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Ex Vivo Raman Spectrochemical Analysis Using a Handheld Probe Demonstrates High Predictive Capability of Brain Tumour Status

1
School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK
2
Neuropathology, Royal Preston Hospital, Lancashire Teaching Hospitals NHS Trust, Sharoe Green Lane, Preston PR2 9HT, UK
*
Author to whom correspondence should be addressed.
Biosensors 2019, 9(2), 49; https://doi.org/10.3390/bios9020049
Received: 9 March 2019 / Revised: 25 March 2019 / Accepted: 29 March 2019 / Published: 30 March 2019
(This article belongs to the Special Issue Spectroscopy-Based Biosensors)
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Abstract

With brain tumour incidence increasing, there is an urgent need for better diagnostic tools. Intraoperatively, brain tumours are diagnosed using a smear preparation reported by a neuropathologist. These have many limitations, including the time taken for the specimen to reach the pathology department and for results to be communicated to the surgeon. There is also a need to assist with resection rates and identifying infiltrative tumour edges intraoperatively to improve clearance. We present a novel study using a handheld Raman probe in conjunction with gold nanoparticles, to detect primary and metastatic brain tumours from fresh brain tissue sent for intraoperative smear diagnosis. Fresh brain tissue samples sent for intraoperative smear diagnosis were tested using the handheld Raman probe after application of gold nanoparticles. Derived Raman spectra were inputted into forward feature extraction algorithms to build a predictive model for sensitivity and specificity of outcome. These results demonstrate an ability to detect primary from metastatic tumours (especially for normal and low grade lesions), in which accuracy, sensitivity and specificity were respectively equal to 98.6%, 94.4% and 99.5% for normal brain tissue; 96.1%, 92.2% and 97.0% for low grade glial tumours; 90.3%, 89.7% and 90.6% for high grade glial tumours; 94.8%, 63.9% and 97.1% for meningiomas; 95.4%, 79.2% and 98.8% for metastases; and 99.6%, 88.9% and 100% for lymphoma, based on smear samples (κ = 0.87). Similar results were observed when compared to the final formalin-fixed paraffin embedded tissue diagnosis (κ = 0.85). Overall, our results have demonstrated the ability of Raman spectroscopy to match results provided by intraoperative smear diagnosis and raise the possibility of use intraoperatively to aid surgeons by providing faster diagnosis. Moving this technology into theatre will allow it to develop further and thus reach its potential in the clinical arena. View Full-Text
Keywords: brain tumour diagnosis; classification; forward feature extraction algorithm; intraoperative use; Raman spectroscopy; Raman probe brain tumour diagnosis; classification; forward feature extraction algorithm; intraoperative use; Raman spectroscopy; Raman probe
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Bury, D.; Morais, C.L.M.; Ashton, K.M.; Dawson, T.P.; Martin, F.L. Ex Vivo Raman Spectrochemical Analysis Using a Handheld Probe Demonstrates High Predictive Capability of Brain Tumour Status. Biosensors 2019, 9, 49.

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