Dataset Information

Preclinical Evaluation of Photoacoustic Imaging as a Novel Noninvasive Approach to Detect an Orthopaedic Implant Infection.

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 ?-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.

SUBMITTER: Wang Y

PROVIDER: S-EPMC6056014 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Preclinical Evaluation of Photoacoustic Imaging as a Novel Noninvasive Approach to Detect an Orthopaedic Implant Infection.

Wang Yu Y Thompson John M JM Ashbaugh Alyssa G AG Khodakivskyi Pavlo P Budin Ghyslain G Sinisi Riccardo R Heinmiller Andrew A van Oosten Marleen M van Dijl Jan Maarten JM van Dam Gooitzen M GM Francis Kevin P KP Bernthal Nicholas M NM Dubikovskaya Elena A EA Miller Lloyd S LS

The Journal of the American Academy of Orthopaedic Surgeons 20170201

<h4>Introduction</h4>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.<h4>Materials</h4>In an established preclinical mouse model of bioluminescent Staphylococcus aureus PJI, fluorescent indocyanine green (ICG) was conjugated to β-cyclodextrin (CDX-ICG) or teicoplani ...[more]

PMID: 27941556

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Project description:BackgroundSevere environmental pollution and contaminants left in the environment due to the abuse of chemicals, such as methylmercury, are associated with an increasing number of embryonic disorders. Ultrasound imaging has been widely used to investigate embryonic development malformation and dysorganoplasia in both research and clinics. However, this technique is limited by its low contrast and lacking functional parameters such as the ability to measure blood oxygen saturation (SaO2) and hemoglobin content (HbT) in tissues, measures that could be early vital indicators for embryonic development abnormality. Herein, we proposed combining two highly complementary techniques into a photoacoustic-ultrasound (PA-US) dual-modality imaging approach to noninvasively detect early mouse embryo abnormalities caused by methylmercury chloride (MMC) in real time.ObjectivesThis study aimed to assess the use of PA-US dual-modality imaging for noninvasive detection of embryonic toxicity at different stages of growth following prenatal MMC exposure. Additionally, we compared the PA-US imagining results to traditional histological methods to determine whether this noninvasive method could detect early developmental defects in utero.MethodsDifferent dosages of MMC were administrated to pregnant mice by gavage to establish models of different levels of embryonic malformation. Ultrasound, photoacoustic signal intensity (PSI), blood oxygen saturation (SaO2), and hemoglobin content (HbT) were quantified in all experimental groups. Furthermore, the embryos were sectioned and examined for pathological changes.ResultsUsing PA-US imaging, we detected differences in PSI, SaO2, HbT, and heart volume at embryonic day (E)14.5 and E11.5 for low and high dosages of MMC, respectively. More important, our results showed that differences between control and treated embryos identified by in utero PA-US imaging were consistent with those identified in ex vivo embryos using histological methods.ConclusionOur results suggest that noninvasive dual-modality PA-US is a promising strategy for detecting developmental toxicology in the uterus. Overall, this study presents a new approach for detecting embryonic toxicities, which could be crucial in clinics when diagnosing aberrant embryonic development. https://doi.org/10.1289/EHP8907.

Project description:BackgroundRecent advances in non-invasive optical, radiographic and ?CT imaging provide an opportunity to monitor biological processes longitudinally in an anatomical context. One particularly relevant application for combining these modalities is to study orthopaedic implant infections. These infections are characterized by the formation of persistent bacterial biofilms on the implanted materials, causing inflammation, periprosthetic osteolysis, osteomyelitis, and bone damage, resulting in implant loosening and failure.Methodology/principal findingsAn orthopaedic implant infection model was used in which a titanium Kirshner-wire was surgically placed in femurs of LysEGFP mice, which possess EGFP-fluorescent neutrophils, and a bioluminescent S. aureus strain (Xen29; 1×10(3) CFUs) was inoculated in the knee joint before closure. In vivo bioluminescent, fluorescent, X-ray and ?CT imaging were performed on various postoperative days. The bacterial bioluminescent signals of the S. aureus-infected mice peaked on day 19, before decreasing to a basal level of light, which remained measurable for the entire 48 day experiment. Neutrophil EGFP-fluorescent signals of the S. aureus-infected mice were statistically greater than uninfected mice on days 2 and 5, but afterwards the signals for both groups approached background levels of detection. To visualize the three-dimensional location of the bacterial infection and neutrophil infiltration, a diffuse optical tomography reconstruction algorithm was used to co-register the bioluminescent and fluorescent signals with ?CT images. To quantify the anatomical bone changes on the ?CT images, the outer bone volume of the distal femurs were measured using a semi-automated contour based segmentation process. The outer bone volume increased through day 48, indicating that bone damage continued during the implant infection.Conclusions/significanceBioluminescent and fluorescent optical imaging was combined with X-ray and ?CT imaging to provide noninvasive and longitudinal measurements of the dynamic changes in bacterial burden, neutrophil recruitment and bone damage in a mouse orthopaedic implant infection model.

Dataset Information

Preclinical Evaluation of Photoacoustic Imaging as a Novel Noninvasive Approach to Detect an Orthopaedic Implant Infection.

Publications

Preclinical Evaluation of Photoacoustic Imaging as a Novel Noninvasive Approach to Detect an Orthopaedic Implant Infection.

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