Handbook of Nuclear Medicine and Molecular Imaging for Physicists: Instrumentation and Imaging Procedures, Volume I (Series in Medical Physics and Biomedical Engineering)

This state-of-the-art handbook, the first in a series that provides medical physicists with a comprehensive overview into the field of nuclear medicine, is dedicated to instrumentation and imaging procedures in nuclear medicine. It provides a thorough treatment on the cutting-edge technologies being used within the field, in addition to touching upon the history of their use, their development, and looking ahead to future prospects. This text will be an invaluable resource for libraries, institutions, and clinical and academic medical physicists searching for a complete account of what defines nuclear medicine. * The most comprehensive reference available providing a state-of-the-art overview of the field of nuclear medicine * Edited by a leader in the field, with contributions from a team of experienced medical physicists * Includes the latest practical research in the field, in addition to explaining fundamental theory and the field's history Cover Half Title Series Information Title Page Copyright Page Table of Contents Preface Editor Contributors 1 Introduction to Biostatistics 1.1 Introduction 1.2 Data Acquisition 1.2.1 Scales of Measurement 1.2.2 Population and Sample 1.2.3 Stochastic Variables 1.2.4 Independent and Identically Distributed Stochastic Variables 1.2.5 Expected Value and Variance 1.3 Characterization and Visualization of Data 1.4 Inference: Hypothesis Testing 1.5 Tests for Difference in Means 1.5.1 One-Sample T-Test 1.5.2 One-Sided and Two-Sided Tests 1.5.3 Two-Sample T-Test 1.5.4 Paired T-Test 1.5.5 Robustness 1.5.6 Non-Parametric Tests for Differences in Medians 1.6 Correlation 1.6.1 Pearson’s Correlation Coefficient 1.6.2 Spearman’s Correlation Coefficient 1.6.3 Correlation and Dependence 1.6.4 Bland–Altman Plots 1.7 Multivariate Regression and the F-Test 1.8 Survival Data 1.8.1 Kaplan–Meier Curves 1.8.2 The Logrank Test 1.9 Statistical Power, Type I and II Errors, and the Multiple Comparisons Problem 1.10 Sensitivity and Specificity 1.11 Limitations of Hypothesis Testing References 2 Radiobiology 2.1 Introduction 2.1.1 The ‘Rs’ of Radiobiology 2.2 Linear Quadratic Model 2.2.1 Repopulation 2.3 EQDX Formalism 2.3.1 Equivalent Uniform Dose 2.3.2 Radiobiological Parameters and Their Uncertainties 2.4 Tumour Control Probability (TCP) 2.4.1 Normal Tissue Control Probability (NTCP) 2.5 Clinical Applications and Proposed Dose-Effect Relationships 2.5.1 Liver Toxicity 2.5.2 Lung Irradiation 2.5.3 Kidneys 2.5.4 Red Marrow 2.6 Bystander and Abscopal Effects 2.7 Conclusion References 3 Diagnostic Dosimetry 3.1 Introduction 3.1.1 Short Historical Review 3.1.2 Dose Tables and Computer Programs 3.2 Purpose 3.3 Radionuclides in Diagnostic Nuclear Medicine 3.4 Absorbed Dose 3.4.1 Basic Internal Dosimetry 3.4.2 Non-Penetrating Radiation 3.4.3 Absorbed Fraction of Energy 3.4.4 In Practise 3.5 Biokinetic and Dosimetric Models 3.5.1 Configuration of a Biokinetic Model 3.5.1.1 Descriptive Biokinetic Models 3.5.1.2 Compartment Models 3.5.1.3 Dosimetry Model for the Skeleton 3.5.2 General Biological Models 3.5.2.1 Model for the Human Alimentary Tract 3.5.2.2 Model for Urinary Bladder and Kidneys 3.5.2.3 Calculating the Cumulated Activity in Urinary Bladder 3.5.2.4 Dynamic Bladder Model 3.5.2.5 Model for Excretion Via the Gall Bladder 3.5.2.6 Intrathecal Model 3.5.2.7 ICRP Model for the Respiratory Tract 3.5.2.8 Model for Very Short-Lived Radionuclides Given Intravenously 3.5.2.9 Lacrimal Gland 3.5.3 Effective Dose 3.5.3.1 Radiation Weighting Factor 3.5.3.2 Tissue-Weighting Factor 3.5.3.3 Calculating the Effective Dose 3.6 Children 3.6.1 Biokinetic Data 3.6.2 Dosimetry 3.7 Dose to Embryo and Foetus 3.7.1 Calculation 3.7.2 Dose to Breast-Fed Infants 3.8 Estimation of Doses for Organs Significantly Deviating From “Reference Man” 3.8.1 Dose Estimations When the Radionuclide Is Known to Be Heterogeneously Distributed in an Organ 3.8.1.1 Kidneys 3.8.1.2 Brain 3.9 Comparison Internal Dosimetry for Medical and Radiation Protection Purposes 3.9.1 Radionuclides 3.9.2 Intake 3.9.3 Biokinetic Models 3.9.4 Dose Calculations 3.9.5 Calculating Organ Doses Using ICRP-133 3.10 Uncertainties 3.10.1 Uncertainties in Utilizing the Effective Dose as a Measure of Risk 3.11 Thyroid Dosimetry, Iodide and Pertechnetate 3.11.1 Iodide 3.11.2 Pertechnetate 3.12 In Memoriam: Lennart Johansson 1951–2020 References 4 Time-Activity Curves: Data, Models, Curve Fitting, and Model Selection 4.1 Introduction 4.2 Data 4.2.1 Number of Sampling Points 4.2.2 Temporal Sampling 4.3 Mathematical Models 4.3.1 Pharmacokinetic Models 4.3.1.1 Empirical Pharmacokinetic Models 4.3.1.2 Analytical Pharmacokinetic Models 4.3.1.3 Compartmental Pharmacokinetic Models 4.3.1.4 Whole-Body Physiologically Based Pharmacokinetic Models 4.3.2 Uncertainty Models 4.4 Curve Fitting 4.4.1 General Idea Behind Curve Fitting 4.4.2 Objective Function 4.4.3 Considerations Before Fitting 4.4.4 Quality Criteria for Fits 4.5 Model Selection 4.5.1 Akaike Information Criterion 4.5.2 Model Selection Procedure 4.6 Time-Activity Curves and Time-Integrated Activity References 5 Tracer Kinetic Modelling and Its Use in PET Quantification 5.1 Introduction 5.2 Compartment Models 5.3 Blood and Plasma Input Function 5.4 Tissue Time-Activity Curves 5.5 Irreversible Tracer Binding 5.5.1 The Patlak Plot 5.6 Reversible Tracer Binding 5.6.1 The Logan Plot 5.7 Reference Tissue Methods 5.8 Standardized Uptake Value 5.9 Parametric Images and Clinical Applications 5.10 PET in Drug Development – Occupancy 5.11 Summary References 6 Principles of Radiological Protection in Healthcare 6.1 Introduction 6.2 Effects of Exposure to Ionizing Radiation 6.3 Absorbed Dose Estimation 6.4 Principles of Radiological Protection 6.5 Exposure Categories 6.5.1 Medical Exposure 6.5.2 Occupational Exposure 6.5.3 Exposure of the Public 6.5.4 Special Situations for Radiological Protection of Patients in Healthcare 6.6 Application of the Principles for RADIOLOGICAL Protection to Patients in Healthcare 6.6.1 Justification 6.6.1.1 Generally for the Method 6.6.1.2 For a Specific Examination/Treatment With a Specified Target 6.6.1.3 For an Individual Patient 6.6.2 Optimization 6.6.3 Dose Limiting 6.7 Management of Patient Exposure From Diagnostic Procedures – Diagnostic Reference Levels, DRLs 6.8 Exposure Resulting From Radiation Therapy 6.9 Embryo/foetus Or Infant During Exposure of Patients, Who Are Pregnant Or Breast-Feeding 6.10 Principles for Radiological Protection of Healthy Volunteers in Biomedical Research 6.11 Principles for Radiological Protection of Personnel, Carers and Helpers, Infants, Small Children and Visitors, and Members of the Public 6.11.1 Personnel 6.11.2 Carers and Helpers (As Family Members and Close Friends) 6.11.3 Infants, Small Children and Visitors, and Members of the Public 6.12 Principles for Radiological Protection of the Environment 6.13 Principles for the Protection of Strong Medical Radiation Sources 6.14 Principles for Screening Investigations 6.14.1 Screening as Part of a Program 6.14.1.1 Screening Programs Screening Programs 6.14.2 Opportunistic “Screening” Or Individual Health Assessment 6.15 Principles for the Radiological Protection in Connection With Radiological and Nuclear Emergency Situations 6.16 Future Actions to Improve RADIOLOGICAL Protection in Medicine 6.17 Education and Training 6.18 Summary References 7 Controversies in Nuclear Medicine Dosimetry 7.1 The Need for Dose Calculations in Therapy With Radiopharmaceuticals 7.2 The Linear, No-Threshold (LNT) Model of Radiation Carcinogenesis 7.3 Calculations for the Release of Radiopharmaceutical Therapy Patients 7.4 The Phantom Menace References 8 Monte Carlo Simulation of Photon and Electron Transport in Matter 8.1 Introduction 8.2 Photon–atom Interactions 8.2.1 Photoelectric Effect 8.2.2 Rayleigh (Elastic, Coherent) Scattering 8.2.3 Compton (Inelastic, Incoherent) Scattering 8.2.4 Pair and Triplet Production 8.2.5 Other Interaction Processes 8.2.6 Databases of Photon Interaction Data 8.3 Electron–atom Interactions 8.3.1 Elastic Scattering 8.3.2 Inelastic Scattering 8.3.3 Bremsstrahlung Emission 8.3.4 Positron Annihilation 8.3.5 Databases of Electron Interaction Data 8.4 Multiple Scattering of Electrons 8.4.1 Multiple Elastic Scattering 8.4.2 Multiple Inelastic Scattering 8.5 Random Numbers and Sampling Methods 8.5.1 Random and Pseudo-Random Numbers 8.5.2 Inverse-Transform Method 8.5.3 Rejection Methods 8.6 PHOTON AND ELECTRON TRANSPORT 8.6.1 Cross Sections and Probability Density Functions 8.6.2 Detailed (Event-By-Event) Simulation 8.6.3 Condensed and Mixed Simulation 8.7 Monte Carlo Codes 8.7.1 Geant4 8.7.2 EGSnrc 8.7.3 PENELOPE 8.7.4 Other General-Purpose MC Codes 8.8 Applications of Monte Carlo Methods in Medical Physics 8.9 A Simulation Example With PENELOPE 8.10 CONCLUSIONS AND FINAL REMARKS Acknowledgements References 9 Patient Models for Dosimetry Applications 9.1 Simple Beginnings 9.2 The Proliferation 9.3 The GSF Voxel Phantoms 9.4 The RADAR NURBS Models 9.5 University of Florida Phantom Series 9.6 Other Realistic Phantoms 9.7 Applications of the Phantoms 9.7.1 Dosimetric Calculations 9.7.2 Image-Based Dosimetry 9.8 Summary References 10 Patient-Specific Dosimetry Calculations 10.1 Introduction 10.2 Radiation Range and Impact On Absorbed Dose Determination 10.3 Absorbed Dose Algorithms 10.3.1 Local Energy Deposition 10.3.2 Convolution (Homogeneous Medium) 10.3.3 Generation of DPK 10.3.4 From DPK to VDK: Different Approaches 10.3.5 Convolution in Heterogeneous Media 10.3.6 Full Monte Carlo Simulation 10.3.7 Choosing the Relevant Absorbed Dose Calculation Approach 10.3.8 Reference Dosimetry 10.3.9 Patient-Specific Dosimetry 10.4 Example of Calculation Approaches 10.5 Conclusion References 11 Whole-Body Dosimetry 11.1 Introduction 11.2 Method 11.2.1 Equipment 11.2.2 Background Readings 11.2.3 First Measurement 11.2.4 Subsequent Readings 11.2.5 Time-Activity Curve (TAC) and Data Fitting 11.2.6 Uncertainty Analysis 11.3 Acceptance Testing and Quality Control 11.3.1 Linearity 11.3.2 Sensitivity and Cross Talk 11.3.3 Field Uniformity 11.3.4 Quality Control 11.4 Clinical Examples and Methodologies 11.4.1 Whole-Body Dosimetry for Treatment Planning 11.4.2 Whole-Body Activity Retention Measurements for Personalized Radiation Protection Advice 11.4.3 Whole-Body Dosimetry Following Pregnancy After Radioiodine Therapy References 12 Personalized Dosimetry in Radioembolization 12.1 Introduction 12.2 Current Activity Planning Methods 12.2.1 Pre-Treatment Safety Procedure 12.2.2 BSA-Based Method for Resin Microspheres 12.2.3 MIRD Mono-Compartment for Glass Microspheres 12.2.4 MIRD Mono-Compartment Method for Holmium Microspheres 12.2.5 Limitations of Current Methods 12.3 Multi-Compartment Dosimetry 12.3.1 Different Methods to Calculate TN Ratio 12.3.2 Definition of Compartments On Anatomical Imaging 12.3.3 Definition of Compartments Using Physiological Information 12.4 Voxel-Based Dosimetry 12.5 Using Spatial Dose Information 12.6 Timing of Dosimetry-Based Treatment Planning 12.7 Quantitative Image Reconstruction 12.7.1 Post-Therapy Imaging 12.7.1.1 Bremsstrahlung SPECT/CT – The Relevance of Physics Modelling 12.7.1.2 90Y PET – The Impact of Machine and Reconstruction Parameters 12.7.1.3 90Y PET Versus BSPECT 12.7.1.4 MR & CT for 166Ho 12.8 Dose-Effect Relationships 12.8.1 Response Measures 12.8.2 Absorbed Dose Calculations 12.8.3 Micro-Distribution 12.9 Dosimetric Models 12.10 Discussion References 13 Thyroid Imaging and Dosimetry 13.1 Introduction 13.2 Iodine Metabolism 13.2.1 The Thyroid 13.3 Imaging 13.3.1 99mTc Pertechnetate 13.3.2 131I Sodium Iodide 13.3.3 123I Sodium Iodide 13.3.4 124I Sodium Iodide 13.4 Absorbed Dose From 131I 13.4.1 Dosimetry of Thyroid Tissue 13.4.2 RIT of Benign Thyroid Diseases 13.4.3 Calculation Example 13.4.4 RIT for Thyroid Cancer 13.4.5 Blood-Based Dosimetry 13.5 Summary and Conclusion References 14 Bone Marrow Dosimetry 14.1 Anatomy, Physiology and Toxicity 14.1.1 Blood Cells, Their Function and Renewal 14.1.2 The Substructure of the Bone Marrow 14.1.3 Regulation as One Organ 14.2 Anatomical Models and S Values for Bone Marrow 14.3 Clinical Bone Marrow Dosimetry 14.3.1 Dosimetry Based On Blood Samples 14.3.2 Image-Based Dosimetry 14.3.3 Total Body Activity Based On Probe Measurements 14.4 Dosimetry and Toxicity for Some Radiopharmaceuticals References 15 Cellular and Multicellular Dosimetry 15.1 Introduction 15.2 Definition of Cellular and Multicellular Dosimetry 15.3 Rationale for Cellular and Multicellular Dosimetry 15.4 MIRD Schema for Cellular and Multicellular Dosimetry 15.5 Cellular Models (self-Dose) 15.6 Multicellular Dosimetry Models (self-Dose and Cross-Dose) 15.6.1 Evolution of Multicellular Dosimetry 15.6.2 MIRDcell V2 15.7 Limitations of Cellular and Multicellular Dosimetry Models 15.8 Time-Integrated Activity 15.9 Examples Using MIRDcell V2 15.9.1 Isolated Tumour Cells Labelled With 225Ac (No Significant Cross-Dose) 15.9.2 3D Multicellular Cluster of Cultured Cells 15.9.3 3D Multicellular Clusters In Vivo References 16 Alpha-Particle Dosimetry 16.1 Introduction 16.2 Radioactivity Measurements 16.3 Targeting Vector 16.4 ABSORBED Dose to a Single Cell 16.5 ABSORBED Dose to TumoUr 16.6 Gamma-Camera Imaging 16.7 Organ and Whole-Body ABSORBED Dose 16.8 Pharmacokinetic Modelling 16.9 Conclusion References 17 Staff Radiation Protection 17.1 Introduction 17.2 Legislation of Radiation Protection 17.2.1 Fundamental Principles of Radiation Protection 17.2.2 Dose Limits 17.2.3 Classification of Working Areas and of Exposed Workers 17.3 Radionuclides in Nuclear Medicine 17.4 Radiation Protection in Nuclear Medicine 17.5 Radiation Protection in Practice 17.5.1 Time 17.5.2 Distance 17.5.3 Radiation Shielding 17.5.3.1 Shielding of Facilities 17.5.3.2 Shielding of Radioactive Sources 17.5.3.3 Shielding of Syringes 17.6 Radiation Protection Aprons 17.6.1 Contamination Risks 17.6.2 Hybrid Techniques 17.7 Radiation Doses to Nuclear Medicine Staff 17.7.1 Whole-Body Radiation Dose 17.7.2 Radiation Doses to Fingers and Hands 17.7.3 Radiation Dose to the Lens of the Eye 17.7.4 Skin Radiation Doses 17.7.5 Radiation Dose to Pregnant Or Breastfeeding Staff 17.8 Monitoring Programs 17.8.1 Monitoring Program for External and Internal Exposure of Staff References 18 IAEA Support to Nuclear Medicine 18.1 Introduction 18.2 Standards and Guidance Documents 18.2.1 Clinical Nuclear Medicine 18.2.2 Quality Assurance and Dosimetry 18.2.3 Radiopharmacy 18.2.4 Radiation Protection and Safety 18.2.5 Education and Clinical Training 18.2.6 Recommendations for Education and Clinical Training 18.2.7 Support to Education and Clinical Training 18.2.8 On-Line Resources 18.3 Nuclear Medicine Medical Physics 18.3.1 Roles and Responsibilities of Medical Physicists in Nuclear Medicine 18.3.2 Staffing Requirements 18.4 Coordinated Research Activities 18.5 Comprehensive Clinical Audits 18.6 Technical Cooperation Programme 18.7 Nuclear Data Services 18.8 Conferences and Technical Meetings References "Mathematical modelling is an important part of nuclear medicine. Therefore, several chapters of this book have been dedicated towards describing this topic. In these chapters, an emphasis has been put on describing the mathematical modelling of the radiation transport of photons and electrons, as well as on the transportation of radiopharmaceuticals between different organs and compartments. It also includes computer models of patient dosimetry. Two chapters of this book are devoted towards introducing the concept of biostatistics and radiobiology. These chapters are followed by chapters detailing dosimetry procedures commonly used in the context of diagnostic imaging, as well as patient-specific dosimetry for radiotherapy treatments. For safety reasons, many of the methods used in nuclear medicine and molecular imaging are tightly regulated. Therefore, this volume also highlights the basic principles for radiation protection. It discusses the process of how guidelines and regulations aimed at minimizing radiation exposure are determined and implemented by international organisations. Finally, this book describes how different dosimetry methods may be utilized depending on the intended target, including whole-body or organ-specific imaging, as well as small-scale to cellular dosimetry. This text will be an invaluable resource for libraries, institutions, and clinical and academic medical physicists searching for a complete account of what defines nuclear medicine. The most comprehensive reference available providing a state-of-the-art overview of the field of nuclear medicine Edited by a leader in the field, with contributions from a team of experienced medical physicists, chemists, engineers, scientists, and clinical medical personnel Includes the latest practical research in the field, in addition to explaining fundamental theory and the field's history"-- Provided by publisher