Please login first
Towards In-Surgery Miniature Fluorescence Detection of Glioma
* , * , , *
1  School of Engineering, RMIT University, VIC (3000), Australia
Academic Editor: Paolo Bollella

Abstract:

Patients diagnosed with glioma have a 5-year survival rate of less than 5% [1]. Due to the difficulty distinguishing between healthy and tumour tissue, recurrence of glioma is likely to occur after surgery [2]. An area of interest in improving tissue distinguishment during surgery is fluorescence-guided surgery. One implementation utilises 5 aminolaevulinic acid (5-ALA) [3], which causes a build-up of Protoporphyrin IX (PpIX) in tumour tissue, caused by different metabolic processes between tumour tissue (glycolysis) and brain tissue (haem) [4]. PpIX fluoresces pink (635 nm peak) under blue light excitation (highest absorption at 405 nm) [5]. This fluorescence is difficult to see with the naked eye in lower concentrations of PpIX (found in edge cases of glioma). There have been many attempts to detect this fluorescence, though most devices are not suitable for miniaturization or for in-surgery use [6] [7]. To tackle this issue, a system for quantitatively measuring these fluorescence spectra has been developed. The system houses a miniature CMOS multispectral sensor alongside micro-LEDs to provide excitation and recording in a small footprint (3 mm x 3mm), which encourages further developments to integrate the system into existing surgical tools. The photosensor was benchmarked using a gelatine model mixed with ink to provide fluorescence close to the desired peaks (515 nm, 625 nm). The system mapped a fluorescence distribution area of 16 mm x 16 mm, with results being compared to a spectrometer's performance. The system achieved a high correlation with the spectrometer (R2>0.98), confirming its accuracy and suitability for real-time detection. Integrating this system into existing surgical tools can help in surgical detection of glioma tissue, increasing the glioma tissue removed, reducing the chance of recurrence, and increasing the survival rate of patients.

References

[1] A. F. Tamimi and M. Juweid, "Epidemiology and outcome of glioblastoma," Exon Publications, pp. 143-153, 2017, doi: http://dx​.doi.org/10​.15586/codon.glioblastoma.2017.ch8.

[2] D. Orringer et al., "Extent of resection in patients with glioblastoma: limiting factors, perception of resectability, and effect on survival," Journal of neurosurgery, vol. 117, no. 5, pp. 851-859, 2012, doi: https://doi.org/10.3171/2012.8.JNS12234.

[3] W. Stummer, H. Stepp, G. Möller, A. Ehrhardt, M. Leonhard, and H. Reulen, "Technical principles for protoporphyrin-IX-fluorescence guided microsurgical resection of malignant glioma tissue," Acta neurochirurgica, vol. 140, pp. 995-1000, 1998, doi: https://doi.org/10.1007/s007010050206.

[4] M. J. Colditz, K. Van Leyen, and R. L. Jeffree, "Aminolevulinic acid (ALA)–protoporphyrin IX fluorescence guided tumour resection. Part 2: Theoretical, biochemical and practical aspects," Journal of Clinical Neuroscience, vol. 19, no. 12, pp. 1611-1616, 2012, doi: https://doi.org/10.1016/j.jocn.2012.03.013.

[5] C. Von Dobbeler, L. Schmitz, K. Dicke, R. Szeimies, and T. Dirschka, "PDT with PPIX absorption peaks adjusted wavelengths: Safety and efficacy of a new irradiation procedure for actinic keratoses on the head," Photodiagnosis and Photodynamic Therapy, vol. 27, pp. 198-202, 2019, doi: https://doi.org/10.1016/j.pdpdt.2019.05.015.

[6] A. Gautheron et al., "Robust estimation of 5-ALA-induced PpIX contributions in multiple-wavelength excitation fluorescence spectroscopy to improve intraoperative glioma detection: application on clinical data," in Clinical Biophotonics III, 2024, vol. 13009: SPIE, pp. 31-35, doi: https://doi.org/10.1117/12.3022093.

[7] D. Black et al., "Towards machine learning-based quantitative hyperspectral image guidance for brain tumor resection," Communications Medicine, vol. 4, no. 1, p. 131, 2024, doi: https://doi.org/10.1038/s43856-024-00562-3.

Keywords: Biosensor, Brain tumor, CMOS color sensors, Fluorescence guided surgery (FGS), Miniaturization
Top