胸椎黄韧带骨化脊髓压迫模型的生物力学研究
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摘要
背景：
胸椎黄韧带骨化导致胸椎管狭窄症的主要病理类型之一，是由于韧带组织的病理性骨化致脊髓受压，进而出现一系列神经系统功能障碍。大量研究证明胸椎黄韧带骨化的发生与基因、生长因子、机械应力、分泌代谢等因素有关，但其病因仍不清楚。流行病学研究表明TOLF多发于亚洲黄种人，黑人及白人少见。
胸椎黄韧带骨化症状表现多样，除部分患者有胸腰椎局部疼痛外，最主要是脊髓受压之后产生的多样化的下肢表现，大部分患者主要表现为上行性发展的下肢麻木、僵硬及无力感，由于深感觉受损，还有可能出现步态不稳及胸腹部束带感。部分患者还可能出现胸部的扩张受限及背部持续的僵硬感，少数压迫严重患者出现大、小便和性功能障碍等。大多数患者可出现肌张力增高，腱反射亢进和病理反射阳性等典型的上位运动神经元损伤表现。但骨化位于下胸段及胸腰段的患者，由于脊髓圆锥以及腰膨大压迫症状。表现为特征性的下肢腱反射减弱或消失、肌肉萎缩、肌张力降低等表现。目前国内外普遍认为：对于TOLF引起的胸段脊髓或神经根压迫症状，手术减压是唯一有效的治疗措施。但手术治疗的效果并非都令人满意。这与多方面因素有关。
由于术前对于脊髓的受压情况只能通过影像学检查来了解，如骨化节段，骨化形状及大小等等。但具体的脊髓受压后所形态变化、应力分布及受力情况却很难得以评估。长期以来，脊髓相关生物力学研究一直鲜有报道。建立恰当的动物模型耗费许多人力物力。而计算机模拟实验模型如三维有限元模型则是一个较为理想的方法，三维有限元对复杂结构有较好适应性，模型建立后，可以模拟反复加载，可重复性好。并且随着现在有限元技术的不断改进及电子计算机技术的迅猛发展，对于脊髓这种柔软脆弱组织的分析也变得更精确、更快捷。
因此本课题通过应用三维有限元方法建立中胸段脊髓黄韧带压迫模型，在不同大小及类型的黄韧带骨化的压迫下，研究脊髓各个部位（包括脊髓白质前索、侧索、后索、灰质前角、后角）的应力变化，从生物力学角度研究黄韧带骨化的致病过程，探讨新的胸椎黄韧带骨化分类系统，为临床疾病的治疗提供参考。同时为临床术式的设计、分析及相关器械的研究奠定基础。
目的：
1、首先对胸椎黄韧带骨化患者术后的疗效进行了回顾性的分析，并且对可能的预后因素进行归纳总结。
2、建立中胸段脊髓三维有限元模型并进行有效性验证。
3、建立不同类型的黄韧带骨化压迫脊髓模型，分析脊髓内部应力及应变分布情况。结合临床及生物力学研究，建立新的胸椎黄韧带骨化分类系统。
方法：
1、回顾性研究自1998年l0月至2011年6月以来收治胸椎黄韧带骨化患者78例，病人术前病史及相关神经学查体均被详细记录。影像学检查包括患者术前常规胸椎正侧位，胸椎核磁共振（MRI）或胸椎三维CT重建。使用JOA（JapaneseOrthopedic Association）评分来进行术前术后神经功能的评估。改善率（Recoveryrate，RR）用来作为术后疗效的衡量标准。
2、查阅相关文献，图像收集、图像数字化处理、利用SolidWorks、Hypermesh和Abaqus有限元分析软件，通过调整相关材料参数，建立非线性的中胸段脊髓三维有限元模型（M0）。
3、在中胸段脊髓三维有限元模型（M0）的基础上，创建6种类型的骨化黄韧带压迫脊髓模型，包括：M1、M2及M3为单侧局部黄韧带骨化模型；M4为双侧局部黄韧带骨化模型；M5为在M4基础上的双侧融合的黄韧带骨化模型；M6为在M4基础上合并后纵韧带骨化的黄韧带骨化模型。最后进行脊髓的生物力学分析。
结果：
1、在至少一年的随访研究中，大部分病人术后症状都得到不同程度的改善，骨化区域（中胸椎）、MRI矢状面压迫度、术前症状持续时间及横轴位分型与术后RR显著相关。
2、建立了健康人中胸段脊髓的超弹性三维有限元模型M0。包含53346个单位，62348个节点。基本符合真实的生物力学要求，真实模拟了脊髓的材料特性。验证了模型的有效性，可进行临床和实验研究。
3、单侧局部黄韧带骨化模型中（M1-M3），骨化黄韧带压迫位于脊髓的侧后方，应力改变主要集中于压迫侧脊髓的侧后方及后方，包括脊髓白质的侧索后外侧和后索，以及灰质前角，当骨化压迫程度大于20%，脊髓健侧开始出现应力变化，当骨化压迫程度大于30%，脊髓内部应力明显增加。
4、双侧局部黄韧带骨化，由于脊髓缺乏足够的逃逸代偿空间，脊髓被压缩成前宽后窄的三角形，应变在双侧脊髓侧后索最明显。双侧融合型骨化（M5）直接作用于脊髓后方，脊髓被压成扁平状，后索应力明显增强，侧索，灰质应力也相应增强。合并后纵韧带骨化(M6)，脊髓前后受压，应力更为集中,脊髓内部应力明显增高。
5、提出新的分类系统，在横轴位上将骨化分为：①单侧型，②双侧型，③融合型；根据骨化压迫程度分为：①0%-20%，②20%-30%，③大于30%；根据是否合并后纵韧带骨化分为：①合并后纵韧带骨化，②不合并后纵韧带骨化；根据骨化区域分为：①中胸椎黄韧带骨化，②上、下胸椎黄韧带骨化。
结论：
1．建立了中胸段脊髓三维有限元模型。验证了模型的有效性，可进行临床与实验研究。
2．骨化黄韧带对脊髓的压迫程度以及双侧融合型黄韧带骨化与脊髓损伤的严重程度有着密切的关系，并且当骨化压迫程度大于30%，脊髓内部应力将明显增加。长期慢性脊髓压迫将会使脊髓内部应力增高，从而导致脊髓功能障碍，随着压迫逐渐加重，脊髓将发生不可逆性损伤，影响术后疗效。如果合并后纵韧带骨化也会使脊髓损伤加重。
3．MRI影像上髓内高信号改变多位于脊髓灰质，与术后疗效并无直接相关性。
4．结合临床及生物力学研究，建立了新的胸椎黄韧带骨化分类系统，根据四项指标进行评分，总分10分，当评分≥5分，手术风险将会增大，而当评分≥8分，手术难度及风险明显增加，术后瘫痪风险增高，预后可能较差，需做好充足的术前准备，术中操作必须谨慎。
Background:
Thoracic ossification of ligamentum flavum (TOLF) of the spine ischaracterized by a heterotopic bone formation in the thoracic ligamentum flavum,which causes slowly progressing spinal cord injury.
The most common symptoms of TOLF include unsteady steps, zonesthesia ofthe abdomen and lower limbs, difficulty with balance and climbing stairs, thepresence or absence of unilateral/bilateral neurogenic claudication, and bladder andbowel involvement are oberseved in the late stage disease. Physical examination ofthe lower extremities reveals both long tract signs and posterior column signs. Anon-operative treatment approach for symptomatic patients is not effective.Immediate surgical intervention and appropriate rehabilitation play important rolesin improving the functional outcomes of patients with myelopathy caused by TOLF.Surgical decompression is the most common treatment of choice for patients withcompressive myelopathy due to TOLF. However, the surgical outcome is not alwayssatisfactory.
Currently, Most studies of thoracic ossification of ligamentum flavumsyndrome focused on clinical aspects, few biomechanical studies have been found inthe literature because of the limitation of the routine experimental method. Thus,meaningful relationship between applied force, resultant deformation patterns andcorresponding tissue damage (functional and anatomical) remains elusive. There is aneed for the development of an analytical model of the spinal cord to supplementexperimental studies.Thus, we developed a computational three-dimensional (3D) FEM（Finite elementmethod）of middle thoracic spinal cord model compressed by thoracic ossifiedligamentum flavum. The intent of the FEM is to provide a computational model ofcompression as well as yield a normalized metric that bridges the gap betweenapplied loads and the severity/distribution of anatomical damage.
Objective:
1. To investigate the clinical features and prognostic factors of TOLF.
2. To create and validate a3D finite element model of middle thoracic spinal cordmodel compressed by thoracic ossified ligamentum flavum.
3. To study and compare the biomechanics of6different types of middle thoracicspinal cord model compressed by thoracic ossified ligamentum flavum, create a newclassification system of TOLF.
Methods:
1. To identify the predictors of surgical outcome, we retrospectively studied theassociations between various clinical and radiological parameters and postoperative recovery in78patients who underwent decompressive laminectomy for thoracicmyelopathy due to TOLF between October1998and June2011. Surgical outcomeswere assessed using modified Japanese Orthopedic Association (mJOA) recovery rate(RR)/outcome scores.
2. A three-dimensional, nonlinear finite element model of middle thoracic spinalcord(M0) was created. geometry generation of middle thoracic spinal cord wasperformed. The morphological data ofcervical cord was obtained from the literature.The commercially available finite element program SolidWorks, Hypermesh andAbaqus were applied to model the spinal segments.
3. Based on the finite element model of middle thoracic spinal cord, new models weregenerated by unilateral ossification of ligamentum flavum with10%ofcompression(M1); unilateral ossification of ligamentum flavum with20%ofcompression(M2); unilateral ossification of ligamentum flavum with30%ofcompression(M3); bilateral non-fused ossification of ligamentum flavum(M4);bilateral fused ossification of ligamentum flavum(M5); bilateral non-fusedossification of ligamentum flavum combined with ossification of the posteriorlongitudinal ligament. Finally, create a classification system of TOLF.
Results:
1. At a minimum of1year after surgery for TOLF treatment, the postoperativeclinical scores showed statistically significant changes with improvement in the JOAscores. The results indicated that a longer duration of preoperative symptoms,fused-type TOLF, and the degree of compression of the anteroposterior diameter andossified region (middle thoracic OLF) was related to poor prognosis.
2. A three-dimensional, nonlinear finite element model of middle thoracic spinal cordwith62348nodes and53346elements was created. Verification of the effectiveness ofthis finite element model were performed. The results indicated that this finite elementmodel of the spinal cord could be used for further biomechanical study.
3. In unilateral ossification of ligamentum flavum model(M1).The result showed thatthe stress were mainly located on the posterior funiculus and the medial part of lateralfuniculus in the white matter, anterior horn in the grey matter. At more than20%compression(M2), the stresses on the other side of the spinal cord increased. At morethan30%compression(M3), the stress distribution became much higher.
4. In bilateral ossification of ligamentum flavum model(M4), the stresses on bothsodes of gray matter, anterior funiculus, lateral funiculus, and posterior funiculus allincreased. In M5, the stress on posterior funiculus increased significantly. Whenossification of ligamentum flavum combined with ossification of the posteriorlongitudinal ligament, high stress distributions in the spinal cord were observed.
5. A new classification system of TOLF were devised based on four characteristics:1)axial configuration of TOLF,2) The degree of compression of the anteroposteriordiameter,3) combining with ossification of the posterior longitudinal ligament, and4)middle thoracic ossification of ligamentum flavum.
Conclusions:
1. The3D finite element middle thoracic spinal cord model was validated and couldbe used on biomechanical test.
2. The degree of compression of the anteroposterior diameter and fused type TOLFwas related to severity of neurological deterioration. At more than20%compression,the stresses on the other side of the spinal cord increased. At more than30%compression(M3), the stress distribution became much higher. When ossification ofligamentum flavum combined with ossification of the posterior longitudinal ligament,the stress distribution becomes much higher, potentially contributing to myelopathy.
3. A new classification system of TOLF were devised based on four characteristics. Acomposite severity score was calculated from these characteristics stratifying patientsinto different groups.
胸椎黄韧带骨化导致胸椎管狭窄症的主要病理类型之一，是由于韧带组织的病理性骨化致脊髓受压，进而出现一系列神经系统功能障碍。大量研究证明胸椎黄韧带骨化的发生与基因、生长因子、机械应力、分泌代谢等因素有关，但其病因仍不清楚。流行病学研究表明TOLF多发于亚洲黄种人，黑人及白人少见。
胸椎黄韧带骨化症状表现多样，除部分患者有胸腰椎局部疼痛外，最主要是脊髓受压之后产生的多样化的下肢表现，大部分患者主要表现为上行性发展的下肢麻木、僵硬及无力感，由于深感觉受损，还有可能出现步态不稳及胸腹部束带感。部分患者还可能出现胸部的扩张受限及背部持续的僵硬感，少数压迫严重患者出现大、小便和性功能障碍等。大多数患者可出现肌张力增高，腱反射亢进和病理反射阳性等典型的上位运动神经元损伤表现。但骨化位于下胸段及胸腰段的患者，由于脊髓圆锥以及腰膨大压迫症状。表现为特征性的下肢腱反射减弱或消失、肌肉萎缩、肌张力降低等表现。目前国内外普遍认为：对于TOLF引起的胸段脊髓或神经根压迫症状，手术减压是唯一有效的治疗措施。但手术治疗的效果并非都令人满意。这与多方面因素有关。
由于术前对于脊髓的受压情况只能通过影像学检查来了解，如骨化节段，骨化形状及大小等等。但具体的脊髓受压后所形态变化、应力分布及受力情况却很难得以评估。长期以来，脊髓相关生物力学研究一直鲜有报道。建立恰当的动物模型耗费许多人力物力。而计算机模拟实验模型如三维有限元模型则是一个较为理想的方法，三维有限元对复杂结构有较好适应性，模型建立后，可以模拟反复加载，可重复性好。并且随着现在有限元技术的不断改进及电子计算机技术的迅猛发展，对于脊髓这种柔软脆弱组织的分析也变得更精确、更快捷。
因此本课题通过应用三维有限元方法建立中胸段脊髓黄韧带压迫模型，在不同大小及类型的黄韧带骨化的压迫下，研究脊髓各个部位（包括脊髓白质前索、侧索、后索、灰质前角、后角）的应力变化，从生物力学角度研究黄韧带骨化的致病过程，探讨新的胸椎黄韧带骨化分类系统，为临床疾病的治疗提供参考。同时为临床术式的设计、分析及相关器械的研究奠定基础。
目的：
1、首先对胸椎黄韧带骨化患者术后的疗效进行了回顾性的分析，并且对可能的预后因素进行归纳总结。
2、建立中胸段脊髓三维有限元模型并进行有效性验证。
3、建立不同类型的黄韧带骨化压迫脊髓模型，分析脊髓内部应力及应变分布情况。结合临床及生物力学研究，建立新的胸椎黄韧带骨化分类系统。
方法：
1、回顾性研究自1998年l0月至2011年6月以来收治胸椎黄韧带骨化患者78例，病人术前病史及相关神经学查体均被详细记录。影像学检查包括患者术前常规胸椎正侧位，胸椎核磁共振（MRI）或胸椎三维CT重建。使用JOA（JapaneseOrthopedic Association）评分来进行术前术后神经功能的评估。改善率（Recoveryrate，RR）用来作为术后疗效的衡量标准。
2、查阅相关文献，图像收集、图像数字化处理、利用SolidWorks、Hypermesh和Abaqus有限元分析软件，通过调整相关材料参数，建立非线性的中胸段脊髓三维有限元模型（M0）。
3、在中胸段脊髓三维有限元模型（M0）的基础上，创建6种类型的骨化黄韧带压迫脊髓模型，包括：M1、M2及M3为单侧局部黄韧带骨化模型；M4为双侧局部黄韧带骨化模型；M5为在M4基础上的双侧融合的黄韧带骨化模型；M6为在M4基础上合并后纵韧带骨化的黄韧带骨化模型。最后进行脊髓的生物力学分析。
结果：
1、在至少一年的随访研究中，大部分病人术后症状都得到不同程度的改善，骨化区域（中胸椎）、MRI矢状面压迫度、术前症状持续时间及横轴位分型与术后RR显著相关。
2、建立了健康人中胸段脊髓的超弹性三维有限元模型M0。包含53346个单位，62348个节点。基本符合真实的生物力学要求，真实模拟了脊髓的材料特性。验证了模型的有效性，可进行临床和实验研究。
3、单侧局部黄韧带骨化模型中（M1-M3），骨化黄韧带压迫位于脊髓的侧后方，应力改变主要集中于压迫侧脊髓的侧后方及后方，包括脊髓白质的侧索后外侧和后索，以及灰质前角，当骨化压迫程度大于20%，脊髓健侧开始出现应力变化，当骨化压迫程度大于30%，脊髓内部应力明显增加。
4、双侧局部黄韧带骨化，由于脊髓缺乏足够的逃逸代偿空间，脊髓被压缩成前宽后窄的三角形，应变在双侧脊髓侧后索最明显。双侧融合型骨化（M5）直接作用于脊髓后方，脊髓被压成扁平状，后索应力明显增强，侧索，灰质应力也相应增强。合并后纵韧带骨化(M6)，脊髓前后受压，应力更为集中,脊髓内部应力明显增高。
5、提出新的分类系统，在横轴位上将骨化分为：①单侧型，②双侧型，③融合型；根据骨化压迫程度分为：①0%-20%，②20%-30%，③大于30%；根据是否合并后纵韧带骨化分为：①合并后纵韧带骨化，②不合并后纵韧带骨化；根据骨化区域分为：①中胸椎黄韧带骨化，②上、下胸椎黄韧带骨化。
结论：
1．建立了中胸段脊髓三维有限元模型。验证了模型的有效性，可进行临床与实验研究。
2．骨化黄韧带对脊髓的压迫程度以及双侧融合型黄韧带骨化与脊髓损伤的严重程度有着密切的关系，并且当骨化压迫程度大于30%，脊髓内部应力将明显增加。长期慢性脊髓压迫将会使脊髓内部应力增高，从而导致脊髓功能障碍，随着压迫逐渐加重，脊髓将发生不可逆性损伤，影响术后疗效。如果合并后纵韧带骨化也会使脊髓损伤加重。
3．MRI影像上髓内高信号改变多位于脊髓灰质，与术后疗效并无直接相关性。
4．结合临床及生物力学研究，建立了新的胸椎黄韧带骨化分类系统，根据四项指标进行评分，总分10分，当评分≥5分，手术风险将会增大，而当评分≥8分，手术难度及风险明显增加，术后瘫痪风险增高，预后可能较差，需做好充足的术前准备，术中操作必须谨慎。
Background:
Thoracic ossification of ligamentum flavum (TOLF) of the spine ischaracterized by a heterotopic bone formation in the thoracic ligamentum flavum,which causes slowly progressing spinal cord injury.
The most common symptoms of TOLF include unsteady steps, zonesthesia ofthe abdomen and lower limbs, difficulty with balance and climbing stairs, thepresence or absence of unilateral/bilateral neurogenic claudication, and bladder andbowel involvement are oberseved in the late stage disease. Physical examination ofthe lower extremities reveals both long tract signs and posterior column signs. Anon-operative treatment approach for symptomatic patients is not effective.Immediate surgical intervention and appropriate rehabilitation play important rolesin improving the functional outcomes of patients with myelopathy caused by TOLF.Surgical decompression is the most common treatment of choice for patients withcompressive myelopathy due to TOLF. However, the surgical outcome is not alwayssatisfactory.
Currently, Most studies of thoracic ossification of ligamentum flavumsyndrome focused on clinical aspects, few biomechanical studies have been found inthe literature because of the limitation of the routine experimental method. Thus,meaningful relationship between applied force, resultant deformation patterns andcorresponding tissue damage (functional and anatomical) remains elusive. There is aneed for the development of an analytical model of the spinal cord to supplementexperimental studies.Thus, we developed a computational three-dimensional (3D) FEM（Finite elementmethod）of middle thoracic spinal cord model compressed by thoracic ossifiedligamentum flavum. The intent of the FEM is to provide a computational model ofcompression as well as yield a normalized metric that bridges the gap betweenapplied loads and the severity/distribution of anatomical damage.
Objective:
1. To investigate the clinical features and prognostic factors of TOLF.
2. To create and validate a3D finite element model of middle thoracic spinal cordmodel compressed by thoracic ossified ligamentum flavum.
3. To study and compare the biomechanics of6different types of middle thoracicspinal cord model compressed by thoracic ossified ligamentum flavum, create a newclassification system of TOLF.
Methods:
1. To identify the predictors of surgical outcome, we retrospectively studied theassociations between various clinical and radiological parameters and postoperative recovery in78patients who underwent decompressive laminectomy for thoracicmyelopathy due to TOLF between October1998and June2011. Surgical outcomeswere assessed using modified Japanese Orthopedic Association (mJOA) recovery rate(RR)/outcome scores.
2. A three-dimensional, nonlinear finite element model of middle thoracic spinalcord(M0) was created. geometry generation of middle thoracic spinal cord wasperformed. The morphological data ofcervical cord was obtained from the literature.The commercially available finite element program SolidWorks, Hypermesh andAbaqus were applied to model the spinal segments.
3. Based on the finite element model of middle thoracic spinal cord, new models weregenerated by unilateral ossification of ligamentum flavum with10%ofcompression(M1); unilateral ossification of ligamentum flavum with20%ofcompression(M2); unilateral ossification of ligamentum flavum with30%ofcompression(M3); bilateral non-fused ossification of ligamentum flavum(M4);bilateral fused ossification of ligamentum flavum(M5); bilateral non-fusedossification of ligamentum flavum combined with ossification of the posteriorlongitudinal ligament. Finally, create a classification system of TOLF.
Results:
1. At a minimum of1year after surgery for TOLF treatment, the postoperativeclinical scores showed statistically significant changes with improvement in the JOAscores. The results indicated that a longer duration of preoperative symptoms,fused-type TOLF, and the degree of compression of the anteroposterior diameter andossified region (middle thoracic OLF) was related to poor prognosis.
2. A three-dimensional, nonlinear finite element model of middle thoracic spinal cordwith62348nodes and53346elements was created. Verification of the effectiveness ofthis finite element model were performed. The results indicated that this finite elementmodel of the spinal cord could be used for further biomechanical study.
3. In unilateral ossification of ligamentum flavum model(M1).The result showed thatthe stress were mainly located on the posterior funiculus and the medial part of lateralfuniculus in the white matter, anterior horn in the grey matter. At more than20%compression(M2), the stresses on the other side of the spinal cord increased. At morethan30%compression(M3), the stress distribution became much higher.
4. In bilateral ossification of ligamentum flavum model(M4), the stresses on bothsodes of gray matter, anterior funiculus, lateral funiculus, and posterior funiculus allincreased. In M5, the stress on posterior funiculus increased significantly. Whenossification of ligamentum flavum combined with ossification of the posteriorlongitudinal ligament, high stress distributions in the spinal cord were observed.
5. A new classification system of TOLF were devised based on four characteristics:1)axial configuration of TOLF,2) The degree of compression of the anteroposteriordiameter,3) combining with ossification of the posterior longitudinal ligament, and4)middle thoracic ossification of ligamentum flavum.
Conclusions:
1. The3D finite element middle thoracic spinal cord model was validated and couldbe used on biomechanical test.
2. The degree of compression of the anteroposterior diameter and fused type TOLFwas related to severity of neurological deterioration. At more than20%compression,the stresses on the other side of the spinal cord increased. At more than30%compression(M3), the stress distribution became much higher. When ossification ofligamentum flavum combined with ossification of the posterior longitudinal ligament,the stress distribution becomes much higher, potentially contributing to myelopathy.
3. A new classification system of TOLF were devised based on four characteristics. Acomposite severity score was calculated from these characteristics stratifying patientsinto different groups.
引文
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