Intraoperative Tissue Identification Using Rapid Evaporative Ionization Mass Spectrometry

Sci Transl Med 17 July 2013:
Vol. 5, Issue 194, p. 194ra93
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3005623

• Research Article

CANCER DIAGNOSTICS

Intraoperative Tissue Identification Using Rapid Evaporative Ionization Mass Spectrometry

1. Júlia Balog¹,*,
2. László Sasi-Szabó²,*,
3. James Kinross³,⁴,
4. Matthew R. Lewis³,
5. Laura J. Muirhead³,⁴,
6. Kirill Veselkov³,
7. Reza Mirnezami⁴,
8. Balázs Dezső⁵,
9. László Damjanovich²,
10. Ara Darzi⁴,
11. Jeremy K. Nicholson³,† and
12. Zoltán Takáts³,†

+ Author Affiliations

1. ¹MediMass Ltd., 1033 Budapest, Hungary.
2. ²Institute of Surgery, Medical and Health Science Centre, University of Debrecen, 4032 Debrecen, Hungary.
3. ³Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Sir Alexander Fleming Building, Imperial College London, London SW7 2AZ, UK.
4. ⁴Section of Biosurgery and Surgical Technology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, QEQM, St. Mary’s Hospital, London W2 1NY, UK.
5. ⁵Institute of Pathology, Medical and Health Science Centre, University of Debrecen, 4032 Debrecen, Hungary.

+ Author Notes

• ↵* These authors contributed equally to this work.

1. ↵†Corresponding author. E-mail: z.takats@imperial.ac.uk (Z.T.); j.nicholson@imperial.ac.uk (J.K.N.)

Abstract

Rapid evaporative ionization mass spectrometry (REIMS) is an emerging technique that allows near–real-time characterization of human tissue in vivo by analysis of the aerosol (“smoke”) released during electrosurgical dissection. The coupling of REIMS technology with electrosurgery for tissue diagnostics is known as the intelligent knife (iKnife). This study aimed to validate the technique by applying it to the analysis of fresh human tissue samples ex vivo and to demonstrate the translation to real-time use in vivo in a surgical environment. A variety of tissue samples from 302 patients were analyzed in the laboratory, resulting in 1624 cancerous and 1309 noncancerous database entries. The technology was then transferred to the operating theater, where the device was coupled to existing electrosurgical equipment to collect data during a total of 81 resections. Mass spectrometric data were analyzed using multivariate statistical methods, including principal components analysis (PCA) and linear discriminant analysis (LDA), and a spectral identification algorithm using a similar approach was implemented. The REIMS approach differentiated accurately between distinct histological and histopathological tissue types, with malignant tissues yielding chemical characteristics specific to their histopathological subtypes. Tissue identification via intraoperative REIMS matched the postoperative histological diagnosis in 100% (all 81) of the cases studied. The mass spectra reflected lipidomic profiles that varied between distinct histological tumor types and also between primary and metastatic tumors. Thus, in addition to real-time diagnostic information, the spectra provided additional information on divergent tumor biochemistry that may have mechanistic importance in cancer.

• Copyright © 2013, American Association for the Advancement of Science

Citation: J. Balog, L. Sasi-Szabó, J. Kinross, M. R. Lewis, L. J. Muirhead, K. Veselkov, R. Mirnezami, B. Dezső, L. Damjanovich, A. Darzi, J. K. Nicholson, Z. Takáts, Intraoperative Tissue Identification Using Rapid Evaporative Ionization Mass Spectrometry. Sci. Transl. Med. 5, 194ra93 (2013).

Read the Full Text

The editors suggest the following Related Resources on Science sites Back to Top

In Science Translational Medicine

• Research Article: Proteomics Reproducible Quantification of Cancer-Associated Proteins in Body Fluids Using Targeted Proteomics

  • Ruth Hüttenhain,
  • Martin Soste,
  • Nathalie Selevsek,
  • Hannes Röst,
  • Atul Sethi,
  • Christine Carapito,
  • Terry Farrah,
  • Eric W. Deutsch,
  • Ulrike Kusebauch,
  • Robert L. Moritz,
  • Emma Niméus-Malmström,
  • Oliver Rinner,
  • and Ruedi Aebersold

  Sci Transl Med 11 July 2012 4:142ra94
  • Editor's Summary
  • Abstract
  • Full Text
  • Full Text (PDF)
  • Supplementary Materials
• Reports: Metabolism Differential Metabolic Impact of Gastric Bypass Surgery Versus Dietary Intervention in Obese Diabetic Subjects Despite Identical Weight Loss

  • Blandine Laferrère,
  • David Reilly,
  • Sara Arias,
  • Nicholas Swerdlow,
  • Prakash Gorroochurn,
  • Baani Bawa,
  • Mousumi Bose,
  • Julio Teixeira,
  • Robert D. Stevens,
  • Brett R. Wenner,
  • James R. Bain,
  • Michael J. Muehlbauer,
  • Andrea Haqq,
  • Lillian Lien,
  • Svati H. Shah,
  • Laura P. Svetkey,
  • and Christopher B. Newgard

  Sci Transl Med 27 April 2011 3:80re2
  • Editor's Summary
  • Abstract
  • Full Text
  • Full Text (PDF)
  • Supplementary Materials
• Research Article: Exercise and Metabolism Metabolic Signatures of Exercise in Human Plasma

  • Gregory D. Lewis,
  • Laurie Farrell,
  • Malissa J. Wood,
  • Maryann Martinovic,
  • Zoltan Arany,
  • Glenn C. Rowe,
  • Amanda Souza,
  • Susan Cheng,
  • Elizabeth L. McCabe,
  • Elaine Yang,
  • Xu Shi,
  • Rahul Deo,
  • Frederick P. Roth,
  • Aarti Asnani,
  • Eugene P. Rhee,
  • David M. Systrom,
  • Marc J. Semigran,
  • Ramachandran S. Vasan,
  • Steven A. Carr,
  • Thomas J. Wang,
  • Marc S. Sabatine,
  • Clary B. Clish,
  • and Robert E. Gerszten

  Sci Transl Med 26 May 2010 2:33ra37
  • Editor's Summary
  • Abstract
  • Full Text
  • Full Text (PDF)
  • Supplementary Material
• Research Article: Cancer Metabolomic Imaging for Human Prostate Cancer Detection

  • Chin-Lee Wu,
  • Kate W. Jordan,
  • Eva M. Ratai,
  • Jinhua Sheng,
  • Christen B. Adkins,
  • Elita M. DeFeo,
  • Bruce G. Jenkins,
  • Leslie Ying,
  • W. Scott McDougal,
  • and Leo L. Cheng

  Sci Transl Med 27 January 2010 2:16ra8
  • Editor's Summary
  • Abstract
  • Full Text
  • Full Text (PDF)