Functional Exercise Response on osteoArthritis Relaxation Imaging
Functional Exercise Response on osteoArthritis Relaxation Imaging
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.
Group 1 Inclusion Criteria:

 -  Meets ACR criteria for OA Kellgren-Lawrence grade 2-3 on knee radiograph

 -  Neutral alignment

 -  Single symptomatic joint

 -  Aged 40-60 years old

 -  Ambulatory and in good general health

 -  Knee able to fit inside in-vivo knee coil (approx. 18 cm diameter)

 Group 2 Inclusion Criteria:

 -  No current symptoms of knee pain or stiffness or other clinical features of OA

 -  Aged 40-60 years old

 -  Written consent to participate in the study

 -  Ambulatory and in good general health

 -  Knee able to fit inside in-vivo knee coil (approx. 18 cm diameter)

 Exclusion Criteria for both groups:

 -  History of ipsilateral lower limb fracture

 -  History of ipsilateral lower limb surgery (including arthroscopy)

 -  Metabolic bone disease

 -  Inflammatory arthritis

 -  Haematological malignancy

 -  Paget's disease

 -  Bone metastases

 -  Contraindication to MR imaging (e.g. pacemaker, severe claustrophobia)

 -  No pregnant patients will be included

 -  Unable to consent