A quantitative one-dimensional magnetic resonance imaging technique in adjuvant arthritis: the assessment of disease progression and indomethacin efficacy.
OBJECTIVE
To demonstrate the use of a one-dimensional proton (1H) nuclear magnetic resonance (NMR) imaging technique to noninvasively monitor the progression of adjuvant arthritis and its response to indomethacin treatment in Lewis rat leg joints.


METHODS
The total hydrogen content of a defined volume of the joint was quantitated at selected time points. The differences in proton T2 relaxation times allowed for characterization and quantitative separation of the fluid (relatively long T2) and nonfluid (relatively short T2) components of hydrogen content in the defined volume. The estimates of hydrogen content of both long and short T2 tissue components were used to assess the severity of the disease and its regression with indomethacin treatment.


RESULTS
A progressive increase of the 2 components of hydrogen content in saline treated arthritic rats is consistent with histological examinations. After 19 days of treatment, 0.1 mg/kg/day and 0.5 mg/kg/day of indomethacin reduced the fluid component (primarily from inflammatory edema) in arthritic leg joints by 39 and 77% respectively, compared to the saline treated arthritic rats. The higher dose of indomethacin also significantly reduced the nonfluid component (primarily from cellular content) suggesting a reduced influx of inflammatory cells into the affected areas. The paw volume measurements, radiologic changes, and histopathology also showed the regression of adjuvant arthritis on treatment.


CONCLUSIONS
The study demonstrated that the NMR method has the sensitivity required to assess the treatment efficacy in adjuvant arthritis and suggests its possible utility in early diagnosis and monitoring of therapy in clinical arthritis on human extremities.
Borah
B
B
Procter & Gamble Pharmaceuticals, Inc. (P&GP), Norwich, NY 13815, USA.
Francis
M D
MD
Hovancik
K
K
Boyce
J T
JT
Szeverenyi
N M
NM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000175:diagnosis* / Q000188:drug therapy; D001862:Bone Resorption / Q000175:diagnosis; D001842:Bone and Bones / Q000000981:diagnostic imaging; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005620:Freund's Adjuvant; D006614:Hindlimb / Q000473:pathology; D006859:Hydrogen / Q000032:analysis; D007213:Indomethacin / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010991:Plethysmography; D011859:Radiography; D051381:Rats; D011917:Rats, Inbred Lew; D012680:Sensitivity and Specificity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006859:Hydrogen; D005620:Freund's Adjuvant; D007213:Indomethacin