Age-related alterations in the in vivo mechanical function of the spine

项目总结 慢性下腰痛在美国是一个重大的社会经济负担，它消耗 工资损失和生产力下降造成的损失约为1000亿美元。在缺乏总体结构的情况下 异常或神经根性疼痛，下腰痛的具体来源很难与目前可用的识别 体检、放射成像和核磁共振成像(MRI)等临床技术导致 经常被诊断为“非特异性”的背部疼痛。因此，迫切需要改进 临床诊断腰背痛工具的敏感性。腰间盘自然退变 随着年龄的增长，并被认为是导致下腰痛的一个因素。具体的功能后果 然而，椎间盘退变及其与下腰痛的关系还没有很好的定义。此外，虽然 对身体的椎间盘进行了广泛的研究，表明与年龄相关的退变影响 在脊柱生物力学的体外研究中，很少有人对腰椎的体内功能进行追踪。 我们对这项工作的总体假设是，腰椎的体内功能受到 与年龄相关的椎间盘成分改变。我们的实验室已经开发出一种动态跟踪元素的方法 通过配准从MRI到双平面X线片的体积模型来研究活体肌肉骨骼系统 图像。在这些实验中，我们将在模拟临床检查中检验年龄对脊柱功能的影响。 (前屈)和日常生活活动(ADL)的结果。在具体目标1中，我们将招募 无症状的人类参与者分成四个年龄组，建立他们的腰椎的三维模型 脊柱，然后在转发过程中将这些模型映射到其脊柱的实时X光照片数据 屈曲，一种在标准临床检查中用于评估背部疼痛的动作。我们将评估脊椎的变化 随着年龄的增长，腰椎位置和椎间的应变。在具体目标2中，使用相同的无症状年龄组， 我们将在早上和晚上分别建立腰椎间盘的三维模型， 利用ADL引起的椎间盘应变的自然波动。我们将评估椎间盘应变的变化 以及这些变化是如何受年龄影响的。在这两个目标中，我们将相互关联 MRI的力学参数和椎间盘成分的血/尿生物标记物。 最终，我们的目标是验证生物力学基准和生物标记物 单纯由于自然衰老导致脊柱功能改变的患者和功能改变的患者之间的差异 由于疾病。在这些研究中，我们将开发与年龄相关的腰椎改变的关键信息。 运动学和圆盘功能。这些实验是未来定义 脊柱功能与脊柱病理的关系。

PROJECT SUMMARY Chronic low back pain is a significant socioeconomic burden in the United States, one that consumes approximately $100 billion through lost wages and decreased productivity. In the absence of gross structural abnormalities or radicular pain, the specific source of low back pain is difficult to identify with currently available clinical techniques like physical examination, radiography and magnetic resonance imaging (MRI), leading to the oft-issued diagnosis of “non-specific” back pain. Thus, there is a pressing need to improve upon the sensitivity of clinical tools for diagnosing back pain. The lumbar intervertebral discs naturally degenerate with age and are implicated as a causative factor in low back pain. The specific functional consequences of disc degeneration and their relationship to low back pain are not well defined, however. Furthermore, while there has been extensive research on cadaveric human discs to show that age-related degeneration affects spine biomechanics ex vivo, there has been little effort to track the in vivo function of the lumbar spine. Our global hypothesis for this work is that the in vivo function of the lumbar spine is affected by age-related alterations in disc composition. Our lab has developed a method to dynamically track elements of the musculoskeletal system in vivo by registering volumetric models from MRI to biplanar radiographic images. In these experiments, we will examine how age affects spine function during a simulated clinical exam (forward flexion), and as a result of activities of daily living (ADL). In Specific Aim 1, we will recruit asymptomatic human participants into four age groups, develop three-dimensional models of their lumbar spines from MRI data, and then map those models to live radiographic data of their spine during forward flexion, a motion used in standard clinical exams to assess back pain. We will evaluate changes in vertebral position and intervertebral disc strain with age. In Specific Aim 2, using the same asymptomatic age groups, we will generate three-dimensional models of the lumbar discs in the morning and then again in the evening, taking advantage of the natural fluctuations in disc strain due to ADL. We will evaluate changes in disc strain over the course of the day and how these changes are affected by age. In both Aims, we will correlate mechanical parameters to MRI and serum/urine biomarkers of disc composition. Ultimately, we aim to validate biomechanical benchmarks and biomarkers that can discriminate between patients with altered spine function due purely to natural aging and those that have altered function due to disease. In these studies, we will develop critical information on age-related alterations in lumbar spine kinematics and disc function. These experiments are a critical foundation for future work in defining the relationships between spine function and spine pathology.