Over 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.
Objectives
We sought to identify cardiac magnetic resonance (CMR) imaging markers of early RT-induced cardiac dysfunction.
Methods
We 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.
Results
The 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.
Conclusions
Our findings suggest MRI regional myocardial strain is a sensitive imaging biomarker for detecting RT-induced subclinical cardiac dysfunction before compromise of global cardiac function.
Central Illustration
Key Words
cardiotoxicity
ejection fraction
heart
MRI
radiation therapy
rat
strain
Abbreviations and Acronyms
CMR
cardiac magnetic resonance
ED
end-diastolic
EF
ejection fraction
ESV
end-systolic volume
H&E
hematoxylin and eosin
LAX
long-axis
LV
left ventricle/ventricular
PBST
phosphate buffered saline with Tween
RT
radiation therapy
SAX
short-axis
SS
salt-sensitive
Cited by (0)
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.