Browsing by Subject "T1rho"

It is possible to investigate in vivo musculoskeletal biomechanics using multimodal medical imaging techniques; however, the analysis of medical image sets is often time-prohibitive. In this dissertation, I outline various projects that utilize magnetic resonance imaging (MRI) scans acquired before and after exercise to quantify cartilage thickness changes incurred by the loading activity. A better understanding of cartilage mechanics is crucial for prediction and prevention efforts related to osteoarthritis, patellofemoral pain, and other musculoskeletal conditions. While this cartilage "stress test'' protocol has been used in the past to investigate knee, ankle, and spine mechanics, this work expands the methodology to the shoulder and hip joints and further addresses the impact of various exercises on the knee joint in different subject populations. For instance, I outline how patellofemoral cartilage deforms after a series of single-legged hops in anterior cruciate ligament-deficient and intact knees, how body mass index impacts patellofemoral cartilage strain and T1rho relaxation times in the context of walking, how tibial cartilage T1rho relaxation times change over the course of the day due to activities of daily living, and how pushups affect glenohumeral cartilage. I also discuss the development and validation of a semi-automated technique to isolate bones from MRIs, which reduces the time required for manual segmentation by approximately 75% and thus significantly improves research efficiency. As an expansion of the semi-automatic segmentation work, I will cover how I developed a technique to assess the minimum moment of inertia along the femoral neck from clinical computed tomography (CT) scans, with the goal of understanding relative fracture risks between individuals with and without diabetes. Finally, I quantify running-induced changes in knee cartilage thickness and composition (as measured by T1rho relaxation times), as well as changes in hip joint bone-to-bone distances and hip cartilage T1rho relaxation times. Running is a known activity linked to patellofemoral pain, yet the underlying etiology of this condition is unknown. As both knee and hip kinematics have been linked to patellofemoral pain, the goal was to assess how running influences these joints biomechanically and biochemically to better understand why people suffer from patellofemoral pain.

Osteoarthritis (OA) is a degenerative disease affecting articular cartilage, leading to loss of its structure and function. Early stage OA is characterized by changes in the extracellular matrix (ECM), including a reduction in proteoglycans (PG) concentration, increased water content within the tissue, and increased synthesis and degradation of matrix molecules with disorganization of collagen network [1, 2]. The ability to noninvasively quantify PG changes in cartilage would therefore be useful for early OA diagnosis, monitoring cartilage response to therapies, and assessing efficacy of cartilage repair procedures [3]. T1rho and T2 weighted magnetic resonance (MR) imaging techniques have been shown to have potential in tracking early biochemical compositional changes within cartilage associated with degeneration [3, 4]. Additionally, this method has the potential to be a powerful tool to better understand how cartilage responds to different loading environments both acutely and over time. The main objective of this work is to validate T1rho and T2 relaxation times as non-invasive measures for the assessment of biochemical and biomechanical properties of cartilage.

The first two studies presented in this work focus on the validation of this T1rho and T2 imaging for non-invasive cartilage assessment. The first study examines both normal and osteoarthritic cartilage containing both OA defect regions and healthy appearing areas. This study aims to comprehensively assess the relationship between OA cartilage composition, biochemical, and biomechanical properties with T1rho and T2 relaxation times in order to validate this technique as an in vivo diagnostic method for early stage OA. The second study utilizes targeted enzymatic depletion of both glycosaminoglycan (GAG) and collagen to determine the specific effect of each ECM component on T1rho and T2 relaxation times. A repeated measures design examines the effect of targeted enzymatic cartilage degradation (to isolate changes in cartilage biochemical composition, mechanical properties, and histology) on the T1rho and T2 relaxation times. These studies utilize confined compression for biomechanical analysis of cartilage, biochemical assays for the determination of S-GAG and collagen content, and histology for visualization of cartilage structure and composition. These measures are compared to the associated T1rho and T2 relaxation times. The results of these studies indicate that increases in T1rho relaxation times are correlated with S-GAG depletion, increased percent extractable collagen, decreases in mechanical strength of cartilage, and areas of OA defects (within which the previously mentioned biomechanical and biochemical conditions exist). Together, the results of these two studies validate T1rho and T2 quantitative imaging techniques for the in vivo diagnosis of early OA and the non-invasive assessment of cartilage biomechanical and biochemical properties.

Altered patterns of mechanical loading can result in morphological and compositional changes to cartilage that lead to cartilage degeneration. Quantitative MR imaging is a unique tool with the potential to provide insight into the relationship between biomechanics and the biophysical environment of cartilage, which is vital to better understanding the development of OA and degeneration of cartilage. The third study presented utilizes T1rho as a method for assessing localized changes to cartilage with dynamic activity. Sagittal MR images were obtained before and immediately after subjects completed a single legged hopping activity to dynamically load cartilage. A system of equally spaced grid points were registered to 3D surface mesh models of the tibial and femoral cartilage surfaces constructed from the MR images. T1rho relaxation times were then determined at each grid point to examine site-specific changes before and after exercise. A significant decrease in relaxation times was found after exercise in both the tibial plateau and the femoral condyle, with a greater decrease observed in the lateral femoral cartilage than in the medial femoral cartilage. No significant correlation between location and exercise was found. At each grid point, T1rho cartilage maps were also divided into superficial and deep regions of cartilage to determine where the greatest changes occurred. Ongoing analysis of the layer specific results will provide insight into where in the cartilage thickness these changes are most localized. The decrease in relaxation times after loading is likely due to the relative increase in PG content that results from the exudation of water from the cartilage ECM due to loading. This study demonstrates how T1rho may be used to non-invasively provide insight into the biophysical environment of cartilage with loading.

T1rho and T2 imaging represent a very powerful tool for the non-invasive assessment of articular cartilage. This work is significant in that it validates this method for the assessment of cartilage biomechanical and biochemical properties. Additionally, these methods can be used in future work to better understand how various risk factors contribute to OA development and to give valuable insight into the connection between biomechanical factors, biochemical composition, and the development of cartilage degeneration.