Optical Tomography for the Diagnosis of Joint Diseases

描述(由申请人提供)： 这是一项竞争性续签申请，建立在之前NIH资助的一个项目的成果基础上。这项研究的长期目标是开发一种光学断层成像模式，以帮助诊断、表征和监测关节疾病。为了实现这一目标，我们成功地实施并测试了手指关节光学断层成像的图像重建方案和仪器。使用这些编码和仪器，我们对30名患者进行了临床初步研究，以探索诊断类风湿关节炎(RA)的可行性。我们发现，可以找到光学派生的分类器，它可以区分受影响的关节和未受影响的关节，并且与超声检查和临床检查有很好的相关性。最初的假设，即滑液的变化提供光学对比似乎是正确的，然而，临床结果表明了一个更复杂的情况，正如最初预期的那样。基于我们的研究，我们现在认为，伴随RA的三个主要过程(渗出、侵蚀和滑膜肥大(滑膜炎))可以通过光学断层扫描(OT)来区分。在没有造影剂的情况下，OT有望为现有的设备提供一种方便、非侵入性和经济的成像附件。然而，为了能够更好地区分这些不同的症状并尽早检测到光学性质的最小变化，需要提高空间分辨率并加强光学吸收和散射效应之间的区分。这种更新应用的主要假设是，这可以通过从稳态成像系统转移到频域成像设备来实现。具体来说，我们提出了以下三个具体的目标：(1)开发了一种基于模型的迭代图像重建程序，该程序使用三维辐射传输的频域方程作为光在组织中传播的准确模型。这样的代码目前还不存在，但对于在包括具有低散射和吸收系数的类空洞空间的小几何图形中进行准确成像是必不可少的。(2)组装和优化频域电荷耦合器件(CCD)相机系统，使其能够在较短的时间内获取大量数据点。通过符合人体工程学的设计，该系统将是患者友好的，并与更快的数据采集一起，最大限度地减少运动伪影。(3)进行临床研究，以量化光学断层成像在检测RA的三个主要方面(渗出、侵蚀和滑膜炎)方面的敏感性和特异性。除了在OT联合成像中获得对比剂机制的基础知识外，我们还将特别关注早期RA的症状特征的检测。新代码和改进后的工具的性能将与目前的现有系统进行比较。这项建议的最终目标是为临床可行的关节成像仪奠定基础，该成像仪可用于后续研究的II期临床试验。

DESCRIPTION (provided by applicant): This is a competitive renewal application that builds on the achievements of a previously NIH funded project. The longterm goal of that study was and is to develop an optical tomographic imaging modality to assist in the diagnosis, chracterization, and monitoring of joint diseases. Towards that goal we have successfully implemented and tested image reconstruction schemes and instrumentation for optical tomographic imaging of finger joints. Using theses codes and instrumentation we have performed clinical pilot studies with 30 patients to explore the feasibility of diagnosing rheumatoid arthritis (RA). We showed that optically derived classifiers can be found that can distinguish between affected and non-affected joints and that correlate well with ultrasound findings and clinical examination. The initial hypothesis that changes in the synovial fluid provide optical contrast appeared to be true, however, the clinical results suggest a more complex scenario as initially expected. Based on our studies we now believe that three main processes (effusion, erosion, and hypertrophy of the synovial membrane (synovitis)) that accompany RA can be distinguished by optical tomography (OT). Doing so without contrast agents, OT promises to provide a convenient, non-invasive, and economical imaging adjunct to existing modalities. However, to be able to better distinguish between these different symptoms and detect smallest changes in optical properties as early as possible, one needs to improve the spatial resolution and enhance differentiation between optical absorption and scattering effects. The main hypothesis of this renewal application is that this can be achieved by moving from a steady-state imaging system to a frequency-domain imaging device. In detail, we propose the following three specific aims: (1) Develop a model-based iterative image reconstruction code that uses the three-dimensional frequency-domain equation of radiative transfer as an accurate model of light propagation in tissue. Such a code does currently not exist but is essential for accurate imaging in small geometries that include void-like spaces with low scattering and absorption coefficients. (2) Assemble and optimize a frequency-domain charge-coupled-device (CCD) camera system that allows for the acquisition of a larger number of data points in a shorter period of time. By being ergonometrically designed the system will be patient friendly and together with faster data acquisition minimizes movement artifacts. (3) Perform clinical studies that will allow quantifying the sensitivity and specificity of optical tomographic imaging with respect to detecting the three major aspects (effusion, erosion, and synovitis) of RA. Besides gaining fundamental knowledge on contrast mechanisms in OT joint imaging, we will specifically focus on detection of symptoms characteristic for early RA. The performance of the new code and improved instrumentation will be compared with the currently existing system. The ultimate goal of this proposal is to lay the groundwork for a clinical viable joint imager that can be used in a phase II clinical trial in i subsequent studies.