Aims Mammalian models have been instrumental in investigating adult heart function and human disease. However, electrophysiological differences with human hearts and high costs motivate the need for non-mammalian models. The zebrafish is a well-established genetic model to study cardiovascular development and function; however, analysis of cardiovascular phenotypes in adult specimens is particularly challenging as they are opaque. Methods and results Here, we optimized and combined multiple imaging techniques including echocardiography, magnetic resonance imaging, and micro-computed tomography to identify and analyze cardiovascular phenotypes in adult zebrafish. Using alk5a/tgfbr1a mutants as a case study, we observed morphological and functional cardiovascular defects that were undetected with conventional approaches. Correlation analysis of multiple parameters revealed an association between hemodynamic defects and structural alterations of the heart, as observed clinically. Conclusion We report a new, comprehensive, and sensitive platform to identify otherwise indiscernible cardiovascular phenotypes in adult zebrafish. Translational Perspective This study further illustrates the importance of the zebrafish model to investigate cardiovascular phenotypes including morphological and functional alterations as observed in human disease settings.

中文翻译：

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整合多个成像平台以发现成年斑马鱼的心血管缺陷

目的 哺乳动物模型有助于研究成人心脏功能和人类疾病。然而，与人类心脏的电生理差异和高成本激发了对非哺乳动物模型的需求。斑马鱼是研究心血管发育和功能的成熟遗传模型；然而，成人样本中心血管表型的分析特别具有挑战性，因为它们是不透明的。方法和结果 在这里，我们优化并结合了多种成像技术，包括超声心动图、磁共振成像和微型计算机断层扫描，以识别和分析成年斑马鱼的心血管表型。使用 alk5a/tgfbr1a 突变体作为案例研究，我们观察到了常规方法无法检测到的形态和功能性心血管缺陷。多个参数的相关性分析揭示了血流动力学缺陷与心脏结构改变之间的关联，正如临床观察到的那样。结论 我们报告了一个新的、全面的、敏感的平台，用于识别成年斑马鱼中难以识别的心血管表型。转化视角 本研究进一步说明了斑马鱼模型对研究心血管表型的重要性，包括在人类疾病环境中观察到的形态和功能改变。