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Fluorescence Imaging of Nerves During Surgery

Walsh, Erika M., MD*; Cole, Denzel, MD; Tipirneni, Kiranya E., MD; Bland, Kirby I., MD; Udayakumar, Neha, BS; Kasten, Benjamin B., PhD§; Bevans, Stephanie L., MD; McGrew, Benjamin M., MD||; Kain, Joshua J., MD||; Nguyen, Quyen T., MD, PhD; Rosenthal, Eben L., MD**; Warram, Jason M., PhD||

doi: 10.1097/SLA.0000000000003130

Objective: This review details the agents for fluorescence-guided nerve imaging in both preclinical and clinical use to identify factors important in selecting nerve-specific fluorescent agents for surgical procedures.

Background: Iatrogenic nerve injury remains a significant cause of morbidity in patients undergoing surgical procedures. Current real-time identification of nerves during surgery involves neurophysiologic nerve stimulation, which has practical limitations. Intraoperative fluorescence-guided imaging provides a complimentary means of differentiating tissue types and pathology. Recent advances in fluorescence-guided nerve imaging have shown promise, but the ideal agent remains elusive.

Methods: In February 2018, PubMed was searched for articles investigating peripheral nerve fluorescence. Key terms used in this search include: “intraoperative, nerve, fluorescence, peripheral nerve, visualization, near infrared, and myelin.” Limits were set to exclude articles exclusively dealing with central nervous system targets or written in languages other than English. References were cross-checked for articles not otherwise identified.

Results: Of the nonspecific agents, tracers that rely on axonal transport showed the greatest tissue specificity; however, neurovascular dyes already enjoy wide clinical use. Fluorophores specific to nerve moieties result in excellent nerve to background ratios. Although noteworthy findings on tissue specificity, toxicity, and route of administration specific to each fluorescent agent were reported, significant data objectively quantifying nerve-specific fluorescence and toxicity are lacking.

Conclusions: Fluorescence-based nerve enhancement has advanced rapidly over the past 10 years with potential for continued utilization and progression in translational research. An ideal agent would be easily administered perioperatively, would not cross the blood-brain barrier, and would fluoresce in the near-infrared spectrum. Agents administered systemically that target nerve-specific moieties have shown the greatest promise. Based on the heterogeneity of published studies and methods for reporting outcomes, it appears that the development of an optimal nerve imaging agent remains challenging.

*Michigan Ear Institute, Farmington Hills, MI

Department of Surgery, University of Alabama, Birmingham, AL

School of Medicine, University of Alabama, Birmingham, AL

§Department of Radiology, University of Alabama, Birmingham, AL

||Department of Otolaryngology, University of Alabama, Birmingham, AL

Department of Surgery, University of California, San Diego, CA

**Department of Otolaryngology, Stanford University, Stanford, CA.

Reprints: Jason M. Warram, PhD, Assistant Professor of Otolaryngology, Surgery, Radiology, and Biomedical Engineering, University of Alabama, Birmingham, AL. E-mail:

Disclosure: This work was supported by grants from NIH T32CA091078 and Robert Jack Armstrong Research Fund. This study was funded by grants from NIH T32CA091078 and Robert Jack Armstrong Research Fund. QTN is a non-employee scientific advisor to Avelas Biosciences. The authors declare no conflict of interest. This article does not contain any studies with human participants or animals performed by any of the authors.

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