Detection of doxorubicin-induced cardiotoxicity using myocardial T1 and T2 relaxation times in childhood acute lymphoblastic leukemia survivors

Doxorubicin leads to dose-dependent cardiotoxicity in childhood acute lymphoblastic leukemia (ALL) survivors. The first aim was to propose a contour-based estimation of T1 and T2 relaxation times based on the myocardial area, while our second aim was to evaluate native T1, post-gadolinium T1 and T2 relaxation time sensitivity to detect myocardial changes. A total of 84 childhood ALL survivors were stratified in regard to their prognostic risk groups: standard risk (SR), n = 20), high-risk with and without dexrazoxane (HR + DEX, n = 39 and HR, n = 25). Survivors’ mean age was of 22.0 ± 6.9 years, with a mean age at cancer diagnosis of 8.0 ± 5.2 years. CMR acquisitions were performed on a 3 T MRI system and included an ECG-gated 3(3)3(3)5 MOLLI sequence for T1 mapping and an ECG-gated T2-prepared TrueFISP sequence for T2 mapping. Myocardial contours were semi-automatically segmented using an interactive implementation of cubic Bezier curves. We found excellent repeatability between operators for native T1 (ICC = 0.91), and good repeatability between operators for post-gadolinium T1 (ICC = 0.84) and T2 (ICC = 0.79). Bland and Altman tests demonstrated a strong agreement between our contour-based method and images analyzed using the CVI42 software on the measure of native T1, post-gadolinium T1, and T2. No significant differences between survivors’ prognostic risk groups in native T1 were reported, while we observed significant differences between survivors’ prognostic risk groups in post-gadolinium T1 and T2. Significant differences were observed between male and female survivors. Differences between groups were also observed in partition coefficients, but no significant differences were observed between male and female survivors. The use of CMR parameters with native T1, post-gadolinium T1, and T2 allowed to show that survivors at a high-risk prognostic were more exposed to doxorubicin-related cardiotoxicity than those who were at a standard risk prognostic or who received dexrazoxane treatments.