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Characterization of anthracycline-induced cardiotoxicity by diffusion tensor magnetic resonance imaging
Basic Research in Cardiology ( IF 7.5 ) Pub Date : 2024-03-14 , DOI: 10.1007/s00395-024-01039-z
David Lohr 1 , Arne Thiele 2, 3, 4, 5, 6 , Max Stahnke 2, 3 , Vera M Braun 2, 3 , Robert Klopfleisch 7 , Oliver Klein 3, 8, 9 , Sandra Dresen 2, 3 , Ulf Landmesser 3, 9, 10 , Anna Foryst-Ludwig 2, 3 , Ulrich Kintscher 2, 3 , Laura M Schreiber 1 , Niklas Beyhoff 2, 3, 9, 10
Affiliation  

Anthracyclines are highly potent anti-cancer drugs, but their clinical use is limited by severe cardiotoxic side effects. The impact of anthracycline-induced cardiotoxicity (AIC) on left ventricular (LV) microarchitecture and diffusion properties remains unknown. This study sought to characterize AIC by cardiovascular magnetic resonance diffusion tensor imaging (DTI). Mice were treated with Doxorubicin (DOX; n = 16) for induction of AIC or saline as corresponding control (n = 15). Cardiac function was assessed via echocardiography at the end of the study period. Whole hearts (n = 8 per group) were scanned ex vivo by high-resolution DTI at 7 T. Results were correlated with histopathology and mass spectrometry imaging. Mice with AIC demonstrated systolic dysfunction (LVEF 52 ± 3% vs. 43 ± 6%, P < 0.001), impaired global longitudinal strain (−19.6 ± 2.0% vs. −16.6 ± 3.0%, P < 0.01), and cardiac atrophy (LV mass index [mg/mm], 4.3 ± 0.1 vs. 3.6 ± 0.2, P < 0.01). Regional sheetlet angles were significantly lower in AIC, whereas helix angle and relative helicity remained unchanged. In AIC, fractional anisotropy was increased (0.12 ± 0.01 vs. 0.14 ± 0.02, P < 0.05). DOX-treated mice displayed higher planar and less spherical anisotropy (CPlanar 0.07 ± 0.01 vs. 0.09 ± 0.01, P < 0.01; CSpherical 0.89 ± 0.01 vs. 0.87 ± 0.02, P < 0.05). CPlanar and CSpherical yielded good discriminatory power to distinguish between mice with and without AIC (c-index 0.91 and 0.84, respectively, P for both < 0.05). AIC is associated with regional changes in sheetlet angle but no major abnormalities of global LV microarchitecture. The geometric shape of the diffusion tensor is altered in AIC. DTI may provide a new tool for myocardial characterization in patients with AIC, which warrants future clinical studies to evaluate its diagnostic utility.



中文翻译:


弥散张量磁共振成像表征蒽环类药物引起的心脏毒性



蒽环类药物是高效抗癌药物,但其临床应用因严重的心脏毒性副作用而受到限制。蒽环类药物引起的心脏毒性 (AIC) 对左心室 (LV) 微结构和扩散特性的影响仍不清楚。本研究试图通过心血管磁共振扩散张量成像 (DTI) 来表征 AIC。用阿霉素(DOX; n = 16)治疗小鼠以诱导 AIC,或用盐水作为相应对照( n = 15)。在研究期结束时通过超声心动图评估心脏功能。通过 7 T 的高分辨率 DTI 对整个心脏(每组n = 8)进行离体扫描。结果与组织病理学和质谱成像相关。患有 AIC 的小鼠表现出收缩功能障碍(LVEF 52 ± 3% vs. 43 ± 6%, P < 0.001)、整体纵向应变受损(−19.6 ± 2.0% vs. -16.6 ± 3.0%, P < 0.01)和心肌萎缩(左心室质量指数 [mg/mm],4.3 ± 0.1 与 3.6 ± 0.2, P < 0.01)。 AIC 中的区域片层角度明显较低,而螺旋角和相对螺旋度保持不变。在 AIC 中,分数各向异性增加(0.12 ± 0.01 与 0.14 ± 0.02, P < 0.05)。 DOX 处理的小鼠表现出较高的平面各向异性和较低的球形各向异性( C平面0.07 ± 0.01 对比 0.09 ± 0.01, P < 0.01; C球形0.89 ± 0.01 对比 0.87 ± 0.02, P < 0.05)。 C PlanarC Spherical产生了良好的区分能力来区分具有和不具有 AIC 的小鼠(c 指数分别为 0.91 和 0.84, P均 < 0.05)。 AIC 与小片角度的局部变化有关,但整体 LV 微结构没有重大异常。 AIC 中扩散张量的几何形状发生了变化。 DTI 可能为 AIC 患者的心肌表征提供一种新工具,这需要未来的临床研究来评估其诊断效用。

更新日期:2024-03-14
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