Functional Exercise Response on osteoArthritis Relaxation Imaging

Overview

Osteoarthritis (OA) is the most prevalent cause of mobility impairment and disability in the elderly. Indications at early stages of OA include decreased organisation of the collagen matrix, loss of proteoglycans and increased hydration. Late-stage joint disease can be diagnosed with X-ray, CT, and conventional MRI, but there are no validated methods to image early changes in cartilage microstructure, which are direly needed in early phase clinical development. Newly developed therapies and evaluation techniques are required at earlier stages of disease to offset the growing numbers and costs of end-stage disease. MRI can probe soft-tissue with physical measurements that are not available through other methods. Quantitative MRI signal relaxation properties are particularly promising for assessing early changes in the cartilage composition. These relaxation properties are sensitive to water content and cartilage macromolecular structure. Mechanical joint-loading and exercise affects quantitative MRI through cartilage compression and nonuniform deformation. A study measuring MRI relaxation times and using static joint-loading weights has shown differences between OA and healthy subjects. Cartilage volume, which is expected to be related to these relaxation times, recovers within an hour after exercise in healthy runners, with the menisci lagging in their volume recovery rate. Previous exercise studies have not measured post-exercise cartilage recovery using compositional techniques, such as physiologically-sensitive T1ρ and T2, nor probed compositional responses with OA subjects. The investigators will examine a single knee of an initial 18 participants with MR. Participants will be drawn from two groups: (1) 12 participants aged 40-60 years old with clinical and x-ray features of OA and (2) 6 control subjects (matched to cases for age, sex and body mass index in a 1:2 ratio) who do not have clinical features of OA. Participants will undergo an initial (baseline) MR examination, followed by repeat MR examinations at approximately 1 month and 1 year following the baseline examination. This will allow the investigators to explore the possibility of mechanical joint-loading and exercise to differentiate early stage OA from healthy subjects and assess both the reliability of the MR measurements and the expected progression in the MR measurements in OA subjects in the absence of any disease-modifying intervention.