The Pathophysiologic Basis of Nuclear Medicine

Description

This book, now in its third edition, aims to promote a deeper understanding of the scientific and clinical basis of nuclear medicine and the new directions in medical imaging. The new edition has been revised and updated to reflect recent changes and to ensure that the contents are in line with likely future directions. The book starts by providing essential information on general pathophysiology, cell structure and cell biology as well as the mechanisms of radiopharmaceutical localization in different tissues and cells. The clinical applications of nuclear medicine are then presented in a series of chapters that cover every major organ system and relate the basic knowledge of anatomy, physiology and pathology to the clinical utilization of various scintigraphic modalities. The therapeutic applications of nuclear medicine are discussed in a separate chapter, and the final chapter is devoted to the biologic effects of ionizing radiations, including radiation from medical procedures. Foreword to First Edition Preface to Third Edition Preface to Second Edition Preface to First Edition Acknowledgement Contents Contributors 1: Pathophysiology: General Principles 1.1 Introduction 1.2 Pathology 1.3 Definition of Disease 1.3.1 Homeostasis 1.3.2 The Genome 1.4 Physiology 1.5 Pathophysiology 1.6 Basic Major Principles of Pathophysiology 1.6.1 Cell Injury 1.6.1.1 Biochemical Cell Injury 1.6.1.2 Intracellular Accumulations 1.6.2 Cell and Tissue Response to Injury 1.6.2.1 Cell Adaptation Atrophy Hypertrophy Hyperplasia Metaplasia Dysplasia 1.6.2.2 Cell Death Necrosis (Non-regulated, Inflammatory, Accidental Cell Death) Apoptosis (Regulated, Non-inflammatory Cell Death) References 2: The Cell and Tissue Biology 2.1 Introduction 2.2 Cell Structure and Function 2.2.1 The Plasma Membrane 2.2.1.1 Plasma Membrane Structure 2.2.1.2 Plasma Membrane Function 2.2.2 Cytoplasm and Its Organelles 2.2.2.1 The Endoplasmic Reticulum 2.2.2.2 The Golgi Complex 2.2.2.3 Lysosomes 2.2.2.4 Peroxisomes 2.2.2.5 Mitochondria 2.2.2.6 Ribosomes 2.2.3 Cytoskeleton 2.2.4 Nucleus 2.3 DNA and Gene Expression 2.3.1 DNA: The Genetic Material 2.3.1.1 DNA Structure 2.3.1.2 DNA Replication 2.3.1.3 Gene Mutation 2.3.1.4 DNA Recombination 2.3.2 Gene Expression and Protein Synthesis 2.3.2.1 DNA Transcription 2.3.2.2 RNA Structure 2.3.3 Genetic Code 2.3.4 DNA Translation: Protein Synthesis 2.4 Cell Reproduction 2.4.1 The Cell Cycle 2.4.2 Mitosis and Cytokinesis 2.4.3 Rates of Cell Division 2.4.4 Chromosomes and Diseases 2.5 Cell Transformation and Differentiation 2.6 Degradation of Cellular Components 2.6.1 Protein Turnover 2.6.2 Lipid Turnover 2.6.2.1 Cholesterol Homeostasis 2.7 Normal and Malignant Growth 2.7.1 Normal Growth 2.7.1.1 Cell Types 2.7.1.2 Tissue Types 2.7.1.3 Cell in Tissues Muscle Tissue Skeletal Muscle Cardiac Muscle Smooth Muscle Nerve Tissue Epithelial Tissue 2.7.1.4 Matrix Cells Indigenous Connective Tissue Cells Fibroblasts Mast Cells Fat Cells Bone Cells Cartilage Cells Immigrant Cells 2.7.2 Malignant Growth 2.7.2.1 Molecular Basis of Cancer (See Also Chap. 11) 2.7.2.2 Tumor Angiogenesis 2.7.2.3 Tumor Antigens 2.8 Cell-to-Cell Communication 2.8.1 Cell–Cell Interaction 2.8.2 Cell Signaling and Cellular Receptors 2.9 Cellular Metabolism 2.9.1 Role of ATP 2.9.2 Production of ATP 2.9.2.1 Glycolysis 2.9.2.2 Oxidative Phosphorylation 2.10 Transport Through the Cell Membrane 2.10.1 Transport of Water and Solutes 2.10.1.1 Diffusion 2.10.1.2 Facilitated Diffusion (Carrier-Mediated Diffusion) 2.10.1.3 Active-Mediated Transport 2.10.2 Transport by Vesicle Formation 2.10.3 Transmission of Electrical Impulses 2.11 Cell Death 2.11.1 Imaging of Cell Death References 3: Basis of Radiopharmaceutical Localization 3.1 Radiopharmaceuticals 3.2 Mechanism(s) of Radiopharmaceutical Localization 3.2.1 Isotope Dilution 3.2.2 Capillary Blockade 3.2.3 Physicochemical Adsorption and Ion Exchange 3.2.4 Cellular Migration and Sequestration 3.2.5 Membrane Transport 3.2.5.1 Simple Diffusion Simple Diffusion and Intracellular Biotransformation Simple Diffusion and Mitochondrial Binding Simple Diffusion and Increased Capillary and Plasma: Membrane Permeability 3.2.5.2 Facilitated Diffusion 18 F-fluorodeoxyglucose (FDG) Hepatobiliary Agents 3.2.5.3 Active Transport 3.2.5.4 Phagocytosis 3.2.5.5 Receptor-Mediated Endocytosis 3.2.6 Metabolic Substrates and Precursors 3.2.6.1 Metabolic Trapping of FDG Radiolabeled Amino Acids 3.2.7 Radiopharmaceuticals for Tissue Hypoxia: Imaging 3.2.8 Cell Proliferation Radiopharmaceuticals 3.2.9 Specific Receptor Binding 3.2.9.1 Radiolabeled Peptides 3.2.9.2 Steroid Hormone Receptors 3.2.9.3 Adrenergic Presynaptic Receptors and Storage 3.2.9.4 LDL Receptors 3.2.9.5 Radiolabeled Antibodies 3.2.10 Imaging Gene Expression Mechanism 3.2.10.1 Antisense Imaging 3.2.10.2 Reporter Gene Imaging References 4: Inflammation 4.1 Introduction 4.2 Classification of Inflammation 4.3 General Pathophysiological Changes of Inflammation 4.3.1 Local Pathophysiological Changes of Inflammation 4.3.1.1 Acute Inflammation Local Vascular Changes Formation of Exudate Local Cellular Events 4.3.1.2 Local Sequelae of Acute Inflammation 4.3.1.3 Chronic Inflammation 4.3.1.4 Abscess Formation 4.3.2 Systemic Pathophysiological Changes of Inflammation 4.3.3 Pathophysiological Changes of Healing 4.4 Pathophysiology of Major Soft Tissue Inflammation 4.4.1 Abdominal Inflammation 4.4.2 Chest Inflammation 4.4.2.1 Sarcoidosis 4.4.2.2 Pneumocystis carinii (jiroveci) Pneumonia 4.4.2.3 Interstitial Pulmonary Fibrosis 4.4.3 Renal Inflammation 4.4.3.1 Acute Pyelonephritis 4.4.3.2 Chronic Pyelonephritis 4.5 Pathophysiology of Major Skeletal Inflammations 4.6 Fever of Unknown Origin 4.7 Radiopharmaceuticals for Inflammation Imaging 4.8 Infection Imaging 4.8.1 Imaging of Soft Tissue Infections 4.8.2 Localizing Signs Present 4.8.2.1 Imaging Abdominal Infections 4.8.2.2 Imaging Chest Infections 4.8.2.3 Imaging Renal Infections 4.8.2.4 Imaging of Skeletal Infection 4.8.3 No Localizing Signs Present 4.9 Summary References 5: Nuclear Hematology 5.1 Introduction 5.2 Hematopoiesis and Hematopoietic Tissues 5.2.1 Blood Cells 5.2.2 The Bone Marrow 5.2.3 Hematopoietic Growth Factors 5.2.4 Hematopoiesis and Hematopoietic Stem Cells 5.2.5 Hematopoietic Cell Lineages 5.3 Erythropoiesis 5.3.1 Globin Chain Synthesis 5.3.2 Heme Synthesis 5.3.3 Essential Hematopoietic Nutrients 5.3.4 Iron Metabolism and Erythropoiesis 5.3.5 Intracellular Regulation of Iron 5.3.6 Qualitative and Quantitative Aspects of Erythropoiesis 5.4 Iron Absorption 5.5 Ferrokinetics 5.5.1 Plasma Iron Clearance 5.5.2 Plasma Iron Turnover 5.5.3 Red Cell Utilization (RCU) of Radioiron 5.5.4 Erythrocyte Iron Turnover 5.5.5 Surface Counts for 59 Fe 5.6 Imaging for Evidence of Erythropoietic Activity 5.7 The Life Spans of Red Blood Cells 5.8 Surface Counts to Determine Sites of Red Cell Destruction Using 51 Cr-Labeled Red Cells 5.9 Use of Radionuclides in the Investigation of Patients with Megaloblastic Anemia 5.9.1 Etiopathogenetic Basis of Megaloblastic Anemia 5.9.2 Vitamin B 12 Radioassay 5.9.3 Determination of Holo-transcobalamin- 5.9.4 Identification of the Cause of Vitamin B 12 Deficiency 5.9.5 Food Cobalamin (Vitamin B 12) Malabsorption 5.9.6 DNA Synthesis and Deoxyuridine (dU) Suppression Test in Megaloblastic Anemia 5.9.7 Deoxyuridine (dU) Suppression Test 5.10 The Spleen 5.10.1 Spleen Imaging 5.10.2 Measurement of Splenic Activity 5.11 Bone Marrow Scintigraphy 5.12 Blood Platelets 5.12.1 Measurement of Platelet Survival References 6: Musculoskeletal System 6.1 Introduction 6.2 Anatomical and Physiological Considerations 6.2.1 Bone Structure 6.2.2 Blood Supply 6.2.3 Bone Remodeling 6.2.4 Bone Marrow 6.2.5 Response to Injury 6.3 Nonneoplastic Bone Diseases 6.3.1 Skeletal Infections 6.3.1.1 Definitions Classification of Osteomyelitis Pathophysiological Changes Multimodality Imaging of Skeletal Infections Acute Osteomyelitis Imaging of Peculiar Forms of Skeletal Infections 6.3.2 Avascular Necrosis (Osteonecrosis) 6.3.3 Complex Regional Pain Syndrome-1(CRPS-1) or Reflex Sympathetic Dystrophy 6.3.4 Fibrous Dysplasia 6.3.5 Trauma 6.3.5.1 Fractures 6.3.5.2 Fracture Healing 6.3.5.3 Trauma to Bone Adjacent Structures 6.3.6 Growth Plate Injury 6.3.7 Metabolic Bone Diseases 6.3.7.1 Paget’s Disease (Osteitis Deformans) 6.3.7.2 Osteoporosis 6.3.7.3 Osteomalacia and Rickets 6.3.7.4 Bone Changes of Hyperparathyroidism 6.3.7.5 Renal Osteodystrophy 6.3.7.6 Hypertrophic Osteoarthropathy 6.3.8 Arthropathy 6.3.8.1 Rheumatoid Arthritis 6.3.8.2 Ankylosing Spondylitis 6.3.8.3 Gouty Arthritis 6.3.8.4 Osteoarthritis 6.3.9 Soft Tissue Calcification 6.3.9.1 Dystrophic Calcification 6.3.9.2 Metastatic Calcification 6.3.9.3 Heterotopic Bone Formation 6.3.9.4 Calcinosis Cutis Calcinosis Cutis Universalis Calcinosis Cutis Circumscripta Calciphylaxis Rhabdomyolysis 6.4 Neoplastic Bone Disease 6.4.1 Primary Bone Tumors 6.4.1.1 Osteogenic Tumors 6.4.1.2 Chondrogenic Tumors 6.4.1.3 Collagenic Tumors 6.4.1.4 Myelogenic Tumors 6.4.1.5 Imaging of Primary Bone Tumors Imaging of Major Specific Tumors Osteoid Osteoma Osteoblastoma Osteochondroma Osteogenic Sarcoma Myeloma Ewing’s Sarcoma 6.4.2 Metastatic Bone Disease 6.4.2.1 Methods of Tumor Cell Transport 6.4.2.2 Bone Response to Metastases 6.4.2.3 Distribution of Bone Metastases 6.4.2.4 Classification of Bone Metastases 6.4.2.5 Sources of Bone Metastases 6.4.2.6 Sequelae of Skeletal Metastases 6.4.2.7 Imaging of Metastatic Bone Disease Tc99m Diphosphonate Bone Scintigraphy Appearance of Bone Metastases on Bone Scan Imaging Metastases with Other Modalities References 7: Thyroid Gland 7.1 Thyroid Anatomy 7.2 Hormone Synthesis and Secretion 7.2.1 Iodide Transport 7.2.2 Hormone Synthesis 7.2.3 Release of Hormone and Thyroglobulin 7.2.4 T 3 and T 4 7.2.5 Antithyroid Drugs 7.2.6 Summary 7.3 Thyroid Handling of Radiotracers 7.3.1 Technetium-99m- 7.3.2 Iodine-123 7.3.3 Iodine-131 7.3.4 Fluorine-18- 7.3.5 Summary 7.4 TSH and Thyroid Function 7.4.1 TSH Secretion 7.4.2 Serum TSH in Thyroid Disorders 7.4.3 Manipulation of TSH Levels 7.4.3.1 Suppressing TSH Levels 7.4.3.2 Increasing TSH Levels 7.4.4 Summary 7.5 Iodine Intake and Thyroid Function 7.5.1 Iodine Deficiency 7.5.2 Iodine Excess 7.5.2.1 Thyroid Autoregulation 7.5.2.2 Thyroid Dysfunction 7.5.2.3 Iodine and Autoimmune Thyroid Disease 7.5.3 Summary 7.6 Endemic Goiter 7.6.1 Goitrogens 7.6.2 Pathophysiology 7.6.3 Radionuclide Procedures 7.6.4 Summary 7.7 Destructive (“Subacute”) Thyroiditis 7.7.1 Postpartum Thyroiditis 7.7.2 Viral Thyroiditis 7.7.3 Thyroiditis and Other Effects of Amiodarone 7.7.4 Radionuclide Procedures 7.7.5 Summary 7.8 Autoimmune Thyroid Disease 7.8.1 Etiological Factors 7.8.2 Pathophysiology 7.8.3 Radionuclide Procedures 7.8.4 Summary 7.9 Nodular Thyroid Disease 7.9.1 Pathophysiology 7.9.1.1 Clinicopathological Criteria Nonneoplastic (“Pseudo”) Nodules Neoplastic Nodules Micronodules 7.9.2 Scintigraphy and Other Procedures 7.9.3 Summary 7.10 Thyroid Dysfunction During Gestation 7.10.1 Hyperthyroidism 7.10.2 Hypothyroidism 7.10.3 Summary References 8: Parathyroid Gland 8.1 Introduction 8.2 Anatomical and Physiological Considerations 8.3 Hyperparathyroidism 8.3.1 Primary Hyperparathyroidism 8.3.2 Secondary Hyperparathyroidism 8.3.3 Tertiary Hyperparathyroidism 8.3.4 Eutopic Parathyroid Disease 8.3.5 Ectopic Parathyroid Disease 8.3.6 Parathyroid Adenoma 8.3.6.1 Solitary Adenoma 8.3.6.2 Double or Multiple Adenomas 8.3.6.3 Cystic Adenoma 8.3.6.4 Lipoadenoma 8.3.6.5 Oncocytic (Oxyphil) Adenoma 8.3.7 Parathyroid Hyperplasia 8.3.8 Parathyroid Carcinoma 8.3.9 Hyperfunctioning Parathyroid Transplant 8.4 Consequences of Hyperparathyroidism 8.5 Management of Hyperparathyroidism 8.6 Preoperative Localization 8.6.1 Scintigraphic Imaging Localization 8.6.1.1 Dual Isotope Method 8.6.1.2 Dual-Phase Method 8.6.1.3 Positron Emission Tomography (PET) 8.6.2 Factors Affecting Scan Sensitivity 8.6.2.1 Tracer and Technique Used 8.6.2.2 Lesion Characteristics 8.6.2.3 Atypical Washout of Radiotracer 8.6.3 Intraoperative Probe Localization 8.7 Summary References 9: Adrenal Gland 9.1 Anatomical and Physiological Considerations 9.2 Adrenal Cortex 9.2.1 Pathophysiology 9.2.1.1 Primary Aldosteronism (Conn’s Syndrome) 9.2.1.2 Cushing’s Syndrome 9.2.1.3 Hyperandrogenism 9.2.2 Scintigraphy 9.2.2.1 Radiolabeled Cholesterol Analogs Patient Preparation 9.2.2.2 PET/CT 9.3 Adrenal Medulla 9.3.1 Pathophysiology 9.3.1.1 Pheochromocytoma 9.3.1.2 Neuroblastoma 9.3.1.3 Ganglioneuroma 9.3.2 Scintigraphy 9.3.2.1 Metaiodobenzylguanidine 9.3.2.2 111Indium-Octreotide 9.3.2.3 Positron Emission Tomography 9.4 Imaging of Incidental Adrenal Masses References 10: Genitourinary System 10.1 Introduction 10.2 General Physiology 10.2.1 The Nephron 10.2.2 Loop Diuretics 10.2.3 Renal Vasculature 10.2.4 Juxtaglomerular Apparatus 10.3 Renal Scintigraphy 10.3.1 Radiopharmaceuticals 10.3.1.1 Rapidly Excreted Radiopharmaceuticals 10.3.1.2 Slowly Excreted Radiopharmaceuticals 10.3.2 Interpretation 10.3.2.1 Rapidly Excreted Radiopharmaceuticals Cortical Uptake Cortical Retention First Visualization of Collecting System Time to Peak 10.3.2.2 Slowly Excreted Radiopharmaceuticals 10.4 Renovascular Hypertension 10.4.1 Introduction 10.4.2 Activation of Renin- 10.4.3 Effects of Angiotensin II 10.4.3.1 Systemic Effects 10.4.3.2 Intrarenal Effects 10.4.4 Scintigraphy in Renovascular Hypertension 10.4.4.1 Principles 10.4.4.2 Interpretation 10.4.4.3 Factors Influencing ACE Inhibitor Scintigraphy 10.4.4.4 Relationship of Renal Artery Stenosis to Renovascular Hypertension 10.5 Urinary Tract Obstruction 10.5.1 Introduction 10.5.2 Ureteropelvic Junction Obstruction 10.5.3 Hydronephrosis 10.5.4 Diuretic Renography 10.5.4.1 Rate of Urine Flow 10.5.4.2 Pelvic Capacity and Tone 10.5.4.3 Disease Fluctuation 10.6 Renal Transplantation 10.6.1 Introduction 10.6.2 Surgical Complications 10.6.2.1 Urine Extravasation, Ureteral Obstruction 10.6.2.2 Hematoma, Lymphocele 10.6.2.3 Renal Artery Stenosis 10.6.3 Medical Complications 10.6.3.1 Acute Tubular Necrosis 10.6.3.2 Rejection 10.6.3.3 Nephrotoxicity of Drugs 10.7 Urinary Tract Infection 10.7.1 Pathophysiology 10.7.2 Scintigraphy 10.8 Vesicoureteral Reflux 10.8.1 Pathophysiology 10.8.2 Scintigraphy 10.9 Testicular Torsion 10.9.1 Pathophysiology 10.9.2 Diagnosis 10.9.3 Scrotal Imaging 10.9.4 Scintigraphy References 11: Nuclear Oncology 1: Principles of Tumor Pathology and Biology 11.1 Tumor Pathology 11.1.1 Biological Behavior 11.1.1.1 Benign Tumors 11.1.1.2 Malignant Tumors 11.1.2 Grading 11.1.3 Tumor Staging 11.1.4 Rate of Growth 11.2 Tumor Biology 11.2.1 Cell Growth and Cell Cycle 11.2.2 Tumor Neovascularization (Angiogenesis) 11.2.3 Distinguishing Features of Tumor Cells 11.2.3.1 Loss of Contact Inhibition of Growth 11.2.3.2 Growth Regulatory Response Pattern 11.2.3.3 Immune Evasion 11.2.3.4 Metabolic Alterations 11.2.4 Invasion and Metastasis 11.2.5 Carcinogenesis 11.2.5.1 Genetic Mutations and Cellular Oncogenes 11.2.5.2 Growth-Promoting Proto-oncogenes 11.2.5.3 Growth Factor Receptors 11.2.5.4 Signal-Transducing Proteins 11.2.5.5 Nuclear Transcription Factors 11.2.5.6 Tumor Suppressor Genes and Tumor Progression 11.2.6 Apoptosis 11.2.7 Senescence 11.2.8 Hereditary Cancer 11.2.8.1 Inherited Cancer Syndromes 11.2.8.2 Familial Cancers 11.2.8.3 Autosomal Recessive Syndromes of Defective DNA Repair 11.3 Summary References 12: Nuclear Oncology 2: Scintigrahic Imaging 12.1 Introduction 12.2 Radiopharmaceuticals 12.2.1 Conventional Radiopharmaceuticals 12.2.2 18F-FDG 12.2.3 18F-fluoride 12.2.4 Proliferation Agents 12.2.5 Hypoxia Agents 12.2.6 68-Ga-DOTATOC and 68-Ga-DOTATATE 12.3 PET Imaging Interpretation 12.3.1 Normal Distribution 12.3.2 Benign Normal Variants 12.3.3 Uptake in Inflammation and Infection 12.3.4 Artifacts 12.3.5 Uptake Patterns of Malignancy 12.4 Clinical Uses of PET/CT in Soft Tissue Malignancies 12.4.1 CNS Tumors 12.4.2 Head and Neck Tumors 12.4.3 Thyroid Cancer 12.4.4 Esophageal Cancer 12.4.5 Breast Cancer 12.4.6 Renal and Bladder Cancers 12.4.7 Gynecologic Cancers 12.4.8 Prostate Cancer 12.4.9 Colorectal Cancer 12.4.10 Lung Cancer 12.4.11 Lymphoma 12.4.12 Melanoma References 13: Respiratory System 13.1 Anatomic and Physiologic Considerations 13.1.1 Respiratory Airways 13.1.2 Pulmonary Vasculature 13.1.3 Respiratory Function 13.1.4 Distribution of Ventilation and Perfusion 13.2 Pulmonary Embolic Disease 13.2.1 Pathogenesis and Risk Factors 13.2.2 Deep Venous Thrombosis 13.2.3 Pulmonary Thromboembolism 13.2.3.1 Consequences 13.2.3.2 Resolution 13.2.3.3 Chronic Pulmonary Thromboembolism 13.2.3.4 Recurrence 13.2.3.5 Diagnosis Scintigraphy Scintigraphic Agents Interpretation of V/Q Scan 13.3 Pulmonary Hypertension 13.4 Pneumocystis carinii ( jiroveci) Pneumonia 13.5 Idiopathic Pulmonary Fibrosis 13.6 Pulmonary Sarcoidosis 13.7 Obstructive Airway Disease 13.8 Pleural Effusions 13.9 Pneumonia 13.10 Bronchial Obstruction 13.11 Lung Cancer References 14: Nuclear Cardiology 1: Myocardial Contractility and Assessment of Cardiac Function 14.1 Anatomical Considerations 14.2 Physiological Considerations 14.2.1 Electrical Excitation 14.2.2 Contraction 14.3 Determination of Left Ventricular Performance 14.3.1 Left Ventricular Function Curve 14.3.2 Ejection Fraction 14.3.3 Pressure-Volume Relationship Measurement 14.3.4 Regional Wall Motion Assessment 14.3.5 Diastolic Function 14.4 Pathophysiological Considerations 14.4.1 Hypertension 14.4.1.1 Changes in LV Function 14.4.2 Pulmonary Hypertension 14.4.3 Valvular Heart Disease 14.4.3.1 Functional Changes 14.4.4 Cardiomyopathies 14.4.4.1 Dilated Cardiomyopathy 14.4.4.2 Hypertrophic Cardiomyopathy 14.4.4.3 Restrictive Cardiomyopathy 14.4.5 Pericardial Effusion 14.5 Scintigraphic Evaluation of Cardiac Function 14.5.1 Imaging Techniques and Interpretation 14.5.1.1 Equilibrium Radionuclide Angiography 14.5.1.2 Image Acquisition 14.5.1.3 Modes of Acquisition 14.5.1.4 Image Processing 14.5.1.5 Image Analysis 14.5.1.6 Qualitative Assessment 14.5.1.7 Quantitative Evaluation 14.5.2 Exercise Radionuclide Angiography 14.5.3 First-Pass Radionuclide Angiography 14.5.4 Nuclear Probe and VEST 14.5.5 SPECT-Gated Equilibrium Radionuclide Angiography 14.5.5.1 Acquisition and Processing 14.6 Clinical Applications 14.6.1 Assessment and Prognosis of Congestive Heart Failure 14.6.2 Monitoring Drug Therapy and Exposure to Cardiotoxins 14.6.2.1 Cardiotoxin Monitoring 14.6.2.2 Other Types of Monitoring 14.6.3 Diagnosis of Coronary Artery Disease 14.6.3.1 Exercise Radionuclide Angiography 14.6.3.2 First-Pass Radionuclide Angiography 14.6.4 Assessment and Prognosis of Myocardial Infarction 14.6.4.1 Acute-Phase Assessment 14.6.4.2 Late-Phase Assessment 14.6.5 Preoperative Cardiac Risk Assessment 14.6.6 Cardiac Transplant Evaluation 14.6.7 Monitoring Valvular Heart Disease 14.6.8 Myocardial Hypertrophy Evaluation 14.6.9 Cardiac Shunt Evaluation 14.6.9.1 Left-to-Right Shunt 14.6.9.2 Right-to-Left Shunt References 15: Nuclear Cardiology 2: Myocardial Perfusion, Metabolism, Infarction, and Receptor Imaging 15.1 Introduction 15.2 Pathophysiology of Coronary Artery Disease 15.3 Myocardial Perfusion SPECT Imaging 15.3.1 SPECT Tracers 15.3.1.1 Thallium-201 15.3.1.2 Tc-99m Sestamibi, Tc-99m Tetrofosmin 15.3.1.3 Investigational Perfusion Radiotracers 15.3.2 Stressors 15.3.2.1 Exercise 15.3.2.2 Pharmacological Stress Testing Adenosine Dipyridamole Regadenoson Dobutamine and Arbutamine 15.3.2.3 Combined Pharmacological and Exercise Stress Testing 15.3.3 Methods of SPECT Imaging 15.3.3.1 SPECT Imaging 15.3.3.2 Gated SPECT Imaging 15.3.3.3 Quantification 15.3.3.4 Attenuation Correction 15.3.3.5 Novel Processing Software 15.3.3.6 New Dedicated Cardiac SPECT Gamma Cameras 15.3.4 Clinical Utility of Myocardial Perfusion Imaging 15.3.4.1 Diagnosis 15.3.4.2 Prognosis Risk Stratification in Stable CAD Acute Chest Pain Syndromes MPI After an Acute Myocardial Infarction MPI in Patients After Revascularization Procedures MPI Prior to Noncardiac Surgery MPI After Cardiac Transplantation 15.4 PET Myocardial Perfusion Imaging 15.4.1 Principles of PET Imaging 15.4.2 Cardiac PET Perfusion Tracers 15.4.3 N-13 Ammonia 15.4.3.1 Rubidium-82 15.4.3.2 Fluorine-18 Flurpiridaz 15.4.3.3 Oxygen-15 Water 15.4.4 Applications of Cardiac PET Perfusion Imaging 15.5 Hybrid Myocardial Perfusion and CT Imaging 15.5.1 CT Attenuation Correction 15.5.2 Calcium Scoring 15.5.3 CT Coronary Angiography 15.6 Infarct-Avid Imaging 15.6.1 Introduction 15.6.2 Pathophysiology of Myocardial Infarction 15.6.3 Infarct-Imaging Agents 15.7 Congestive Heart Failure 15.7.1 Introduction 15.7.2 Therapy 15.7.3 Clinical Risk Stratification 15.7.4 Ventricular Function 15.7.5 Selection for Bypass 15.7.6 Assessment of Ischemia 15.7.7 Assessment of Viability 15.7.8 Selection for Transplantation 15.7.8.1 Neuroendocrine Evaluation 15.7.8.2 Sympathetic Receptor Imaging 15.7.9 Imaging of Cardiac Transplant Rejection References 16: Digestive System 1: Gastrointestinal Tract 16.1 The Esophagus 16.1.1 Anatomic and Physiological Considerations 16.1.1.1 Upper Esophageal Sphincter 16.1.1.2 Esophageal Body 16.1.1.3 Lower Esophageal Sphincter 16.1.2 Esophageal Motor Disorders 16.1.2.1 Disorders of the UES and Cervical Esophagus 16.1.2.2 Disorders of Esophageal Body and LES Achalasia Nonspecific Esophageal Dysmotility 16.1.2.3 Gastroesophageal Reflux Disease Pathophysiology 16.2 The Stomach 16.2.1 Anatomic and Physiological Considerations 16.2.1.1 Anatomic Features 16.2.1.2 Overall Functions 16.2.1.3 Gastric Motor Physiology 16.2.2 Disorders of Gastric Emptying 16.2.3 Duodenogastric Reflux 16.3 The Intestines 16.3.1 The Small Intestine 16.3.1.1 Anatomic and Histologic Consideration 16.3.1.2 Functional Considerations 16.3.1.3 Small Intestinal Dysmotility 16.3.1.4 Malabsorption Protein-Losing Enteropathy (PLE) Vitamin B-12 Malabsorption 16.3.2 The Colon 16.3.2.1 Anatomic and Functional Considerations 16.3.2.2 Pathophysiology of Relevant Colon Diseases Inflammatory Bowel Disease Acute Appendicitis Colorectal Cancer Gastrointestinal Bleeding 16.4 Salivary Gland 16.4.1 Anatomic Considerations 16.4.2 Pathophysiology 16.5 Ascites 16.6 Gastrointestinal Scintigraphy 16.6.1 Radionuclide Esophageal Transit Time Study 16.6.2 Gastroesophageal Reflux Study 16.6.3 Gastric Emptying Study 16.6.4 Duodenogastric Reflux Study 16.6.5 Gastrointestinal Bleeding Localization Study 16.6.6 Meckel’s Diverticulum Study 16.6.7 Imaging of Inflammatory Bowel Disease 16.6.8 Salivary Gland Imaging 16.6.9 Imaging of Appendicitis 16.6.10 Scintigraphic Non- 16.6.10.1 Carbon-14 Breath Tests Helicobacter Pylori Infections Lactase Deficiency Malabsorption Secondary to Bacterial Overgrowth 16.6.10.2 Schilling Test References 17: Digestive System 2: Liver and Biliary Tract 17.1 Introduction 17.2 Anatomical and Physiological Considerations 17.3 Hepatobiliary Radiopharmaceuticals 17.4 Evaluation of Liver Diseases 17.4.1 Functional Hepatic Mass/Reserve 17.4.2 Primary Hepatic Neoplasms and Tumor-Like Conditions 17.4.2.1 Hepatocellular Carcinoma 17.4.2.2 Hepatic Cavernous Hemangioma 17.4.2.3 Focal Nodular Hyperplasia 17.4.2.4 Hepatocellular Adenoma 17.5 Evaluation of Biliary Tract Diseases 17.5.1 Acute Cholecystitis 17.5.1.1 Morphine Augmentation Versus Delayed Imaging 17.5.1.2 Sincalide Preadministration for the Diagnosis of Acute Cholecystitis 17.5.1.3 Sincalide Pretreatment Versus Morphine Augmentation 17.5.1.4 Potential Causes of False-Positive Results 17.5.1.5 Variants Associated with CCK Preadministration and Morphine 17.5.1.6 Ancillary Findings 17.5.2 Chronic Acalculous Biliary Diseases 17.5.2.1 Chronic Acalculous Gallbladder and Cystic Duct Diseases 17.5.2.2 Sphincter of Oddi Dysfunction 17.5.3 Hyperbilirubinemia 17.5.3.1 Common Bile Duct Obstruction and Medical Jaundice 17.5.3.2 Neonatal Hyperbilirubinemia 17.5.4 Postoperative Evaluation 17.5.4.1 Complications After Hepatobiliary Surgery 17.5.4.2 Effect of Sphincter Dilation Procedures on Sphincter Function 17.5.4.3 Effectiveness of Gastrointestinal Reconstruction Surgery 17.5.5 Miscellaneous 17.6 Summary References 18: Nuclear Medicine Imaging of CNS: Basis and Clinical Applications 18.1 Introduction 18.2 Anatomy and Physiology 18.2.1 Anatomy 18.2.2 Physiology 18.2.2.1 Perfusion 18.2.2.2 Metabolism 18.3 Pathophysiology 18.3.1 Cerebrovascular Disease 18.3.2 Dementia 18.3.2.1 Alzheimer’s Disease (AD) 18.3.3 Seizures and Epilepsy 18.3.4 Brain Tumors 18.3.5 Movement Disorders 18.3.6 Hydrocephalus 18.3.6.1 Anatomy and Physiology of Hydrocephalus 18.3.6.2 Pathology Causing Hydrocephalus 18.3.6.3 Cerebrospinal Fluid Leakage 18.4 Scintigraphic Evaluation of CNS Diseases 18.4.1 Radiopharmaceuticals 18.4.1.1 99mTc- Hexamethylpropyleneamine Oxime (99mTc-HMPAO) 18.4.1.2 Technetium-99m Ethyl Cysteinate Dimer (99mTc-ECD) 18.4.1.3 133 Xe for Quantitative Regional Cerebral Blood Flow 18.4.1.4 15O-water for Quantitative Regional Cerebral Perfusion Measured by PET 18.4.1.5 Thallium-201(201Tl) 18.4.1.6 99mTc-Hexakis-2-methoxy-2-isobutyl Isonitrile (99mTc-Sestamibi) 18.4.1.7 2-[F-18]-Fluoro-2-deoxy- d -glucose (18F-FDG) 18.4.1.8 l -[Methyl- 11 C] methionine (11C-MET) 18.4.1.9 O-(2-[ 18 F] fluoroethyl)- l - tyrosine (18F-FET) 18.4.1.10 3,4-Dihydroxy-6- 18 F-fluoro- 18.4.1.11 18 F-Fluoromisonidazole ( 18F-FMISO) 18.4.1.12 Cell Proliferation Imaging with 18F-FLT PET 18.4.2 Scintigraphic Imaging Techniques 18.4.2.1 Image Acquisition SPECT Image Acquisition PET Image Acquisition Dual PET–MRI Acquisition 18.4.2.2 Registration and Analysis Methods Image Registration SPECT and PET Image Analysis 18.4.3 Clinical Applications 18.4.3.1 Cerebrovascular Disease Hemodynamic Vascular Constraint Assessment for Carotid Artery Sacrifice: Balloon Occlusion Test (BOT) 18.4.3.2 Dementia Alzheimer’s Disease SPECT Imaging of Alzheimer’s Disease PET Imaging of Alzheimer’s Disease 18 F-FDG Imaging 18 F-Florbetapir (AMYViD or 18 F-AV-45) imaging Summary of Centers for Medicare & Medicaid Services Decision Memorandum for PET Imaging in Suspected Dementia, September 2013 Imaging of Vascular Dementia with rCBF SPECT Tracers Imaging of Other Causes of Dementia 18.4.3.3 Epilepsy: Epileptogenic Focus Localization Imaging Ictal 99m Tc-HMPAO or 99m Tc-ECD SPECT 18 F-FDG Brain PET Assessment in the Interictal State Ictal and Interictal SPECT Analysis Method and Illustration of SPM Image Analysis in Epilepsy 18.4.3.4 Psychiatry and Learning Disabilities 18.4.3.5 Brain Tumors Brain Tumor Evaluation with 201 Tl 99m Tc-sestamibi (Tc-99m Hexakis-2- Effect of Chemotherapy on Metabolism 2-[F-18] Fluoro-2-deoxy- d -glucose 18 F-FDG Imaging of Brain Tumors Nucleic Acid Analog: [F-18]-Fluoro-3′-deoxy-3′- l -fluorothymidine ( 18 F-FLT) Imaging of Brain Tumors 18.4.3.6 Parkinsonism and Dopamine Receptor Imaging Dopamine Transporter Receptor Binding Agents and Image Interpretation 18.4.3.7 Radionuclide Cisternography 18.4.3.8 Brain Death References 19: Lymphoscintigraphy 19.1 Introduction 19.2 Anatomy and Physiology of the Lymphatic System 19.3 Pathophysiology 19.3.1 Lymphedema 19.3.2 Lymph Nodes with Metastases 19.4 Nuclear Medicine Applications 19.4.1 Basic Principles of Nuclear Medicine Imaging 19.4.2 Detection and Follow-Up of Lymphedema 19.4.2.1 Normal Scintigraphic Pattern 19.4.2.2 Scintigraphic Patterns of Lymphedema 19.4.3 Detection of Lymph Node Metastases 19.4.4 Sentinel Node Detection 19.4.4.1 Concept 19.4.4.2 Radioisotopes for SLN Lymphoscintigraphy 19.4.4.3 Tumors Breast Cancer Melanoma Penile Squamous Cell Carcinoma Prostate Cancer Squamous Cell Carcinoma of Head and Neck Colorectal Cancer 19.5 Summary References 20: Basis of Therapeutic Nuclear Medicine 20.1 Introduction 20.2 Treatment of Hyperthyroidism 20.2.1 Pathophysiology 20.2.2 Factors Affecting the Dose of I-131 Used for Therapy of Hypothyroidism 20.3 Treatment of Differentiated Thyroid Cancer 20.4 Treatment of Pain Secondary to Skeletal Metastases 20.4.1 Radiopharmaceuticals 20.4.1.1 Strontium-89 Chloride (Sr-89 Chloride) 20.4.1.2 Samarium-153 Ethylenediaminetet 20.4.1.3 Rhenium-186 Ethylene Hydroxy Diphosphonate (Re-186-EHDP) 20.4.1.4 Tin-117m- Diethylenetriamine 20.4.1.5 Phosphorus-32 Orthophosphate 20.4.1.6 Rhenium-188 Dimercaptosuccinic Acid Complex [Re-188(V)DMSA] 20.4.2 Mechanism of Action 20.4.3 Choice of Radiopharmaceutical 20.4.4 Clinical Use 20.5 Treatment of Neuroendocrine Tumors 20.5.1 Neuroblastoma 20.5.2 Pheochromocytoma 20.5.3 Carcinoid Tumor 20.6 Radioimmunotherapy 20.7 Radionuclide Synovectomy 20.7.1 Radiopharmaceuticals for Synovectomy 20.7.1.1 Yttrium-90 Colloid ( 90 Y) 20.7.1.2 Rhenium-186 Sulfide ([ 186 Re] Colloid) 20.7.1.3 Erbium-169 Citrate [ 169 Er] Colloid 20.7.1.4 Phosphorus-32 Chromic Sulfate (P-32) 20.7.1.5 Radioactive Gold Au-198 20.7.1.6 Rhenium-188 Colloid 20.7.1.7 Dysprosium-165 (Dy-165) 20.7.1.8 Ho-166-Ferric Hydroxide 20.7.2 Mechanism of Action 20.7.3 Choice of Radiopharmaceutical 20.7.4 Clinical Use 20.8 Treatment of Primary and Secondary Liver Malignancies 20.9 Peptide Receptor Radionuclide Therapy 20.10 Treatment of Malignant Effusions 20.11 Other Therapeutic Procedures 20.11.1 Treatment of Bone Tumors 20.11.1.1 Osteogenic Sarcoma 20.11.1.2 Multiple Myeloma 20.11.1.3 Metastatic Prostate Carcinoma 20.12 Combined Therapeutic Approach 20.13 Summary References 21: Biological Effects of Ionizing Radiation 21.1 Introduction 21.2 Mechanisms of Radiation Effects 21.2.1 Direct Effect 21.2.2 Indirect Effect 21.3 Factors Affecting Radiation Hazards 21.3.1 Factors Related to Ionizing Radiation 21.3.2 Factors Related to Biological Target 21.4 Radiation-Induced Cell Injury 21.5 Various Effects of Radiation 21.5.1 Dose-Response Models 21.5.1.1 Early Radiation Effects Acute Whole-Body Exposure Syndromes 21.5.1.2 Acute Regional Effects 21.5.2 Delayed Radiation Effects 21.5.2.1 Cancer 21.5.2.2 Genetic Effects 21.5.2.3 Effects on the Unborn Child 21.5.2.4 Other Delayed Somatic Effects 21.6 Exposure from Medical Procedures 21.7 Summary References Glossary Index