MSACL 2016 US Abstract

Mass Spectrometry for Image Guided Neurosurgery and Drug Development

Nathalie Agar (Presenter)
Brigham and Women's Hospital, Harvard Medical School

Short Abstract

Mass spectrometry provides multiple options for the direct characterization of tissue to support surgical decision-making, and provides significant insight in the development of drugs targeting tumors of the central nervous system (CNS). Using an array of mass spectrometry (MS) applications, we rapidly analyze specific tumor markers such as metabolites, fatty acids, lipids, and proteins from surgical tissue for surgical guidance and rapid diagnosis. Using similar clinical protocols, we visualize drug and metabolites penetration in brain tumor tissue and correlate with tumor heterogeneity and response to support drug development.

Long Abstract

Mass spectrometry provides multiple options for the direct characterization of tissue to support surgical decision-making, and provides significant insight in the development of drugs targeting tumors of the central nervous system (CNS).

Using ambient ionization mass spectrometry (MS), we rapidly detect tumor metabolites such as 2-hydroxyglutarate, fatty acids, and lipids from surgical tissue without complex or time-consuming preparation. The method was validated by correlating 2D mass spectrometry imaging (MSI) of brain tumor specimens with histopathology and MRI, and used to detect tumor tissue within seconds to minutes. Imaging tissue sections with ambient MS shows that molecular signatures overlap with areas of tumor, and reveal diagnostic features in tumors such as gliomas and meningiomas. We have installed a mass spectrometer in our Advanced Multimodality Image Guided Operating (AMIGO) suite at Brigham and Women's Hospital and validate the molecular characterization of surgical tissue during brain tumor surgery, and more recently breast conserving surgery for the management of breast cancer. Using matrix assisted laser desorption ionization (MALDI) MSI we can further detect specific peptide and protein hormones in tumors of the pituitary gland during surgery for the lateralization and more specific localization of functioning and non-functioning adenomas. Using different MALDI MSI approaches for the analysis of pre-clinical animal models and clinical trial samples, we visualize drug and metabolites penetration in brain tumor tissue and correlate with tumor heterogeneity and response.


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