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

项目摘要 慢性腰痛是美国一个重要的社会经济负担， 大约1000亿美元，因为工资损失和生产力下降。在缺乏结构性 异常或神经根性疼痛，腰痛的具体来源很难确定与目前可用的 临床技术，如体格检查、放射照相术和磁共振成像（MRI），导致 经常被诊断为"非特异性"背痛。因此，迫切需要改进 诊断背痛的临床工具的敏感性。腰椎间盘自然退化 随着年龄的增长，并牵连作为一个致病因素在腰痛。具体的功能性后果 然而，椎间盘退变及其与腰痛的关系还没有很好的定义。此外，虽然 对尸体椎间盘的广泛研究表明， 脊柱生物力学离体，有很少的努力来跟踪腰椎的体内功能。 我们对这项工作的总体假设是，腰椎的体内功能受到以下因素的影响 与年龄相关的椎间盘组成改变。我们的实验室开发了一种方法来动态跟踪元素 通过从MRI到双平面X射线照相的体积模型配准体内肌肉骨骼系统 图像.在这些实验中，我们将在模拟临床检查中检查年龄如何影响脊柱功能 （前屈），并作为日常生活活动（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为四个年龄组，开发他们腰椎的三维模型， 脊柱，然后将这些模型映射到其脊柱在前进过程中的实时射线照相数据。 屈曲，标准临床检查中用于评估背痛的运动。我们将评估脊椎的变化， 腰椎间盘突出与年龄有关。在特定目标2中，使用相同的无症状年龄组， 我们将在早上和晚上分别生成腰椎间盘的三维模型， 利用由于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 以及这些变化如何受到年龄的影响。在这两个目标中，我们将 MRI和椎间盘组成的血清/尿液生物标志物的机械参数。 最终，我们的目标是验证生物力学基准和生物标志物， 纯粹由于自然衰老而导致脊柱功能改变的患者与 因为疾病在这些研究中，我们将开发与年龄相关的腰椎改变的关键信息， 运动学和椎间盘功能。这些实验是未来工作的重要基础， 脊柱功能和脊柱病理之间的关系。

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.