TY - JOUR
T1 - Cardiac Magnetic Resonance for Early Detection of Radiation Therapy-Induced Cardiotoxicity in a Small Animal Model
AU - Ibrahim, El Sayed H.
AU - Baruah, Dhiraj
AU - Croisille, Pierre
AU - Stojanovska, Jadranka
AU - Rubenstein, Jason C.
AU - Frei, Anne
AU - Schlaak, Rachel A.
AU - Lin, Chieh Yu
AU - Pipke, Jamie L.
AU - Lemke, Angela
AU - Xu, Zhiqiang
AU - Klaas, Amanda
AU - Brehler, Michael
AU - Flister, Michael J.
AU - Laviolette, Peter S.
AU - Gore, Elizabeth M.
AU - Bergom, Carmen
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/3
Y1 - 2021/3
N2 - Background: 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.
AB - Background: 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.
KW - MRI
KW - cardiotoxicity
KW - ejection fraction
KW - heart
KW - radiation therapy
KW - rat
KW - strain
UR - http://www.scopus.com/inward/record.url?scp=85102143842&partnerID=8YFLogxK
U2 - 10.1016/j.jaccao.2020.12.006
DO - 10.1016/j.jaccao.2020.12.006
M3 - Article
C2 - 33912843
AN - SCOPUS:85102143842
SN - 2666-0873
VL - 3
SP - 113
EP - 130
JO - JACC: CardioOncology
JF - JACC: CardioOncology
IS - 1
ER -