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A Control Matched Spectral Analysis of Optically Corrected 5-ALA Derived Glioma Fluorescence: Objective Fluorescence Mapping of the Glioma Infiltrating Margin

Friday, May 3, 2024

Presenting Author(s)

Matthew Elliot

Clinical Research Fellow/Neurosurgery Resident
School of Biomedical Engineering and Imaging Sciences, King’s College London, UK / Department of Neurosurgery, King’s College Hospital NHS Foundation Trust, UK
London, GB

Co-Author(s)

SA

Safa Al-Sarraj, MB ChB, FRCPath

Professor of Neuropathology, Head of Clinical Neuropathology
Department of Clinical Neuropathology, King's College Hospital NHS Foundation Trust, UK, United States
KA

Keyoumars Ashkan, MB BCh, MD, MRCP, FRCS(NSurg)

Professor of Neurosurgery, Clinical Lead for Neuro-Oncology
Department of Neurosurgery, King's College London NHS Foundation Trust, UK, United States
RB

Ranjeev Bhangoo, MB ChB, FRCS(Nsurg)

Consultant Neurosurgeon, Clinical Director for Neuroscience
Department of Neurosurgery, King's College Hospital NHS Foundation Trust, UK, United States
BD

Bappaditya Debnath, PhD

Post Doctoral Research Associate
School of Biomedical Engineering and Imaging Sciences, King's College London, UK, United States
RG

Richard Gullan, MB BS, MRCP, FRCS(NSurg)

Consultant Neurosurgeon
Department of Neurosurgery, King's College Hospital NHS Foundation Trust, UK, United States
FI

Fowzia Ibrahim, PhD

Medical Statistician
King's Technology Evaluation Centre, School of Biomedical Engineering and Imaging Sciences, King's College London, UK, United States
JL

Jose Lavrador, MD

Consultant Neurosurgeon
Department of Neurosurgery, King's College Hospital NHS Foundation Trust, UK
London, United Kingdom
OM

Oscar MacCormac, BMBS, MRCS(Eng)

Clinical Research Fellow - Neurosurgery / Neurosurgery Resident
School of Biomedical Engineering and Imaging Sciences, King's College London, UK / Department of Neurosurgery, King's College London NHS Foundation Trust, UK, United States
SO

Sebastien Ourselin, FREng, FMedSci

Professor of Healthcare Engineering, Head of School - BMEIS
School of Biomedical Engineering and Imaging Sciences, King's College London, UK, United States
SP

Sabina Patel, MPAS

Lead Physician Associate
Department of Neurosurgery, King's College Hospital NHS Foundation Trust, UK, United States
ZR

Zita Reisz, MD, EFN, FRCPath

Consultant Neuropathologist
Department of Clinical Neuropathology, King's College Hospital NHS Foundation Trust, UK, United States
SS

Silvère Ségaud, PhD

Post Doctoral Research Associate
School of Biomedical Engineering and Imaging Sciences, King's College London UK, United States
JS

Jonathan Shapey, BMBS, PhD, FRCS(NSurg)

Senior Clinical Lecturer, Honorary Consultant Neurosurgeon
School of Biomedical Engineering and Imaging Sciences, King's College London, UK / Department of Neurosurgery, King's College London NHS Foundation Trust, UK, United States
GS

Graeme Stasiuk, PhD

Reader in Imaging Chemistry
School of Biomedical Engineering and Imaging Sciences, King's College London, UK, United States
TV

Tom Vercauteren, PhD

Professor of Interventional Image Computing
School of Biomedical Engineering and Imaging Sciences, King's College London, UK, United States
FV

Francesco Vergani, MD, PhD, FRCS(NSurg)

Consultant Neurosurgeon
Department of Neurosurgery, King's College Hospital NHS Foundation Trust, UK, United States
YX

Yijing Xie, PhD

Royal Academy of Engineering Research Fellow
School of Biomedical Engineering and Imaging Sciences, King's College London, UK, United States

Introduction: Fluorescence guided surgery (FGS) in high-grade glioma (HGG) has been shown to increase resection and overall survival. FGS benefits are limited in low-grade glioma (LGG) and HGG infiltrative margins (IM) by subjectivity and low emission. Quantitative fluorescence could address these issues, however there is limited evidence and supporting data in tightly controlled conditions. We present a novel method for optically corrected spectral analysis of ex-vivo glioma fluorescence, benchmarked against non-neoplastic controls using an indicative HGG case.

Methods: Biopsy specimens were mounted with fixed ROI orientation. Spectrofluorometer measurements of emission, excitation and lifetime-decay were paired with calibrated measurements of optical properties. Morphology was assessed by a consultant neuropathologist and cell density calculated digitally. Control readings were generated from patients undergoing partial temporal lobectomy for epilepsy. Ratios of raw and corrected fluorescence versus control were calculated using algorithmic correction for optical properties integrated over the known spectra of 5-ALA/PpIX fluorescence.

Results: Twenty control samples were obtained from 4 patients and 12 samples from a single patient with a WHO Grade 4 GBM. 3 represented IM, 5 tumour-core, 4 tumour with necrosis. Tumour specimens showed high fluorescence ratios vs control for raw and corrected fluorescence: Tumour-core raw = 7.56 (p=0.003), corrected = 10.81 (p < 0.001), tumour with necrosis raw =5.26 (p=0.002), corrected = 10.41 (p < 0.001). IM raw=2.35 (p=0.025), corrected 2.61 (p=0.012). All increased following optical correction, which was marked in samples containing necrosis. Raw fluorescence correlated with cell density (R=0.615, p=0.03), which decreased following optical correction (R=0.56, p=0.06).

Conclusion : Our results suggest an ability to distinguish tumour core, necrotic tumour tissue and IM versus non-neoplastic tissue using our novel quantitative fluorescence pipeline. This forms the foundations for developing wide-field quantitative fluorescence imaging utilising hyperspectral imaging. Using this pipeline 16 HGG, 4 LGG and 4 control patients have been recruited, generating 294 specimens for validation and database population.