MALDI Mass Spectrometry Imaging: From Fundamentals to Spatial Omics

Description

This book gathers, in a single resource, knowledge about matrix-assisted laser desorption ionisation (MALDI) mass spectrometry imaging. It includes fundamentals in the MALDI ionisation process, different source geometries and capabilities, detection systems and the latest research and applications in the range of –omics area as well as other broader areas. Chapters will touch on dedicated sample preparation protocols specific for the class of compounds of interest, instrumentation used with strengths and current limitations, strategies for structural analysis and identification and applications. It will be a welcomed addition to the literature in this fast-moving field and provide a guide to new innovations and applications especially in metabolomics and proteomics. With contributions from leading experts, this book will be an authoritative guide to this method. Aimed at postgraduate and professional researchers, in academia and in the industrial market where it has direct application to clinical research. It will be a supporting volume for those just entering the field as well as experienced practitioners. Cover Dedication Preface Biographies Biography of the Editor Biographies of the Authors Contents Section 1 1 An Introduction to MALDI Ionization Mechanisms for Users of Mass Spectrometry Imaging 1.1 Introduction 1.2 Laser Ablation in MALDI 1.2.1 Laser Pulse Dependence 1.2.2 Plume Pressure, Temperature and Velocity 1.2.3 Laser Spot Size 1.2.4 Local Thermal Equilibrium 1.3 Primary Ionization 1.3.1 Preformed Ions and ‘‘Lucky Survivors’’ 1.3.2 Mechanical Charge Separation 1.3.3 Thermal Ionization 1.3.4 Non-thermal Ionization 1.3.5 Metal Surfaces 1.4 Secondary Ionization 1.4.1 Matrix Suppression Effect 1.4.2 Analyte Suppression Effect 1.5 MALDI-2 1.6 Conclusions References 2 MALDI Mass Spectrometry Imaging – Past, Present, and Future Challenges 2.1 Opening Statement 2.2 The Beginning 2.3 The Last Two Decades 2.3.1 MSI Data Acquisition and Instrumentation 2.3.2 Automated Matrix Deposition 2.3.3 On-tissue Chemistries 2.3.4 Imaging of Xenobiotics 2.4 Future Challenges 2.4.1 The Push for Higher Spatial Resolution 2.4.2 Standard Protocols and Methods 2.4.3 Increasing Sensitivity and Specificity 2.5 Concluding Remarks References 3 Instrumentation for MALDI-MSI – Part I Ionization Sources and Design 3.1 Introduction 3.2 Pressure Regime 3.2.1 Plume Development 3.2.2 Vacuum Ion Sources 3.2.3 Intermediate Pressure Ion Sources 3.2.4 Atmospheric Pressure Ion Sources 3.3 Spatial Resolution in MALDI-MSI 3.4 Optical Setups 3.4.1 Front Side Illumination 3.4.2 Transmission Mode Illumination 3.5 Post-ionization 3.5.1 MALDI-2 3.5.2 MALDESI/LAESI 3.5.3 Alternative Approaches 3.6 Conclusions and Future Directions References 4 Instrumentation for MALDI-MSI – Part II Detection Systems 4.1 Introduction 4.2 Mass Analyzers and Their Performance for MALDI Imaging 4.2.1 Sector Analyzers 4.2.2 Quadrupole Mass Filters 4.2.3 Time-of-flight 4.2.4 QTOF 4.2.5 Ion Traps 4.2.6 Triple Quadrupoles 4.2.7 FT-ICR 4.2.8 Orbitrap 4.3 Ion Mobility Spectrometry for Improved MALDI-MSI Performance 4.3.1 Drift Tube Ion Mobility Spectrometry 4.3.2 Traveling Wave Ion Mobility Spectrometry 4.3.3 Trapped Ion Mobility Spectrometry 4.3.4 High-field Asymmetric Waveform Ion Mobility 4.4 Conclusion and Future Perspectives Abbreviations Acknowledgements References 5 Sample Preparation of Biological Tissues for MALDI-MSI 5.1 Introduction 5.2 Sample Collection 5.3 Embedding and Storage 5.4 Sectioning 5.4.1 Frozen Material 5.4.2 FFPE Material 5.4.3 Important Considerations for Tissue Sectioning 5.5 Washing 5.5.1 Metabolites 5.5.2 Lipids 5.5.3 Proteins, Glycans and Peptides 5.6 Enzymatic Digestion 5.6.1 Proteins 5.6.2 Glycans 5.7 Derivatization 5.7.1 Reagent Selection 5.7.2 Deposition Method of Derivatization Reagents 5.8 Matrix Selection and Application Methods 5.8.1 Matrix Application and Recrystallization 5.9 General Considerations, Conclusion and Future Directions References 6 Quantitative MSI: A Review of Biomarker and Drug Quantifications Using Mass Spectrometry Imaging 6.1 Introduction 6.2 History and Progress 6.3 Method Workflow 6.3.1 Method Development (MD) 6.3.2 Method Validation (MV) 6.3.3 Data Analysis 6.4 Versatility of QMSI 6.4.1 Lipids 6.4.2 Peptides and Amines 6.4.3 Polymers and Polyimides 6.4.4 Alcohol and Phenols 6.4.5 Nanoparticles 6.5 Current Challenges 6.6 Conclusion and Future Directions References Section 2 7 MALDI Mass Spectrometry Imaging and Metabolomics – A Glimpse into the Local Metabolic State of Cells and Tissues 7.1 Introduction 7.2 You Can’t Have it All – Sample Retrieval, Preparation and Matrix Deposition – Crucial Steps of the MSI Experiment for Metabo 7.2.1 Metabolic Quenching 7.2.2 Preparation of Flash-frozen Tissue Samples 7.2.3 If Matrix Chemistry Fails to Ionize the Target Metabolite or Metabolite Group – Derivatization 7.2.4 Selection of the Right Matrix for the MALDI-ionization Process – Targeting the Peak of the Iceberg in Metabolomics Researc 7.3 Most Used Instrumentation with Strengths and Current Limitations 7.3.1 Resolution Power, Exact Mass and Isotope Distribution 7.3.2 Tandem Mass Spectrometry and Ion Mobility 7.4 Strategies for Structural Analysis/Identification 7.5 Applications 7.5.1 MALDI-MSI of Plant Metabolites 7.5.2 Application of Metabolite Imaging to Animal Tissues 7.5.3 MALDI-MSI in Pharmacology and Toxicology 7.5.4 MALDI-MSI of Metabolites in Animal Disease Models 7.5.5 Spatial Analysis of Metabolites in Human Tissues 7.5.6 Imaging of Metabolites with High Lateral Resolution – Emerging Applications 7.6 Conclusions and Future Directions Acknowledgements References 8 MALDI Mass Spectrometry Imaging in Lipidomics 8.1 Introduction 8.2 Sample Preparation for Lipid MSI 8.2.1 Tissue Fixation 8.2.2 Tissue Washing 8.2.3 MALDI Matrices 8.2.4 Matrix Application 8.3 Lipid Identification in MSI 8.3.1 Identification of Lipids Detected with MALDI-MSI 8.4 Selected Applications of MALDI-MSI of Lipids 8.4.1 Cancer Research 8.4.2 Brain Injury and Disease 8.4.3 Liver Disease 8.5 Recent Developments in MALDI-MSI of Lipids 8.5.1 Strategies to Improve the Ionization Efficiency of Lipids 8.5.2 Lipid Analysis and Imaging from Single Cells 8.5.3 Imaging Stable Isotope Labeled Lipids 8.6 Conclusions and Future Directions Abbreviations Acknowledgements References 9 MALDI Mass Spectrometry Imaging of Neuropeptides 9.1 Introduction 9.2 Methods 9.2.1 Sample Preparation for MALDI-MS Imaging of Neuropeptides 9.2.2 Data Acquisition and Data Analysis 9.2.3 Molecular Identification 9.3 MALDI MS-based Neuropeptide Imaging in Biological Research 9.3.1 Neuropeptide Imaging in Cells and Animal Models 9.3.2 MALDI-MSI of Neuropeptides in Neurodegenerative Diseases 9.4 Conclusions and Future Directions Acknowledgements References 10 MALDI Mass Spectrometry Imaging and Glycomics 10.1 Introduction 10.2 glycans 10.2.1 glycan Method Development and Optimization 10.2.2 glycan Biological Applications 10.3 Glycosphingolipids 10.3.1 Glycosphingolipids Method Development and Optimization 10.3.2 Biological Application of Glycosphingolipids 10.4 Glycosaminoglycans 10.5 Glycosides 10.6 Non-conjugated Saccharides 10.7 Conclusions and Future Directions Acknowledgements References 11 MALDI Mass Spectrometry Imaging and Spatially-resolved Proteomics 11.1 From Protein MS Imaging to Spatially-resolved Proteomics: Combining Deep Proteome Identification with Spatial Information 11.2 MALDI-MSI of Proteins 11.2.1 MALDI-MSI of Intact Proteins or Top-down pMSI 11.2.2 MALDI-MSI of Digested Proteins or Bottom-up pMSI 11.2.3 Specific MALDI of Proteins Using Tagged Probes 11.3 Protein Identification in MALDI-MSI and Spatially-resolved Proteomics 11.3.1 Identification 11.3.2 Off-tissue Identification and Spatially-resolved Proteomics 11.3.3 MALDI-MSI Guided Spatially-resolved Proteomics 11.4 Conclusions and Future Directions Abbreviations Acknowledgements References 12 The Role of Informatics and Data Analysis in MALDI Mass Spectrometry Imaging 12.1 Introduction – The Role of Informatics for the Success of Mass Spectrometry Imaging in Biomedical Research 12.2 Software for MSI Data Creation and Handling 12.2.1 Software for MSI Data Acquisition 12.2.2 MSI Data Representation and Handling 12.3 Data Processing 12.3.1 Baseline Subtraction 12.3.2 Smoothing 12.3.3 Spectral Resampling 12.3.4 Spectral Alignment and Recalibration 12.3.5 Normalization 12.3.6 Peak Picking and Peak Filtering 12.3.7 Image Processing and Visualization 12.4 Data Analysis 12.4.1 Finding Discriminatory Values 12.4.2 Supervised Machine Learning 12.4.3 Unsupervised Projection and Clustering Methods 12.4.4 Identification of Values 12.4.5 Data Integration 12.5 Image Registration 12.5.1 Integration with Techniques 12.5.2 Integration with Techniques 12.6 Outlook – MSI Software in the AI Age References Section 3 13 MALDI Mass Spectrometry Imaging for Microbiology 13.1 Introduction to Microbiology as a Field of Study for MSI Development 13.2 Sample Preparation for Microbial MSI 13.3 Applications for Imaging Microbial Monocultures 13.4 Applications for Imaging Microbial Co-cultures 13.5 Applications for Imaging Host–Microbe Interactions 13.6 Compound Identification 13.7 Conclusions and Future Directions Abbreviations Acknowledgements References 14 MALDI Mass Spectrometry Imaging in Drug Discovery and Development 14.1 Introduction 14.1.1 Mass Spectrometry Imaging 14.1.2 The Drug Discovery and Development Pipeline 14.2 Early Discovery 14.2.1 High-throughput Screening 14.2.2 Complex Models 14.3 Preclinical Phase of Development 14.3.1 Drug Disposition and Pharmacokinetics 14.3.2 Targeted Drug Delivery 14.3.3 Pharmacodynamics 14.3.4 Disease Pathogenesis 14.3.5 Toxicology and Safety Investigations 14.4 Clinical and Beyond 14.5 Conclusion and Future Directions References 15 MALDI Mass Spectrometry Imaging in the Forensic Arena 15.1 Introduction 15.2 MALDI-MSI Application in Forensics 15.2.1 Fingermarks 15.2.2 Biological Tissues ( Analysis) 15.3 MALDI-MSI Application in Forensic Toxicology 15.3.1 MALDI-MSI of Drugs and Metabolites in Hair 15.3.2 Potential use of MALDI-MSI of Drugs and Metabolites in Tissues 15.4 Prospective Applications of MALDI-MSI in the Forensic Arena 15.4.1 Forensic Entomology 15.4.2 Microbial Forensics 15.4.3 Forensic Botany 15.4.4 Food Forensics 15.4.5 Forensic Analysis of Fibers 15.4.6 Ink/Documents 15.5 Conclusions References 16 MALDI Mass Spectrometry Imaging for Toxicological Evaluation of Environmental Pollutants 16.1 Introduction 16.2 Sample Preparation for the Study of Environmental Pollutant Distribution 16.2.1 Tissue Collection 16.2.2 Quantification (Optional) 16.2.3 On-tissue Chemical Derivatization (Optional) 16.2.4 Matrix Deposition 16.2.5 Acquisition 16.3 Application of MALDI-MSI for the Study of Environmental Pollutant Distribution 16.3.1 Quantitative MALDI-MSI of Environmental Pollutants 16.3.2 MALDI-MSI of Pesticides in Plants 16.3.3 MALDI-MSI of Nanoparticles and Plastics 16.4 Combination of MALDI-MSI and LC–MS/MS for the Identification of Responses Induced by the Exposure to Environmental Pollutan 16.4.1 Alteration of Energy and Lipid Metabolisms after Exposure to Bisphenol S 16.4.2 Metabolic Responses in Plants 16.5 Conclusions and Future Directions Abbreviations References 17 MALDI Mass Spectrometry Imaging in the Clinical Landscape 17.1 Introduction 17.2 Possibilities and Advantages of MALDI-MSI in Pathology Research and Practice 17.3 Tumor and Disease Detection 17.4 Tumor and Disease Subtyping 17.5 Outcome and Response Prediction 17.6 Challenges and Considerations 17.7 Conclusions and Future Directions References 18 MALDI Mass Spectometry Imaging for Eye Diseases 18.1 Ocular Structure, Function, and Common Diseases 18.1.1 General Introduction to the Eye 18.1.2 Anterior Eye – Cornea, Lens, and Cataract 18.1.3 Posterior Eye – Retina, Macular Degeneration and Optic Nerve 18.2 MALDI-MSI in the Anterior Eye 18.2.1 Corneal Structure, Corneal Dystrophies and Keratoconus 18.2.2 The Lens in Aging and Cataracts 18.3 MALDI-MSI in the Posterior Eye 18.3.1 Retina and Macular Degeneration 18.3.2 Optic Nerve, Trauma and Glioma 18.4 MALDI-MSI for Ocular Therapeutics Detection 18.4.1 Advantages and Applications in Pre-clinical Settings 18.4.2 Drug Detection in the Eye for Off-target Effects 18.4.3 On-target Ocular Drug Detection 18.5 Conclusions and Future Directions Acknowledgements References 19 Correlative Multimodal Mass Spectometry Imaging – Imaging Across the Scales 19.1 Introduction 19.2 Correlative, Hybrid, Multisensor, Multimodal Imaging – Is There a Difference? 19.3 MSI in the Context of Correlative Multimodal Imaging 19.4 Combination of MS Techniques 19.5 Combination of MS with Other Modalities 19.5.1 and Imaging 19.5.2 X-Ray Fluorescence Imaging 19.5.3 Optical Imaging 19.5.4 Electron Microscopy 19.5.5 Atomic Force Microscopy 19.6 Challenges for Multimodal Imaging 19.7 Conclusions and Future Directions References Subject Index