Optical Tomography for the Diagnosis of Joint Diseases

描述（由申请人提供）： 这是一个有竞争力的更新应用程序，建立在以前NIH资助的项目的成就。该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，我们已经成功地实施和测试图像重建计划和仪器的光学断层成像的手指关节。使用这些代码和仪器，我们进行了临床试点研究与30例患者，以探讨诊断类风湿关节炎（RA）的可行性。我们发现，光学衍生的分类器可以发现，可以区分受影响和非受影响的关节，并与超声检查结果和临床检查。滑液变化提供光学对比度的最初假设似乎是正确的，然而，临床结果表明，正如最初预期的那样，情况更为复杂。根据我们的研究，我们现在认为，伴随RA的三个主要过程（渗出、糜烂和滑膜肥大（滑膜炎））可以通过光学断层扫描（OT）进行区分。这样做没有造影剂，OT承诺提供一个方便的，非侵入性的，经济的成像辅助现有的方式。然而，为了能够更好地区分这些不同的症状并尽早检测光学特性的最小变化，需要提高空间分辨率并增强光学吸收和散射效应之间的区分。该更新申请的主要假设是，这可以通过从稳态成像系统移动到频域成像设备来实现。具体而言，我们提出了以下三个具体目标：（1）开发基于模型的迭代图像重建代码，该代码使用三维频域辐射传输方程作为光在组织中传播的精确模型。这样的代码目前还不存在，但在小的几何形状，包括低散射和吸收系数的空洞状空间的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，以便在更短的时间内采集更多的数据点。通过人体工程学设计，该系统将对患者友好，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，量化光学断层成像检测RA三个主要方面（积液、糜烂和滑膜炎）的灵敏度和特异性。除了获得OT关节成像对比机制的基础知识外，我们将特别关注早期RA特征性症状的检测。新代码和改进的仪器的性能将与目前现有的系统进行比较。该提案的最终目标是为临床可行的关节成像仪奠定基础，该关节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.