Abstract

Immediate, real-time accurate tissue characterisation is a crucial unmet need during surgery for the maximal resection of CNS tumours whilst causing minimum damage to surrounding functioning brain tissue. We describe the first ever use of mass spectrometry and Raman spectroscopy to immediately characterize brain tumours during surgery with accuracy rivaling that of traditional histopathological techniques. A prospective observational study was designed consisting of 40 patients undergoing Neurosurgical resection of a range of WHO grade I-IV brain tumours and metastases. A Neuronavigational platform was devised combining advanced spectrometry technologies together with intraoperative imaging to allow accurate 3D spectral acquisition during surgery taking into account brain shift. The resulting data from 40 cases consists of over 1,500 brain spectra acquired during surgery with high spatial localization. Analysis shows unique spectra for each type of tumour with sensitivity and specificity comparable to the current gold standard of histopathological analysis. The spatial heterogeneity of tumour spectra sheds important light into underlying genomic and metabolomic profiles of the tumours studied including IDH-1 mutation and MGMT status. We have demonstrated that the use of molecular data with high spatial resolution obtained through mass spectral and Raman spectral analysis shows that real-time biopsies are obtainable and represent an invaluable resource in the decision making process during surgery. This also represents an opportunity to fast track vital post surgical therapies currently offered to high grade brain tumours and investigate novel aspects of in-vivo tumour biology through a new modality with the possibility of novel biomarker discovery. This sets the stage for a formal clinical trial looking into the benefits of spectral guided resection in terms of safer and more complete resection, rapid progress to further treatment and improved overall survival.

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