In vivo Mechanical Metrics for the Quantitative Assessment of Cartilage Health

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2019

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Abstract

Osteoarthritis (OA) is a common joint disorder, affecting over 27 million Americans. OA is characterized by the degeneration of cartilage tissue, and presents clinically with joint pain, stiffness, and limited range of motion. As such, it is a leading cause of disability in the United States. Current treatment options for OA focus on relieving pain (either pharmacologically or through surgical joint replacement), but do not treat or reverse cartilage degeneration. A main reason for this is that the diagnosis of OA depends on pain and radiographic findings, which are not present until advanced stages of the disease. Development of therapies focused on treating or reversing OA degeneration would therefore be enhanced if OA pathology was detectable at earlier stages of the disease. Because changes in mechanical properties (i.e. the stiffness and permeability) occur in OA cartilage before pain and radiographic features are visible, measurement of cartilage mechanics may be used for earlier assessment of OA degeneration. As cartilage mechanics are traditionally measured in the ex vivo environment, the goal of this dissertation was to develop a noninvasive methodology for measuring cartilage mechanical properties in vivo.

Specifically, the methodology consists of a combination of noninvasive magnetic resonance imaging (MRI) techniques to quantify in vivo cartilage composition and mechanical response, as well as a statistical model predicting cartilage stiffness based on these MRI measurements. Porcine knee joint cartilage was used to develop the statistical model, where stiffness was quantified in the traditional manner using ex vivo mechanical testing. The statistical model was then applied to in vivo data from a cohort of healthy human volunteers, for whom the noninvasive MRI techniques were used to measure the composition and mechanical response of their tibial cartilage. Thus, human tibial cartilage stiffness in vivo was quantified.

Overall, the in vivo estimates of healthy human tibial cartilage stiffness (ranging from 0.39 ± 0.05 MPa to 1.06 ± 0.24 MPa) compare well with ex vivo measurements of human cadaveric tibial cartilage stiffness (ranging from 0.45 ± 0.28 MPa to 0.65 ± 0.25 MPa). This finding supports the validity of the methodology developed in this dissertation. Future work using this in vivo methodology for measuring cartilage mechanical properties has diverse applications regarding cartilage health. For instance, this technique may be used clinically to provide earlier detection of OA pathology, or it may be used in future biomechanics research to evaluate the efficacy of different therapeutic approaches toward ameliorating OA pathology and restoring healthy cartilage mechanics. Therefore, the methodology for measuring cartilage mechanical properties in vivo developed here represents an important contribution to the fields of biomechanics and OA research.

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Cutcliffe, Hattie Christine (2019). In vivo Mechanical Metrics for the Quantitative Assessment of Cartilage Health. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/20101.

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