Intraoperative Mass Spectrometry for Personalized Treatment of Brain Tumors

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Dr. Agar has recently set up a new laboratory at BWH, oriented towards the validation and implementation of spectroscopic applications to serve surgical and clinical needs in cancer patient care. The interdisciplinary laboratory structure is innovative in itself as it is the fruit of a concerted effort between the Departments of Neurosurgery, Radiology, and Pathology at BWH to create an environment capitalizing on cross-discipline approaches to expedite progress in personalized medicine. The laboratory will soon harbor high-end mass spectrometers, as well as an NMR magnet dedicated to clinical magnetic resonance spectroscopy (MRS), and a specialized microscope scanner to allow telepathology and validation of spectroscopic approaches to the gold standard of histopathology.

Dr. Agar’s own multidisciplinary training has evolved from B.Sc. in Biochemistry, Ph.D. in Chemistry, Postdoctoral training in Neurology and Neurosurgery from McGill University, and Postdoctoral training in Neurosurgery at the Brigham and Women’s Hospital in the laboratory of Dr. Peter Black. Through this distinctive training, she has acquired knowledge and developed skills to better understand requirements and limitations related to technology implementation from the instrumentation standpoint, to sample and data analysis, to cancer and surgical needs, and to medical environment.

The scope of her initial project supported by the Brain Science Foundation is the development of a rapid, accurate, and high-throughput approach for characterizing meningiomas and other brain tumors at the molecular level at the time of surgery. The technology, called Matrix Assisted Laser Desorption Ionization (MALDI) Mass Spectrometry Imaging (MSI), provides information on hundreds of proteins from frozen tumor tissue in minutes.

Biochemical factors responsible for tumor development, maintenance, and progression vary from one cancer to another, as well as from one patient to another. A comprehensive molecular diagnosis obtained during surgery will enable surgeons to tailor treatment during surgery by knowing how aggressive and invasive a tumor may be by its biochemical profile, and can form the basis for adjuvant therapy such as chemotherapy including agents given into the tumor cavity at the time of surgery, and will orient the choice of chemotherapy given systemically.

With prognosis being intimately related to the appropriateness of treatment modality, identifying and grading tumors with such high sensitivity and molecular accuracy would maximize treatment efficacy. Current diagnosis and treatment rely upon observations of tissue and cellular characteristics such as proliferation, cellular and nuclear morphology, vascularization, and specific available biomarkers. Current histopathological approaches would certainly be augmented by the proposed detailed molecular profiling.

BSF awarded funding for this project in 2009 and 2010.