Imaging Inflammation

Preface
Acknowledgements
Contents
About the Editors
Imaging Inflammation: A Historical Perspective
1 Microscopy for Imaging Inflammation: The Germ Theory
2 Imaging Leukocyte Function in Humoral and Cell-Mediated Immunity
3 The Dawn of Radiology and Noninvasive Imaging of Inflammation
4 Conclusion
References
Nuclear Imaging of Inflammation
1 Introduction to Nuclear Imaging
1.1 Basic Principles of PET and SPECT
1.2 Benefits and Limitations of Nuclear Imaging
1.3 Radiotracers: Radionuclides, Targeting Moieties, and Practical Considerations
1.3.1 Radionuclides
1.3.2 Radiotracers: Structural Classes
1.3.3 Multimodal and Multi-Tracer Imaging
1.3.4 Practical Considerations for Preclinical Nuclear Imaging of Inflammation
2 Clinical Nuclear Imaging of Inflammation
2.1 Current Uses and Tracers
2.1.1 Inflammation in the Gastrointestinal Tract
2.1.2 Cardiovascular Inflammation
2.1.3 Neuroinflammation
2.1.4 Musculoskeletal Diseases
2.1.5 Fever of Unknown Origin (FUO)
2.1.6 Infection Imaging
2.2 Challenges and Recent Developments
2.2.1 Increasing Specificity
2.2.2 Quantification and Multimodal Imaging
2.2.3 Radiomics
3 Recent Developments in Preclinical Nuclear Imaging of Inflammation
3.1 Metabolic Pathways Involved in Inflammation
3.1.1 Translocator Protein (TSPO) Ligands
3.1.2 Amino Acid Metabolism: LAT1
3.1.3 Folate Receptor β
3.1.4 Imaging Hypoxia
3.1.5 Aldehyde Radiotracers
3.1.6 Radioactive Gallium in the Host-Pathogen Fight over Iron
3.2 Adhesion Molecules and Intercellular Signalling Pathways
3.2.1 Fibroblast Activation Protein (FAP)
3.2.2 Antigen-Presenting Cell Activation Markers: CD80/CD86
3.2.3 Macrophage Activation Marker: Mannose Receptor/CD206
3.2.4 Chemokine Receptors
3.2.5 Cell-Adhesion Molecules (CAMs): Integrins and Selectins
3.2.6 Matrix Metalloproteinases
3.2.7 Radionuclide Imaging of T Cells and B Cells in Inflammation
3.2.8 Vascular Adhesion Protein-1 (VAP-1)
4 Conclusion and Perspectives
References
Magnetic Resonance Imaging of Neuroinflammation
1 Introduction
1.1 MRI
1.2 Molecular MRI
2 Molecular MRI to Reveal Inflammation in the Brain
2.1 Multiple Sclerosis
2.2 Stroke
2.3 Epilepsy
2.4 Brain Cancer
3 Extension of Molecular MRI to Other Diseases and Tissues
4 Future Perspective
5 Conclusions
References
Ultrasound Imaging in Inflammation Research
1 Introduction
1.1 Ultrasound Physics
1.2 Ultrasound Modalities
2 B-Mode and Doppler Ultrasound Imaging of Inflammation
2.1 Renal B-Mode and Doppler Ultrasound Imaging
2.2 Rheumatoid Arthritis Imaging
2.3 Plaque Imaging
3 Contrast-Enhanced Ultrasound (CEU) Molecular Imaging
3.1 CEU Molecular Imaging of Cardiovascular Inflammation
3.1.1 Ischemic Memory
3.1.2 Atherosclerosis
3.2 Organ-Specific Applications of CEU Molecular Imaging
3.3 Limitations and Benefits Compared to Other Molecular Imaging Approaches
4 Conclusion
References
Whole-Body Chemiluminescence and Fluorescence Imaging of Inflammation
1 Introduction and Background
1.1 Significance of Imaging Inflammation in Animal Models
1.2 Unique Cell Biology of Inflammation: Phagocytes
1.3 Unique Inflammatory Enzymes for ROS Production
1.4 Unique Inflammatory Proteases
1.5 Advantages of Whole-Body Optical Imaging for Inflammation Research
1.6 Chemiluminescence Imaging (CLI) and Fluorescence Imaging (FLI): An Overview
2 Imaging Inflammation Using ROS-Sensitive Chemiluminescent Compounds
2.1 Small Chemiluminescent Compounds
2.2 Energy Transfer Luminescence Imaging Using Small CLI Substrates as Energy Sources
3 Noninvasive Fluorescence Imaging for Tissue Inflammation
3.1 Targeting Enhanced Vascular Permeability at Inflamed Sites
3.2 Selective Binding and Targeting of Inflammatory Protein Markers
3.3 ROS-Reactive Fluorescent Probes for Inflammation Imaging
3.4 Activatable Fluorescent Probes for Imaging Specific Inflammatory Protease Activity
4 Conclusion
References
Photoacoustic Imaging in Inflammation Research
1 Introduction to Photoacoustic Imaging
2 Label-Free Photoacoustic Imaging of Inflammation
2.1 Evaluation of Inflammation by Photoacoustic Imaging of Hemoglobin
2.2 Label-Free Photoacoustic Imaging of Blood Oxygen Saturation and Collagen in Crohn´s Disease
3 Probe-Based Photoacoustic Imaging of Inflammation
3.1 Activatable Photoacoustic Probes Responsive to Inflammatory Stimuli
3.1.1 Reactive Oxygen Species (ROS)-Responsive Probes
3.1.2 Reactive Oxygen Species/Glutathione-Responsive Probes
3.1.3 Carbon Monoxide-Responsive Probes
3.1.4 Leukotriene A4 Hydrolase-Responsive Probes
3.2 Photoacoustic Probe Targeted Toward Inflammation Markers
3.2.1 Photoacoustic Probes Targeted Toward CD36
3.2.2 Photoacoustic Imaging of Arthritis Based on an IL-6 Targeted Probe
3.3 Direct Labeling of Immune Cells for Photoacoustic Imaging of Inflammation
4 Conclusion and Prospects of Photoacoustic Imaging in Inflammation Research
References
Imaging Inflammation by Intravital Microscopy
1 Introduction
2 Leukocyte Migration to the Site of Inflammation: Imaging Trafficking in Intravascular (and Non-vascular) Spaces
2.1 Imaging Classical Leukocyte Rolling and Firm Adhesion
2.2 Imaging Novel Leukocyte Trafficking Events
3 Visualising the Inflammatory Response in Sterile Injury, Infection and Cancer
3.1 Imaging Sterile Injury
3.2 Imaging Infection
3.2.1 Bacterial Infections and Bacterial PAMPs
3.2.2 Viral Infection
3.2.3 Parasite Infection
3.3 Imaging the Tumour Microenvironment: Inflammation in Cancer
4 Conclusion and Future Perspectives
References
Spatial Transcriptomics in Inflammation: Dissecting the Immune Response in 3D in Complex Tissues
1 The Importance of Spatial Dimensions When Studying Immune Responses in Tissue
1.1 Lymphoid Tissues: It´s All About Space
1.2 Spatial Organization of Immune Cells in Nonlymphoid Tissues Is Vital to Their Function
1.3 Immune Cells in the Physical Space of the Tumor: Order from Chaos
1.4 Spatial Aspects of Autoimmunity
1.5 Summary: Capturing Spatial Information is Vital for Understanding Immunity
2 The Spatial Transcriptomic Toolbox
2.1 The Ever-Evolving Spatial Transcriptomic Toolbox
2.1.1 Targeted Approaches
2.1.2 ``Whole´´ or ``Untargeted´´ Transcriptome Capture Techniques
Solid-Phase Capture
Region-Based Selection
Combining Grids with ``True´´ Single-Cell Transcriptomics
2.2 Parameters to Consider
2.2.1 Targeted Versus Untargeted Approaches
2.2.2 Lost in Reverse Transcription: Transcriptome Capture Efficiency
2.2.3 Spatial Resolution: How Low Can We Go?
2.2.4 What Kind of Samples Can We Use?
3 What Has Been Done with Spatial Transcriptomics in Studying Immunology?
3.1 Skin Wound Healing
3.2 The Tumor Microenvironment
3.3 Lymphoid Tissues
3.4 Infectious Disease and Autoimmunity
4 We Have Our Data, Now What? How Do We Analyze Spatial Transcriptomic Data? And Where Can We Go from Here?
4.1 Deconvolving Spatial Transcriptomes
4.2 Extracting Cell-Cell Communication
4.3 Building a Spatial Compendium of Tumors
4.4 Spatial Transcriptomics Applied to Organoids
5 Conclusion
References