Cardiac Magnetic Resonance for Early Detection of Radiation Therapy-Induced Cardiotoxicity in a Small Animal Model

Abstract

BackgroundOver one-half of all cancer patients receive radiation therapy (RT). However, radiation exposure to the heart can cause cardiotoxicity. Nevertheless, there is a paucity of data on RT-induced cardiac damage, with limited understanding of safe regional RT doses, early detection, prevention, and management. A common initial feature of cardiotoxicity is asymptomatic dysfunction, which, if left untreated, may progress to heart failure. The current paradigm for cardiotoxicity detection and management relies primarily upon assessment of ejection fraction. However, cardiac injury can occur without a clear change in ejection fraction. ObjectivesWe sought to identify cardiac magnetic resonance (CMR) imaging markers of early RT-induced cardiac dysfunction. MethodsWe investigated the effect of RT on global and regional cardiac function and myocardial T1/T2 values at 2 time points post-RT using CMR in a rat model of localized cardiac RT. Rats who received image-guided whole-heart radiation of 24 Gy were compared with sham-treated rats. ResultsThe rats maintained normal global cardiac function post-RT. However, a deterioration in strain was particularly notable at 10 weeks post-RT, and changes in circumferential strain were larger than changes in radial or longitudinal strain. Compared with sham treatment, circumferential strain changes occurred at the basal, mid-ventricular, and apical levels (p < 0.05 for all at both 8 weeks and 10 weeks post-RT), most of the radial strain changes occurred at the mid-ventricular (p = 0.044 at 8 weeks post-RT) and basal (p = 0.018 at 10 weeks post-RT) levels, and most of the longitudinal strain changes occurred at the apical (p = 0.002 at 8 weeks post-RT) and basal (p = 0.035 at 10 weeks post-RT) levels. Regionally, lateral myocardial segments showed the greatest worsening in strain measurements, and histological changes supported these findings. Despite worsened myocardial strain post-RT, myocardial tissue displacement measures were maintained, or even increased. T1/T2 measurements showed small nonsignificant changes post-RT compared with values in nonirradiated rats. ConclusionsOur findings suggest MRI regional myocardial strain is a sensitive imaging biomarker for detecting RT-induced subclinical cardiac dysfunction before compromise of global cardiac function.