Multi-modality Synchrotron X-ray Imaging as a Novel Platform for Imaging Joint Function in Response to Mechanical Stimuli

健康动物和人类的骨骼通常通过吸收老化或受损的组织并以新组织代替而恢复活力；这个过程叫做重塑。外部机械载荷会影响这一过程。在关节（如膝关节）中，关节所涉及的所有组织，如软骨、韧带、肌腱、滑膜、血管等，都可能影响或受适应过程的影响。任何这些组织的健康功能的破坏都会导致骨骼和其他组织的结构和功能变化。然而，除了肌肉和骨骼之间的相互作用外，我们对其他组织之间的相互作用知之甚少。此外，关节中哪个组织首先对机械刺激作出反应，反应能力如何，目前还不清楚。由于缺乏对软组织和致密组织都敏感的成像方法，2)提供高分辨率到细胞细节的成像方法，3)提供高质量（即高信噪比）的成像方法，以及4)三维（3D）的成像方法，对关节中所有组织的时空微观结构变化及其串扰的研究从未高细节地实现。本研究计划的长期目标是开发方法和工具，以了解定义关节中所有组织在响应外部机械刺激时相互关系的基本机制。同步加速器源系统是理想的，因为它的相干光束对软组织和骨骼都很敏感，在纳米尺度上具有非常高的分辨率，其单色性显著提高了图像质量，并且相关的层析成像技术是3D的。这项研究计划的短期目标是调查局限性，并开发或优化现有的基于同步加速器的x射线成像技术，以检测软组织的早期微观结构变化。改变的力传递（即适应）对关节相关变化的作用将被研究。此外，将开发新的成像技术，用于软骨和骨炎症在活体动物模型中的成像。揭示关节组织之间微观结构变化的相互关系将增加我们对健康关节如何功能，它们如何适应衰老过程以及损伤如何导致关节相关疾病的基本知识。主要申请人工作的加拿大光源是一个国家设施，因此在该研究计划中开发或优化的技术将为许多使用该设施的研究人员提供平台。此外，这项研究将影响新兴技术，如双能量计算机断层扫描（DECT）和非同步（多色）相位光栅成像（预计在十年内商业化），通过开发更敏感的图像采集和数据处理管道，用于早期检测软组织（如乳腺癌）的微观结构变化。

Bones of healthy animals and humans routinly undergo rejuvenation through resorption of aged or compromised tissue and replacing it with new tissue; a process called remodeling. External mechanical loads affect that process. In articulating joints (e.g., knee joint), all tissues involved in the joint such as, cartilage, ligaments, tendons, synovial membrane, blood vessels, etc. may affect, or be affected by, the adaptation process. Disruption in healthy function of any of those tissues leads to structural and functional changes in bone and other tissues. However, with the exception for muscle-bone interaction, very little is known about the cross talk among other tissues. Moreover, it is not known which tissue responds first to the mechanical stimulus in joint, and in what capacity. Investigating spatio-temporal micro-structural changes among all tissues in joints and their cross talk has never been achieved in high detail due to the lack of imaging methods that 1) are sensitive to both soft and dense tissues, 2) provide high resolution up to the cellular details, 3) provide high quality (i.e., high Signal-to-Noise Ratio, and 4) are three-dimensional (3D). The long-term goal of this research program is to develop the methods and tools to understand the fundamental mechanism(s) that defines the inter-relations of all tissues involved in a joint in response to external mechanical stimuli. A synchrotron source system is ideal for that purpose as its coherent beam is sensitive to soft tissues as well as bone, has very high resolution in nanometer scale, its monochromaticity significantly increases image quality, and the associated tomographic techniques are 3D. The short-term objectives of this research program are to investigate limits, and develop or optimize existing synchrotron-based X-ray imaging techniques for detecting early micro-structural changes in soft tissues. The role(s) of altered force transfer (i.e., adaptation) on the associated changes in a joint will be investigated. In addition, novel imaging techniques for imaging cartilage, and bone inflammation in live animal models will be developed. Unveiling the inter-relation of micro-structural changes among joint tissues will increase our fundamental knowledge of how healthy joints function, how they adapt to the aging process, and how injuries will lead to joint related disease. Canadian Light Source, where the principle applicant works, is a national facility, therefore techniques developed or optimized in this research program will serve as a platform for many of the researchers that use the facility. Furthermore, this research will affect emerging technologies such as Dual Energy Computed Tomography (DECT) and non-synchrotron (polychromatic) phase grating imaging (anticipated to be commercially available within a decade) by developing more sensitive image acquisition and data processing pipelines for early detection of micro-structural changes in soft tissues (e.g., breast cancer).