Data from: Characterization of regional left ventricular function in nonhuman primates using magnetic resonance imaging biomarkers: a test-retest repeatability and inter-subject variability study

Pre-clinical animal models are important to study the fundamental biological and functional mechanisms involved in the longitudinal evolution of heart failure (HF). Particularly, large animal models, like nonhuman primates (NHPs), that possess greater physiological, biochemical, and phylogenetic similarity to humans are gaining interest. To assess the translatability of these models into human diseases, imaging biomarkers play a significant role in non-invasive phenotyping, prediction of downstream remodeling, and evaluation of novel experimental therapeutics. This paper sheds insight into NHP cardiac function through the quantification of magnetic resonance (MR) imaging biomarkers that comprehensively characterize the spatiotemporal dynamics of left ventricular (LV) systolic pumping and LV diastolic relaxation. MR tagging and phase contrast (PC) imaging were used to quantify NHP cardiac strain and flow. Temporal inter-relationships between rotational mechanics, myocardial strain and LV chamber flow are presented, and functional biomarkers are evaluated through test-retest repeatability and inter subject variability analyses. The temporal trends observed in strain and flow was similar to published data in humans. Our results indicate a dominant dimension based pumping during early systole, followed by a torsion dominant pumping action during late systole. Early diastole is characterized by close to 65% of untwist, the remainder of which likely contributes to efficient filling during atrial kick. Our data reveal that moderate to good intra-subject repeatability was observed for peak strain, strain-rates, E/circumferential strain-rate (CSR) ratio, E/longitudinal strain-rate (LSR) ratio, and deceleration time. The inter-subject variability was high for strain dyssynchrony, diastolic strain-rates, peak torsion and peak untwist rate. We have successfully characterized cardiac function in NHPs using MR imaging. Peak strain, average systolic strain-rate, diastolic E/CSR and E/LSR ratios, and deceleration time were identified as robust biomarkers that could potentially be applied to future pre-clinical drug studies.

临床前动物模型是研究心力衰竭（HF）纵向演变过程中涉及的核心生物学与功能机制的重要工具。其中，非人类灵长类动物（NHPs）这类大型动物模型，因其与人类在生理、生化及系统发育层面具有更高的相似性，正日益受到关注。为评估此类模型向人类疾病研究的可转化性，影像学生物标志物在无创表型分析、下游重构预测以及新型实验性治疗手段评估中发挥着关键作用。本文通过量化磁共振（MR）成像生物标志物，深入解析了非人类灵长类动物的心脏功能，这些标志物可全面表征左心室（LV）收缩泵血与左心室舒张松弛的时空动态特征。研究采用MR标记成像与相位对比（PC）成像技术，量化了非人类灵长类动物的心肌应变与血流情况。本文呈现了旋转力学、心肌应变与左心室腔血流之间的时间关联，并通过重测重复性分析与受试者间变异性分析，对功能性生物标志物进行了评估。研究观察到的应变与血流时间趋势与已发表的人类相关数据具有一致性。我们的研究结果表明，心脏在收缩早期以基于心室维度的泵血为主导，而在收缩晚期则转为以扭转为主导的泵血模式。舒张早期以接近65%的解旋为特征，剩余的解旋过程可能助力心房收缩期实现高效充盈。数据显示，峰值应变、应变率、E/周向应变率（CSR）比值、E/纵向应变率（LSR）比值以及减速时间均表现出中等至良好的受试者内重复性。而应变不同步性、舒张期应变率、峰值扭转与峰值解旋速率则表现出较高的受试者间变异性。本研究成功通过磁共振成像表征了非人类灵长类动物的心脏功能。其中，峰值应变、平均收缩期应变率、舒张期E/CSR与E/LSR比值以及减速时间被确定为稳健的生物标志物，有望应用于未来的临床前药物研究。