Imaging of Inflammation and Infection in Cardiovascular Diseases

This book addresses the most relevant imaging techniques in order to detect inflammation and infection in the most common cardiovascular diseases. The book presents data concerning molecular imaging (SPECT and PET) and cardiac magnetic resonance imaging (MRI) for each disease, with a special focus on the emerging role of hybrid PET/MR imaging. Different non-ischemic and ischemic diseases as well as cardiac infections are addressed in detail; these include: Cardiac sarcoidosis, Cardiac amyloidosis, the vulnerable plaque, Post-infarction inflammatory alterations, Pericarditis, Myocarditis, Cardiac devices infections, and Endocarditis. The book also provides a comprehensive discussion on new targets and new tracers, to date mostly investigated at a pre-clinical stage, thus constituting an excellent basis for translational imaging. Imaging of Inflammation and Infection in Cardiovascular Diseases will be of interest not only for experts in clinical imaging, but also pre-clinical scientists and will be invaluable for both nuclear medicine physicians and radiologists. Preface Contents Part I: Challenges in Patient Preparation 1: Challenges in Patient Preparation 1.1 Introduction 1.2 Prolonged Intervals of Fasting 1.3 Dietary Modifications 1.4 Pharmacologic Approaches 1.5 Conclusion References Part II: Non-ischemic Diseases 2: Cardiac Sarcoidosis 2.1 Introduction 2.2 Screening for Cardiac Sarcoidosis 2.3 Diagnosis 2.4 Endomyocardial Biopsy: Imaging Guidance 2.5 CMR for Diagnosis/CMR Imaging Protocol 2.6 Late Gadolinium Enhancement (LGE) 2.7 Imaging Myocardial Inflammation and Quantitative Tissue Characterization with CMR T1 and T2 Mapping 2.8 Additional CMR Findings Suggestive of Cardiac Sarcoidosis 2.9 Differential Diagnosis 2.10 Treatment: Anti-Inflammatory Therapy 2.11 CMR for Arrhythmogenic Risk Stratification/ICD 2.12 Positron Emission Tomography 2.13 Positron Emission Tomography with Tracers Other than 18F-FDG 2.14 Prognosis 2.15 Follow-up and Monitoring of Anti-Inflammatory Response 2.16 Hybrid PET-CMR Imaging 2.17 Outlook 2.18 Conclusion References 3: Cardiac Amyloidosis 3.1 Introduction 3.1.1 Different Phenotypes of Cardiac Amyloidosis 3.1.1.1 AL Amyloidosis 3.1.1.2 ATTR Amyloidosis 3.1.2 Screening for Cardiac Amyloidosis 3.2 Diagnosis 3.2.1 Endomyocardial Biopsy 3.2.2 Cardiac Magnetic Resonance (CMR) Imaging 3.2.2.1 CMR Diagnosis and Imaging Protocol 3.2.2.2 Late Gadolinium Enhancement (LGE) 3.2.2.3 Quantitative Tissue Characterization with CMR Native T1, T2 and ECV Mapping 3.2.2.4 Differential Diagnosis of AL vs. ATTR Amyloid 3.2.3 Scintigraphy 3.2.3.1 Bone Avid Radiotracers Imaging Protocols and Interpretation Diagnostic Accuracy 3.2.3.2 Innervation Radiotracers 3.2.4 Positron Emission Tomography (PET) 3.2.5 Hybrid Imaging: PET/MRI 3.2.6 Diagnostic Algorithm for Diagnosis and Sub-Typing of Cardiac Amyloidosis 3.3 Treatment 3.4 Prognosis 3.5 Conclusion References Part III: Ischemic Diseases 4: Molecular Imaging of Vulnerable Plaque 4.1 Introduction 4.2 Biology and Pathogenesis of Atherosclerosis 4.2.1 History 4.2.2 Mechanisms of Atherosclerosis 4.2.2.1 Initiation of Atherosclerosis Vascular Endothelium and Atherosclerosis Hemodynamics Forces in Atherosclerosis Low-Density Lipoprotein Cholesterol Surface Adhesion Molecules Foam Cells Formation Progression of Atherosclerosis Smooth Muscle Cells and Atherosclerosis Calcification Plaque Neoangiogenesis Innate Immunity Cells in Atherosclerosis Adaptive Immunity in Atherosclerosis 4.2.3 Complication of Atherosclerosis 4.2.3.1 Inducible Ischemia 4.2.3.2 Plaque Rupture 4.2.3.3 Plaque Erosion 4.3 Metabolism of Glucose in Atherosclerosis 4.3.1 Glucose and Immune Cells 4.3.2 Imaging Inflammation in Atherosclerosis Using Glucose Metabolism 4.4 Targeting Chemokine Receptor Expression in Vulnerable Plaque 4.4.1 Technological Advancements: PET/MRI and Chemokine Receptor 4.4.2 Radiopharmaceutical Agents Advancements: Theragnostic and Chemochine Receptor 4.5 Targeting Microcalcification in Atherosclerosis 4.5.1 Atherosclerotic Plaque Calcium Deposition 4.5.2 Cardiovascular Risk Quantification 4.5.3 High/Risk Coronary Plaque Evaluation 4.5.4 Atherosclerotic Plaque Composition/Activity Assessment 4.6 Targeting Neovascularization in Atherosclerosis 4.7 Targeting SSRT-2 Receptor Expression in Atherosclerosis with DOTA-Derivatives-PET 4.8 Summary References 5: Post-Infarction Inflammatory Alterations 5.1 General Introduction 5.2 Biology of Ventricular Remodeling 5.2.1 Pathobiology of Ventricular Remodeling Post-MI 5.2.2 The Inflammatory Response 5.2.2.1 Resident Inflammatory Cells Mast Cells Macrophages 5.2.2.2 Infiltrating Inflammatory Cells Polymorphonuclear Leukocytes Monocytes and Macrophages Dendritic Cells T and B Lymphocytes 5.2.2.3 Cardiomyocytes and ECM 5.2.3 Animal Models to Study Post-AMI Inflammation 5.2.3.1 Small Animal Models Open Chest Coronary Artery Ligation Topical Application of FeCl3 Closed Chest Isoproterenol Injection 5.2.3.2 Large Animal Models Open Chest Coronary Artery Ligation Gradual Constriction Hydraulic Occluder Topical Application of FeCl3 Closed Chest Balloon Inflation Embolization Endothelial Electrical Injury 5.3 The Role of Molecular Imaging 5.3.1 Cardiac MRI 5.3.2 Single-Photon Emission Computed Tomography 5.3.3 Positron Emission Tomography 5.4 Imaging Targets 5.4.1 Metabolic Activity 5.4.2 Labeled Cells 5.4.3 Membrane Receptors 5.4.4 Somatostatin Receptors 5.4.5 Mannose Receptor 5.4.6 Folate Receptor 5.4.7 Translocator Protein 5.4.8 Glucagon-like Peptide-1 Receptor (GLP-1R) 5.4.9 Chemokine Receptors 5.4.10 Lymphocyte Markers 5.4.10.1 Adhesion Molecules 5.4.10.2 Extracellular (Matrix) Components 5.5 Hybrid Imaging: The Added Value of Hybrid Imaging 5.6 Concluding Remarks References Part IV: Infection 6: Infection: Pericarditis 6.1 Pericardial Anatomy 6.2 Pericardial Pathologies 6.3 Aetiology and Pathophysiology 6.4 Clinical Manifestations and Diagnosis 6.5 Computed Tomography 6.6 Cardiovascular Magnetic Resonance (CMR) 6.6.1 Typical CMR Protocol for the Evaluation of Pericardial Disease 6.6.2 CMR and Acute Pericarditis 6.6.3 CMR and Pericardial Effusions 6.6.4 CMR and Pericardial Constriction 6.6.5 Constrictive–Effusive Pericarditis 6.7 Molecular Imaging 6.8 Basics of Treatment 6.9 Conclusion References 7: Infection: Myocarditis 7.1 Introduction 7.2 Aetiology and Pathogenesis 7.3 From Acute Myocarditis to Chronic Inflammatory Cardiomyopathy and Heart Failure 7.4 Clinical Presentations and Diagnosis 7.5 Endomyocardial Biopsy 7.6 Cardiovascular Magnetic Resonance (CMR) 7.7 Infectious Inflammatory Cardiomyopathy 7.7.1 Idiopathic/Post-Viral Myocarditis 7.8 Coronavirus Disease-2019 (COVID-19) and Myocarditis 7.9 Non-Infectious Inflammatory Cardiomyopathy 7.9.1 Connective Tissue Disease 7.9.1.1 Systemic Lupus Erythematosus 7.9.1.2 Rheumatoid Arthritis 7.9.1.3 Systemic Sclerosis/Systemic Scleroderma 7.9.1.4 Behçet’s Disease 7.9.1.5 Polyarteritis Nodosa 7.10 Eosinophilic Myocarditis/Endomyocardial fibrosis 7.10.1 EGPA 7.10.2 Infectious Endomyocarditis and Endomyocardial Fibrosis 7.10.3 Haematological 7.11 Drug-Induced or Toxic Myocarditis 7.12 Inflammatory Myositis 7.13 Giant Cell Myocarditis 7.14 Genetic Causes 7.15 Molecular Imaging 7.16 Hybrid Imaging 7.17 Summary References 8: Cardiac Devices Infection 8.1 Introduction 8.2 Scintigraphy in Cardiac Devices Infection 8.2.1 Radiolabelling of White Blood Cells with 99mTc-HMPAO or 111In-oxine 8.2.2 Image Acquisition 8.2.3 Image Interpretation 8.2.4 Radiolabelled WBC Scintigraphy of CIED Infection 8.2.5 Radiolabelled WBC Imaging of Left Ventricular Assist Devices Infection 8.2.6 Merits and Limitations of Radiolabelled WBC Scintigraphy in Cardiac Devices Infection: Alternative SPECT Tracers 8.3 FDG PET/CT Imaging of Cardiac Devices Infection 8.3.1 Patient Preparation 8.3.1.1 Suppression of Myocardial FDG Uptake 8.3.1.2 Withdrawal of Medications 8.3.2 Image Acquisition and Interpretation 8.3.3 FDG PET/CT Imaging of CIED Infection 8.3.4 FDG PET/CT Imaging of LVAD Infection 8.3.5 FDG PET/CT for Extra-Cardiac Disease in Patients Assessed for Cardiac Devices Infection 8.4 Comparative Performance of Radionuclide WBC Scintigraphy and FDG PET/CT in Cardiac Devices Infection 8.5 Conclusion References 9: Endocarditis 9.1 Introduction 9.2 Single Photon Emission Tomography (SPECT) 9.2.1 67Ga-citrate Scintigraphy 9.2.2 Labelled Leukocytes Scintigraphy 9.2.3 Other SPECT Tracers 9.3 Positron Emission Tomography (PET) 9.4 Concluding Remarks References