Emission Tomography

By Miles N. Wernick and John N. Aarsvold

ContributorsForewordPrefaceAcknowledgments1. Imaging Science Bringing the Invisible to Light I. Preamble II. Introduction III. Imaging Science IV. Fundamental and Generic Issues of Imaging Science V. Methodology and Epistemology VI. A View of the Future2. Introduction to Emission Tomography I. What is Emission Tomography? A. The Tracer Principle B. Tomography II. The Making of an Emission Tomography Image A. Single-Photon Emission Computed Tomography B. Positron Emission Tomography C. Image Reconstruction D. Image Analysis III. Types of Data Acquisition: Static, Dynamic, Gated, and List Mode IV. Cross-Sectional Images V. Radiopharmaceuticals and Their Applications VI. Developments in Emission Tomography3. Evolution of Clinical Emission Tomography I. Introduction II. The Beginnings of Nuclear Medicine A. Developments Before 1945 B. The Next 25 Years (1945–1970) III. Early Imaging Devices A. Early Scanning Imagers B. Early Devices Based on Gamma Cameras C. Early Dedicated Positron-Emission Imagers IV. Evolution of Emission Tomography and Initial Applications A. Anger Camera Developments B. Radiopharmaceutical Targeting Agents C. Early Theoretical Developments V. Clinical Applications A. Brain Imaging B. Thyroid Imaging and Therapy C. Parathyroid Disease D. Cardiac Imaging E. Lung Imaging F. Kidney Imaging G. Bone Imaging H. Reticuloendothelial System Imaging I. Pancreas Imaging J. Tumor Imaging K. Molecular Biology Applications VI. Summary4. Basic Physics of Radioisotope Imaging I. Where Do the Nuclear Emissions Used in Imaging Come From? A. Nuclear Constituents B. Nuclear Forces and Binding Energy C. Nuclear Energy Levels D. Nuclear De-excitation E. Nuclear Stability F. Nuclear Transmutation G. Nuclear Decay Probability II. Relevant Modes of Nuclear Decay for Medical Radionuclide Imaging A. Isomeric Transitions: Gamma-Ray Emission B. Isobaric Transitions: Beta (ß) Emission III. Production of Radionuclides for Imaging A. The Nuclear Reactor B. The Nuclear Generator C. The Cyclotron IV. Interactions of Nuclear Emissions in Matter A. Interactions of Electrons and Positrons in Matter B. Interactions of High-Energy Photons in Matter V. Exploiting Radiation Interactions in Matter for Emission Imaging A. Statistics of Ionization Production B. Detector and Position-Sensitive Detector Basics VI. Physical Factors That Determine the Fundamental Spatial Resolution Limit in Nuclear Emission Imaging A. Overview of Physical Factors That Affect Emission Imaging Performance B. What Is the Fundamental Spatial Resolution Limit in Radioisotope Imaging?5. Radiopharmaceuticals for Imaging the Brain I. Introduction II. Biochemical Processes in the Brain III. New Radiopharmaceutical Development A. Steps in Radiopharmaceutical Development B. Criteria for Pharmaceuticals Used for In Vivo Receptor Imaging IV. Neuroscience Studies A. Dopaminergic System B. Cholinergic System C. Serotonergic System D. Other Systems V. Applications of Imaging Studies: Dopamine System A. Distribution of Receptors, Transporters, and Enzymes B. Distribution and Pharmacokinetics of Radiolabeled Drugs C. Receptor Occupancy of Therapeutic Drugs D. Integrity of the Presynapse E. Alterations in the Levels of Endogenous Ligand Dopamine F. Study of Substance Abuse Drugs G. Interactions with Other Neurotransmitter Systems H. Posttreatment Monitoring of the System I. Etiological Studies of the System J. Neurotoxicity of Drugs VI. Oncology Studies VII. Genomic Studies A. Imaging Protein Products B. Use of Antisense RNA to Image mRNA VIII. Summary6. Basics of Imaging Theory and Statistics I. Introduction II. Linear Systems A. Linear Shift-Invariant Systems B. Point Spread Functions C. Fourier Transform and Spectrum D. System Transfer Functions III. Discrete Sampling A. Sampling Theorem and Aliasing B. Discrete Fourier Transform C. Relationship among FT, DFT, and Sampling D. Interpolation IV. Noise and Signal A. Random Variables B. Stochastic Processes C. Noise Models D. Power Spectrum V. Filtering A. Pseudoinverse B. Tikhonov Regularization C. Wiener Filtering VI. Smoothing A. Smoothing Filters B. Median Filters C. Smoothing Splines VII. Estimation A. Bayesian Parameter Estimation B. Maximum Likelihood Estimation C. Bias and Variance VIII. Objective Assessment of Image Quality A. ROC Analysis B. Ideal Observer: Likelihood Ratio C. Noise Equivalent Quanta and Detective Quantum Efficiency D. Model Observer: (Channelized) Hoteling Observer7. Single-Photon Emission Computed Tomography I. Planar Single-Photon Emission Imaging A. Thyroid Studies B. Ventilation/Perfusion Studies C. Whole-Body Bone Studies D. Other Nuclear Medicine Studies II. Conventional Gamma Cameras A. The Anger Camera B. Principles of Collimation C. Collimator Types D. Scintillation Detection E. Event Positioning F. Photon Interactions G. Camera Performance III. Tomography A. Tomographic Imaging B. Transmission Imaging C. Emission Imaging D. Transmission Tomography E. Emission Tomography IV. Single-Photon Emission Computed Tomography Systems A. System Configurations B. Gantry Motions C. Transmission-Source Tomography D. SPECT/CT E. System Performance V. Tomographic Single-Photon Emission Imaging A. Bone SPECT B. Brain SPECT C. Myocardial Perfusion SPECT VI. Other Detectors and Systems A. Multiple-Pinhole Coded Apertures B. Multisegment Slant-Hole Collimators C. Rotating-Slat Collimators D. Compton Cameras E. Segmented-Scintillator Detectors F. Solid-State Detectors VII. Summary8. Collimator Design for Nuclear Medicine I. Basic Principles of Collimator Design II. Description of the Imaging System and Collimator Geometry III. Description of Collimator Imaging Properties IV. Septal Penetration V. Optimal Design of Parallel-Hole Collimators VI. Secondary Constraints A. Collimator Weight B. Septal Thickness C. Visibility of Collimator Hole-Pattern VII. Summary9. Annular Single-Crystal SPECT Systems I. Overview: Annular Single-Photon Emission Computed Tomography Systems II. Principles and Design of CeraSPECT III. Annular SensOgrade Collimators IV. Modification of Light Optics in a Scintillation Camera V. NeurOtome, A Bridge between Single-Photon Emission Computed Tomography and Positron Emission Tomography VI. MammOspect, an Annular Breast Single-Photon Emission Computed Tomography Camera VII. Small Animal Single-Photon Emission Computed Tomography Using an Annular Crystal VIII. Discussion10. PET Systems I. Basic Positron Emission Tomography Principles II. Detector Designs III. Tomography System Geometry IV. Positron Emission Tomography Scintillators V. Positron Emission Tomography System Electronics VI. Attenuation Correction VII. Scatter Correction VIII. Noise Equivalent Count Rate IX. Future Trends11. PET/CT Systems I. Introduction II. Motivation III. Initial Development IV. Design A. General Considerations B. Detectors C. Gantry D. Patient Handling System E. Software and Computers V. Protocols VI. Image Registration and Fusion VII. Attenuation Correction VIII. Dosimetry A. CT Effective Dose B. Effective Dose in PET C. Total Effective Dose in PET/CT IX. The Future12. Small Animal PET Systems I. Introduction A. Why Use PET in Laboratory Animal Research? B. Laboratory Animal Models of Human Disease C. Opportunities for PET in Small Animal Imaging II. Challenges in Small Animal PET A. Spatial Resolution B. Sensitivity C. Injected Dose and Injected Mass D. Specific Activity of Tracers E. Measurement of the Input Function F. Anesthesia G. Other Issues III. Early Development of Animal PET Scanners A. Large Animal PET Scanners B. Hammersmith RAT-PET IV. New Generation Small Animal PET Scanners A. Sherbrooke Animal PET B. microPET C. HIDAC Animal PET D. Other Small Animal PET Systems V. Applications of Small Animal PET A. Measurement of Glucose Metabolism in the Rat Brain and Heart B. Studies of the Dopaminergic System in Rat Brain C. Animal PET in Oncology D. Imaging of Gene Expression by PET VI. Future Opportunities and Challenges A. Small Animal PET Research Challenges B. Resolution Limits of Small Animal PET C. Multimodality Small Animal Imaging D. Use of PET for High-Throughput Phenotyping and Drug Screening VII. Summary13. Scintillators I. Introduction II. Gamma-Ray Interactions in Scintillation Crystals A. The Photoelectric Process B. The Compton Effect C. Pair Production III. The Characteristics and Physical Properties of Scintillators A. Light Output B. Scintillator Energy Resolution C. Material Density D. Optical Properties E. Mechanical Properties and Intrinsic Background IV. Scintillation Detectors: Design and Fabrication A. Detector Design B. Detector Components C. Detector Fabrication V. Measurements with Scintillators A. Measurement Systems VI. Summary and Comments14. Photodetectors I. Introduction A. Light Emission of Common Scintillators B. Important Performance Factors of Light Detectors II. Photomultiplier Tubes A. The Photocathode of a PMT B. Quantum Efficiency of PMTs C. Electron Multiplication, Gain, and Dynode Structures D. Electronic Properties of PMTs E. Effects of Magnetic Fields F. Position-Sensitive Photomultiplier Tubes G. Photomultiplier Tubes: Future Trends III. Semiconductor Diode Detectors IV. PIN Diodes V. Avalanche Photodiodes A. Structure and Properties of APDs B. Theory of Avalanche Multiplication C. Noise Behavior of APDs D. Guard Structures VI. Comparison of PMT and APD Properties VII. Drift Diodes VIII. Direct Detection of Gamma Rays: CdTe and CdZnTe Detectors15. CdTe and CdZnTe Semiconductor Detectors for Nuclear Medicine Imaging I. Introduction A. Semiconductors as Radiation Detectors B. Crystal Growth and Contacts C. Advantages of CdTe and CZT D. Relevant Societies and Scientific Exchange II. Energy Spectrum Performance A. Energy Resolution B. The Low-Energy Tail C. Neighboring Pixel Effects D. Depth-of-Interaction Effects E. The Small Pixel Effect III. Imaging Performance A. Electronics and Signal Processing B. Energy Windowing C. Uniformity and Other Corrections D. Cooling E. Timing Resolution F. Spatial Resolution G. Collimation IV. Nuclear Medicine Applications A. Prototypes and Products B. Cardiac Imaging C. Breast Imaging D. Handheld and Surgical Imagers E. Dual-Modality Single-Photon Emission Computed Tomography and X-ray Computed Tomography F. Small Animal Imaging G. Compton Camera V. Conclusion16. Application-Specific Small Field-of-View Nuclear Emission Imagers in Medicine I. Overview of Application-Specific Small Field-of-View Imagers A. Motivation for the Small Camera Concept B. General Design Principles II. Scintillation Detector Designs of Small Field-of-View Imagers A. Scintillation Crystal Design B. Collimation for Scintillation Crystal Designs C. Photodetector Design D. Electronic Readout of Position-Sensitive Photodetectors E. Electronic Processing and Data Acquisition for Imaging F. Event Positioning Schemes and Image Formation III. Semiconductor Detector Designs of Small Field-of-View Imagers A. Semiconductor versus Scintillation Crystals B. Semiconductor Imaging Array Configurations IV. Review of Current Designs and Applications for Small Field-of-View Imagers A. Small-FOV Gamma-Ray Imagers in Medicine B. Small-FOV Coincidence Imagers in Medicine C. Small-FOV Beta Imagers in Medicine17. Intraoperative Probes and Imaging Probes I. Introduction II. Early Intraoperative Probes A. Geiger-Müller Counters B. Scintillation Detectors C. Solid-State Detectors D. Detector Configurations E. Summary of Intraoperative Probe Instrumentation III. Clinical Applications A. Radioimmunoguided Surgery B. Location of Sentinel Nodes C. Summary of Clinical Applications IV. The Future: Imaging Probes? A. Early Intraoperative Imaging Probes B. Beta Imaging Probes C. Gamma Imaging Probes D. Imaging Probe Summary V. Discussion VI. Conclusion18. Noble Gas Detectors I. Why Noble Gas Detectors are Interesting for Medical Gamma-Ray Imaging A. Brief History of Gas Detectors B. Intrinsic Energy Resolution C. Position Resolution D. Technical Features II. Basic Processes of Energy Dissipation and Generation of Light Signals A. Ionization and Scintillation B. Drift of Charge Carriers C. Gas Gain and Electroluminescence D. Electron Emission from Condensed Phases III. Earlier Developments of Gas Detectors for Medical Applications A. Ionization Chambers B. Analog Imaging C. Digital Imaging with Multiwire Proportional Drift Chambers IV. Luminescence Detectors A. Electroluminescence Drift Chambers B. Multilayer Electroluminescence Chamber C. Liquid Xenon Detectors V. Technical Features of Luminescence Detectors A. Gas Purification B. Photosensors C. UV Wavelength Shifting D. Construction VI. Applications for Single-Photon Emission Computed Tomography A. Small Gamma Camera B. Cylindrical Gamma Camera C. Compton Camera VII. Concluding Remarks19. Compton Cameras for Nuclear Medical Imaging I. Introduction A. Method and Motivation B. Brief History II. Factors Governing System Performance A. Geometric Effects B. Statistical and Electronic Effects C. Physics Effects D. Combined Effects III. Analytical Prediction of System Performance A. Noise Propagation and Lower Bound B. Observer Performance C. Predicted Efficiency Gains for Various Geometries IV. Image Reconstruction for Compton Cameras A. Background B. The Forward Problem C. The Inverse Problem D. Overview of Compton Reconstruction Methods E. Direct or “Analytic” Solutions F. Statistically Motivated Solutions G. Regularization V. Hardware and Experimental Results A. Silicon Pad Detectors B. C-Sprint C. Scintillation Drift Chambers as Compton Cameras VI. Future Prospects for Compton Imaging A. Compton Probes B. Combined PET-SPECT Imaging C. Very High Resolution Animal PET D. Coincidence SPECT E. Imaging of High Energy Radiotracers VII. Discussion and Summary20. Analytic Image Reconstruction Methods I. Introduction II. Data Acquisition A. Two-Dimensional Imaging B. Fully Three-Dimensional Imaging C. The Relationship between the Radon and X-Ray Transforms III. The Central Section Theorem A. The Two-Dimensional Central Section Theorem B. The Three-Dimensional Central Section Theorem for X-Ray Projections C. Other Versions of the Central Section Theorem IV. Two-Dimensional Image Reconstruction A. Backprojection B. Reconstruction by Backprojection Filtering C. Reconstruction by Filtered Backprojection D. Reconstruction by Direct Fourier Methods E. Other Data Acquisition Formats F. Regularization V. Three-Dimensional Image Reconstruction from X-Ray Projections A. Spatial Variance and the Three-Dimensional Reprojection Algorithm B. Three-Dimensional Backprojection C. Three-Dimensional Reconstruction by Backprojection Filtering D. Three-Dimensional Reconstruction by Filtered Backprojection E. Other Three-Dimensional Reconstruction Methods VI. Summary21. Iterative Image Reconstruction I. Introduction II. Tomography as a Linear Inverse Problem A. Linear Model of the Imaging Process B. Statistical Model of Event Counts C. Spatiotemporal (4D) Imaging Model III. Components of an Iterative Reconstruction Method IV. Image Reconstruction Criteria A. Constraint Satisfaction B. Maximum-Likelihood Criterion C. Least-Squares and Weighted-Least-Squares Criteria D. Shortcoming of Maximum-Likelihood, Least-Squares, and Weighted-Least-Sqaures Methods E. Bayesian Methods F. Criteria for Reconstruction of Image Sequences: 4D Reconstruction V. Iterative Reconstruction Algorithms A. General Structure of Iterative Algorithms B. Constraint-Satisfaction Algorithms C. The Maximum-Likelihood Expectation-Maximization Algorithm D. Least-Squares and Weighted-Least Squares Algorithms E. Maximum A Posteriori Reconstruction Algorithms F. Subset-Based Reconstruction Algorithms G. Iterative Filtered Backprojection Algorithms VI. Evaluation of Image Quality A. Bias and Variance B. Effective Spatial Resolution C. Numerical Observers VII. Summary VIII. Appendices A. Modeling the Projection of a Pixel B. Projections onto Convex Sets C. Details of the Maximum-Likelihood Expectation-Maximization Algorithm22. Attenuation, Scatter, and Spatial Resolution Compensation in SPECT I. Review of the Sources of Degradation and Their Impact in SPECT Reconstruction A. Ideal Imaging B. Sources of Image Degradation C. Impact of Degradations II. Nonuniform Attenuation Compensation A. Estimation of Patient-Specific Attenuation Maps B. Compensation Methods for Correction of Nonuniform Attenuation C. Impact of Nonuniform Attenuation Compensation on Image Quality III. Scatter Compensation A. Scatter Estimation Methods B. Reconstruction-Based Scatter Compensation Methods C. Impact of Scatter Compensation on Image Quality IV. Spatial Resolution Compensation A. Restoration Filtering B. Modeling Spatial Resolution in Iterative Reconstruction C. Impact of Resolution Compensation on Image Quality V. Conclusion23. Kinetic Modeling in Positron Emission Tomography I. Introduction A. What’s in a Compartment? B. Constructing a Compartmental Model II. The One-Compartment Model: Blood Flow A. One-Tissue Compartmental Model B. One-Compartment Model in Terms of Flow C. Volume of Distribution/Partition Coefficient D. Blood Flow E. Dispersion, Delay Corrections F. Noninvasive Methods G. Tissue Heterogeneity III. Positron Emission Tomography Measurement of Regional Cerebral Glucose Use A. The Basic Compartmental Model B. Protocol for Measurement of Regional Cerebral Glucose Use C. Estimation of Rate Constants D. The Lumped Constant E. Tissue Heterogeneity IV. Receptor-Ligand Models A. Three-Compartmental Model B. Modeling Saturability C. Parameter Identifiability: Binding Potential or Other Compound Parameters D. Neurotransmitter Changes—Nonconstant Coefficients E. Neurotransmitter Levels V. Model Simplifications A. Reference Region Methods B. Compartmental Model Simplifications C. Logan Analysis D. Limitations and Biases of the Reference Region Methods E. Practical Use VI. Limitations to Absolute Quantification A. Spatial Resolution Effects B. Correcting for the Spatial Resolution Effect VII. Functional Imaging of Neurochemistry—Future Uses A. Can Neurotransmitter Activation Imaging Really Work? B. Activation of the Dopamine System by a Task Can Be Imaged C. Clinical Uses of Neurotransmitter Activation Studies D. Caution in the Interpretation of Neurotransmitter Activation Studies E. PET Imaging and Kinetic Modeling Issues in Gene Therapy VIII. A Generalized Implementation of the Model Equations A. State Equation B. Output Equation C. Implementing an Arbitrary Model24. Computer Analysis of Nuclear Cardiology Procedures I. Introduction II. Advances in Single-Photon Emission Computed Tomography Instrumentation III. Advances in Computer Methods A. Automatic Oblique Reorientation and Reslicing B. Stress-Rest Studies C. Automated Perfusion Quantification D. Image Display E. Automatic Quantification of Global and Regional Function F. Artificial Intelligence Techniques Applied to SPECT G. Software Registration of Multimodality Imagery: Image Fusion IV. Conclusion25. Simulation Techniques and Phantoms I. Introduction A. Why Simulation? Limitations and Benefits B. Probability Distribution Functions C. The Random Number Generator II. Sampling Techniques A. The Distribution Function Method B. The Rejection Method III. Mathematical Phantoms A. Analytical Phantoms B. Voxel-Based Phantoms C. Other Types of Phantoms IV. Photon and Electron Simulation A. Cross-sectional Data for Photons B. Path-Length Simulation C. Sampling Interaction Types D. Photoabsorption E. The Compton Process F. Bound Electrons G. Coherent Scattering H. Electron Simulation V. Detector Simulation A. Simulation of Energy Resolution B. Simulation of Temporal Resolution C. Backscattering of Photons behind the NaI(T1) Crystal D. Collimator Penetration and Scattering VI. Variance Reduction Methods A. The Idea behind the Weight B. Forced Detection (Angular and Spatial) VII. Examples of Monte Carlo Programs for Photon and Electrons A. The SIMIND Program B. The SimSET Program C. The EGS4 Package D. The MCNP4 Program VIII. Examples of Monte Carlo Applications in Nuclear Medicine Imaging A. General Detector Parameters and Energy Spectrum Analysis B. Evaluation of Scatter and Attenuation Correction Methods C. Collimator Simulation D. Transmission SPECT Simulation E. MC Calculations and SPECT in Dose Planning of Radionuclide Therapy IX. Conclusion