Zhou, QifaRayes, Adnan2025-06-172025-05https://hdl.handle.net/20.500.14154/75556Alterations in the mechanical properties of biological tissues, particularly stiffness, often emerge as early biomarkers of disease, preceding detectable morphological changes. Early and accurate characterization of tissue biomechanics is pivotal for improving diagnostic precision, monitoring disease progression, and guiding effective therapeutic interventions. However, existing non-invasive diagnostic techniques frequently lack the resolution and specificity necessary for precise biomechanical assessments, particularly for dynamic tissue properties that evolve over time. This underscores the critical need for dynamic, non-invasive tools capable of capturing temporal biomechanical variations across different biological structures. This thesis advances the application of Shear Wave Ultrasound Elastography (SWUE) for biomechanical assessments across multiple spatial scales, spanning from tissue-level structures (cartilage) to thrombus and down to the extracellular matrix (ECM). The primary goal is to utilize SWUE with high resolution and acquisition to be able detect displacement variations for application that not been widely studied, aiming for early diagnosis and treatment optimization based on mechanical property evaluation. Within a dynamic elastography framework, this work integrates a mechanical shaker for tissue excitation with a high-frequency ultrasound system for motion detection. Advanced signal processing techniques, including group velocity analysis, are employed to reconstruct the biomechanical properties of various biological structures. First, thrombus elasticity is quantified using SWUE to guide ultrasound-mediated thrombolysis for deep vein thrombosis (DVT). Shear wave speed (SWS) measurements inform the optimization of High-Intensity Focused Ultrasound (HIFU) treatment using a uniquely designed 3.2 MHz transducer with a small focal zone and adjustable power levels. Results reveal that thrombus stiffness strongly influences the acoustic power required for effective thrombolysis, with softer thrombi associated with higher hematocrit levels and stiffer thrombi necessitating greater acoustic energy. Second, cartilage degradation associated with osteoarthritis (OA) progression is characterized using SWUE. Cartilage samples subjected to enzymatic degradation, mechanical injury, and chemically induced subchondral bone changes model various OA stages. Elastography assessment demonstrates that surface and enzymatic degradation reduce SWS, indicating cartilage softening, whereas subchondral bone abnormalities elevate SWS. These findings support the potential of SWUE for early OA diagnosis through integrated mechanical and structural assessment. Third, the dynamic remodeling of the ECM induced by breast cancer cells is investigated. Three-dimensional collagen-based matrices seeded with highly invasive (MDA) and less invasive (MCF-7) breast cancer cells are measured using SWUE. Highly invasive cells demonstrated a clear ability to increase ECM stiffness over time across both 2 mg/mL and 4 mg/mL collagen concentrations, indicating active mechanical remodeling. In contrast, non- invasive cells showed reduced viability and no significant stiffness changes. Fluorescence imaging supported these findings, revealing persistent MDA cell growth and matrix interaction, while MCF-7 cells losses viability. These results highlight the mechanobiological differences between cancer cell types and emphasize the potential of elastography for monitoring dynamic ECM changes associated with tumor progression.110enUltrasound ElastographyShear WaveElasticityAdvanced Elastography in Biomedical Applications: Assessing Elasticity from Extracellular Matrix to TissueThesis