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Quantitative Evaluation of 3D Mouse Behaviors and Motor Function in the Open-Field after Spinal Cord Injury Using Markerless Motion Tracking

机译:使用无标记运动跟踪对脊髓损伤后开放视野中的3D鼠标行为和运动功能进行定量评估

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摘要

Thousands of scientists strive to identify cellular mechanisms that could lead to breakthroughs in developing ameliorative treatments for debilitating neural and muscular conditions such as spinal cord injury (SCI). Most studies use rodent models to test hypotheses, and these are all limited by the methods available to evaluate animal motor function. This study’s goal was to develop a behavioral and locomotor assessment system in a murine model of SCI that enables quantitative kinematic measurements to be made automatically in the open-field by applying markerless motion tracking approaches. Three-dimensional movements of eight naïve, five mild, five moderate, and four severe SCI mice were recorded using 10 cameras (100 Hz). Background subtraction was used in each video frame to identify the animal’s silhouette, and the 3D shape at each time was reconstructed using shape-from-silhouette. The reconstructed volume was divided into front and back halves using k-means clustering. The animal’s front Center of Volume (CoV) height and whole-body CoV speed were calculated and used to automatically classify animal behaviors including directed locomotion, exploratory locomotion, meandering, standing, and rearing. More detailed analyses of CoV height, speed, and lateral deviation during directed locomotion revealed behavioral differences and functional impairments in animals with mild, moderate, and severe SCI when compared with naïve animals. Naïve animals displayed the widest variety of behaviors including rearing and crossing the center of the open-field, the fastest speeds, and tallest rear CoV heights. SCI reduced the range of behaviors, and decreased speed (r = .70 p<.005) and rear CoV height (r = .65 p<.01) were significantly correlated with greater lesion size. This markerless tracking approach is a first step toward fundamentally changing how rodent movement studies are conducted. By providing scientists with sensitive, quantitative measurement methods, subjectivity and human error is reduced, potentially providing insights leading to breakthroughs in treating human disease.
机译:成千上万的科学家努力寻找可能导致开发改善神经和肌肉疾病(如脊髓损伤(SCI))的改善疗法的突破的细胞机制。大多数研究使用啮齿动物模型来检验假设,而这些都受到可用于评估动物运动功能的方法的限制。这项研究的目的是在SCI鼠模型中开发一种行为和运动评估系统,通过使用无标记运动跟踪方法,可以在开阔地自动进行定量运动学测量。使用10台摄像机(100 Hz)记录了八只幼稚,五只轻度,五只中度和四只严重SCI小鼠的三维运动。在每个视频帧中都使用了背景减法来识别动物的轮廓,并使用“从轮廓形状”来重建每次3D形状。使用k均值聚类将重建的体积分为前半部分和后半部分。计算动物的前额体积中心(CoV)高度和全身CoV速度,并用于对动物行为进行自动分类,包括定向运动,探索性运动,蜿蜒,站立和站立。对定向运动过程中CoV高度,速度和侧向偏差的更详细分析显示,与单纯动物相比,患有轻度,中度和重度SCI的动物的行为差异和功能受损。幼稚的动物表现出最广泛的行为,包括饲养和越过旷野的中心,最快的速度以及最高的后冠状病毒高度。 SCI减少了行为范围,并且速度下降(r = 0.70 p <.005)和后冠状动脉高度降低(r = 0.65 p <.01)与更大的病变大小显着相关。这种无标记跟踪方法是从根本上改变啮齿动物运动研究方式的第一步。通过为科学家提供灵敏的定量测量方法,可以减少主观性和人为错误,从而有可能提供洞见,从而在治疗人类疾病方面取得突破。

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