Abstract
INTRODUCTION AND OBJECTIVES: Inadvertent injury to nerves is a significant and often inevitable consequence of surgery that can lead post-operative morbidity and loss of function. Nerve-sparing during radical prostatectomy can reduce the incidence of post-surgical erectile dysfunction. In retroperitoneal lymph node dissection for testis cancer, the prospective identification and preservation of nerves in is essential in maintaining ejaculatory function and fertility. Although there is a significant need, there is no widely adopted system for real-time identification of nerves in either the open or laparoscopic surgical settings. We sought to investigate the performance of a myelin-targeted fluorophore and optical imaging instrumentation in the intraoperative visualization of nerves. METHODS: A myelin-targeting small molecule fluorophore, GE3126, was synthesized and characterized for its optical and myelinbinding properties using purified myelin basic protein. 2 Yorkshire pigs were utilized in a non-survival study. Peripheral and retroperitoneal nerves were exposed and control images taken using a dedicated compact imaging device adapted to both open and minimally-invasive approaches. Both white light and 405nm illumination were used. Following intravenous injection of the agent, blood, urine, and bile were drawn at fixed intervals to determine the pharmacokinetics of the agent. Central and peripheral nerves were visualized. Tissues were harvested for ex-vivo analysis and histopathology. 4 blinded observers evaluated captured images. RESULTS: The primary route of excretion was renal. The fluorescence peak was achieved at 60-80 min following injection. Label/nonlabel fluorescence signal ratio was 5:1 at peak. Nerve to muscle signal was 7:1. Fluorescence polarization showed specific and strong binding to purified myelin basic protein. Retroperitoneal nerves from 100mm-10mm were evaluated. Inter-observer disagreement was 22% with white light images, and 0% with fluorescence images, which was confirmed by histology. No adverse effects were noted in the animals. CONCLUSIONS: GE3126 provides a safe and effective means of identifying nerves through fluorescence imaging and is adaptable to both open and minimally invasive surgical procedures.
Published Version
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