Complementary Molecular and Elemental Mass-Spectrometric Imaging of Human Brain Tumors Resected by Fluorescence-Guided Surgery.
Sabrina KrögerAnn-Christin NiehoffAstrid JeibmannMichael SperlingWerner PaulusWalter StummerUwe KarstPublished in: Analytical chemistry (2018)
Fluorescence-guided surgery (FGS) has been established as a powerful technique for glioblastoma resection. After oral application of the prodrug 5-aminolevulinic acid (5-ALA), protoporphyrin IX (PpIX) is formed as an intermediate of the heme-biosynthesis cascade and accumulates within the tumor. By intraoperative fluorescence microscopy, the specific PpIX fluorescence can be used to differentiate the tumor from healthy brain tissue. To investigate possible limitations of fluorescence diagnosis, the complementary use of molecular and elemental mass-spectrometry imaging (MSI) is presented. Matrix-assisted laser-desorption-ionization mass spectrometry (MALDI-MS) is used to examine the distribution of PpIX and heme b in human brain tumors. MALDI-MS/MS imaging is performed to validate MS data and improve the signal-to-noise ratio (S/N). Comparing the imaging results with histological evaluation, increased PpIX accumulation in areas of high tumor-cell density is observed. Heme b accumulation are only found in areas of blood vessels and hemorrhage, confirming the hampered transformation from PpIX to heme b in glioblastoma tissue. Investigation of non-neoplastic brain tissue and glioblastoma resected without external 5-ALA administration as control samples with true-negative fluorescence verified the absence of PpIX accumulation. Analysis of necrotic tumor tissue and gliosarcoma, one rare type of glioma appearing nonfluorescent during FGS, as case examples with false-negative-fluorescence diagnosis, revealed the absence of significant amounts of PpIX, indicating an impairment of PpIX formation. Molecular analysis is complemented by quantitative laser ablation-inductively coupled plasma (LA-ICP) MSI correlating heme b and Fe distribution. Mathematical pixel-by-pixel correlation of molecular and elemental data revealed a positive correlation with heteroscedasticity for the spatially resolved heme b signal intensities and Fe concentrations.
Keyphrases
- mass spectrometry
- single molecule
- high resolution
- ms ms
- energy transfer
- liquid chromatography
- minimally invasive
- endothelial cells
- capillary electrophoresis
- single cell
- gas chromatography
- multiple sclerosis
- coronary artery bypass
- photodynamic therapy
- stem cells
- induced pluripotent stem cells
- electronic health record
- deep learning
- big data
- coronary artery disease
- drug delivery
- machine learning
- cerebral ischemia
- bone marrow
- fluorescence imaging
- cancer therapy
- metal organic framework
- prognostic factors
- optical coherence tomography
- high resolution mass spectrometry
- blood brain barrier