Rheumatoid arthritis (RA) is a debilitating inflammatory disease which results in 9 million physician visits and 250,000 hospitalizations per year. New molecularly-targeted pharmaceuticals are available to treat this disease, but clinical examination and conventional imaging do not accurately distinguish long-term responders from non-responders to these expensive therapies. We hypothesize that longitudinal information gained from high resolution MRI, CT and PET imaging of wrists of RA patients receiving therapy will be synergistic and thus, in combination will lead to the development of new imaging metrics that will help clinicians match clinical response with active joint disease. These metrics could potentially be used to separate responders to therapy from non-responders at early time points in the course of the disease. To test this hypothesis, we aim to use a unique high resolution extremity PET/CT scanner built by UC Davis researchers and a knee coil in a 1.5T MRI whole-body scanner. A multimodality wrist restraint system (WRS) has been designed and fabricated, and is used to immobilize the wrist during and between scans. Phantom experiments have been carried out for the scanners in the presence of the WRS. No apparent image degradation due to the WRS was observed. Images from the three modalities have been rigidly registered using a fiducial marker-based approach. A repositioning study was carried out in healthy volunteers using the MRI scanner. Results from this study examining repositioning error in wrist bones look promising. Instrumentation development has been completed and proof-of-principle scans have been carried out. A clinical trial in 10 patients for monitoring response in RA has been approved by IRB and recruiting has begun in early November.