The surgical intelligent knife distinguishes normal, borderline and malignant gynaecological tissues using rapid evaporative ionisation mass spectrometry (REIMS)

• Published in: British journal of cancer Vol. 118; no. 10; pp. 1349 - 1358
• Main Authors: Phelps, David L, Balog, Júlia, Gildea, Louise F, Bodai, Zsolt, Savage, Adele, El-Bahrawy, Mona A, Speller, Abigail VM, Rosini, Francesca, Kudo, Hiromi, McKenzie, James S, Brown, Robert, Takáts, Zoltán, Ghaem-Maghami, Sadaf
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2018; Nature Publishing Group
• Subjects: 631/61/320; 631/67/1517/1709; 692/4028/546; Aerosols; Biomedical and Life Sciences; Biomedicine; Cancer Research; Diagnosis; Drug Resistance; Electrosurgery - methods; Epidemiology; Ethanolamine; Female; Gynecology; Histology; Humans; Ionization; Lipid Metabolism - genetics; Lipids - genetics; Lipids - isolation & purification; Margins of Excision; Mass spectra; Mass spectrometry; Mass spectroscopy; Metabolomics; Molecular Medicine; Monitoring, Intraoperative - methods; Oncology; Ovarian cancer; Ovarian carcinoma; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - physiopathology; Ovarian Neoplasms - surgery; Phosphatidic acid; Principal Component Analysis; Scientific imaging; Sensitivity; Spectrometry, Mass, Electrospray Ionization; Surgery; Tissue analysis; Tissues; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/s41416-018-0048-3

Background Survival from ovarian cancer (OC) is improved with surgery, but surgery can be complex and tumour identification, especially for borderline ovarian tumours (BOT), is challenging. The Rapid Evaporative Ionisation Mass Spectrometric (REIMS) technique reports tissue histology in real-time by analysing aerosolised tissue during electrosurgical dissection. Methods Aerosol produced during diathermy of tissues was sampled with the REIMS interface. Histological diagnosis and mass spectra featuring complex lipid species populated a reference database on which principal component, linear discriminant and leave-one-patient-out cross-validation analyses were performed. Results A total of 198 patients provided 335 tissue samples, yielding 3384 spectra. Cross-validated OC classification vs separate normal tissues was high (97·4% sensitivity, 100% specificity). BOT were readily distinguishable from OC (sensitivity 90.5%, specificity 89.7%). Validation with fresh tissue lead to excellent OC detection (100% accuracy). Histological agreement between iKnife and histopathologist was very good (kappa 0.84, P  < 0.001, z  = 3.3). Five predominantly phosphatidic acid (PA(36:2)) and phosphatidyl-ethanolamine (PE(34:2)) lipid species were identified as being significantly more abundant in OC compared to normal tissue or BOT ( P  < 0.001, q  < 0.001). Conclusions The REIMS iKnife distinguishes gynaecological tissues by analysing mass-spectrometry-derived lipidomes from tissue diathermy aerosols. Rapid intra-operative gynaecological tissue diagnosis may improve surgical care when histology is unknown, leading to personalised operations tailored to the individual.