Identification of tumour margins during resection of the brain is critical for improving the post-operative outcomes. Present research aims to develop a miniaturized, optical system for simultaneous measurement of DRS and auto-fluorescence for brain tumour detection

Andersson-Engels, Stefan

Burke, Ray

Georgel, Rachel

Grygoryev, Konstantin

Li, Celina L.

Lu, Huihui

Oâ  Hare, Daniel

Sorensen, Simon

Cork Open Research Archive

UCC Library and UCC researchers have made this item openly available.Please let us know how this has helped you. Thanks!Title Miniaturized, multi-spectral optics for tissue differentiationAuthor(s) Grygoryev, Konstantin; Lu, Huihui; Sorensen, Simon; Li, Celina L.;Georgel, Rachel; Oâ  Hare, Daniel; Burke, Ray; Andersson-Engels,StefanPublication date 2022-04Original citation Grygoryev, K., Lu, H., Sorensen, S., Li, C.L., Georgel, R., O’Hare, D.,Burke, R. and Andersson-Engels, S. (2022) ‘Miniaturized, multi-spectraloptics for tissue differentiation’, in Biophotonics Congress: BiomedicalOptics 2022 (Translational, Microscopy, OCT, OTS, BRAIN). FortLauderdale, Florida, 24-27 April, Optica Publishing Group, JM3A.63 (2pp). https://doi.org/10.1364/TRANSLATIONAL.2022.JM3A.63.Type of publication Conference itemLink to publisher'sversionhttps://doi.org/10.1364/TRANSLATIONAL.2022.JM3A.63Access to the full text of the published version may require asubscription.Rights © 2022 The Author(s). Published by Optical Publishing GroupItem downloadedfromhttp://hdl.handle.net/10468/13745Downloaded on 2022-12-08T08:55:21ZMiniaturized, multi-spectral optics for tissuedifferentiationKonstantin Grygoryev, Huihui Lu, Simon Sorensen, Celina L. Li, Rachel Georgel, Daniel O’Hare, Ray Burke and Stefan Andersson-EngelsTyndall National Institute, Lee Maltings Complex, Dyke parade, Cork, Ireland, T12R5CPkonstantin.grygoryev@tyndall.ieAbstract: Identification of tumour margins during resection of the brain i s critical for improving the post-operative outcomes. Present research aims to develop a miniaturized, optical system for simultaneous measurement of DRS and auto-fluorescence for brain tu-mour detection.1. IntroductionDue to the highly infiltrative nature of Glioblastoma multiforme (GBM) and limited intraoperative visualization ofthe tumour margin, incomplete surgical resection has been observed to occur in up to 80 % of GBM cases, leadingto nearly universal tumour recurrence and overall poor prognosis of 14.6 months median survival [1,2]. The currentgold standard for tumour delineation is fluorescence guided resection (FGR) which used a surgical microscope incombination with a fluorescent contrast agent, the 5-aminolevulinic acid (5-ALA) [3, 4].Unfortunately even withuse of FGR, definitive delineation between tumour infiltration zone and healthy brain tissue remains challengingdue to subjectivity of visually identifying the magnitude of fluorescent signal [5, 6].To address this problem, we have previously investigated a number of multi-spectral, clinical and laboratorybased instruments designed to provide simultaneous diffuse reflectance spectroscopy (DRS) and quantitative flu-orescence measurements [7, 8]. Our current aim is to miniaturize the detector optics and sensor footprint withoutsacrificing low-light sensitivity while maintaining the ability of the instrument to account for strong ambient illu-mination.2. Materials and methodsFig. 1. a) Schematic of of spatial light separation between the SiPMTs. b) PCB with an array ofeight SiPMTs. c) The schematic of hybrid light source which consists of 5 laser diodes in a foldedarrangement as well as three LEDs.JM3A.63 Biophotonics Congress: Biomedical Optics (Translational, Microscopy, OCT, OTS, BRAIN) © Optica Publishing Group 20222.1. DetectorsThe DRS and auto-fluorescence measurements are performed using eight separate silicon photo-multipliers(SiPMT). Figure 1(a) shows a schematic of wavelengths-dependant spatial separation of light where a customprism with eight dichroic surfaces is positioned above eight SiPMT. A set of eight bandpass filters, placed be-tween detectors and the dichroics, further define the collection band and reduce channel cross-talk. The SiPMTsin turn are soldered to a compact PCB that houses amplifiers and an analog output for data acquisition (Figure1(b)).2.2. Light sourceFigure 1(c) shows the CAD design of the hybrid light source. The source consists of five laser diodes and threeLEDs. The wavelengths of each source are matched to one detection band. The laser diodes and LEDs are coupledinto 200µm and 600µm fibres, respectively. Both the detector boards and the source are packaged into a compactenclosure of standard size.Fig. 2. Measured, normalized spectra of the detector array.3. Preliminary resultsAs part of the development, this instrument is currently undergoing characterization of the optical elements. Figure2 shows the measured spectra of six, longer wavelengths channels intended for measurement of auto-fluorescenceintensity. In early 2022, further characterization experiments, such as estimation of dynamic range as well asfluorophore detection limits, will be performed prior to deployment of the instrument in the clinic.References1. M. Mischkulnig, B. Kiesel, M. Borkovec, L. I. Wadiura, D. Benner, A. Hosmann, S. Hervey-Jumper, E. Knosp,K. Roessler, M. S. Berger, and G. Widhalm, “High Interobserver Agreement in the Subjective Classification of 5-Aminolevulinic Acid Fluorescence Levels in Newly Diagnosed Glioblastomas,” Lasers Surg. Medicine pp. 1–8 (2020).2. S. W. Cramer and C. C. Chen, “Photodynamic Therapy for the Treatment of Glioblastoma,” Front. Surg. 6, 1–11 (2020).3. W. Stummer, U. Pichlmeier, T. Meinel, O. D. Wiestler, F. Zanella, H.-J. Reulen, A.-G. S. Group et al., “Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phaseiii trial,” The lancet oncology 7, 392–401 (2006).4. N. Sanai, M.-Y. Polley, M. W. McDermott, A. T. Parsa, and M. S. Berger, “An extent of resection threshold for newlydiagnosed glioblastomas,” J. neurosurgery 115, 3–8 (2011).5. C. G. Hadjipanayis, G. Widhalm, and W. Stummer, “What is the surgical benefit of utilizing 5-aminolevulinic acid forfluorescence-guided surgery of malignant gliomas?” Neurosurgery 77, 663–673 (2015).6. J. C. Richter, N. Haj-Hosseini, M. Hallbeck, and K. Wårdell, “Combination of hand-held probe and microscopy forfluorescence guided surgery in the brain tumor marginal zone,” Photodiagnosis photodynamic therapy 18, 185–192(2017).7. H. Lu, K. Grygoryev, N. Bermingham, M. Jansen, M. O’Sullivan, G. Nunan, K. Buckley, K. Manley, R. Burke, andS. Andersson-Engels, “Combined autofluorescence and diffuse reflectance for brain tumour surgical guidance: initialex vivo study results,” Biomed. Opt. Express 12, 2432–2446 (2021).8. K. Grygoryev, H. Lu, C. L. Li, A. V. Zhdanov, R. Burke, and S. Andersson-Engels, “Multi-spectral clinical prototypefor fluorophore detection,” Front. Phys. 9, 476 (2021).JM3A.63 Biophotonics Congress: Biomedical Optics (Translational, Microscopy, OCT, OTS, BRAIN) © Optica Publishing Group 2022

Miniaturized, multi-spectral optics for tissue differentiation

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Miniaturized, multi-spectral optics for tissue differentiation

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