Yu Wang1, John M Thompson, Alyssa G Ashbaugh, Pavlo Khodakivskyi, Ghyslain Budin, Riccardo Sinisi, Andrew Heinmiller, Marleen van Oosten, Jan Maarten van Dijl, Gooitzen M van Dam, Kevin P Francis, Nicholas M Bernthal, Elena A Dubikovskaya, Lloyd S Miller. 1. 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).
Abstract
INTRODUCTION: 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. MATERIALS: 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. CONCLUSION: Photoacoustic imaging successfully localized PJI in this proof-of-concept study and demonstrates potential for clinical translation in orthopaedics.
INTRODUCTION: 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. MATERIALS: 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. CONCLUSION: Photoacoustic imaging successfully localized PJI in this proof-of-concept study and demonstrates potential for clinical translation in orthopaedics.
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