Volume-normalized transfer constant as an imaging biomarker for chronic inflammatory arthritis: A dynamic contrast enhanced MRI study.
Proper diagnosis and treatment of rheumatoid arthritis are extremely important to optimize treatment outcomes. Dynamic contrast-enhanced MRI (DCE-MRI) may be used as a biomarker to detect inflammatory changes in synovial joints and to discriminate active and inactive stages of the disease. The aim of this study was to investigate vascular permeability changes associated with inflammatory arthritis progression and its treatment.



Arthritis was induced in DBA/1J mice by immunization with type-II collagen emulsified in complete Freund's adjuvant. Severity of arthritis was monitored using the clinical arthritis index. MR images of mice were obtained at different stages of arthritis progression and at 3 weeks after methotrexate treatment. Immunohistochemical staining using an anti-CD31 antibody was used to assess vessel density.



Volume-normalized transfer constant increased progressively until the active stage of arthritis was reached, and thereafter declined gradually. The pattern of volume-normalized transfer constant changes quantified using DCE-MRI correlated with vascular densities and immunohistochemical findings. Furthermore, volume-normalized transfer constant and densities decreased significantly in a dose-dependent manner after treatment with methotrexate.



Volume-normalized transfer constant assessed by DCE-MRI can be used as an imaging biomarker for tracking disease progression and for monitoring therapeutic efficacy in inflammatory arthritis. Magn Reson Med 76:926-934, 2016. © 2016 Wiley Periodicals, Inc.
Department of Molecular Medicine, Kyungpook National University School of Medicine, Daegu, Korea.|Department of Medical & Biological Engineering, Kyungpook National University, Daegu, Korea.|Department of Radiology, Kyungpook National University School of Medicine, Daegu, Korea.
Yongmin
Y
Chang
Department of Medical & Biological Engineering, Kyungpook National University, Daegu, Korea.
Jang Woo
JW
Park
Department of Internal Medicine (Rheumatology), Kyungpook National University School of Medicine, Daegu, Korea.
Shijin
S
Sung
Department of Internal Medicine (Rheumatology), Kyungpook National University School of Medicine, Daegu, Korea.
Jungwan
J
Hong
Department of Internal Medicine (Rheumatology), Kyungpook National University School of Medicine, Daegu, Korea.
Hasan
H
Al Faruque
Laboratory Animal Center, Osong Medical Innovation Foundation, Osong, Korea.
Eun-Hee
EH
Kim
Laboratory Animal Center, Osong Medical Innovation Foundation, Osong, Korea.
Jae Jun
JJ
Lee
Department of Radiology, Kyungpook National University School of Medicine, Daegu, Korea.
Jongmin
J
Lee
Department of Internal Medicine (Rheumatology), Kyungpook National University School of Medicine, Daegu, Korea.
Young Mo
0000-0002-7409-0729
YM
Kang
D000465:Algorithms; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000378:metabolism*; D015415:Biomarkers; D003198:Computer Simulation; D003287:Contrast Media / Q000493:pharmacokinetics; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008536:Meglumine / Q000493:pharmacokinetics*; D051379:Mice; D008811:Mice, Inbred DBA; D008954:Models, Biological; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D015415:Biomarkers; D003287:Contrast Media; D009942:Organometallic Compounds; D008536:Meglumine; C072417:gadoterate meglumine
angiogenesis; imaging biomarker; inflammatory arthritis; magnetic resonance imaging; vascular permeability