A new spin on an old model: in vivo evaluation of disease progression by magnetic resonance imaging with respect to standard inflammatory parameters and histopathology in the adjuvant arthritic rat.
OBJECTIVE
To noninvasively examine the pathogenesis of rat adjuvant-induced arthritis (AIA) by magnetic resonance imaging (MRI), and to correlate MRI indices of disease progression with classic inflammatory parameters and histologic evaluation.


METHODS
AIA was established in male Lewis rats following subcutaneous injection in the right hindpaw with 0.5 mg of heat-killed Mycobacterium butyricum suspended in light mineral oil. In vivo MRI evaluations of soft tissue and bony changes in AIA rats with matched histopathology were correlated with changes in left hindpaw volumes, circulating leukocytes, acute-phase reactants, and urinary collagen crosslinks throughout the disease process.


RESULTS
MRI of arthritic tibiotarsal joints of the uninjected left hindpaws from AIA rats demonstrated 2 distinct phases of disease activity. The first phase, apparent between days 10 and 18, was characterized by periarticular inflammation with marked synovitis, synovial fibroplasia, and distension of the joint capsule into the surrounding tissue. The secondary phase, occurring between days 18 and 30, was marked by continued soft tissue inflammation, periostitis with osteolysis, and periosteal new bone formation progressing to a state of near complete ankylosis by day 30. These 2 phases of disease activity observed by MRI paralleled biochemical, cellular, and histologic markers of disease progression.


CONCLUSIONS
MRI can be used to noninvasively detect, monitor, and quantify the chronic synovitis and progressive destruction of soft tissue and bone in live AIA rats, thereby improving the ability to evaluate disease progression in this preclinical animal model of rheumatoid arthritis.
Jacobson
P B
PB
Department of Diabetes and Metabolic Diseases, Abbott Laboratories, Abbott Park, Illinois 60064-6115, USA.
Morgan
S J
SJ
Wilcox
D M
DM
Nguyen
P
P
Ratajczak
C A
CA
Carlson
R P
RP
Harris
R R
RR
Nuss
M
M
D000818:Animals; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D007249:Inflammation / Q000000981:diagnostic imaging; D008279:Magnetic Resonance Imaging; D008297:Male; D011379:Prognosis; D011859:Radiography; D051381:Rats; D011917:Rats, Inbred Lew