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Abstract

Invasive and biomaterial-associated infections in humans are often difficult to diagnose and treat. Here, guided by recent advances in clinically relevant optical imaging technologies, we explore the use of fluorescently labelled vancomycin (vanco-800CW) to specifically target and detect infections caused by Gram-positive bacteria. The application potential of vanco-800CW for real-time in vivo imaging of bacterial infections is assessed in a mouse myositis model and a human post-mortem implant model. We show that vanco-800CW can specifically detect Gram-positive bacterial infections in our mouse myositis model, discriminate bacterial infections from sterile inflammation in vivo and detect biomaterial-associated infections in the lower leg of a human cadaver. We conclude that vanco-800CW has a high potential for enhanced non-invasive diagnosis of infections with Gram-positive bacteria and is a promising candidate for early-phase clinical trials.

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Going deeper than microscopy: the optical imaging frontier in biology.

Vasilis Ntziachristos (2010)

Optical microscopy has been a fundamental tool of biological discovery for more than three centuries, but its in vivo tissue imaging ability has been restricted by light scattering to superficial investigations, even when confocal or multiphoton methods are used. Recent advances in optical and optoacoustic (photoacoustic) imaging now allow imaging at depths and resolutions unprecedented for optical methods. These abilities are increasingly important to understand the dynamic interactions of cellular processes at different systems levels, a major challenge of postgenome biology. This Review discusses promising photonic methods that have the ability to visualize cellular and subcellular components in tissues across different penetration scales. The methods are classified into microscopic, mesoscopic and macroscopic approaches, according to the tissue depth at which they operate. Key characteristics associated with different imaging implementations are described and the potential of these technologies in biological applications is discussed.

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Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: a prospective study in 52 consecutive patients.

W Stummer, A. Novotný, H Stepp … (2000)

It has been established that 5-aminolevulinic acid (5-ALA) induces the accumulation of fluorescent porphyrins in glioblastoma multiforme (GBM), a phenomenon potentially exploitable to guide tumor resection. In this study the authors analyze the influence of fluorescence-guided resection on postoperative magnetic resonance (MR) imaging and survival in a series of patients who underwent surgery in the authors' department. Fifty-two consecutive patients with GBM received oral doses of 5-ALA (20 mg/kg body weight) 3 hours before induction of anesthesia. Intraoperatively, tumor fluorescence was visualized using a modified operating microscope. Fluorescing tissue was removed whenever it was considered safely possible. Residual enhancement on early postoperative MR imaging was quantified and related to each patient's characteristics to determine which factors influenced resection. Survival was analyzed using the Kaplan-Meier method and multivariate analysis was performed in which the Karnofsky Performance Scale (KPS) score, residual fluorescence, patient age, and residual enhancement on MR images were considered. Intraoperatively, two fluorescence qualities were perceived: solid fluorescence generally reflected coalescent tumor, whereas vague fluorescence mostly corresponded to infiltrative tumor. Complete resection of contrast-enhancing tumor was accomplished in 33 patients (63%). Residual intraoperative tissue fluorescence left unresected for safety reasons predicted residual enhancement on MR images in 18 of the 19 remaining patients. Age, residual solid fluorescence, and absence of contrast enhancement in MR imaging were independent explanatory factors for survival, whereas the KPS score was significant only in univariate analysis. No perioperative deaths and one case of permanent morbidity were encountered. The observations in this study indicate the usefulness of 5-ALA-induced tumor fluorescence for guiding tumor resection. The completeness of resection, as determined intraoperatively from residual tissue fluorescence, was related to postoperative MR imaging findings and to survival in patients suffering from GBM.

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Diagnosis and treatment of infections associated with fracture-fixation devices.

Andrej Trampuz, Werner Zimmerli (2006)

The pathogenesis of infections associated with fracture-fixation devices is related to microorganisms growing in biofilms, which render these infections difficult to treat. These infections are classified as early ( 10 weeks) according to the implant surgery. Most infections are caused by staphylococci and are acquired during trauma (in penetrating injuries) or subsequent fracture-fixation procedures. A combination of clinical, laboratory, histopathology, microbiology, and imaging studies are usually needed to accurately diagnose infection. Magnetic resonance imaging (MRI) and computed tomography (CT) scans are often used to diagnose infection and plan surgical treatment. Positron emission tomography (PET) and PET-CT are promising new tools for diagnosing implant-associated osteomyelitis. The treatment goal is achieving bone consolidation and avoiding development of chronic osteomyelitis. Successful treatment requires adequate surgical procedures combined with 6-12 weeks of antimicrobial therapy acting on adhering stationary-phase microorganisms. In chronic osteomyelitis, orthopedic and plastic- reconstructive surgery is combined in the same procedure or within a short time span. In this article, pathogenesis, classification, diagnosis, and treatment of infections associated with intramedullary nails, external-fixation pins, plates, and screws are reviewed.

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DOI:: 10.1038/ncomms3584

PubMed ID:: 24129412

ScienceOpen disciplines: Chemistry

Keywords: methods,Animals,Image Interpretation, Computer-Assisted,Benzenesulfonates,Humans,growth & development,Diagnostic Imaging,diagnosis,Disease Models, Animal,Mice,Biocompatible Materials,Fluorescent Dyes,Myositis,Indoles,Anti-Bacterial Agents,Gram-Positive Bacterial Infections,Cadaver,chemistry,adverse effects,Vancomycin,Gram-Positive Bacteria,diagnostic use,Time Factors,microbiology

Real-time in vivo imaging of invasive- and biomaterial-associated bacterial infections using fluorescently labelled vancomycin.

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Most cited references 24

Going deeper than microscopy: the optical imaging frontier in biology.

Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: a prospective study in 52 consecutive patients.

Diagnosis and treatment of infections associated with fracture-fixation devices.

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