Front Cover -- Applications of Mass Spectrometry Imaging to Cancer -- Copyright -- Contents -- Contributors -- Preface -- References -- Chapter One: The Importance of Histology and Pathology in Mass Spectrometry Imaging -- 1. Importance of Pathology -- 2. Possible Errors Caused by Tissue Inherent Factors-Why Histology Is Important for Supervised Analysis -- 3. Possible Errors Caused by Sample Inherent Factors-Small Pretherapeutic Biopsies -- 4. Possible Errors Caused by Sample Preparations-Artifacts Are Not Your Friend -- 5. Possible Errors Caused by Ill-Defined Sample Groups in the Training Set-Keep It Black and White/Shades of Gray Are Not ... -- 6. Conclusion -- References -- Chapter Two: Applications of Mass Spectrometry Imaging to Cancer -- 1. Introduction -- 1.1. The Advantages of MSI -- 1.2. The Basic Principles of MSI -- 1.2.1. MALDI-TOF -- 1.2.2. MALDI-FT-ICR -- 1.2.3. SIMS-TOF -- 1.2.4. DESI -- 2. Protein MSI in Cancer Research -- 2.1. Distinguishing Tissue Types by Peptide MSI -- 2.2. Determining Tumor Margins by Peptide MSI -- 2.3. Prediction of Metastasis by Peptide MSI -- 2.4. Analysing Chemoresponse by Peptide MSI -- 2.5. Identification of Diagnostic and Prognostic Markers by Peptide MSI -- 2.6. Characterisation of Intra- and Intertumor Variability by Peptide MSI -- 2.7. Practical Considerations for Proteolytic Peptide MSI: Sample Preparation -- 2.8. Practical Considerations for Peptide MSI: Spatial Resolution -- 2.9. Practical Considerations for Peptide MSI: Mass Analysers -- 2.10. Practical Considerations for Peptide MSI: Identification -- 3. Lipid MSI in Cancer Research -- 3.1. Profiling Lipids in Cancer by DESI-MSI -- 3.2. Profiling Lipids in Cancer by SIMS-MSI -- 4. Glycan MSI in Cancer Research -- 5. Drug Imaging in Cancer Research -- 5.1. MALDI-MSI on Tissue Sections -- 5.2. MALDI-MSI on Whole Body Sections.

5.3. MALDI-MSI on 3D Tissue Cultures -- 6. Data Analysis -- 6.1. Spatial Information -- 6.2. Preprocessing: Peak Detection -- 6.3. Classification of FFPE-TMAs and the Importance of Dimension Reduction -- 7. Concluding Remarks -- 7.1. The Future of MSI: Molecular Pathology -- References -- Chapter Three: Assessing the Potential of Metal-Assisted Imaging Mass Spectrometry in Cancer Research -- 1. Introduction -- 2. Material -- 3. Silver-Assisted IMS -- 3.1. Preparation of Silver-Coated Glass Slides -- 3.2. Tissue Deposition on Silver- or ITO-Coated Slides -- 3.3. Silver Deposition on Tissue Section -- 3.4. LDI Data Acquisition of a Silver-Coated Tissue Section -- 3.5. Fast Optimization of New Tissue Sections -- 4. Gold-Assisted IMS -- 4.1. Preparation of Gold-Coated Glass Slides -- 4.2. Tissue Deposition on ITO- or Gold-Coated Slides -- 4.3. Sodium Salt Deposition -- 4.4. Gold Deposition on Tissue Section -- 4.5. LDI Data Acquisition of a CBS-Au-Coated Tissue Section -- 5. Applications to Cancer Research -- 6. Concluding Remarks -- References -- Chapter Four: MALDI Mass Spectrometry Imaging of N-Linked Glycans in Cancer Tissues -- 1. Introduction -- 2. Glycosylation and Cancer -- 2.1. Function and Types of Glycosylation -- 2.2. N-Linked Glycan Biosynthesis -- 2.3. N-Linked Glycans and Cancer -- 3. Methodology for N-Linked Glycan Detection by MALDI Imaging -- 3.1. Tissue Sources -- 3.2. Glycan Visualization in Tissues: Lectins and Anticarbohydrate Antibodies -- 3.3. Histochemistry Stains -- 3.4. Peptide N-Glycosidase F -- 3.5. Matrix and Instrumentation Choices for N-Glycans -- 3.6. Structural Confirmation -- 4. N-Glycan Distribution Linked With Histopathology -- 4.1. Major Structural Classes -- 4.2. High-Mannose N-Glycans -- 4.3. Nontumor Stroma and Normal Tissue Glycans -- 4.4. N-Glycan Branching and Sialylation.

4.5. Fucosylation and the Glycan Isomer Problem -- 5. Emerging Applications -- 5.1. Combined Glycan and Peptide MS Imaging -- 5.2. Custom Multitumor TMA and Other Enzymes -- 5.3. Linkage to Genomic Studies -- 5.4. Potential Clinical Diagnostic Applications of N-Glycan MSI Data -- 6. Summary -- References -- Chapter Five: In Situ Metabolomics in Cancer by Mass Spectrometry Imaging -- 1. Metabolomics in Cancer -- 2. In Situ Metabolomics by MALDI Imaging -- 3. Fresh-Frozen- vs Formalin-Fixed Paraffin-Embedded Tissue Samples -- 4. Tissue-Based Disease Classification-Diagnostic Markers and Metabolic Signatures -- 5. Therapy Response Prediction and Prognosis -- 6. Intra- and Intertumoral Heterogeneity -- 7. Conclusion -- References -- Chapter Six: Mass Spectrometry Imaging in Oncology Drug Discovery -- 1. Introduction -- 2. How MSI Can Inform Our Understanding of Pharmacokinetic-Pharmacodynamic Relationships -- 3. Biodistribution -- 4. Tumor Metabolism: MSI Analysis for More Than Just Drug Distribution -- 5. Sample Preparation -- 6. Quantitation -- 7. Toxicity and Safety Assessment -- 8. Biomarkers for Efficacy -- 9. Drug Delivery -- 10. Tumor Microenvironment -- 11. Assessing Hypoxia -- 12. BBB Penetration -- 13. Beyond Small Molecules -- 14. Clinical Translation -- 15. Emerging Applications: Spheroids -- 16. Increased Spatial Resolution -- 17. Metrology for MS Imaging -- 18. Conclusion -- References -- Chapter Seven: MALDI IMS and Cancer Tissue Microarrays -- 1. Introduction -- 2. TMA Technology -- 2.1. Preparation of the Donor Block -- 2.2. FFPE TMA Construction -- 3. MALDI IMS Analysis of TMAs -- 3.1. Sample Preparation -- 3.1.1. Cutting, Deparaffinization, and AR -- 3.1.2. In Situ Enzymatic Digestion -- 3.1.3. Matrix Deposition -- 3.2. MALDI IMS Analysis -- 3.3. Data Analysis -- 4. Identification of Peptides -- 5. Application of MALDI IMS on FFPE TMAs.

6. Perspectives and Concluding Remarks -- Acknowledgments -- References -- Chapter Eight: Mass Spectrometry Imaging for the Investigation of Intratumor Heterogeneity -- 1. Tumor Heterogeneity -- 1.1. Intratumor Heterogeneity -- 1.2. The Study of ITH -- 1.3. Clinical Relevance of ITH -- 1.4. Techniques to Study Spatial Organization of ITH -- 2. MSI to Study Tumor Heterogeneity -- 3. Multivariate Data Analysis Strategies in MSI -- 3.1. Unsupervised Analysis -- 3.2. Supervised Classification -- 3.3. Projection Methods -- 4. MSI Applications for the Investigation of ITH -- 4.1. Revealing ITH by Clustering -- 4.2. Supervised Classification of ITH -- 4.3. Investigating the Degree of ITH -- 4.4. Investigation of ITH on Different Molecular Levels -- 5. Future Applications of MSI in ITH Research -- 6. Perspective -- References -- Chapter Nine: Ambient Mass Spectrometry in Cancer Research -- 1. Desorption Electrospray Ionization -- 2. Intraoperative Mass Spectrometry -- 3. REIMS Instrumentation -- 4. DESI-MSI for Drug Imaging in Cancer Research -- References -- Chapter Ten: Rapid Mass Spectrometry Imaging to Assess the Biochemical Profile of Pituitary Tissue for Potential Intraope ... -- 1. Introduction -- 2. Current Imaging and Visualization Techniques -- 3. Mass Spectrometry in Clinical Usage -- 3.1. Atmospheric Pressure Ionization Mass Spectrometry -- 3.2. Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry -- 4. Future Directions -- References -- Chapter Eleven: Mass Spectrometry Imaging in Cancer Research: Future Perspectives -- 1. MSI-Based Diagnostics -- 2. Biological Insights -- 3. Multimodal MSI -- 4. Targeted MSI -- 5. Summary -- References -- Index -- Back Cover.