Sodium magnetic resonance imaging of proteoglycan depletion in an in vivo model of osteoarthritis.
OBJECTIVE
The aim of the study was to investigate the feasibility of using sodium magnetic resonance imaging (MRI) as a noninvasive quantitative technique for measuring proteoglycan (PG) content in an in vivo porcine model of osteoarthritis (OA).


METHODS
Biochemical conditions similar to those of OA were created by an intra-articular injection of recombinant porcine interleukin-1beta (IL-1beta) into the knee joint of pigs (n = 6) before performing MRI. The contralateral knee joint was given a saline injection to serve as an internal control. Sodium MRI data were acquired on a 4-T clinical MR scanner and used to compute quantitative sodium and fixed charge density (FCD) maps based on a previously established methodology. In vivo FCD maps were compared with FCD maps obtained using ex vivo patellae harvested from the specimens. The tissue and joint fluid were subjected to histologic and immunohistochemical analyses as independent measurements of IL-1beta activity and PG loss.


RESULTS
The average FCD of IL-1beta-treated patellae was measured to be 49% lower than that of saline-treated patellae, indicating a loss of PG content. These results were supported by histologic and immunochemical findings, most notably a reduction in staining for PG and an increase in matrix metalloproteinases in the synovial fluid.


CONCLUSIONS
Sodium MRI can serve as a quantitative method to measure in vivo changes in PG content in an animal model of OA. The use of a noninvasive quantitative in vivo PG measurement technique such as sodium MRI on an animal model would aid greatly in efforts to monitor the efficacy of treatments for OA. Furthermore, these results indicate that early degenerative events could be detected noninvasively in vivo in humans with PG-depleting diseases such as OA.
Wheaton
Andrew J
AJ
Department of Radiology, University of Pennsylvania, B1 Stellar-Chance Laboratories, 422 Curie Blvd, Philadelphia, PA 19104-6100, USA.
Borthakur
Arijitt
A
Dodge
George R
GR
Kneeland
J Bruce
JB
Schumacher
H Ralph
HR
Reddy
Ravinder
R
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002358:Cartilage, Articular / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D017364:Collagenases / Q000378:metabolism; D004195:Disease Models, Animal; D007120:Immunochemistry; D007375:Interleukin-1 / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging* / Q000378:metabolism*; D010329:Patella / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D011509:Proteoglycans / Q000187:drug effects* / Q000378:metabolism*; D011856:Radiographic Image Enhancement; D012979:Sodium Radioisotopes / Q000378:metabolism; D013552:Swine
D015415:Biomarkers; D007375:Interleukin-1; D011509:Proteoglycans; D012979:Sodium Radioisotopes; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3