The real-time molecular characterisation of human brain tumours during surgery using Rapid Evaporative Ionization Mass Spectrometry [REIMS] and Raman spectroscopy: a platform for precision medicine in neurosurgery

Aim: To investigate new methods for the chemical detection of tumour tissue during neurosurgery. Rationale: Surgeons operating on brain tumours currently lack the ability to directly and immediately assess the presence of tumour tissue to help guide resection. Through developing a first in human application of new technology we hope to demonstrate the proof of concept that chemical detection of tumour tissue is possible. It will be further demonstrated that information can be obtained to potentially aid treatment decisions. This new technology could, therefore, become a platform for more effective surgery and introducing precision medicine to Neurosurgery. Methods: Molecular analysis was performed using Raman spectroscopy and Rapid Evaporative Ionization Mass Spectrometry (REIMS). These systems were first developed for use in brain surgery. A single centre prospective observational study of both modalities was designed involving a total of 75 patients undergoing craniotomy and resection of a range of brain tumours. A neuronavigation system was used to register spectral readings in 3D space. Precise intraoperative readings from different tumour zones were taken and compared to matched core biopsy samples verified by routine histopathology. Results: Multivariate statistics including PCA/LDA analysis was used to analyse the spectra obtained and compare these to the histological data. The systems identified normal versus tumour tissue, tumour grade, tumour type, tumour density and tissue status of key markers of gliomagenesis. Conclusions: The work in this thesis provides proof of concept that useful real time intraoperative spectroscopy is possible. It can integrate well with the current operating room setup to provide key information which could potentially enhance surgical safety and effectiveness in increasing extent of resection. The ability to group tissue samples with respect to genomic data opens up the possibility of using this information during surgery to speed up treatment, escalate/deescalate surgery in specific phenotypic groups to introduce precision medicine to Neurosurgery.Open Acces