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Rapid Evaporative Ionisation Mass Spectrometry of Electrosurgical Vapours for the Identification of Breast Pathology: Towards an Intelligent Knife for Breast Cancer Surgery

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Title: Rapid Evaporative Ionisation Mass Spectrometry of Electrosurgical Vapours for the Identification of Breast Pathology: Towards an Intelligent Knife for Breast Cancer Surgery
Authors: St John, ERC
Leff, D
Takats, Z
Darzi, A
Item Type: Journal Article
Abstract: Background: Re-operation for positive resection margins following breast-conserving surgery occurs frequently (average = 20–25%), is cost-inefficient, and leads to physical and psychological morbidity. Current margin assessment techniques are slow and labour intensive. Rapid evaporative ionisation mass spectrometry (REIMS) rapidly identifies dissected tissues by determination of tissue structural lipid profiles through on-line chemical analysis of electrosurgical aerosol toward real-time margin assessment. Methods: Electrosurgical aerosol produced from ex-vivo and in-vivo breast samples was aspirated into a mass spectrometer (MS) using a monopolar hand-piece. Tissue identification results obtained by multivariate statistical analysis of MS data were validated by histopathology. Ex-vivo classification models were constructed from a mass spectral database of normal and tumour breast samples. Univariate and tandem MS analysis of significant peaks was conducted to identify biochemical differences between normal and cancerous tissues. An ex-vivo classification model was used in combination with bespoke recognition software, as an intelligent knife (iKnife), to predict the diagnosis for an ex-vivo validation set. Intraoperative REIMS data were acquired during breast surgery and time-synchronized to operative videos. Results: A classification model using histologically validated spectral data acquired from 932 sampling points in normal tissue and 226 in tumour tissue provided 93.4% sensitivity and 94.9% specificity. Tandem MS identified 63 phospholipids and 6 triglyceride species responsible for 24 spectral differences between tissue types. iKnife recognition accuracy with 260 newly acquired fresh and frozen breast tissue specimens (normal n = 161, tumour n = 99) provided sensitivity of 90.9% and specificity of 98.8%. The ex-vivo and intra-operative method produced visually comparable high intensity spectra. iKnife interpretation of intra-operative electrosurgical vapours, including data acquisition and analysis was possible within a mean of 1.80 seconds (SD ±0.40). Conclusions: The REIMS method has been optimised for real-time iKnife analysis of heterogeneous breast tissues based on subtle changes in lipid metabolism, and the results suggest spectral analysis is both accurate and rapid. Proof-of-concept data demonstrate the iKnife method is capable of online intraoperative data collection and analysis. Further validation studies are required to determine the accuracy of intra-operative REIMS for oncological margin assessment.
Issue Date: 23-May-2017
Date of Acceptance: 25-Apr-2017
URI: http://hdl.handle.net/10044/1/46147
DOI: https://dx.doi.org/10.1186/s13058-017-0845-2
ISSN: 1465-542X
Publisher: BioMed Central
Journal / Book Title: Breast Cancer Research
Volume: 19
Issue: 1
Copyright Statement: © 2017 The Author(s). Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Sponsor/Funder: Micromass UK Ltd
Royal College Of Surgeons Of England
Funder's Grant Number: ICL 01/02/03
WSSS_P63613
Keywords: Breast
Cancer
Intelligent knife
Intraoperative margin assessment
Margins
Mass spectrometry
REIMS
Rapid evaporative ionisation mass spectrometry
Surgery
iKnife
1112 Oncology And Carcinogenesis
Publication Status: Published
Article Number: 59
Appears in Collections:Division of Surgery
Department of Medicine
Faculty of Medicine



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