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

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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).