In vivo MRI of cartilage pathogenesis in surgical models of osteoarthritis.
OBJECTIVE
To examine in vivo time-course changes in macromolecular composition of articular cartilage in two surgical models of osteoarthritis (goat: meniscal transection and cartilage incision; rabbit: medial meniscectomy).


METHODS
Collagen integrity and proteoglycan (PG) content were evaluated in both models by magnetization transfer (MT) and contrast-enhanced MRI, respectively. The MT rate k(m) for the exchange process between the bulk water and water bound to collagen was determined as a marker of the collagen network. Local changes in cartilage fixed charge density, i.e., where PGs are depleted, were derived from T(1) relaxation maps as obtained after an infusion of Gd(DTPA)(2-), a paramagnetic agent.


RESULTS
In the goat model, the MT rate constant k(m) was significantly higher at 2 weeks post surgery, a possible sign of cartilage swelling, then decreased below baseline values, most likely indicative of disruption in the collagen framework. Meanwhile, post-Gd(DTPA)(2-) MRI acquisition indicated a significant and sustained loss of PGs. The rabbit model produced milder lesions. Although the difference was non-significant, k(m) steadily decreased in response to the surgical insult while kinetics of Gd(DTPA)(2-) uptake, after reaching a peak level at 6 weeks, were back to normal values after 12 weeks.


CONCLUSIONS
In the goat model, joint instability and cartilage damage was a permanent trigger for cartilage degeneration producing MRI changes. However, biomechanical stress due to partial medial meniscectomy in knees of mature rabbits produced only mild, focal lesions and PG depletion that was partially reversible. This proof-of-concept study identified MT and T(1) parameters as useful surrogate markers in animal models of osteoarthritis.
Laurent
Didier
D
Novartis Institutes for Biomedical Research, Inc., 250 Massachusetts Avenue, Cambridge, MA 02139, USA. didier.laurent@novartis.com
O'Byrne
Elizabeth
E
Wasvary
James
J
Pellas
Theodore C
TC
D000704:Analysis of Variance; D000818:Animals; D002358:Cartilage, Articular / Q000737:chemistry / Q000473:pathology*; D003287:Contrast Media; D005260:Female; D019786:Gadolinium DTPA; D006041:Goats; D008279:Magnetic Resonance Imaging / Q000379:methods*; D010003:Osteoarthritis / Q000473:pathology*; D011509:Proteoglycans / Q000737:chemistry; D011817:Rabbits
D003287:Contrast Media; D011509:Proteoglycans; D019786:Gadolinium DTPA