Intraoperative assessment of tumor margins during glioma resection by desorption electrospray ionization-mass spectrometry

Valentina Pirro, Clint M. Alfaro, Alan K. Jarmusch, Eyas M. Hattab, Aaron A. Cohen-Gadol, R. Graham Cooks

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Intraoperative desorption electrospray ionization-mass spectrometry (DESI-MS) is used to characterize tissue smears by comparison with a library of DESI mass spectra of pathologically determined tissue types. Measurements are performed in the operating room within 3 min. These mass spectra provide direct information on tumor infiltration into white or gray brain matter based on N-acetylaspartate (NAA) and on membrane-derived complex lipids. The mass spectra also indicate the isocitrate dehydrogenase mutation status of the tumor via detection of 2-hydroxyglutarate, currently assessed postoperatively on biopsied tissue using immunohistochemistry. Intraoperative DESI-MS measurements made at surgeon-defined positions enable assessment of relevant disease state of tissue within the tumor mass and examination of the resection cavity walls for residual tumor. Results for 73 biopsies from 10 surgical resection cases show that DESI-MS allows detection of glioma and estimation of high tumor cell percentage (TCP) at surgical margins with 93% sensitivity and 83% specificity. TCP measurements from NAA are corroborated by indirect measurements based on lipid profiles. Notably, high percentages (>50%) of unresected tumor were found in one-half of the margin biopsy smears, even in cases where postoperative MRI suggested gross total tumor resection. Unresected tumor causes recurrence and malignant progression, as observed within a year in one case examined in this study. These results corroborate the utility of DESI-MS in assessing surgical margins for maximal safe tumor resection. Intraoperative DESI-MS analysis of tissue smears, ex vivo, can be inserted into the current surgical workflow with no alterations. The data underscore the complexity of glioma infiltrations.

Original languageEnglish (US)
Pages (from-to)6700-6705
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number26
DOIs
StatePublished - Jun 27 2017

Keywords

  • Ambient ionization
  • Glioma
  • Lipids
  • Neurological smears
  • Tumor infiltration

ASJC Scopus subject areas

  • General

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