Online

Ramsdell, John Curtis

Electrical and Biomedical Engineering

2023

Ph. D.

The long-term consequence for many individuals who suffer ACL injury, especially when the meniscus suffers injury as well, is the development of early-onset osteoarthritis (OA), commonly referred to as post-traumatic OA (PTOA). Target therapies to reduce PTOA incidence are desperately needed, as upwards of 200,000 ACL injuries occur each year in the United States; however, therapeutic advancements are hindered by the lack of understanding for the mechanisms that drive PTOA onset and progression. A prevailing hypothesis is that post-surgical alterations to the injured knee's arthrokinematics (the way the cartilage surfaces of the femur and tibia articulate) introduce an unusual loading environment which drives cartilage degeneration and thus the onset and development of PTOA. While prior literature has revealed altered arthrokinematics and cartilage degeneration many years following surgery, the existence and timing of these alterations shortly after surgery are unknown mainly due to the limitations of traditional imaging approaches and the difficulty in comparing arthrokinematics with measures of cartilage degeneration. The first part of this work developed and validated an imaging approach for quantifying arthrokinematic measurements using model-based tracking (MBT) with a high-speed dual fluoroscopic imaging system. MBT is a time-consuming and semiautomatic approach, and thus subject to errors during the tracking process. This work was the first to quantify the effects that intra-user variability and interpolation, which may help speed up the MBT process albeit at the cost of fidelity, have on the arthrokinematic measurement accuracy using MBT. The second part of this work involved the development and assessment of quantitative magnetic resonance imaging (qMRI) parameters, T1[rho] and T2*, as biomarkers for the knee PTOA disease progression. With this work we quantified: 1) the repeatability (side-to-side and visit-to-visit) of qMRI measurements in phantoms and healthy knees, 2) the effect of region of interest size on the repeatability of qMRI measurements, and 3) the effects of acute loading via an MR-compatible loading device on qMRI measurements. The remainder of this work utilized the approaches from the first two parts to test the aforementioned hypothesis in a patient population 1-year following ACL reconstruction and meniscus repair or resection (ACLR+M). Side-to-side differences in arthrokinematic measurements were compared to side-to-side differences in qMRI measurements. Overall, the outcomes of this work define the capacity of our measurement systems to detect abnormalities in arthrokinematic and qMRI measurements. Furthermore, it provides us with evidence of arthrokinematic differences and signs of disease onset 1 year following ACLR+M. Ongoing work will quantify how these measurements change from 1 to 2 years. Ultimately, the results of this work will provide us with a better understanding of the mechanisms that drive PTOA, and will inform future therapeutics, such as new rehabilitation programs, aimed at slowing down or eliminating early changes in patients at high risk for PTOA.