Detection of Radiation Induced Heart Disease Applying Speckle Tracking Echocardiography in a Mouse Model

Abstract

Despite recent advances in radiation delivery and treatment planning, radiation-induced heart disease (RIHD) remains a potentially severe side effect of radiation therapy of breast and thoracic tumors. Following radiation exposure, the myocardium undergoes accelerated degeneration, characterized by gradual tissue fibrosis which may lead to structural remodeling and heart-failure. However, this deleterious consequence may be apparent only after several years. Speckle Tracking Echocardiography (STE) is a novel cardiac imaging technique which measures Left ventricular (LV) regional and global deformations. We hypothesized that using STE may detect initial cardiac remodeling, potentially enabling earlier intervention. Female apoE-deficient mice were placed in a lead irradiation chamber shielding their entire body except for chest wall, and were subjected to thoracic irradiation at 0, 5 or 10 Gy in a single fraction. Cardiac structure and function were evaluated using a small animal echocardiography system and STE analysis. Serial measurements were performed before (baseline), 1 and 4 months after chest irradiation. 12 weeks old, Female apoE-deficient mice were subjected to thoracic irradiation at 0, 5 or 10 Gy. One month after radiation no difference in cardiac structure or function was noted between the three treatment groups as assessed by echocardiography. Four months after radiation, mice which received 10 Gy, developed cardiac structural remodeling characterized by decreased LV end diastolic diameter (P = 0.048) and reduced endocardial diastolic area (P = 0.003) with no difference in ejection fraction or fractional shortening. No difference was noted between in cardiac structure was noted between the control group and mice receiving 5 Gy. Preforming STE 1 month after radiation showed a significant change in the LV anterior wall in mice receiving 10 Gy (P = 0.048). We found that thoracic irradiation induces cardiac remodeling 4 months after radiation in a preclinical apoE deficient mouse model. STE analysis enabled to detect cardiac structural changes after 1 months a time point where standard echocardiography was ineffective. Thus, we purpose a STE analysis to improve RIHD detection in high risk patients undergoing thoracic radiation.