Diffuse Optical Tomography of Osteoarthritis

描述（由申请人提供）： 骨关节炎（OA），或退行性关节病，是最常见的关节疾病形式。它是一种进展缓慢的疾病，是50岁以上人群发病的主要原因，影响了4000多万美国人。这也给医疗保健系统带来了相当大的开支。虽然目前没有治愈这种疾病的方法，但最近的研究表明，如果早期发现这种疾病，可以通过药物或手术干预来改变关节损伤的进展。这些研究加上基因治疗的最新进展，产生了大量的需求，用于检测关节的早期变化，当干预可能有其最大的效果非侵入性技术。X线摄影对于硬组织成像是极好的，并且已经成为检查OA的常规方式，主要用于晚期OA阶段。X射线的局限性在于其不能对关节中的软组织进行成像，以及其不能获得与OA功能相关的生理信息。扩散光学断层扫描（DOT）是一种很有前途的方法，用于检测软骨的变化和炎症过程中的滑膜。它还可以提供有关OA功能和进展的信息。然而，与X射线相比，DOT具有有限的空间分辨率。为了克服这一限制，在本申请中，我们提出了一个组合的X射线/DOT的方法，使我们可以使用的X射线图像作为结构的指导DOT重建。我们的目标是推进与3D X射线断层合成共配准的关节组织的3D DOT成像。我们的具体目标包括：（1）研究用于3D X射线成像的几种断层合成重建方法，（2）开发用于3D X射线图像分割的算法，（3）开发3D渲染环境，（4）先进的DOT重建方法，包括自动自适应网格化方案，并行计算和高阶扩散模型，（5）设计，用于关节组织的3D成像的组合数字X射线/光学成像系统的构造和测试，（6）使用组织模型实验的该系统的评估和优化，以及（7）在人类受试者中的组合X射线/光学成像系统的测试和评估。如果成功，所提出的多模态成像方法将对进行早期和适当的治疗干预、常规监测进展/临床结局和协助评估新治疗方式的能力产生重大影响。

DESCRIPTION (provided by applicant): Osteoarthritis (OA), or degenerative joint disease, is the most common form of joint diseases. It is a slowly progressing disease, and a major cause of morbidity in the population over 50, affecting more than 40 million Americans. It also imposes considerable expense on the health care system. While there is currently no cure for this disease, recent studies have shown that the progression of articular damage may be modified by medical or surgical intervention if the disease is detected early. These studies coupled with recent developments in gene therapy have generated substantial demand for noninvasive techniques for detecting early changes in the joints, when intervention is likely to have its greatest effect. X-ray radiography is excellent for imaging hard tissues and has been a routine modality for examining OA, primarily for advanced OA stages. The limitation of x-ray is its incapability for imaging soft tissues in the joints as well as its incapability for obtaining physiological information related to the functioning of OA. Diffuse optical tomography (DOT) is a promising method for detecting changes in cartilage and inflammation process in synovium. It can also provide information about the functioning and progression of OA. However, DOT has limited spatial resolution comparing to x-ray. To overcome this limitation, in this application we propose a combined x-ray/DOT approach so that we can use the x-ray images as structure guidance for DOT reconstruction. We aim to advance 3D DOT imaging of joint tissue co-registered with 3D x-ray tomosynthesis. Our specific aims include (1) investigation of several tomosynthetic reconstruction methods for 3D x-ray imaging, (2) development of algorithms for segmentation of 3D xray images, (3) development of 3D rendering environment, (4) advanced DOT reconstruction methods including automatic adaptive meshing scheme, parallel computing and a higher-order diffusion model, (5) design, construction and testing of a combined digital x-ray/optical imaging system for 3D imaging of joint tissue, (6) evaluation and optimization of this system using tissue phantom experiments, and (7) testing and evaluation of the combined xray/ optical imaging system in human subjects. If successful, the proposed mulfi-modality imaging method will have a major impact on the ability to make an early and appropriate therapeutic intervention, routinely monitor the progression/clinical outcome and assist in evaluating new treatment modalities.