title: Intraoperative mass spectrometry mapping of an onco-metabolite to guide brain tumor surgery.
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.
authors: 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;
authors: Sandro
authors: S
authors: Santagata
authors: Department of Chemistry andCenter for Analytical Instrumentation Development, Purdue University, West Lafayette, IN 47907;
authors: Livia S
authors: LS
authors: Eberlin
authors: Neurosurgery, and.
authors: Isaiah
authors: I
authors: Norton
authors: Neurosurgery, and.
authors: David
authors: D
authors: Calligaris
authors: Departments of Pathology,Neurosurgery, and.
authors: Daniel R
authors: DR
authors: Feldman
authors: Neurosurgery, and.
authors: Jennifer L
authors: JL
authors: Ide
authors: Neurosurgery, and.
authors: Xiaohui
authors: X
authors: Liu
authors: Department of Chemistry andCenter for Analytical Instrumentation Development, Purdue University, West Lafayette, IN 47907;
authors: Joshua S
authors: JS
authors: Wiley
authors: Neurosurgery, and.
authors: Matthew L
authors: ML
authors: Vestal
authors: Departments of Pathology,Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115;
authors: Shakti H
authors: SH
authors: Ramkissoon
authors: Neurosurgery, and.
authors: Daniel A
authors: DA
authors: Orringer
authors: Departments of Pathology.
authors: Kristen K
authors: KK
authors: Gill
authors: Neurosurgery, and.
authors: Ian F
authors: IF
authors: Dunn
authors: Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02115; and.
authors: Dora
authors: D
authors: Dias-Santagata
authors: 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.
authors: Keith L
authors: KL
authors: Ligon
authors: Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
authors: Ferenc A
authors: FA
authors: Jolesz
authors: Neurosurgery, and.
authors: Alexandra J
authors: AJ
authors: Golby
authors: Department of Chemistry andCenter for Analytical Instrumentation Development, Purdue University, West Lafayette, IN 47907; cooks@purdue.edu Nathalie_Agar@dfci.harvard.edu.
authors: R Graham
authors: RG
authors: Cooks
authors: 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.
authors: Nathalie Y R
authors: NY
authors: Agar
mesh_terms: D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000628:therapy; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging / Q000378:metabolism / Q000601:surgery; D005977:Glutarates / Q000378:metabolism*; D006801:Humans; D007430:Intraoperative Care / Q000379:methods*; D008279:Magnetic Resonance Imaging; D008297:Male; D013058:Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D011859:Radiography
chemical_list: D005977:Glutarates; C019417:alpha-hydroxyglutarate
keywords: IDH1; brain cancer; intrasurgical diagnosis; mass spectrometry imaging; oncometabolite