Data_Sheet_1_Correlation Analysis Between Magnetic Resonance Imaging-Based Anatomical Assessment and Behavioral Outcome in a Rat Contusion Model of Chronic Thoracic Spinal Cord Injury.docx

Although plenty of evidences from preclinical studies have led to potential treatments for patients with spinal cord injury (SCI), the failure to translate promising preclinical findings into clinical advances has long puzzled researchers. Thus, a more reliable combination of anatomical assessment and behavioral testing is urgently needed to improve the translational worth of preclinical studies. To address this issue, the present study was designed to relate magnetic resonance imaging (MRI)-based anatomical assessment to behavioral outcome in a rat contusion model. Rats underwent contusion with three different heights to simulate various severities of SCI, and their locomotive functions were evaluated by the grid-walking test, Louisville swim scale (LSS), especially catwalk gait analysis system and basic testing, and Basso, Beattie, Bresnahan (BBB) score. The results showed that the lesion area (LA) is a better indicator for damage assessment compared with other parameters in sagittal T2-weighted MRI (T2WI). Although two samples are marked as outliers by the box plot analysis, LA correlated closely with all of the behavioral testing without ceiling effect and floor effect. Moreover, with a moderate severity of SCI in a contusion height of 25 mm, the smaller the LA of the spinal cord measured on sagittal T2WI the better the functional performance, the smaller the cavity region and glial scar, the more spared the myelin, the higher the volatility, and the thicker the bladder wall. We found that LA significantly related with behavior outcomes, which indicated that LA could be a proxy of damage assessment. The combination of sagittal T2WI and four types of behavioral testing can be used as a reliable scheme to evaluate the prognosis for preclinical studies of SCI.

尽管临床前研究已积累大量证据，为脊髓损伤（spinal cord injury, SCI）患者催生了潜在治疗策略，但如何将颇具前景的临床前研究成果转化为临床治疗进展，始终是困扰科研人员的难题。因此，亟需建立更为可靠的解剖学评估与行为学测试联合方案，以提升临床前研究的转化价值。为解决这一问题，本研究旨在构建大鼠脊髓挫伤模型中，基于磁共振成像（magnetic resonance imaging, MRI）的解剖学评估与行为学结局之间的关联。研究者通过三种不同打击高度构建脊髓挫伤模型，以模拟不同严重程度的SCI，并采用网格行走试验、路易斯维尔游泳评分（Louisville swim scale, LSS）、猫步步态分析系统及基础功能测试，以及Basso、Beattie、Bresnahan（BBB）评分，对大鼠的运动功能进行评估。结果显示，相较于矢状位T2加权磁共振成像（sagittal T2-weighted MRI, T2WI）中的其他参数，损伤面积（lesion area, LA）是更优的损伤评估指标。尽管箱线图分析将两个样本标记为异常值，但LA与所有未出现天花板效应及地板效应的行为学测试结果均呈显著相关。此外，当打击高度为25 mm、脊髓损伤程度为中度时，矢状位T2WI测得的脊髓LA越小，大鼠运动功能恢复越好；脊髓空洞区域与胶质瘢痕越小，保留的髓鞘越多，膀胱活动波动性越高，膀胱壁越厚。本研究证实，LA与行为学结局显著相关，表明LA可作为脊髓损伤评估的替代指标。矢状位T2WI与四种行为学测试的联合方案，可作为评估SCI临床前研究预后的可靠体系。