title: Optoacoustic imaging and staging of inflammation in a murine model of arthritis.
abstract: OBJECTIVE
  Rheumatoid arthritis (RA) is one of the most frequent inflammatory diseases, causing pain and disability in the affected joints. Early diagnosis is essential for the efficiency of symptom-targeting treatments, but its diagnosis requires careful clinical, serologic, and imaging examinations, such as magnetic resonance imaging (MRI), which is both expensive and time consuming. In an effort to provide the biomedical community with a more accessible way to assess the advancement of arthritis, this study sought to investigate the use of multispectral optoacoustic tomography (MSOT) in a murine arthritis model, to visualize the extent of inflammation in vivo through an L-selectin/P-selectin-targeting contrast agent.
  
  
  METHODS
  Mice with collagen-induced arthritis were studied as a model of RA. MSOT was performed using an L-selectin/P-selectin-targeting contrast agent, polyanionic dendritic polyglycerol sulfate (dPGS) labeled with a near-infrared (NIR) fluorophore, to increase the contrast of the arthritic joint. The signal intensity ratios between healthy legs and arthritic legs were calculated. Findings on contrast-enhanced MRI, clinical observations, the lymphocyte:granulocyte ratio, and histologic findings served as referents for comparison.
  
  
  RESULTS
  MSOT using an inflammation-targeting contrast agent, dPGS-NIR, allowed for accurate diagnosis of inflammation in the mouse joints. In addition, use of this technique resulted in significant differentiation of the inflamed joints from the healthy joints (P = 0.023). The observed advancement of arthritis on the MSOT images was confirmed by clinical observation, blood analysis, contrast-enhanced MRI, and ex vivo histologic examinations.
  
  
  CONCLUSIONS
  This study demonstrates that the combination of an inflammation-targeting contrast agent and optoacoustic tomographic imaging presents a promising means for the diagnosis of RA and the staging of arthritis-related inflammation.
authors.affiliation: Technische Universität München, Munich, Germany, and Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Beziere
authors.forename: C
authors.initials: C
authors.lastname: von Schacky
authors.forename: Y
authors.initials: Y
authors.lastname: Kosanke
authors.forename: M
authors.initials: M
authors.lastname: Kimm
authors.forename: A
authors.initials: A
authors.lastname: Nunes
authors.forename: K
authors.initials: K
authors.lastname: Licha
authors.forename: M
authors.initials: M
authors.lastname: Aichler
authors.forename: A
authors.initials: A
authors.lastname: Walch
authors.forename: E J
authors.initials: EJ
authors.lastname: Rummeny
authors.forename: V
authors.initials: V
authors.lastname: Ntziachristos
authors.forename: R
authors.initials: R
authors.lastname: Meier
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000175:diagnosis*; D003952:Diagnostic Imaging / Q000379:methods*; D004195:Disease Models, Animal; D007249:Inflammation / Q000175:diagnosis*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D061088:Photoacoustic Techniques