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Proc Natl Acad Sci U S A. 2014 Jul 29;111(30):11121-6. doi: 10.1073/pnas.1404724111. Epub 2014 Jun 30.

Intraoperative mass spectrometry mapping of an onco-metabolite to guide brain tumor surgery.

Author information

1
Departments of Pathology,Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115;Department of Cancer Biology, Harvard Medical School and Dana-Farber Cancer Institute, Boston, MA 02115;
2
Department of Chemistry andCenter for Analytical Instrumentation Development, Purdue University, West Lafayette, IN 47907;
3
Neurosurgery, and.
4
Departments of Pathology,Neurosurgery, and.
5
Departments of Pathology,Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115;
6
Departments of Pathology.
7
Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02115; and.
8
Departments of Pathology,Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115;Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02215.
9
Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
10
Department of Chemistry andCenter for Analytical Instrumentation Development, Purdue University, West Lafayette, IN 47907; cooks@purdue.edu Nathalie_Agar@dfci.harvard.edu.
11
Department of Cancer Biology, Harvard Medical School and Dana-Farber Cancer Institute, Boston, MA 02115;Neurosurgery, andRadiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; cooks@purdue.edu Nathalie_Agar@dfci.harvard.edu.

Abstract

For many intraoperative decisions surgeons depend on frozen section pathology, a technique developed over 150 y ago. Technical innovations that permit rapid molecular characterization of tissue samples at the time of surgery are needed. Here, using desorption electrospray ionization (DESI) MS, we rapidly detect the tumor metabolite 2-hydroxyglutarate (2-HG) from tissue sections of surgically resected gliomas, under ambient conditions and without complex or time-consuming preparation. With DESI MS, we identify isocitrate dehydrogenase 1-mutant tumors with both high sensitivity and specificity within minutes, immediately providing critical diagnostic, prognostic, and predictive information. Imaging tissue sections with DESI MS shows that the 2-HG signal overlaps with areas of tumor and that 2-HG levels correlate with tumor content, thereby indicating tumor margins. Mapping the 2-HG signal onto 3D MRI reconstructions of tumors allows the integration of molecular and radiologic information for enhanced clinical decision making. We also validate the methodology and its deployment in the operating room: We have installed a mass spectrometer in our Advanced Multimodality Image Guided Operating (AMIGO) suite and demonstrate the molecular analysis of surgical tissue during brain surgery. This work indicates that metabolite-imaging MS could transform many aspects of surgical care.

KEYWORDS:

IDH1; brain cancer; intrasurgical diagnosis; mass spectrometry imaging; oncometabolite

PMID:
24982150
PMCID:
PMC4121790
DOI:
10.1073/pnas.1404724111
[Indexed for MEDLINE]
Free PMC Article

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