title: Combined in vivo optical and µCT imaging to monitor infection, inflammation, and bone anatomy in an orthopaedic implant infection in mice.
abstract: Multimodality imaging has emerged as a common technological approach used in both preclinical and clinical research. Advanced techniques that combine in vivo optical and μCT imaging allow the visualization of biological phenomena in an anatomical context. These imaging modalities may be especially useful to study conditions that impact bone. In particular, orthopaedic implant infections are an important problem in clinical orthopaedic surgery. These infections are difficult to treat because bacterial biofilms form on the foreign surgically implanted materials, leading to persistent inflammation, osteomyelitis and eventual osteolysis of the bone surrounding the implant, which ultimately results in implant loosening and failure. Here, a mouse model of an infected orthopaedic prosthetic implant was used that involved the surgical placement of a Kirschner-wire implant into an intramedullary canal in the femur in such a way that the end of the implant extended into the knee joint. In this model, LysEGFP mice, a mouse strain that has EGFP-fluorescent neutrophils, were employed in conjunction with a bioluminescent Staphylococcus aureus strain, which naturally emits light. The bacteria were inoculated into the knee joints of the mice prior to closing the surgical site. In vivo bioluminescent and fluorescent imaging was used to quantify the bacterial burden and neutrophil inflammatory response, respectively. In addition, μCT imaging was performed on the same mice so that the 3D location of the bioluminescent and fluorescent optical signals could be co-registered with the anatomical μCT images. To quantify the changes in the bone over time, the outer bone volume of the distal femurs were measured at specific time points using a semi-automated contour based segmentation process. Taken together, the combination of in vivo bioluminescent/fluorescent imaging with μCT imaging may be especially useful for the noninvasive monitoring of the infection, inflammatory response and anatomical changes in bone over time.
authors.affiliation: Orthopaedic Hospital Research Center, Orthopaedic Hospital Department of Orthopaedic Surgery, David Geffen School of Medicine at University of California, Los Angeles (UCLA).
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Bernthal
authors.affiliation: PerkinElmer.
authors.forename: Brad N
authors.initials: BN
authors.lastname: Taylor
authors.affiliation: PerkinElmer.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Meganck
authors.affiliation: Department of Dermatology, Johns Hopkins University School of Medicine.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Johns Hopkins University School of Medicine.
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Shahbazian
authors.affiliation: Orthopaedic Hospital Research Center, Orthopaedic Hospital Department of Orthopaedic Surgery, David Geffen School of Medicine at University of California, Los Angeles (UCLA).
authors.forename: Jared A
authors.initials: JA
authors.lastname: Niska
authors.affiliation: PerkinElmer.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Francis
authors.affiliation: Department of Dermatology, Johns Hopkins University School of Medicine; Department of Medicine, Division of Infectious Diseases, Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine; lloydmiller@jhmi.edu.
authors.forename: Lloyd S
authors.initials: LS
authors.lastname: Miller
mesh_terms: D000818:Animals; D001864:Bone Wires / Q000382:microbiology*; D001842:Bone and Bones / Q000382:microbiology / Q000473:pathology*; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D007249:Inflammation / Q000382:microbiology / Q000473:pathology; D008163:Luminescent Measurements / Q000379:methods; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D064847:Multimodal Imaging / Q000379:methods; D061848:Optical Imaging / Q000379:methods*; D016459:Prosthesis-Related Infections / Q000382:microbiology* / Q000473:pathology*; D013203:Staphylococcal Infections / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism; D055114:X-Ray Microtomography / Q000379:methods*
chemical_list: D008164:Luminescent Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins