Walilko Timothy J, Sewsankar Kiran, Wagner Christina D, Podolski Alexandria, Smith Krista, Zai Laila, Bentley Timothy B
Applied Research Associates, Inc., Albuquerque, NM 87110, USA.
Brambleton, VA 20148, USA.
Mil Med. 2023 Mar 20;188(3-4):e600-e606. doi: 10.1093/milmed/usab410.
The Office of Naval Research sponsored the Blast Load Assessment Sense and Test program to develop a rapid, in-field solution that could be used by team leaders, commanders, and medical personnel to make science-based stand-down decisions for service members exposed to blast overpressure. Toward this goal, the authors propose an ensemble approach based on machine learning (ML) methods to derive a threshold surface for potential neurological deficits that encompasses the intensity of the blast events, the number of exposures, and the period over which the exposures occurred. Because of collection challenges presented by human subjects, the authors utilized data representing a comprehensive set of measures, including structural, behavioral, and cellular changes, from preclinical large animal studies on minipig models. This article describes the development process used to procure the resulting methodology from these studies.
Using an ensemble of ML methods applied to experimental data obtained from 71 Yucatan minipigs, the relationship between blast exposure and neurological deficits was delineated. Despite a relatively small sample size, ML methods with k-fold cross-validation (with k = 5) were justified because of the complexity of the dataset reflecting numerous nonlinear relationships between cellular, structural, and behavioral markers. Based on the physiological responses and environmental measures collected during the large animal study, two models were developed to investigate the relationship between multiple outcome measures and exposure to blast. The histological features model was trained on single-exposure animal data to predict a binary injury response (injured or not) using histological features. The environmental features model related the observed behavioral changes to the environmental parameters collected.
The histological features model predicted a binary injury outcome from cellular and physiological measurements. Features identified in developing this classification model showed some level of correlation to observed behavioral changes, suggesting that glial activation inflammation and neurodegenerative responses occur even at the lowest levels of blast exposures tested. The results of the environmental features model, which estimated injury risk from environmental blast exposure characteristics, suggested that the observed changes are not just a function of impulse but an average dynamic impulse rate. Noticeable behavioral deficits were observed at loading rates of 100 kPa (impulse/positive duration) or peak pressures of 300-350 kPa, with an approximate positive phase duration of 3.4 ms for single exposure. Based on this analysis, a 3D threshold surface was developed to characterize the potential risk of neurological deficits.
The ensemble approach facilitated the identification of a pattern of changes across multiple variables to predict the occurrence of changes in brain function. Many changes observed after blast exposure were subtle, making them difficult to measure in human subjects. ML methodologies applied to minipig data demonstrated the value of these techniques in analyzing complex datasets to complement human studies. Importantly, the threshold surface supports the development of science-based blast exposure guidelines.
美国海军研究办公室发起了“爆炸载荷评估传感与测试”项目,旨在开发一种快速的现场解决方案,供团队领导、指挥官和医务人员使用,以便为遭受爆炸超压的军人做出基于科学的停工决策。为实现这一目标,作者提出了一种基于机器学习(ML)方法的集成方法,以得出潜在神经功能缺损的阈值曲面,该曲面涵盖爆炸事件的强度、暴露次数以及暴露发生的时间段。由于人体受试者带来的数据收集挑战,作者利用了来自小型猪模型临床前大型动物研究的一组全面测量数据,包括结构、行为和细胞变化。本文描述了从这些研究中获得最终方法所使用的开发过程。
使用应用于从71只尤卡坦小型猪获得的实验数据的ML方法集成,描绘了爆炸暴露与神经功能缺损之间的关系。尽管样本量相对较小,但由于数据集的复杂性反映了细胞、结构和行为标记之间众多非线性关系,采用k折交叉验证(k = 5)的ML方法是合理的。基于大型动物研究期间收集的生理反应和环境测量数据,开发了两个模型来研究多个结果测量与爆炸暴露之间的关系。组织学特征模型在单次暴露动物数据上进行训练,以使用组织学特征预测二元损伤反应(受伤或未受伤)。环境特征模型将观察到的行为变化与收集的环境参数相关联。
组织学特征模型从细胞和生理测量中预测二元损伤结果。在开发此分类模型时确定的特征与观察到的行为变化显示出一定程度的相关性,这表明即使在测试的最低爆炸暴露水平下,也会发生胶质细胞活化炎症和神经退行性反应。环境特征模型的结果根据环境爆炸暴露特征估计损伤风险,表明观察到的变化不仅仅是冲量的函数,而是平均动态冲量率。在加载速率为100 kPa(冲量/正相持续时间)或峰值压力为300 - 350 kPa时观察到明显的行为缺损,单次暴露的正相持续时间约为3.4 ms。基于此分析,开发了一个三维阈值曲面来表征神经功能缺损的潜在风险。
集成方法有助于识别多个变量之间的变化模式,以预测脑功能变化的发生。爆炸暴露后观察到的许多变化很细微,难以在人体受试者中测量。应用于小型猪数据的ML方法证明了这些技术在分析复杂数据集以补充人体研究方面的价值。重要的是,阈值曲面支持基于科学的爆炸暴露指南的制定。