Fluorescence-Guided Surgical Techniques in Neurosurgery

Fluorescence-guided surgery in neurosurgery enhances the surgeon’s ability to distinguish neoplastic tissue from healthy parenchyma by employing molecules that emit visible or near-infrared light when excited. Techniques such as the administration of 5-aminolevulinic acid, which leads to selective accumulation of protoporphyrin IX in malignant cells, or the use of exogenous fluorophores including indocyanine green, have become integral adjuncts to white-light microscopy. Beyond the well-established methods, recent innovations encompass hyperspectral imaging platforms that capture emission spectra across multiple wavelengths, machine-learning algorithms that classify tissue types intraoperatively, and miniaturised systems integrated into handheld tools. These approaches improve the completeness of tumour resection while minimising neurological morbidity. Globally, fluorescence guidance has been shown to increase gross total resection rates, particularly in high-grade gliomas, and to inform more accurate sampling in low-grade lesions. The field continues to evolve towards real-time quantitative imaging, multiplexed fluorophore detection and targeted molecular probes that traverse the blood–brain tumour barrier with high specificity.

Research from Nature Portfolio

One study has demonstrated the integration of hyperspectral imaging with machine-learning classifiers to differentiate tumour grade, margin status and isocitrate dehydrogenase mutation status. By analysing five distinct fluorophore emission spectra in over 180 patients, random forest and neural network models distinguished pathological classes with accuracies exceeding 84%, underscoring the potential of optical biomarkers for on-the-fly tissue classification. Another development employs a birefringent spectral demultiplexer capable of simultaneous acquisition of 64 spectral channels at high frame rates. This snapshot hyperspectral system notably increases throughput by over 70-fold compared with tunable-filter devices, enabling real-time quantification of protoporphyrin IX during glioma resection without disrupting surgical workflow. Such advances pave the way for quantitative, wide-field assessment of fluorophore concentration to guide the extent of resection with unprecedented speed and sensitivity.

Fluorescence-Guided Surgical Techniques in Neurosurgery publication trend

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

Technical terms

5-aminolevulinic acid (5-ALA): A precursor in the haem biosynthesis pathway that accumulates as fluorescent protoporphyrin IX in tumour cells upon administration.

Protoporphyrin IX (PpIX): An endogenously generated fluorophore emitting red light under blue-violet excitation, used to visualise tumour tissue intraoperatively.

Hyperspectral imaging: An optical technique that acquires a wide range of spectral bands for each pixel, enabling quantitative analysis of multiple fluorophore signatures.

Fluorophore: A molecule that absorbs light at one wavelength and emits at another, employed to label or highlight biological structures.

Indocyanine green (ICG): A near-infrared fluorophore approved for vascular imaging, repurposed for tumour visualisation based on enhanced permeability and retention effects.

References

1. Lower-grade gliomas surgery guided by GRPR-targeting PET/NIR dual-modality image probe: a prospective and single-arm clinical trial. Theranostics (2024).
2. Towards machine learning-based quantitative hyperspectral image guidance for brain tumor resection. Communications Medicine (2024).
3. A birefringent spectral demultiplexer enables fast hyper-spectral imaging of protoporphyrin IX during neurosurgery. Communications Biology (2023).
4. Next‐generation agents for fluorescence‐guided glioblastoma surgery. Bioengineering & Translational Medicine (2023).
5. 5-Aminolevulinic Acid Induced Fluorescence Is a Powerful Intraoperative Marker for Precise Histopathological Grading of Gliomas with Non-Significant Contrast-Enhancement. PLOS ONE (2013).
6. Blood-Brain Barrier, Blood-Brain Tumor Barrier, and Fluorescence-Guided Neurosurgical Oncology: Delivering Optical Labels to Brain Tumors. Frontiers in Oncology (2020).
7. 5-ALA Fluorescence Image Guided Resection of Glioblastoma Multiforme: A Meta-Analysis of the Literature. International Journal of Molecular Sciences (2015).
8. Indocyanine-Green for Fluorescence-Guided Surgery of Brain Tumors: Evidence, Techniques, and Practical Experience. Frontiers in Surgery (2019).