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Ambient ionization mass spectrometry in brain cancer diagnosis

Mahdiyeh Shahi,R. G. Cooks

Published 2025 in Journal of Mass Spectrometry and Advances in the Clinical Lab

ABSTRACT

Cancer is the second leading cause of death in the United States, and with ongoing population growth and aging, its annual incidence continues to rise. Glioma is a malignant tumor of the brain and central nervous system (CNS). Neurosurgical tumor resection is a critical component of glioma treatment, significantly affecting patient prognosis. However, due to the diffuse nature of gliomas, achieving gross total resection is challenging, and residual tumor cells often lead to recurrence and disease progression following surgery. Intraoperative cancer diagnosis using rapid and sensitive techniques, such as ambient ionization mass spectrometry (AIMS), can provide crucial molecular insights to guide surgical decision-making and potentially improve patient outcomes. AIMS techniques, including desorption electrospray ionization-mass spectrometry (DESI-MS), require minimal or no sample pretreatment, making them particularly advantageous for intraoperative applications where time efficiency is essential. Several AIMS methods have been investigated in brain cancer studies, either intraoperatively or offline, to analyze molecular alterations in cancerous tissues. Among these, DESI-MS is the most extensively reported AIMS technique in brain cancer research. This review focuses on the developments and applications of DESI-MS in both offline and intraoperative brain cancer diagnosis. Additionally, other AIMS methods employed in brain cancer research are discussed. The potential impact of AIMS techniques on glioma diagnosis is also explored. Abbreviations: 5-ALA, 5-Aminolevulinic Acid; 2HG, 2-Hydroxyglutaric Acid; AIMS, Ambient Ionization Mass Spectrometry; AI, Artificial Intelligence; Arg, Arginine; AUC, Area Under the Curve; BWH, Brigham and Women’s Hospital; CBS-MS, Coated Blade Spray Mass Spectrometry; CL, Cardiolipins; CNS, Central Nervous System; CT, Computed Tomography; CUSA, Cavitron Ultrasonic Surgical Aspirator; CUSA/SSI-MS, Cavitron Ultrasonic Surgical Aspiration/Sonic Spray Ionization Mass Spectrometry; DESI, Desorption Electrospray Ionization; DSC, Direct Sampling Cartridge; e.e.%, Enantiomeric Excess %;ESI, Electrospray Ionization; Extraction-nESI, Extraction-Nanoelectrospray Ionization; FA, Fatty Acid; FAIMS, High-Field Asymmetric Ion Mobility Spectrometry; GABA, Higher Gamma-Aminobutyric Acid; GalCer, Galactoceramides; GBM, Glioblastoma; Glu, Glutamate; PC, Glycerophosphocholines; PI, Glycerophosphoinositols; PG, Glycerophosphoglycerols; PS, Glycerophosphoserines; H&E, Hematoxylin and Eosin; HLB, Hydrophilic–Lipophilic Balance; HRMS, High Resolution Mass Spectrometry; HT, High-Throughput; ICE, Inline Cartridge Extraction; IC, Ion Counts; IDH, Isocitrate Dehydrogenase; IDH-mut, IDH-Mutant; IDH-wt, IDH-Wildtype; iKnife, Intelligent Knife; LASSO, Least Absolute Shrinkage and Selection Operator; LC, Liquid Chromatography; LDA, Linear Discriminant Analysis; LIT, Linear Ion Trap; LMJ-SSP, Liquid Micro-Junction Surface Sampling Probe; MALDI, Matrix-Assisted Laser Desorption Ionization; MB, Medulloblastoma; ML, Machine Learning; MRI, Magnetic Resonance Imaging; MRM, Multiple Reaction Monitoring; MRS, Magnetic Resonance Spectroscopy; MS, Mass Spectrometry; MS/MS, Tandem Mass Spectrometry; MSI, Mass Spectrometry Imaging; NAA, N-Acetyl-Aspartic Acid; NF2, Neurofibromatosis Type 2; NSCLC, Non-Small Cell Lung Cancer; OCT, Optical Coherence Tomography; PCA, Principal Component Analysis; PCA-LDA, Principal Component Analysis/Linear Discriminant Analysis; PE, Plasmenylethanolamines; PESI-MS, Probe Electrospray Ionization Mass Spectrometry; PG, Phosphatidylglycerol; PI, Phosphatidylinositol; PIRL-MS, Picosecond Infrared Laser Mass Spectrometry; Plasmenyl-PE, Plasmenyl Glycerophosphoethanolamines; PLS-DA, Partial Least Squares-Discriminant Analysis; PLSR, Partial Least Squares Regression; PMMA, Polymethylmethacrylate; POC, Point-of-Care; PS, Phosphatidylserines; PTFE, Polytetrafluoroethylene; REIMS, Rapid Evaporative Ionization Mass Spectrometry; SIMS, Secondary Ion Mass Spectrometry; SM, Sphingomyelins; SPME, Solid-Phase Microextraction; SSI, Sonic Spray Ionization; ST, Sulfatides; SVM, Support Vector Machine; TCP, Tumor Cell Percentage; TQ, Triple Quadrupole; TS, Touch Spray.

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