Iatrogenic nerve injuries during surgery present significant risks, often leading to severe functional deficits and increased morbidity. Surgeons aim to reduce the effects of iatrogenic nerve injuries by quickly detecting them during surgery using gross visualization and tactile feedback. However, current intraoperative detection methods, such as white light visualization and intraoperative nerve monitoring using electromyography (EMG), are not sufficiently reliable or sensitive, creating an urgent need for more effective techniques. Our research focuses on the application of a novel near-infrared (NIR) nerve-specific fluorophore, LGW16-03, developed to enhance the visualization of peripheral nerves during surgery. Pharmacokinetic and pharmacodynamic studies have demonstrated that LGW16-03 provides high nerve-specific contrast, achieving an optimal signal-to-background ratio (SBR) of ≥2.5 within one hour of intravenous administration. This novel fluorophore demonstrated a unique property which enables the differentiation between healthy and injured nerve tissues, as the fluorophore showed reduced accumulation in damaged nerve regions. Utilizing rodent models with sciatic nerve crush and transection injuries, our experiments revealed significantly lower fluorescence intensity in the injured regions compared to healthy areas, providing clear visual distinction and enhanced detection compared to white light visualization alone. Long-term studies conducted on CD-1 mice, which involved inducing varying degrees of sciatic nerve injuries, showed that LGW16-03 maintained its effectiveness over different recovery periods, with increased contrast between proximal and distal nerve regions following mild, moderate, and severe injuries. These promising results suggest that LGW16-03 could serve as a critical tool for fluorescence-guided surgery (FGS), offering surgeons real-time, quantitative assessments of nerve injury severity. By enabling earlier and more accurate detection of nerve damage, this methodology has the potential to significantly improve surgical outcomes, reduce postsurgical complications, and enhance patient quality of life. Our ongoing research aims to further validate the clinical applicability of LGW16-03 in both animal models and future human trials, ultimately leading to a transformative approach in intraoperative nerve injury detection and assessment.

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