Biomechanical Tolerance Criterion for the Spinal Cord

急性脊髓损伤 (SCI) 始于机械损伤，称为原发性损伤，然后是延长的生物反应，称为继发性损伤。过去十年的研究进展表明，在动物模型中，原发性损伤的特征（例如负荷率、方向）对 SCI 的模式和严重程度具有深远的影响。这些损伤的计算机模拟强调了这些机械效应对组织损伤的重要性。这些模拟作为预防伤害的设备和环境（例如头盔和汽车内饰）的设计工具具有巨大的潜力。不幸的是，这些计算机模型作为预测工具存在局限性。需要改进的主要领域包括脊髓组织建模（例如灰质与白质、各向异性）以及将机械响应与组织损伤相关联（即确定适当的耐受标准）。 该发现资助计划的总体目标是确定脊髓组织更好的耐受标准。具体目标是确定：1​​）脊髓灰质和白质的准静态材料特性； 2）脊髓灰质和白质的相对各向异性； 3) 与脊髓组织损伤最相关的机械标准（例如最大主应变）。拟议的研究是我目前的 NSERC 发现补助金的自然进展。 为了实现这些具体目标，将进行计算建模、体内实验和磁共振 (MR) 成像。对于对象。如图1和2所示，将使用定制的内部MR SCI装置和从变形脊髓获得的MR图像在大鼠体内产生相关SCI。图像分析将能够估计绳索中的应变模式。将使用逆有限元（FE）方法来确定灰质和白质的相对材料特性。对于 Obj 3，将生成三种类型的 SCI，并使用 FE 模型来预测具有几种可能的容差标准的损坏模式。 按照国际标准，该研究项目非常新颖。我们是使用体内模型解决生物力学变量方面的领导者，也是唯一能够在 MR 扫描仪孔内产生 SCI 的团队。我们对这些伤害进行计算建模的能力已经非常成熟，并且是这项拟议研究的重要组成部分。这项研究将增进我们对脊髓组织材料特性的理解，从而提高我们预测组织损伤的计算模型的质量。由于脊髓是中枢神经系统组织损伤的良好模型系统，因此这些结果可能会转化为脑损伤。这将有助于设计预防脊柱和脊髓损伤的环境（例如车内）。 我们为 HQP 提供了丰富的跨学科培训环境，我们预计在此时间范围内培训两名硕士生和两名博士生。

Acute spinal cord injury (SCI) begins with a mechanical insult, termed primary injury, followed by an extended biological response, called secondary injury. Research advances over the past decade show, in animal models, that features of the primary injury (e.g. loading rate, direction) have profound influences on the pattern and severity of SCI. Computer simulations of these injuries emphasized the importance of these mechanical effects on tissue damage. These simulations have great potential as design tools for devices and environments for injury prevention (e.g. helmets and automobile interiors). Unfortunately, there exist limitations with these computer models as predictive tools. The main areas for improvement include spinal cord tissue modelling (e.g. grey vs. white matter, anisotropy) and relating the mechanical response to tissue damage (i.e. identifying an appropriate tolerance criterion). The overall goal of this Discovery Grant program is to determine better tolerance criteria for spinal cord tissue. The specific objectives are to determine the: 1) quasi-static material properties of spinal cord grey and white matter; 2) relative anisotropy of spinal cord grey and white matter; and 3) mechanical criteria (e.g. max. principal strain) that best correlate with spinal cord tissue damage. The proposed research is a natural progression of my current NSERC Discovery Grant. To address these specific objectives, computational modelling, in vivo experiments, and magnetic resonance (MR) imaging will be conducted. For Obj. 1 and 2, relevant SCIs will be produced in vivo in rats using a custom intra-MR SCI device and MR images obtained of the deformed spinal cords. Image analysis will enable strain pattern estimation in the cord. Inverse finite element (FE) approaches will be used to determine the relative material properties of the grey and white matter. For Obj 3, three types of SCIs will be produced and the FE model used to predict damage patterns with several possible tolerance criteria. This research program is highly novel by international standards. We are leaders in addressing the biomechanical variables using an in vivo model, and the only group able to produce SCIs inside the bore of an MR scanner. Our ability to computationally model these injuries is well developed and an important component of this proposed research. This research will advance our understanding of the material properties of spinal cord tissue and thus will enhance the quality of our computational models in predicting tissue damage. As the spinal cord is a good model system for injury to central nervous system tissue, these results are likely translatable to brain injury. This will aid the design of environments (e.g. inside of a car) for the prevention of spine and spinal cord injuries. We have a rich, interdisciplinary training environment for HQP and we expect to train two MASc and two PhD students in this timeframe.