Experimental Cardiology, Baker Heart and Diabetes Institute , Melbourne, Victoria , Australia.
Baker Heart and Diabetes Institute , Melbourne, Victoria , Australia.
Am J Physiol Heart Circ Physiol. 2018 Jul 1;315(1):H58-H70. doi: 10.1152/ajpheart.00157.2018. Epub 2018 Apr 20.
Informal training in preclinical research may be a contributor to the poor reproducibility of preclinical cardiology research and low rates of translation into clinical research and practice. Mouse echocardiography is a widely used technique to assess cardiac structure and function in drug intervention studies using disease models. The interobserver variability of clinical echocardiographic measurements has been shown to improve with formalized training, but preclinical echocardiography lacks similarly critical standardization of training. The aims of this investigation were to assess the interobserver variability of echocardiographic measurements from studies in mice and address any technical impediments to reproducibility by implementing standardized guidelines through formalized training. In this prospective, single-site, observational cohort study, 13 scientists performing preclinical echocardiographic image analysis were assessed for measurement of short-axis M-mode-derived dimensions and calculated left ventricular (LV) mass. Ten M-mode images of mouse hearts acquired and analyzed by an expert researcher with a spectrum of LV mass were selected for assessment and validated by autopsy weight. After the initial observation, a structured formal training program was introduced, and accuracy and reproducibility were reevaluated. Mean absolute percentage error for expert-calculated LV mass was 6 ± 4% compared with autopsy LV mass and 25 ± 21% for participants before training. Standardized formal training improved participant mean absolute percentage error by ~30% relative to expert-calculated LV mass ( P < 0.001). Participants initially categorized with high-range error (25-45%) improved to low-moderate error ranges (<15-25%). This report reveals an example of technical skill training insufficiency likely endemic to preclinical research and provides validated guidelines for echocardiographic measurement for adaptation to formalized in-training programs. NEW & NOTEWORTHY The informal training common to academic/research institutions may be a contributor to the relatively poor reproducibility observed for preclinical cardiac research. In our observation of echocardiography analysis in murine models, we present evidence of moderate interobserver variability in standard preclinical research practice at an Australian heart research institute. These observations give rise to our recommendations for practical guidelines for echocardiography analysis in an adaptable approach to general preclinical research skill training. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/preclinical-echocardiography-training-and-guidelines/ .
非正规的临床前研究培训可能是导致临床前心脏病研究结果可重复性差和转化为临床研究及实践的比例低的原因之一。心脏超声心动图是一种广泛应用的技术,可用于在疾病模型中使用药物干预研究来评估心脏结构和功能。已经证明,临床超声心动图测量的观察者间变异性可以通过正式培训得到改善,但是临床前超声心动图缺乏类似的、关键的培训标准化。本研究的目的是评估在小鼠研究中超声心动图测量的观察者间变异性,并通过正式培训实施标准化指南来解决任何可能导致重现性受限的技术障碍。在这项前瞻性、单站点、观察性队列研究中,对 13 名进行临床前超声心动图图像分析的科学家进行了评估,以测量短轴 M 型衍生的二维尺寸和计算左心室(LV)质量。选择了由一位专家研究人员获取和分析的 10 张具有不同 LV 质量范围的小鼠心脏 M 型图像进行评估,并通过尸检重量进行验证。初始观察后,引入了结构化的正式培训计划,并重新评估了准确性和重现性。专家计算的 LV 质量的平均绝对百分比误差与尸检 LV 质量相比为 6 ± 4%,与培训前的参与者相比为 25 ± 21%。标准化的正式培训使参与者相对于专家计算的 LV 质量的平均绝对百分比误差提高了约 30%(P < 0.001)。最初被归类为高误差范围(25-45%)的参与者的误差范围降低到中低范围(<15-25%)。本报告揭示了一种可能普遍存在于临床前研究中的技术技能培训不足的实例,并提供了经过验证的超声心动图测量指南,以适应正式的培训计划。