Quantitative Assessment of Dynamic Joint Instabilities Using 4D CT Imaging

描述（申请人提供）：临床诊断腕关节异常运动的技术是高度主观的，假阳性率高。此外，常规x线检查不能证实动态腕关节不稳定。这是一个重要的临床问题，因为患有腕关节不稳定的个体会经历进行性退行性疾病，导致功能残疾和骨关节炎（OA）。相关的疼痛不仅使他们无法进行重要的职业任务，而且经常使他们无法进行简单的日常生活活动。然而，如果医生能够在早期诊断出动态关节不稳定，手术干预可以在关节炎或静态畸形发作之前恢复正常功能。因此，为了对临床结果产生关键影响，迫切需要一种能够早期发现功能性腕关节异常的方法。为了解决这一重大的公共健康问题，我们团队的长期目标是无创诊断和量化手腕的细微动态关节不稳定性，这些不稳定性只能在关节运动中观察到。我们已经证明，我们可以使用四维（4D； 3D +时间）CT成像技术来满足这一关键需求。基于我们成功的初步工作，我们的中心假设是我们可以使用4D CT成像技术非侵入性地确定腕骨的复杂运动路径。我们的目的是开发一种实用的4D CT检查，以检测由于舟月骨不稳定而导致的腕关节异常运动。具体来说，在目标1中，我们将开发一种强大的低剂量4D CT成像技术来成像手腕关节运动。我们的工作假设是，低剂量双源CT可以以类似于日常生活活动的速度提供无伪影的运动手腕图像。我们将开发生物力学运动装置，在尸体标本中检验这一假设，并确定最低辐射剂量水平。在目标2中，我们将使用尸体标本、基于光学的运动分析系统、图像配准技术和自定义运动模拟器来测量所开发技术的准确性和精度。最后，在Aim 3中，我们将确定无症状受试者和关节不稳定受试者的4D CT腕关节成像的临床可行性。该方案的创新之处在于使用了最先进的CT技术，提供了一种强大的低剂量成像技术，能够检测动态手腕关节的不稳定性。我们期待三个重要的结果：1)优化的低剂量临床CT技术用于腕部关节的量化，2)所开发技术的准确性和精度数据，以及3)首次在有症状和无症状的人类受试者中进行腕部关节的体内4D评估。这些数据将为量化规范和病理腕关节运动的临床试验提供基础。该建议的意义在于，通过早期诊断动态手腕关节不稳定，通过干预恢复正常运动，可以显著减少人类痛苦、生产力损失以及与手腕OA相关的个人和社会成本。

DESCRIPTION (provided by applicant): Clinical techniques to diagnose abnormal wrist joint motion are highly subjective and have a high false positive rate. Additionally, routine radiographic examinations cannot demonstrate dynamic wrist instabilities. This is a significant clinical problem, since individuals suffering from wrist joint instabilities experience progressive degenerative disease that leads to functional disabilities and osteoarthritis (OA). The associated pain prevents them not only from conducting important occupational tasks, but often simple activities of daily living. However, if physicians are able to diagnose dynamic joint instabilities at an early stage, surgical intervention can restore normal function before the onset of arthritis or static deformities. Thus, to have a critical impact on clinical outcomes, a method that allows early detection of functional wrist joint abnormalities is desperately needed. To address this significant public health problem, the long-term goal of our team is to non-invasively diagnose and quantify subtle dynamic joint instabilities of the wrist that can only be observed during joint motion. We have shown that we can meet this critical need using four-dimensional (4D; 3D + time) CT imaging techniques. Based on our successful preliminary work, our central hypothesis is that we can non-invasively determine the complex motion paths of the carpal bones using 4D CT imaging techniques. Our objective in this application is to develop a practical 4D CT examination to detect abnormal wrist joint motion occurring as a result of scapholunate instability. Specifically, in Aim 1, we will develop a robust low dose 4D CT imaging technique to image joint motion in the wrist. Our working hypothesis is that low dose dual-source CT can provide artifact-free images of the moving wrist, at velocities similar to those of activities of daily living. We will develop biomechanical motion devices to test this hypothesis in cadaveric specimens, and determine the minimum radiation dose levels. In Aim 2, we will measure the accuracy and precision of the developed techniques using cadaveric specimens, an optical-based motion analysis system, image registration techniques, and a custom motion simulator. Finally, in Aim 3, we will determine the clinical feasibility of 4D CT wrist joint imaging in asymptomatic subjects and subjects with joint instability. The innovation of this proposal is the use of state-of-the-art CT technology to provide a robust, low dose imaging technique capable of detecting dynamic wrist joint instabilities. We expect three important outcomes: 1) an optimized low dose clinical CT technique for the quantification of wrist articulation, 2) accuracy and precision data for the developed technique, and 3) the first in vivo 4D assessments of wrist joint articulation in both symptomatic and asymptomatic human subjects. These data will provide the foundation for clinical trials to quantify normative and pathologic wrist joint motion. The significance of this proposal is that by diagnosing dynamic wrist joint instabilities at an early stage, intervention to restore normal motion can markedly reduce the human suffering, loss of productivity, and personal and societal costs associated with OA of the wrist. PUBLIC HEALTH RELEVANCE: The goal of this proposal is to design a computed tomography exam (CT, or CAT scan) that can take highly-detailed pictures of the wrist joint while the patient is moving the joint. These three-dimensional movies of the patient's bones can be played back, looking at the joint from any angle, to let the physician see and measure exactly how the surfaces of the bones move. This is very important because abnormal joint motion, which is currently very hard to accurately diagnose, can lead to pain, arthritis or crippling deformities when left untreated.