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Applying High Resolution X-Ray Microscopy to Reveal Microstructural Changes in Early-stage Osteoarthritic Knee Joint

dc.contributor.advisorGrandfield, Kathryn
dc.contributor.advisorTang, Tengteng
dc.contributor.authorSoomal, Harghun
dc.contributor.departmentBiomedical Engineeringen_US
dc.date.accessioned2025-05-23T18:50:18Z
dc.date.available2025-05-23T18:50:18Z
dc.date.issued2025
dc.description.abstractBackground: In Canada, osteoarthritis affects 4 million people and costs over 1.3 billion CAD annually in joint replacements. However, early detection remains a major challenge, as current clinical imaging tools cannot capture subtle tissue changes in the early stages, and the underlying mechanisms that drive disease progression are still not fully understood. Research Objectives: This thesis investigates microstructural changes in TMM-induced OA mouse models using high-resolution X-ray microscopy (XRM). It focuses on optimizing imaging and segmentation methods to assess cartilage thickness, bone architecture, and cell morphology, with the goal of improving early OA diagnostics through detailed tissue-level insights. Methodology: 6 Male C57BL/6 mice underwent TMM on the right knee at 8 weeks old. Two weeks later, operated and control contralateral knees were EpoFix resin embedded, harvested, and then imaged with XRM. Tissue components, including articular and calcified cartilage, subchondral bone plate, cortical and trabecular bone, and osteocytes and chondrocytes, were segmented using Attention U-Net deep learning. Cartilage thickness and cell volume changes were then quantified to assess tissue degradation. Results: High-resolution XRM analysis revealed early osteoarthritis-induced increases in osteocyte volume and altered spatial organization in the femur. Chondrocyte sphericity was preserved, but depth-dependent shifts in cell distribution were detected. Calcified cartilage thickness increased regionally, while articular cartilage and subchondral bone plate thicknesses remained stable. Bone morphometry showed subtle femoral-specific changes in cortical and trabecular regions. Conclusions and Future Work: High-resolution XRM enabled early detection of OA-related changes in joint morphology and cell organization, including osteocyte volume, chondrocyte distribution, and articular cartilage remodeling. Future work should explore comparative segmentation tools, regional cell density, and articular cartilage surface roughness, while expanding analysis beyond the early stages to better capture site-specific adaptations and improve OA diagnostics.en_US
dc.description.degreeMaster of Applied Science (MASc)en_US
dc.description.degreetypeThesisen_US
dc.description.layabstractKnee osteoarthritis (OA) is a progressive joint disease marked by early changes in cartilage and bone that are difficult to detect using traditional imaging methods. There is a growing need for high-resolution methodologies that can capture these subtle changes at the microstructural and cellular level shedding light into how OA develops and progresses. In response to these limitations, this thesis focuses on using phase contrast high-resolution X-ray microscopy (XRM) to visualize and quantify changes in mouse knee joints following total medial meniscectomy (TMM) surgery. Utilizing this technique, this research visualizes and quantifies changes in knee tissues, emphasizing cartilage and bone cell morphology, cell volume, and how cell volume varies with tissue depth. This research provides a deeper insight into the importance of early detection and offers a more comprehensive understanding of microstructural changes during the initial stages of osteoarthritis.en_US
dc.identifier.urihttp://hdl.handle.net/11375/31710
dc.language.isoenen_US
dc.titleApplying High Resolution X-Ray Microscopy to Reveal Microstructural Changes in Early-stage Osteoarthritic Knee Jointen_US
dc.typeThesisen_US

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