title: Preclinical Evaluation of Photoacoustic Imaging as a Novel Noninvasive Approach to Detect an Orthopaedic Implant Infection.
abstract: BACKGROUND
  Diagnosing prosthetic joint infection (PJI) poses significant challenges, and current modalities are fraught with low sensitivity and/or potential morbidity. Photoacoustic imaging (PAI) is a novel ultrasound-based modality with potential for diagnosing PJI safely and noninvasively.
  
  
  METHODS
  In an established preclinical mouse model of bioluminescent Staphylococcus aureus PJI, fluorescent indocyanine green (ICG) was conjugated to β-cyclodextrin (CDX-ICG) or teicoplanin (Teic-ICG) and injected intravenously for 1 week postoperatively. Daily fluorescent imaging and PAI were used to localize and quantify tracer signals. Results were analyzed using 2-way analysis of variance.
  
  
  RESULTS
  Fluorescence clearly localized to the site of infection and was significantly higher with Teic-ICG compared with CDX-ICG (P = 0.046) and ICG alone (P = 0.0087). With PAI, the photoacoustic signal per volumetric analysis was substantially higher and better visualized with Teic-ICG compared with CDX-ICG and ICG alone, and colocalized well with bioluminescence and fluorescence imaging.
  
  
  CONCLUSIONS
  Photoacoustic imaging successfully localized PJI in this proof-of-concept study and demonstrates potential for clinical translation in orthopaedics.
authors.affiliation: From Washington University, St. Louis, MO (Dr. Wang), Johns Hopkins University School of Medicine, Baltimore, MD (Dr. Thompson), the University of California, Los Angeles, Los Angeles, CA (Ms. Ashbaugh), École Polytechnique Fédérale de Lausanne (Dr. Khodakivskyi and Dr. Dubikovskaya) and Intrace Medical SA (Dr. Budin and Dr. Sinisi), Lausanne, Switzerland, FUJIFILM VisualSonics, Toronto, Ontario, Canada (Mr. Heinmiller), the University of Groningen, Groningen, The Netherlands (Dr. van Oosten, Dr. van Dijl, and Dr. van Dam), PerkinsElmer, Waltham, MA (Dr. Francis), Ronald Reagan University of California, Los Angeles Medical Center, Santa Monica, CA (Dr. Bernthal), and the Division of infectious Diseases and Department of Orthopaedic Surgery, The Johns Hopkins Hospital, Baltimore, MD (Dr. Miller).
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: John M
authors.initials: JM
authors.lastname: Thompson
authors.forename: Alyssa G
authors.initials: AG
authors.lastname: Ashbaugh
authors.forename: Pavlo
authors.initials: P
authors.lastname: Khodakivskyi
authors.forename: Ghyslain
authors.initials: G
authors.lastname: Budin
authors.forename: Riccardo
authors.initials: R
authors.lastname: Sinisi
authors.forename: Andrew
authors.initials: A
authors.lastname: Heinmiller
authors.forename: Marleen
authors.initials: M
authors.lastname: van Oosten
authors.forename: Jan Maarten
authors.initials: JM
authors.lastname: van Dijl
authors.forename: Gooitzen M
authors.initials: GM
authors.lastname: van Dam
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Francis
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Bernthal
authors.forename: Elena A
authors.initials: EA
authors.lastname: Dubikovskaya
authors.forename: Lloyd S
authors.initials: LS
authors.lastname: Miller
mesh_terms: D000818:Animals; D019643:Arthroplasty, Replacement / Q000009:adverse effects*; D008163:Luminescent Measurements / Q000379:methods; D008297:Male; D008810:Mice, Inbred C57BL; D061848:Optical Imaging / Q000379:methods; D061088:Photoacoustic Techniques / Q000379:methods*; D016459:Prosthesis-Related Infections / Q000000981:diagnostic imaging*