Nathalie Y.R. Agar, Ph.D.
Assistant Professor of Neurosurgery
Assistant Professor of Radiology
Harvard Medical School
Department of Neurosurgery
Brigham and Women's Hospital
Department of Cancer Biology
Dana-Farber Cancer Institute
Boston, MA 02115
Monday, April 14, 2014, 10:30 AM
140 The Fenway, conference suite 378TF
“Mass Spectrometry Imaging for Brain Tumors:
Molecular Pathology and Drug Development”
Mass spectrometry provides a new tool for the direct imaging of tissue during neurosurgery, and can also provide
significant insight in the development of drugs targeting tumors of the central nervous system. Using desorption
electrospray ionization mass spectrometry (DESI MS), we rapidly detect tumor metabolites from tissue sections of
surgically-resected gliomas without complex or time-consuming preparation.
The method was validated by correlating 2D mass spectrometry imaging of glioma specimens with histopathology, and
used to detect tumor tissue within seconds to minutes. Imaging tissue sections with DESI MS shows that diagnostic
molecular signatures overlap with areas of tumor, thereby indicating tumor margins. We have installed a mass
spectrometer in our Advanced Multimodality Image Guided Operating (AMIGO) suite at BWH and demonstrate the
molecular analysis of surgical tissue during brain surgery. Drug transit through the blood-brain barrier (BBB) is essential
for therapeutic responses in brain tumors. Using matrix assisted laser desorption ionization mass spectrometry imaging
(MALDI MSI) in pre-clinical animal models, we visualize drug and metabolites penetration in brain tissue without
molecular labeling. We validated heme as a simple and robust MALDI MSI marker of the vasculature and go on to
provide examples of how MALDI MSI can provide chemical and biological insights into BBB penetrance and metabolism
of small molecule signal transduction inhibitors in the brain.
Nathalie Y.R. Agar, Ph.D. is the founding Director of the Surgical Molecular Imaging Laboratory (SMIL) in the Department of Neurosurgery at
Brigham and Women’s Hospital, and an Assistant Professor of Neurosurgery and Radiology at Harvard Medical School. Dr. Agar’s multidisciplinary
training includes a B.Sc. in Biochemistry, Ph.D. in Chemistry, a postdoctoral fellowship in Neurology and Neurosurgery from McGill University, and
further postdoctoral training in Neurosurgery at Brigham and Women’s Hospital. From this unique background, she has developed distinct skills to
better understand the requirements and limitations regarding the implementation of novel instrumentation, sample and data analysis, and cancer
and surgical needs in the medical environment. She has also developed a network of specialists to satisfy the many different aspects of
translational research activities.
Her research aims to develop and implement comprehensive molecular diagnoses through improved biochemical classifications. This will
ultimately enable surgeons and oncologists to tailor treatment from the time of surgery, and allow personalized cancer care using molecular
imaging with mass spectrometry. She is also developing and validating a direct in vivo mass spectrometry analysis of surgical tissue to assist in the
evaluation of tumor margins. This state-of-the-art application relies on the integration of a surgical probe with an ambient ionization mass
spectrometry probe. Her laboratory also focuses on the mass spectrometry imaging of drugs and metabolites from pre-clinical animal models to
clinical trials’ samples to study and screen for targeted therapeutics for brain cancers considering their ability to access the central nervous system.
For more information, please contact Nancy Carbone at n.carbone@neu.edu or http://www.northeastern.edu/barnett/?p=803