Fluorescence Imaging of Nerves During Surgery

Abstract

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.

Fluorescent Nanoagents for Biomedical Applications

“…Dmitry Korolev 1,2 , Maria Istomina 1,3 *, Anton Belorus 3 , Artem Brovko 4 , Dmitry Sonin 1,2 , Galina Shulmeyster 1 , Natalya Evreinova 1,5 and Vyacheslav Moshnikov 3 1 Almazov National Medical Research Centre, Saint Petersburg, Russia *Address all correspondence to: ist_maria@mail.ru original first set. The functionalization of the surface of nanoparticles with the drug (gentamicin) third sets (PLPor-Si-Gent) entails the more intensive passivation of the surface by the drug molecules, which reduces the intensity of the photoluminescence line by more than (a) factor of 3.…”

“…It happens, often, that the area of localization and distribution of the studied substances after injection is unknown. The application of the fluorescence imaging in preclinical studies allows us to noninvasively track the total biodistribution, localization, and accumulation of the injectable drugs with a fluorescent label complementary to the studied structures [2][3][4][5][6][7].…”

Fluorescence labeling of a NaV1.7-targeted peptide for near-infrared nerve visualization

“…Oncologic surgery, in particular, poses a risk of nerve injury as anatomy is often distorted by the disease [10][11][12][13][14][15][16][17]. Tools for pre and perioperative nerve enhancement exist [18][19][20] and fluorescent nerve imaging agents, as well as multimodal optical imaging techniques, are raising interest for intraoperative applications [21][22][23][24][25][26][27][28][29][30][31].…”

Fluorescence Imaging of Peripheral Nerves by a Nav1.7-Targeted Inhibitor Cystine Knot Peptide

“…Some researchers, including the groups of Gibbs, 19 Frangioni, 20 and Nguyen, 21 among others, have developed tracers for peripheral nerve imaging, and two recent reviews provide an overview of the field. 22,23 However, more development has to occur to advance nerve imaging agents to a point where routine clinical use is feasible.…”