Abstract
BackgroundFluorescein sodium (FNa) is a fluorescence agent used with a wide-field operating microscope for intraoperative guidance and with confocal laser endomicroscopy (CLE) to evaluate brain tissue. Susceptibility of FNa to degradation over time may affect CLE image quality during prolonged surgeries. This study describes improved characteristics of CLE images after intraoperative redosing with FNa.MethodsA retrospective analysis was performed using CLE images obtained ex vivo from samples obtained during tumor resections with FNa-based fluorescence guidance with a wide-field operating microscope. The comparison groups included CLE images acquired after FNa redosing (redose imaging group), images from the same patients acquired after the initial FNa dose (initial-dose imaging group), and images from patients in whom redosing was not used (single-dose imaging group). A detailed assessment of image quality and interpretation regarding different FNa dosage and timing of imaging after FNa administration was conducted for all comparison groups.ResultsThe brightest and most contrasting images were observed in the redose group compared to the initial-dose and single-dose groups (P<0.001). The decay of FNa signal negatively correlated with brightness (rho = -0.52, P<0.001) and contrast (rho = -0.57, P<0.001). Different doses of FNa did not significantly affect the brightness (P=0.15) or contrast (P=0.09) in CLE images. As the mean timing of imaging increased, the percentage of accurately diagnosed images decreased (P=0.03).ConclusionsThe decay of the FNa signal is directly associated with image brightness and contrast. The qualitative interpretation scores of images were highest for the FNa redose imaging group. Redosing with FNa to improve the utility of CLE imaging should be considered a safe and beneficial strategy during prolonged surgeries.
Highlights
Intraoperative confocal laser endomicroscopy (CLE) is an emerging technology that evaluates brain tissue and pathologic tumor tissue via optical fluorescence-based interrogation
Our observations revealed that fluorescein sodium (FNa) signal intensity on CLE images was not always adequate to delineate the tissue at the time of surgical actions on the tumor
335 images acquired with the CLE Z-stack image acquisition mode were excluded because the automatically recorded range of images from different focal depths represents an alternate image acquisition process that obstructs the analysis of image intensity
Summary
Intraoperative confocal laser endomicroscopy (CLE) is an emerging technology that evaluates brain tissue and pathologic tumor tissue via optical fluorescence-based interrogation. CLE has the potential to maximize safe brain tumor resection and improve the positive yield and result time of tissue biopsy, compared to frozen section biopsy, which may require significant time to return information vital to the progress of the surgical procedure. Unlike conventional clinical tools used for diagnostic work-up or in the operating room, CLE can provide real-time histopathologic information to distinguish tumor, non-tumor, and normal tissues in vivo. To induce sufficient image contrast, either intravenous or topical exogenous fluorescence agents are used with CLE. Fluorescein sodium (FNa) is a fluorescence agent used with a wide-field operating microscope for intraoperative guidance and with confocal laser endomicroscopy (CLE) to evaluate brain tissue. This study describes improved characteristics of CLE images after intraoperative redosing with FNa
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