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Updated: Jun 6, 2026
On-Site Sampling and Extraction of Brain Tumors for Metabolomics and Lipidomics Analysis
Published on: May 31, 2020
Development of stereotactic mass spectrometry for brain tumor surgery
Nathalie Y R Agar1, Alexandra J Golby, Keith L Ligon
1Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. nagar@bwh.harvard.edu
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.
Insights
Mass spectrometry enables real-time, in vivo molecular tissue characterization during surgery. This technique precisely defines brain tumor boundaries, improving resection accuracy and patient outcomes without contrast agents.
Area of Science:
- Neurosurgery
- Analytical Chemistry
- Molecular Imaging
Background:
- Surgery is crucial for solid tumor treatment, but residual tumor impacts prognosis.
- Maximizing tumor resection while preserving neurological function is a key neurosurgical challenge.
- Accurate intraoperative tumor boundary definition is essential for effective surgical intervention.
Purpose of the Study:
- To integrate desorption electrospray ionization mass spectrometry (DESI-MS) into surgical procedures.
- To enable in vivo molecular tissue characterization for intraoperative tumor boundary definition.
- To achieve this without requiring systemic injection of contrast agents.
Main Methods:
- Utilized a frameless stereotactic sampling approach integrated with 3D navigation and an ultrasonic probe.
- Obtained image-registered surgical specimens for analysis.
- Analyzed samples using ambient desorption/ionization mass spectrometry (DESI-MS) and validated against histopathology.
Main Results:
- Demonstrated proof of concept for intraoperative mass spectrometry in real-time molecular measurement.
- Successfully detected tumor boundaries by correlating lipid constitution with tumor cell prevalence in an oligodendroglioma.
- Achieved high sensitivity and specificity in spatially resolved molecular tissue characterization.
Conclusions:
- Mass spectrometry measurements reveal complex molecular structures, enabling 3D molecular imaging.
- Integration with frameless stereotaxy and imaging provides detailed surgical margin delineation.
- This rapid, agent-free method is applicable to surgical margins of any organ.
