A new spin on an old model - In vivo evaluation of disease progression by magnetic resonance imaging with respect to standard inflammatory parametersand histopathology in the adjuvant arthritic rat

Objective. To noninvasively examine the pathogenesis of rat adjuvant-induce d arthritis (AIA) by magnetic resonance imaging (MRI), and to correlate MRT indices of disease progression with classic inflammatory parameters and hi stologic evaluation. Methods. AIA was established In male Lewis rats following subcutaneous inje ction in the right hindpaw with 0.5 mg of heat-killed Mycobacteriun butyric um suspended in light mineral oil, In vivo MRI evaluations of soft tissue a nd bony changes in ALA rats with matched histopathology were correlated wit h changes in left hindpaw volumes, circulating leukocytes, acute-phase reac tants, and urinary collagen crosslinks throughout the disease process. Results. MRI of arthritic tibiotarsal joints of the uninjected Left hindpaw s from AIA rats demonstrated 2 distinct phases of disease activity. The fir st phase, apparent between days 10 and 18, was characterized by periarticul ar inflammation with marked synovitis, synovial fibroplasia, and distension of the joint capsule into the surrounding tissue. The secondary phase, occ urring between days 18 and 30, was marked by continued soft tissue inflamma tion, periostitis with osteolysis, and periosteal new bone formation progre ssing to a state of near complete ankylosis by day 30, These 2 phases of di sease activity observed by MRI paralleled biochemical, cellular, and histol ogic markers of disease progression, Conclusion. MRI can be used to noninvasively detect, monitor, and quantify the chronic synovitis and progressive destruction of soft tissue and bone i n live AIA rats, thereby improving the ability to evaluate disease progress ion in this preclinical animal model of rheumatoid arthritis.