MALDI Mass Spectrometry Imaging: From Fundamentals to Spatial Omics

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