The Role of Vibrational Spectroscopy in the Diagnosis of Brain Tumours

Abstract

With the incidence of many cancers, including brain tumours, increasing worldwide, the diagnostic pathway and new innovative treatments have often failed to keep pace. The main stay of cancer diagnosis remains at the Histopathologists’ microscope, with little change in light microscopy within recent times. Research promises many new diagnostic tools, aiming to improve turn around times and provide instant accurate answers. One such tool is vibrational spectroscopy. This thesis aims to use spectroscopy as a proof of concept within brain tumour diagnostics to demonstrate its abilities within the cancer diagnostic pathway.
Proof of concept studies aimed at targeting both biofluid and tissue diagnosis of primary and metastatic brain tumours has been performed, along with involvement of Patients’ and Clinicians’ to aid development of diagnostic tools. Spectrochemical methods including Raman and attenuated total reflectance- Fourier transform infrared spectroscopy (ATR-FTIR) have shown an ability to diagnose primary and metastatic tumours; with fresh frozen tissue ATR-FTIR proved superior with a classification
accuracy of non-tumour brain versus primary brain tumours of 97.2%, though this decreased when comparing tumour types (79% accuracy); when differentiating metastatic brain tumours from formalin fixed tissue accuracy was similar for both
spectroscopic techniques at 60% for colorectal adenocarcinomas, 68% for lung adenocarcinomas and 70% for melanoma; finally, with biofluids, using ATR-FTIR to determine a primary versus metastatic tumour and the type of each tumour, accuracy was low at non tumour 85%, high grade glioma 92%, low grade glioma 61%, meningioma 43%, melanoma metastasis 21%, colorectal adenocarcinoma metastasis 50% and lung adenocarcinoma metastasis 24%. The final, novel study, trialled a handheld Raman spectrometer within the histopathology department at Royal Preston Hospital, Lancashire
Teaching Hospitals NHS Trust, to determine if the benefits of spectroscopy lay within the intraoperative diagnosis. The final results demonstrate accuracies from 64-94% depending on tumour type, demonstrating that with further training, Raman spectroscopy may provide a clinically useful diagnostic tool within the operating theatre, to replace the need for intraoperative smear preparations and diagnosis by a Neuropathologist.
Overall, this thesis highlights the need to involve Patients’ and Clinicians’ within research to ensure uptake and accurately targeted diagnostic tools. It also demonstrates the potential of spectroscopy, when well targeted within the diagnostic pathway. Moving forward, further work to move Raman spectroscopy into the operating theatre, is likely to prove beneficial to patients.