{"title":"Characterization of anthracycline-induced cardiotoxicity by diffusion tensor magnetic resonance imaging","authors":"","doi":"10.1007/s00395-024-01039-z","DOIUrl":null,"url":null,"abstract":"<h3>Abstract</h3> <p>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; <em>n</em> = 16) for induction of AIC or saline as corresponding control (<em>n</em> = 15). Cardiac function was assessed via echocardiography at the end of the study period. Whole hearts (<em>n</em> = 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%, <em>P</em> < 0.001), impaired global longitudinal strain (−19.6 ± 2.0% vs. −16.6 ± 3.0%, <em>P</em> < 0.01), and cardiac atrophy (LV mass index [mg/mm], 4.3 ± 0.1 vs. 3.6 ± 0.2, <em>P</em> < 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, <em>P</em> < 0.05). DOX-treated mice displayed higher planar and less spherical anisotropy (<em>C</em><sub>Planar</sub> 0.07 ± 0.01 vs. 0.09 ± 0.01, <em>P</em> < 0.01; <em>C</em><sub>Spherical</sub> 0.89 ± 0.01 vs. 0.87 ± 0.02, <em>P</em> < 0.05). <em>C</em><sub>Planar</sub> and <em>C</em><sub>Spherical</sub> yielded good discriminatory power to distinguish between mice with and without AIC (c-index 0.91 and 0.84, respectively, <em>P</em> 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.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"8 1","pages":""},"PeriodicalIF":7.5000,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Basic Research in Cardiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00395-024-01039-z","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
Basic Research in Cardiology is an international journal for cardiovascular research. It provides a forum for original and review articles related to experimental cardiology that meet its stringent scientific standards.
Basic Research in Cardiology regularly receives articles from the fields of
- Molecular and Cellular Biology
- Biochemistry
- Biophysics
- Pharmacology
- Physiology and Pathology
- Clinical Cardiology