Fluorescence-Guided Nerve Imaging in Surgical Applications

Fluorescence-guided nerve imaging has emerged as a transformative approach to enhance nerve preservation during diverse surgical procedures. By administering molecules that selectively bind to or permeate nerve tissue and emit light under specific wavelengths, surgeons can visualise critical neural pathways in real time, thereby reducing inadvertent nerve injury. This technique addresses limitations of standard white-light illumination, which relies on anatomical landmarks and subtle tissue contrast, and offers superior delineation of peripheral, autonomic and central nerves. Fluorescent probes vary in their mechanisms: peptide-based agents target nerve surface receptors discovered through phage display; antibody conjugates exploit ganglioside recognition to deliver fluorophores intraneuronally; small-molecule dyes traverse the blood-nerve barrier to highlight myelin sheaths; and non-labelled optical methods leverage intrinsic tissue properties. Integration of near-infrared (NIR) excitation further improves depth penetration and reduces autofluorescence. Advances in probe chemistry, imaging hardware and dual-mode systems have established a pipeline from preclinical validation in rodents and large mammals to first-in-human applications. As regulatory approvals expand, fluorescence guidance promises to become a standard adjunct in oncological, thoracic, urological and neurosurgical practice, with a demonstrable impact on postoperative function and quality of life.

Research from Nature Portfolio

Selective delivery of a fluorescently conjugated anti-ganglioside antibody has demonstrated clear labelling of motor, sensory and autonomic fibres following systemic administration in murine models. The antibody approach achieves high neuronal uptake, with bright intraneuronal signal and low off-target background in non-neural tissues, enabling precise intraoperative mapping of peripheral nerve trunks. Biodistribution studies confirm retention within the peripheral nervous system and minimal systemic accumulation. This proof-of-concept establishes antibodies and their fragments as versatile delivery vectors for cargoes ranging from small dyes to therapeutic agents, opening avenues for simultaneous imaging and modulation of nerve function during surgery.

Fluorescence-Guided Nerve Imaging in Surgical Applications publication trend

The graph below shows the total number of articles in fluorescence-guided nerve imaging in surgical applications across all publications each year (not limited to Nature Index journals).

Technical terms

Fluorophore: A molecule that absorbs light at one wavelength and emits it at a longer wavelength, used to label biological structures.

Near-infrared (NIR) fluorescence: Emission between 650 and 900 nm, beneficial for deeper tissue penetration and reduced background signal.

Signal-to-background ratio (SBR): Quantitative measure of fluorescence intensity from target tissue relative to surrounding structures.

Blood-nerve barrier: A selective physiological barrier that regulates molecular exchange between blood and peripheral nerves.

Phage display: A technique for identifying peptide sequences with high affinity for specific targets by presenting them on bacteriophage surfaces.

Ganglioside: A class of glycolipids abundant in neuronal membranes, serving as binding sites for targeted antibodies.

References

1. Fluorescently-tagged anti-ganglioside antibody selectively identifies peripheral nerve in living animals. Scientific Reports (2015).
2. Fluorescently Labeled Peptide Increases Identification of Degenerated Facial Nerve Branches during Surgery and Improves Functional Outcome. PLOS ONE (2015).
3. Near-infrared Intraoperative Imaging of Thoracic Sympathetic Nerves: From Preclinical Study to Clinical Trial. Theranostics (2018).
4. Improved Intraoperative Visualization of Nerves through a Myelin-Binding Fluorophore and Dual-Mode Laparoscopic Imaging. PLOS ONE (2015).
5. Real-time, label-free, intraoperative visualization of peripheral nerves and micro-vasculatures using multimodal optical imaging techniques.. Biomedical Optics Express (2018).