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Development of Stereotactic Mass Spectrometry for Brain Tumor Surgery

Agar, Nathalie YR PhD*; Golby, Alexandra J MD*†; Ligon, Keith L MD, PhD‡; Norton, Isaiah BS*; Mohan, Vandana PhD§; Wiseman, Justin M PhD∥; Tannenbaum, Allen PhD¶; Jolesz, Ferenc A MD†

doi: 10.1227/NEU.0b013e3181ff9cbb
Concepts, Innovations, and Techniques: Editor's Choice

BACKGROUND: Surgery remains the first and most important treatment modality for the majority of solid tumors. Across a range of brain tumor types and grades, postoperative residual tumor has a great impact on prognosis. The principal challenge and objective of neurosurgical intervention is therefore to maximize tumor resection while minimizing the potential for neurological deficit by preserving critical tissue.

OBJECTIVE: To introduce the integration of desorption electrospray ionization mass spectrometry into surgery for in vivo molecular tissue characterization and intraoperative definition of tumor boundaries without systemic injection of contrast agents.

METHODS: Using a frameless stereotactic sampling approach and by integrating a 3-dimensional navigation system with an ultrasonic surgical probe, we obtained image-registered surgical specimens. The samples were analyzed with ambient desorption/ionization mass spectrometry and validated against standard histopathology. This new approach will enable neurosurgeons to detect tumor infiltration of the normal brain intraoperatively with mass spectrometry and to obtain spatially resolved molecular tissue characterization without any exogenous agent and with high sensitivity and specificity.

RESULTS: Proof of concept is presented in using mass spectrometry intraoperatively for real-time measurement of molecular structure and using that tissue characterization method to detect tumor boundaries. Multiple sampling sites within the tumor mass were defined for a patient with a recurrent left frontal oligodendroglioma, World Health Organization grade II with chromosome 1p/19q codeletion, and mass spectrometry data indicated a correlation between lipid constitution and tumor cell prevalence.

CONCLUSION: The mass spectrometry measurements reflect a complex molecular structure and are integrated with frameless stereotaxy and imaging, providing 3-dimensional molecular imaging without systemic injection of any agents, which can be implemented for surgical margins delineation of any organ and with a rapidity that allows real-time analysis.

*Department of Neurosurgery, †Department of Radiology, and ‡Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; §Schools of Electrical and Computer and Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia; ∥Prosolia, Inc, Indianapolis, Indiana; and ¶Schools of Electrical and Computer and Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia

Received, November 13, 2009.

Accepted, June 28, 2010.

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Correspondence: Nathalie Y.R. Agar, PhD, Department of Neurosurgery, Brigham and Women's Hospital/Harvard Medical School, 221 Longwood Ave, BLI-137, Boston, MA 02115. E-mail:

Copyright © by the Congress of Neurological Surgeons