How Suitable is Matrix-Assisted Laser Desorption/Ionization-Time-of-Flight for Metabolite Imaging from Clinical Formalin-Fixed and Paraffin-Embedded Tissue Samples in Comparison to Matrix-Assisted Laser Desorption/Ionization-Fourier Transform Ion Cyclotron Resonance Mass Spectrometry?

In research and clinical settings, formalin-fixed and paraffin-embedded (FFPE) tissue specimens are collected routinely and therefore this material constitutes a highly valuable source to gather insight in metabolic changes of diseases. Among mass spectrometry techniques to examine the molecular content of FFPE tissue, mass spectrometry imaging (MSI) is the most appropriate when morphological and histological features are to be related to metabolic information. Currently, high-resolution mass spectrometers are widely used for metabolomics studies. However, with regards to matrix-assisted laser desorption/ionization (MALDI) MSI, no study has so far addressed the necessity of instrumental mass resolving power in terms of clinical diagnosis and prognosis using archived FFPE tissue. For this matter we performed for the first time a comprehensive comparison between a high mass resolution Fourier-transform ion cyclotron resonance (FTICR) mass spectrometer and a time-of-flight (TOF) instrument with lower mass resolving power. Spectra analysis revealed that about one-third of the detected peaks remained unresolved by MALDI-TOF, which led to a 3-5 times lower number of m/z features compared to FTICR measurements. Overlaid peak information and background noise in TOF images made a precise assignment of molecular attributes to morphological features more difficult and limited classification approaches. This clearly demonstrates the need for high-mass resolution capabilities for metabolite imaging. Nevertheless, MALDI-TOF allowed reproducing and verifying individual markers identified previously by MALDI-FTICR MSI. The systematic comparison gives rise to a synergistic combination of the different MSI platforms for high-throughput discovery and validation of biomarkers.

[1]  P. Trim,et al.  Small molecule MALDI MS imaging: Current technologies and future challenges. , 2016, Methods.

[2]  J. Polańska,et al.  Tissue fixed with formalin and processed without paraffin embedding is suitable for imaging of both peptides and lipids by MALDI‐IMS , 2016, Proteomics.

[3]  Timothy M. Errington,et al.  Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor Prevents Steroid-Associated Osteonecrosis of the Femoral Head in Rabbits by Promoting Angiogenesis and Inhibiting Apoptosis , 2014, PloS one.

[4]  Michael Becker,et al.  Use of advantageous, volatile matrices enabled by next-generation high-speed matrix-assisted laser desorption/ionization time-of-flight imaging employing a scanning laser beam. , 2015, Rapid communications in mass spectrometry : RCM.

[5]  K. Polański,et al.  Detection of metabolites discriminating subtypes of thyroid cancer: Molecular profiling of FFPE samples using the GC/MS approach , 2015, Molecular and Cellular Endocrinology.

[6]  M. Wuhrer,et al.  Two-Dimensional N-Glycan Distribution Mapping of Hepatocellular Carcinoma Tissues by MALDI-Imaging Mass Spectrometry , 2015, Biomolecules.

[7]  R. Langer,et al.  High‐resolution MALDI‐FT‐ICR MS imaging for the analysis of metabolites from formalin‐fixed, paraffin‐embedded clinical tissue samples , 2015, The Journal of pathology.

[8]  Matthew D. Zimmerman,et al.  The association between sterilizing activity and drug distribution into tuberculosis lesions , 2015, Nature Medicine.

[9]  A. Feuchtinger,et al.  Distribution and quantification of irinotecan and its active metabolite SN-38 in colon cancer murine model systems using MALDI MSI , 2015, Analytical and Bioanalytical Chemistry.

[10]  A. Walch,et al.  A rapid ex vivo tissue model for optimising drug detection and ionisation in MALDI imaging studies , 2014, Histochemistry and Cell Biology.

[11]  Benjamin A. Neely,et al.  MALDI imaging mass spectrometry profiling of proteins and lipids in clear cell renal cell carcinoma , 2014, Proteomics.

[12]  Lingjun Li,et al.  Visualizing neurotransmitters and metabolites in the central nervous system by high resolution and high accuracy mass spectrometric imaging. , 2013, ACS chemical neuroscience.

[13]  Feng Xian,et al.  Mass resolution and mass accuracy: how much is enough? , 2013, Mass spectrometry.

[14]  J. Asara,et al.  A positive/negative ion–switching, targeted mass spectrometry–based metabolomics platform for bodily fluids, cells, and fresh and fixed tissue , 2012, Nature Protocols.

[15]  Richard M Caprioli,et al.  Imaging Mass Spectrometry—A New and Promising Method to Differentiate Spitz Nevi From Spitzoid Malignant Melanomas , 2012, The American Journal of dermatopathology.

[16]  S. Rauser,et al.  MALDI imaging identifies prognostic seven-protein signature of novel tissue markers in intestinal-type gastric cancer. , 2011, The American journal of pathology.

[17]  J. Asara,et al.  Metabolomic Profiling from Formalin-Fixed, Paraffin-Embedded Tumor Tissue Using Targeted LC/MS/MS: Application in Sarcoma , 2011, PloS one.

[18]  Oliver Fiehn,et al.  Applying in-silico retention index and mass spectra matching for identification of unknown metabolites in accurate mass GC-TOF mass spectrometry. , 2011, Analytical chemistry.

[19]  Michaela Scigelova,et al.  Fourier Transform Mass Spectrometry , 2011, Molecular & Cellular Proteomics.

[20]  R. Caprioli,et al.  High-Speed MALDI-TOF Imaging Mass Spectrometry: Rapid Ion Image Acquisition and Considerations for Next Generation Instrumentation , 2011, Journal of the American Society for Mass Spectrometry.

[21]  C. Baessmann,et al.  Evaluation of a High Resolving Power Time-of-Flight Mass Spectrometer for Drug Analysis in Terms of Resolving Power and Acquisition Rate , 2011, Journal of the American Society for Mass Spectrometry.

[22]  Gérard Hopfgartner,et al.  Can MS fully exploit the benefits of fast chromatography? , 2011, Bioanalysis.

[23]  M. Clench,et al.  Introduction of a 20 kHz Nd:YVO4 laser into a hybrid quadrupole time-of-flight mass spectrometer for MALDI-MS imaging , 2010, Analytical and bioanalytical chemistry.

[24]  Martin Strohalm,et al.  mMass 3: a cross-platform software environment for precise analysis of mass spectrometric data. , 2010, Analytical chemistry.

[25]  William DeMaio,et al.  Spectral accuracy of molecular ions in an LTQ/Orbitrap mass spectrometer and implications for elemental composition determination , 2009, Journal of the American Society for Mass Spectrometry.

[26]  K. Dreisewerd,et al.  Effect of gas pressure and gas type on the fragmentation of peptide and oligosaccharide ions generated in an elevated pressure UV/IR-MALDI ion source coupled to an orthogonal time-of-flight mass spectrometer. , 2009, Analytical chemistry.

[27]  Oliver Fiehn,et al.  Seven Golden Rules for heuristic filtering of molecular formulas obtained by accurate mass spectrometry , 2007, BMC Bioinformatics.

[28]  Eric D. Dodds,et al.  Atmospheric pressure MALDI Fourier transform mass spectrometry of labile oligosaccharides. , 2005, Analytical chemistry.

[29]  Catherine E Costello,et al.  Coupling thin-layer chromatography with vibrational cooling matrix-assisted laser desorption/ionization Fourier transform mass spectrometry for the analysis of ganglioside mixtures. , 2004, Analytical chemistry.

[30]  Ross Prentice,et al.  Research issues and strategies for genomic and proteomic biomarker discovery and validation: a statistical perspective. , 2004, Pharmacogenomics.

[31]  Jochen Franzen,et al.  A novel MALDI LIFT-TOF/TOF mass spectrometer for proteomics , 2003, Analytical and bioanalytical chemistry.

[32]  C. Costello,et al.  A high pressure matrix-assisted laser desorption/ionization Fourier transform mass spectrometry ion source for thermal stabilization of labile biomolecules. , 2001, Rapid communications in mass spectrometry : RCM.

[33]  Alan G. Marshall,et al.  ADVANTAGES OF HIGH MAGNETIC FIELD FOR FOURIER TRANSFORM ION CYCLOTRON RESONANCE MASS SPECTROMETRY , 1996 .