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Ultrahigh-field cardiovascular magnetic resonance T1 and T2 mapping for the assessment of anthracycline-induced cardiotoxicity in rat models: validation against histopathologic changes

Authors
 Heae Surng Park  ;  Yoo Jin Hong  ;  Kyunghwa Han  ;  Pan Ki Kim  ;  Eunkyung An  ;  Ji Yeon Lee  ;  Chul Hwan Park  ;  Hye-Jeong Lee  ;  Jin Hur  ;  Young Jin Kim  ;  Byoung Wook Choi 
Citation
 JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE, Vol.23(1) : 76, 2021-06 
Journal Title
JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE
ISSN
 1097-6647 
Issue Date
2021-06
Keywords
Cardiotoxicity ; Edema ; Inflammation ; Magnetic resonance imaging ; Myocardial fibrosis ; Rats ; T1 mapping
Abstract
Background: Chemotherapy-induced cardiotoxicity is a well-recognized adverse effect of chemotherapy. Quantitative T1-mapping cardiovascular magnetic resonance (CMR) is useful for detecting subclinical myocardial changes in anthracycline-induced cardiotoxicity. The aim of the present study was to histopathologically validate the T1 and T2 mapping parameters for the evaluation of diffuse myocardial changes in rat models of cardiotoxicity.

Methods: Rat models of cardiotoxicity were generated by injecting rats with doxorubicin (1 mg/kg, twice a week). CMR was performed with a 9.4 T ultrahigh-field scanner using cine, pre-T1, post-T1 and T2 mapping sequences to evaluate the left ventricular ejection fraction (LVEF), native T1, T2, and extracellular volume fraction (ECV). Histopathological examinations were performed and the association of histopathological changes with CMR parameters was assessed.

Results: Five control rats and 36 doxorubicin-treated rats were included and classified into treatment periods. In the doxorubicin-treated rats, the LVEF significantly decreased after 12 weeks of treatment (control vs. 12-week treated: 73 ± 4% vs. 59 ± 9%, P = 0.01). Increased native T1 and ECV were observed after 6 weeks of treatment (control vs. 6-week treated: 1148 ± 58 ms, 14.3 ± 1% vs. 1320 ± 56 ms, 20.3 ± 3%; P = 0.005, < 0.05, respectively). T2 values also increased by six weeks of treatment (control vs. 6-week treated: 16.3 ± 2 ms vs. 10.3 ± 1 ms, P < 0.05). The main histopathological features were myocardial injury, interstitial fibrosis, inflammation, and edema. The mean vacuolar change (%), fibrosis (%), and inflammation score were significantly higher in 6-week treated rats than in the controls (P = 0.03, 0.03, 0.02, respectively). In the univariable analysis, vacuolar change showed the highest correlation with native T1 value (R = 0.60, P < 0.001), and fibrosis showed the highest correlation with ECV value (R = 0.78, P < 0.001). In the multiple linear regression analysis model, vacuolar change was a significant factor for change in native T1 (P = 0.01), and vacuolar change and fibrosis were significant factors for change in ECV (P = 0.006, P < 0.001, respectively) by adding other histopathological parameters (i.e., inflammation and edema scores) CONCLUSIONS: Quantitative T1 and T2 mapping CMR is a useful non-invasive tool reflecting subclinical histopathological changes in anthracycline-induced cardiotoxicity.
Files in This Item:
T202102668.pdf Download
DOI
10.1186/s12968-021-00767-8
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Young Jin(김영진) ORCID logo https://orcid.org/0000-0002-6235-6550
Kim, Pan Ki(김판기)
Park, Chul Hwan(박철환) ORCID logo https://orcid.org/0000-0002-0004-9475
Lee, Hye Jeong(이혜정) ORCID logo https://orcid.org/0000-0003-4349-9174
Choi, Byoung Wook(최병욱) ORCID logo https://orcid.org/0000-0002-8873-5444
Han, Kyung Hwa(한경화)
Hur, Jin(허진) ORCID logo https://orcid.org/0000-0002-8651-6571
Hong, Yoo Jin(홍유진) ORCID logo https://orcid.org/0000-0002-7276-0944
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/184238
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