In this longitudinal pilot study, magnetic resonance imaging (MRI) and Early Erosions in Rheumatoid Arthritis (EERA) software were used to quantify bone erosive damage in the metacarpophalangeal (MCP) 2-5 joints of the worst-affected hand (i.e. greatest swelling and tenderness at baseline) of patients with rheumatoid arthritis (n=35). Firstly, Spearman’s rho (rs) was used to evaluate the correlation between total change in sum erosive damage and change in functional ability, as well as the correlation between rate of change in sum erosive damage and change in functional ability. The rs (p-value) for total change and rate of change in sum erosive damage was 0.099 (0.585) and 0.104 (0.565), respectively. Therefore, the null hypothesis that neither variable was associated with change in functional ability could not be rejected. Participants were also classified into three groups based on total change in sum erosive damage (improvement, stable or progression) and were examined for possible differences in a variety of measures using an exploratory, non-statistical approach. Most notably, participants in the improvement group had more than five times the mean sum erosive damage at baseline compared to the progression group and also appeared to be the least aggresively medicated of the three cohorts. This study is the first to apply EERA in a way that helps to address clinically important questions related to change in erosive damage and functional ability. Future studies should use the ideas and concepts generated in this pilot study to further explore the use of this highly reproducible erosion quantification software, with the ultimate goal of expanding the applications of EERA in both the research and clinical settings. / Thesis / Master of Science (MSc) / In this study, the hands of patients with rheumatoid arthritis (RA) were assessed using magnetic resonance imaging (MRI) to investigate how erosive damage to the bone changes over time. Specialized computer software entitled Early Erosions in Rheumatoid Arthritis (EERA) was used to perform this analysis. Firstly, change in erosive damage was not found to be related to change in functional ability (e.g. eating, grip, etc.). Secondly, it appeared that individuals who demonstrated improvement in bone damage over time had significant damage at the beginning of the study period. Overall, this study provides new information for researchers and clinicians in terms of how this unique software can be used to enhance our understanding of RA. Future studies will continue to explore ways in which this software can be applied to address questions that are important to RA patients.

Introduction Disease monitoring in rheumatoid arthritis (RA) can be improved by incorporating imaging technologies. Clinical examination fails to detect subclinical inflammation in half of metatarsophalangeal joints (MTPJs), but the effectiveness of using ultrasonography (US) in MTPJs is unclear. We aimed to evaluate US assessment of disease activity in the MTPJs using MRI as the reference standard, in comparison to clinical examination. Methods Patients newly diagnosed with RA (ACR criteria) were recruited and assessed at baseline, 6 weeks, 3 months, 6 months, and 12 months. A rheumatologist assessed the MTPJs 2-5 bilaterally for swelling and tenderness (presence=1), and for erosion (presence=1), synovial thickening, and power Doppler (PD) by US. Synovial thickening and PD were graded semi-quantitatively (grade 0-3). The most clinically symptomatic foot was scanned using extremity MRI (1.0T) at the baseline and 12-month visits. MTPJs 2-5 were graded semi-quantitatively for synovitis, bone marrow edema (BME) (grade 0-3), and erosions (grade 0-10). Results Forty-one patients were recruited (mean (SD) age=51.9 (10.3) years, 81% female). Kappa agreement was moderate between PD and grade ≥2 synovitis (k=0.46) and BME (k=0.47), but poor agreement was found for clinical examination and synovial thickening. US was able to visualize subclinical inflammation in 41% of non-swollen joints. After 12 months, the average total score for synovial thickening, PD, and BME all significantly decreased, but not swollen or tender joint counts. US visualized few erosions (n=8) compared to MRI (n=101) in the most symptomatic foot. MRI observed erosion repairs in patients treated with DMARDs, and repairs appeared to be preferential for MTPJs that had low inflammation seen by US. Conclusion US appears to better visualize MTPJ inflammation than swollen and tender joint counts, and may be used in combination with clinical examination to improve routine disease monitoring in RA. / Thesis / Master of Science (MSc) / Current assessment of rheumatoid arthritis (RA) relies on physical examination for joint swelling and tenderness, but these methods often miss underlying inflammation. Ultrasonography (US) may help improve the diagnosis and monitoring of disease activity, but its effectiveness in imaging the feet is unclear. With MRI (another imaging technology) as the standard of reference, we compared the use of physical examination and US in assessing inflammation in the feet, and explored the potential of using US to see damage to bones. In 41 patients with early RA (<2 years of disease), US was able to detect inflammation in many joints that appeared normal, and was better at detecting decreased inflammation over 1 year than physical examination. Although US was limited at assessing early bone damage, it was able to see several large erosions. In conclusion, US can better visualize disease activity than clinical examination and can improve RA assessments.

<p>Rheumatoid arthritis (RA) is a systemic disease that can affect the nervous system, lungs, heart, skin, reticuloendothelium and joints. Currently, the gold-standard measurement for tracking the progression of the disease involves a semi-quantitative assessment of bone erosion, bone marrow edema and synovitis, as seen in magnetic resonance (MR) images, by a musculoskeletal radiologist. The work presented in this thesis identifies how computer automation can be used to quantify bone erosion volumes in MR images without a radiologists' expert and time consuming intervention. A new semi-automated hybrid segmentation algorithm that combines two established techniques: region growing and level-set segmentation, is described and evaluated for use in a clinical setting. A total of 40 participants with RA were scanned using a 1-Tesla peripheral MR scanner. Eight of the participant scans were used to train the algorithm with the remaining used to determine the accuracy, precision, and speed of the technique. The reproducibility of the hybrid algorithm and that of manual segmentation were defined in terms of intra-class correlation coefficients (ICCs). Both techniques were equally precise with ICC values greater than 0.9. According to a least squares fit between erosion volumes obtained by the hybrid algorithm with those obtained from manual tracings drawn by a radiologist, the former was found to be highly accurate ( m=1.030, b=1.385: r-squared=0.923). The hybrid algorithm was significantly faster than manual segmentation, which took two to four times longer to complete. In conclusion, computer automation shows promise as a means to quantitatively assess bone erosion volumes. The new hybrid segmentation algorithm described in this thesis could be used in a clinical setting to track the progression of RA and to evaluate the effectiveness of treatment.</p> / Doctor of Philosophy (PhD)