscle exceeded those of the LV. The mean native T1 value in the mid-LV increased significantly increased from week 6, and LV myocardium ECV correlated strongly with the degree of fibrosis (r = 0.979, p < 0.001). Myocardial T1 mapping, particularly ECV values, reliably and non-invasively detected early cardiotoxicity, allowing serial monitoring of chemotherapy-induced cardiotoxicity.
Subject(s)
Antibiotics, Antineoplastic/toxicity , Cardiotoxicity/diagnostic imaging , Cardiotoxins/toxicity , Doxorubicin/toxicity , Heart/diagnostic imaging , Magnetic Resonance Imaging/methods , Animals , Heart/drug effects , Heart Ventricles/diagnostic imaging , Heart Ventricles/drug effects , Heart Ventricles/pathology , Magnetic Resonance Imaging, Cine/methods , Male , Myocardium/pathology , Rabbits , Sensitivity and SpecificityABSTRACT
OBJECTIVES: This study sought to evaluate whether patterns of myocardial change in doxorubicin-induced dilated cardiomyopathy determined using dual-energy computed tomography (CT) were similar to characterization by extracellular volume fraction (ECV) using cardiac magnetic resonance (CMR) T1-mapping and collagen volume fraction (CVF) measured using histology. BACKGROUND: Anthracycline chemoagents are effective against a wide range of malignant conditions. However, cardiotoxicity is a well-known adverse effect of these drugs. Dual-energy CT could be as useful as magnetic resonance (MR) to evaluate myocardial change in anthracycline-induced cardiotoxicity. METHODS: A dilated cardiomyopathy rabbit model was generated by injecting 11 adult New Zealand rabbits with 1.0 mg/kg of doxorubicin twice weekly for 16 weeks. Contrast-enhanced dual-energy CT and pre-contrast and post-contrast T1-mapping CMR using a prototype modified Look-Locker inversion recovery on a clinical 3-T scanner were performed on 15 rabbits, including 4 control animals, to calculate ECV at baseline, and at 6, 12, and 16 weeks after doxorubicin administration. RESULTS: The mean ECV values (%) on CT and CMR at 6, 12, and 16 weeks after modeling were significantly higher than those measured at baseline (CT ECV: 35.3%, 41.9%, 42.1% vs. 28.5%; MR ECV: 32.6%, 35.8%, 41.3% vs. 28.8%, respectively; all p < 0.001). CT ECV and MR ECV values were well correlated (r = 0.888; p < 0.001). Both were well correlated with CVF on histology (CT ECV vs. CVF, r = 0.925, p < 0.001 and MR ECV vs. CVF, r = 0.961, p < 0.001, respectively). CONCLUSIONS: Dual-energy CT ECV correlated well with CMR and histology. Dual-energy CT is useful for characterizing doxorubicin-induced cardiomyopathy by measuring ECV fraction; however, further technical improvements are desirable to lower motion artifact and improve image quality of the iodine map.
