NOVEL X-RAY TECHNOLOGY FOR DEGENERATIVE JOINT DISEASE

我们建议将生物医学（拉什医学院）和生物工程（伊利诺伊理工学院和麻省理工学院）方法结合起来，测试和完善一种用于关节病理诊断的新型x射线技术，特别是骨关节炎。该技术可以帮助开发用于预防和治疗关节疾病的疾病修饰剂和治疗策略。该项目采用了一种称为衍射增强成像（DEI）的新型同步加速器x射线技术，通过利用x射线的折射和散射抑制（消光），除了传统x射线照相的吸收外，还能获得比传统x射线照相更大的对比度。这项技术最初是为乳腺癌成像而开发的，以高对比度图像分析软组织，空间分辨率非常高（大于0.05mm）。虽然同步加速器目前用于DE成像，但原则上，该技术与DE成像无关。我们已经证明，DEI能够成像滑膜关节的正常和退化的关节软骨，显示出这种类型的成像的独特特征，使用与普通x线摄影相当的曝光时间。从第一年开始，我们将通过使用通过形态学、生化和生物物理分析获得的基质成分的生物概况，来解释通过我们的DEI方法获得的软骨和骨骼数据。在DE图像中观察到的一些特征不能立即用分子、化学或结构术语来解释。通过使用一种独特的综合实验方法，将生化和形态学组织特征与DE图像相关联，我们希望改进整个DEI系统，以检测关节疾病，并可能用于其他病理。我们将对人类和动物滑膜关节进行成像，并开始改进成像技术，以最佳地识别早期软骨病变。软骨退变的动物模型将特别用于软骨退变可见迹象之前的DE成像。从第二年开始，我们将在受控条件下对生物力学损伤的人体软骨进行成像，通过DE成像进行观察。我们还将开始开发新的DEI方法，以产生关于软骨组织特性的更全面信息的图像，首先用于平面，然后用于3D计算机断层扫描。在拟建项目的第一年到第五年，将有一个迭代的过程，将生物分析数据与成像数据进行比较，以改进关节组织的DEI技术。我们的长期目标是识别和定位软骨退变的初始阶段，并跟踪其进展，最终目的是监测疾病进展和治疗干预。

We propose a program to integrate biomedical (Rush Medical College) with bioengineering (Illinois Institute of Technology and Massachusetts Institute of Technology) approaches to test and refine a novel X-ray technology for the diagnosis of joint pathology, particularly osteoarthritis. This technology may aid in the development of disease modifying agents and treatment strategies for the prevention and treatment of joint diseases. This project utilizes a novel synchrotron x-ray technique called diffraction enhanced imaging (DEI) which derives dramatic gains in contrast over conventional radiographs by exploiting x-ray refraction and scatter rejection (extinction) in addition to the usual absorption of conventional radiography. This technique, originally developed for mammary carcinoma imaging analyzes soft tissue as high contrast images with very high (greater than 0.05mm) spatial resolution. Although the synchrotron is currently used for DE imaging, the technique is not, in principle, tied to it. We have already shown that DEI is capable of imaging normal and degenerated articular cartilage of synovial joints showing features unique to this type of imaging using exposure times comparable to those of ordinary radiography. Beginning in the first year, we will interpret the cartilage and bone data obtained through our DEI methodologies by using the biological profiles of the matrix components as garnered through morphologic, biochemical and biophysical analysis. Some of the features observed in the DE images are not immediately explainable in molecular, chemical or structural terms. By using a unique integrated experimental approach, correlating biochemical and morphological tissue profiles with DE images, we hope to refine the overall DEI system for the detection of joint disease and, potentially, for other pathologies. We will image human and animal synovial joints and begin the refinement of the imaging technique for the optimal identification of early cartilage lesions. Animal models of cartilage degeneration will be used particularly for DE imaging of cartilage prior to visible signs of degeneration. Beginning in year two, we will image human cartilage that has been biomechanically damaged under controlled conditions for observation through DE imaging. We will also begin developing new DEI methodologies to produce images conveying more comprehensive information about the properties of the cartilage tissue, first for planar and then for 3D computed tomography. Throughout years one through five of the proposed project, there will be an iterative process of comparing biological analytical data with imaging data for the refinement of the DEI technique for joint tissues. Our long-term goal is to identify and localize initial phases of cartilage degeneration and follow their progression with the ultimate aim of monitoring disease progression and therapeutic interventions.