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. 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. 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) Quantitative T1 and T2 mapping CMR is a useful non-invasive tool reflecting subclinical histopathological changes in anthracycline-induced cardiotoxicity.

中文翻译：

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超高场心血管磁共振 T1 和 T2 映射用于评估大鼠模型中蒽环类药物引起的心脏毒性：针对组织病理学变化的验证


化疗引起的心脏毒性是众所周知的化疗不良反应。定量 T1 映射心血管磁共振 (CMR) 可用于检测蒽环类药物引起的心脏毒性中的亚临床心肌变化。本研究的目的是通过组织病理学验证 T1 和 T2 映射参数，以评估心脏毒性大鼠模型中弥漫性心肌变化。通过向大鼠注射阿霉素（1 mg/kg，每周两次）来产生大鼠心脏毒性模型。使用 9.4 T 超高场扫描仪使用电影、T1 前、T1 后和 T2 映射序列进行 CMR，以评估左心室射血分数 (LVEF)、天然 T1、T2 和细胞外体积分数 (ECV)。进行组织病理学检查并评估组织病理学变化与 CMR 参数的关联。纳入 5 只对照大鼠和 36 只阿霉素治疗大鼠，并分为不同的治疗期。在阿霉素治疗的大鼠中，治疗 12 周后 LVEF 显着下降（对照与治疗 12 周：73 ± 4% vs. 59 ± 9%，P = 0.01）。治疗 6 周后观察到自然 T1 和 ECV 增加（对照与治疗 6 周：分别为 1148 ± 58 ms、14.3 ± 1% vs. 1320 ± 56 ms、20.3 ± 3%；P = 0.005、< 0.05） ）。治疗六周后，T2 值也有所增加（对照与治疗 6 周：16.3 ± 2 毫秒 vs. 10.3 ± 1 毫秒，P < 0.05）。主要组织病理学特征为心肌损伤、间质纤维化、炎症和水肿。治疗 6 周的大鼠的平均空泡变化 (%)、纤维化 (%) 和炎症评分显着高于对照组（P 分别为 0.03、0.03、0.02）。 单变量分析中，空泡变化与天然T1值的相关性最高（R = 0.60，P < 0.001），纤维化与ECV值的相关性最高（R = 0.78，P < 0.001）。在多元线性回归分析模型中，空泡变化是原生T1变化的显着因素（P = 0.01），空泡变化和纤维化是ECV变化的显着因素（分别为P = 0.006，P < 0.001）。其他组织病理学参数（即炎症和水肿评分） 定量 T1 和 T2 映射 CMR 是一种有用的非侵入性工具，反映蒽环类药物引起的心脏毒性的亚临床组织病理学变化。