Pet and Spect in Neurology

Description

PET and SPECT in Neurology highlight the combined expertise of renowned authors whose dedication to the investigation of neurological disorders through nuclear medicine technology has achieved international recognition. Classical neurodegenerative disorders are discussed as well as cerebrovascular disorders, brain tumors, epilepsy, head trauma, coma, sleeping disorders and inflammatory and infectious diseases of the CNS. The latest results in nuclear brain imaging are detailed. Most chapters are written jointly by a clinical neurologist and a nuclear medicine specialist to ensure a multidisciplinary approach. This state-of-the-art compendium will be valuable not only to neurologists and radiologists/nuclear medicine specialists but also to interested general practitioners and geriatricians. It is the second volume of a trilogy on PET and SPECT imaging in the neurosciences, the other volumes covering PET and SPECT in psychiatry and in neurobiological systems. Foreword Preface Contents Contributors Part I: Basics 1: Nuclear Medicine Imaging Tracers for Neurology 1.1 Introduction 1.2 Glucose Consumption 1.3 Translocator Protein TSPO (Formerly Named Peripheral Benzodiazepine Receptor) 1.4 GABA Receptor 1.5 Dopaminergic System 1.5.1 Dopamine Transporter (DAT) 1.5.2 D 1 Receptor 1.5.3 D 2 Receptor 1.5.4 D 2 /D 3 Agonists 1.6 Beta-Amyloid Deposition 1.7 NMDA Receptor, Glycine Transport 1.8 P-Glycoprotein 1.9 Cholinergic System 1.10 Metabotropic Glutamate-5 Receptor 1.11 Vesicular Monoamine Transporter 1.12 Adenosine Receptors 1.13 Serotonergic System 1.13.1 5-HT Receptor Ligands 1.14 Nonadrenergic System 1.15 Opioid Receptors 1.16 Monoamine Oxidase Conclusions References 2: 18 F-Fluorodeoxyglucose PET Procedures: Health Economic Aspects in Neurology 2.1 Introduction 2.1.1 Cost-Effectiveness of 18 F-FDG PET Neuroimaging Procedures 2.1.2 Health Economic and Outcome Research 2.2 18 F-FDG PET Imaging: A Resource-Consuming Activity 2.2.1 Financial Aspects of PET Imaging Production Patient-Throughput Issue for Management of Imaging Production 2.2.2 Financial Aspects of PET Tracer Production 2.2.3 Financial Aspects of FDG Supply 2.3 New Paradigms in Supply and Demand Balance 2.3.1 Challenges for FDG Supply 2.3.2 18 F-FDG PET Imaging in Brain Disorders: Health Economics Issues Dementia and Alzheimer’s Disease Parkinson’s Disease and Movement Disorders Pre-surgical Evaluation for Partial Epilepsy Brain Tumours and Neuro-Oncology 2.3.3 Health Technology Assessment and Diffusion of Innovation Differences Between Diagnostic Tests and Therapeutic Interventions Purposes of HTA 2.4 Approval and Coverage: Reimbursement Issues 2.4.1 A Short History of 18 F-FDG PET Approval in the USA 2.4.2 Dealing with Uncertainty: The Concern for Payers 2.5 Trends in PET Neuroimaging and Business Risk Management 2.5.1 PET Providers as Quality Managers: A Challenging Role 2.5.2 Third-Party Payers: The Gatekeepers of ‘Affordability’ 2.5.3 Valuing Patient and Caregiver Perspectives: The Quality of Life 2.5.4 Expert Forecasts Conclusion References 3: Tracer Kinetic Modelling 3.1 Introduction 3.2 Principles of Modelling 3.3 Single-Tissue Compartment Model 3.4 Principles and Practice of Quantification 3.5 An Example: Measurement of CBF Using [ 15 O]H 2 O 3.6 Two-Tissue Compartment Model 3.7 Reference Tissue Models 3.8 Parametric Methods Conclusions References 4: Quantification in Brain SPECT: Noninvasive Cerebral Blood Flow Measurements Using 99m Tc-Labeled Tracers 4.1 Introduction 4.2 Method 4.2.1 Theory of Graphical Analysis 4.2.2 Brain Perfusion Index (BPI) 4.2.3 Comparison of BPI and CBF Values Measured by Other Invasive Methods 4.2.4 Alternative Approach to Estimation of BPI 4.2.5 Calculation of Regional CBF from BPI 4.2.6 Consecutive rCBF Measurements at Baseline and Acetazolamide Challenge 4.3 Clinical Application 4.3.1 Cerebrovascular Diseases 4.3.2 Heart Failure 4.3.3 Idiopathic Normal Pressure Hydrocephalus 4.3.4 Neurodegenerative Disorder 4.3.5 Mood Disorder 4.3.6 Other Neuropsychiatric Diseases Conclusion References 5: MRI/PET Brain Imaging 5.1 MRI Basics 5.1.1 Nuclear Magnetic Resonance (NMR) (Gibby 2005 ; Pooley 2005 .; McRobbie 2003 ; NessAiver 1997 ; Elster and Burdette 2001) 5.1.2 Magnetic Resonance Imaging (MRI) (Paschal and Morris 2004 ; Hennig 1999 ; Elster and Burdette 2001 ; NessAiver 1997 ; McRobbie 2003) 5.2 MR Imaging Sequences (Bitar et al. 2006 ; Boyle et al. 2006 ; Poustchi-Amin et al. 2001) 5.2.1 Spin Echo (SE) Sequence 5.2.2 Gradient Echo (GE) Sequence 5.2.3 Echo-Planar Imaging (EPI) Sequence 5.3 MR Imaging Contrasts 5.3.1 T1, T2(*), and PD-Weighted Image Contrasts (Gibby 2005 ; Pooley 2005 ; McRobbie 2003 ; NessAiver 1997) 5.3.2 Inversion Recovery (IR) 5.3.3 Susceptibility-Weighted Imaging (SWI) 5.3.4 Diffusion-Weighted Imaging (DWI) (Luypaert et al. 2001 ; Bammer 2003 ; Le Bihan et al. 2006 ; Huisman 2003 ; Hagmann et al. 2006) 5.3.5 Perfusion-Weighted Imaging (PWI) Arterial Spin Labeling (ASL) Dynamic Susceptibility-Weighted Contrast-Enhanced MRI (DSC-MRI) Dynamic Contrast-Enhanced (DCE) MR 5.3.6 MR Angiography (MRA) 5.3.7 Advanced Functional MRI Techniques BOLD fMRI Diffusion Tensor Imaging (DTI) MRI 5.3.8 High-Field MRI 5.4 PET Basics 5.5 [ 15 O]H 2 O Brain PET 5.6 [ 18 F]FDG Brain PET 5.7 Simultaneous [ 15 O]H 2 O and [ 18 F]FDG Brain PET 5.8 Integrated PET/MRI Quantification 5.9 Future Perspectives of Hybrid PET/MRI References 6: An Investigation of Statistical Power of [ 15 O]-H 2 O PET Perfusion Imaging: The Influence of Delay and Time Interval 6.1 Introduction 6.1.1 Using PET to Study Brain Function 6.1.2 Optimization of PET Studies of the Brain 6.2 Materials and Methods 6.2.1 Participants and Imaging Procedures 6.2.2 Experimental Tasks 6.2.3 Data Preprocessing 6.2.4 Statistical Analysis 6.3 Results 6.3.1 SPM Analysis 6.3.2 TAC Analysis 6.4 Discussion Conclusion References 7: Molecular Imaging Using Magnetic Resonance Spectroscopy in Neurology: The Past, the Present, and the Future 7.1 Introduction 7.2 The Past 7.2.1 Cerebrovascular Disorders 7.2.2 White Matter Disorders 7.2.3 Epilepsy 7.2.4 Neonatal Disorders 7.2.5 Primary Brain Tumors 7.2.6 Metastatic Brain Tumors 7.2.7 Follow-Up After Radiation Therapy 7.3 The Present 7.3.1 Multivoxel MRS 7.3.2 High-Field MRS 7.3.3 Current Neurological Applications of MRS 7.4 The Future 7.4.1 High-Field MRS 7.4.2 Multivoxel MRS 7.4.3 The Use of Short Echo Times (TEs) 7.4.4 Other Nuclei Such as 31 P and 13 C 7.5 Summary References 8: The Default Network of the Brain 8.1 Discovery of the Default Network 8.2 Measuring Default Network Function 8.2.1 Deactivation During Attention-Demanding Cognitive Tasks 8.2.2 Tasks That Rely on Default Network Activation 8.2.3 Assessment of Functional Connectivity 8.2.4 Molecular Function and Metabolic Connectivity 8.3 Clinical Relevance of Measuring Default Network Integrity References Part II: Dementia 9: Dementia Due to Neurodegenerative Disease: Molecular Imaging Findings 9.1 Introduction 9.2 FDG-PET in Patients with Dementia 9.2.1 Introduction 9.2.2 FDG-PET in Alzheimer’s Disease 9.2.3 FDG-PET in Dementia with Lewy Bodies 9.2.4 FDG-PET in Frontotemporal Dementia 9.2.5 FDG-PET in Corticobasal Degeneration and Progressive Supranuclear Palsy 9.2.6 Conclusion 9.3 Amyloid Imaging Using PET 9.3.1 Introduction 9.3.2 Amyloid PET in Alzheimer’s Disease 9.3.3 Amyloid PET in Non-Alzheimer Dementias 9.3.4 Amyloid PET in Mild Cognitive Impairment 9.3.5 Amyloid PET in Cognitively Normal Elderly 9.3.6 Amyloid PET Versus CSF Measurements 9.3.7 Conclusions/Concluding Remarks 9.4 DAT SPECT 9.4.1 Introduction 9.4.2 Role of DAT Imaging in the Differential Diagnosis DLB Versus AD 9.4.3 DAT Imaging Versus FDG-PET in DLB 9.4.4 DAT Versus Cardiac Sympathetic Imaging with MIBG SPECT in DLB 9.4.5 Concluding Remarks 9.5 Experimental Radiotracers in Alzheimer’s Disease 9.5.1 Imaging-Activated Microglia in Alzheimer’s Disease 9.5.2 Imaging Microglial Activation Using (R) -[ 11 C]PK11195 PET 9.5.3 Future Perspectives of Microglial Imaging 9.5.4 Imaging Astrocytes in Alzheimer’s Disease 9.5.5 Imaging Neurofibrillary Tangles in Alzheimer’s Disease 9.5.6 Imaging the Cholinergic System in Alzheimer’s Disease Conclusion References 10: Aβ Imaging in Aging, Alzheimer’s Disease and Other Neurodegenerative Conditions 10.1 Introduction 10.2 Aβ Imaging Radiotracers 10.2.1 11 C-Labelled Radiotracers 11 C-PiB 11 C-BF-227 10.2.2 18 F-Labelled Radiotracers 18 F-FDDNP 18 F-AZD4694 18 F-Florbetaben 18 F-Florbetapir 18 F-Flutemetamol 10.3 Aβ Imaging in Alzheimer’s Disease 10.4 Antemortem and Postmortem Correlations 10.5 Aβ Deposition in Non-Demented Individuals and Its Relation with Cognition 10.6 Relationship of Aβ Imaging with Other Biomarkers 10.6.1 FDG 10.6.2 CSF 10.6.3 MRI 10.6.4 Neuroinflammation 10.7 Relationship of Aβ Deposition with Genetic Risks and Predisposing Factors 10.8 Aβ Imaging in Other Neurodegenerative Conditions 10.8.1 Cerebral Amyloid Angiopathy 10.8.2 Lewy Body Diseases 10.8.3 Frontotemporal Lobar Degeneration 10.8.4 Prion Diseases 10.9 Aβ Imaging in the Development of Disease-Specific Therapeutics 10.10 Pending Issues 10.11 CODA References 11: PET Imaging of the α4β2* Nicotinic Acetylcholine Receptors in Alzheimer’s Disease 11.1 Introduction 11.2 Pathogenesis of AD 11.3 Radioligands for Imaging the Cholinergic System 11.4 Imaging of α4β2*-nAChRs 11.5 2-FA-PET to Assess α4β2*-nAChR Binding in AD: Findings of Monocentric Studies 11.5.1 2-FA-PET: Methods 11.5.2 2-FA-PET: Results and Discussion 11.6 Monocentre 2-FA-PET Data in Context with Other Available PET/SPECT Studies on α4β2*-nAChR Binding in AD/MCI 11.6.1 Own Data (Kendziorra et al. 2011 ; Sabri et al. 2008) 11.6.2 Differences and Similarities Between the nAChR PET/SPECT Studies Conducted So Far in AD 11.6.3 Possible Reasons for Discrepancies Between the Different PET/SPECT Studies 11.7 New Radiotracers for Imaging α4β2*-nAChRs Conclusions References 12: Neuroimaging Findings in Mild Cognitive Impairment 12.1 Introduction 12.2 Morphological MRI 12.2.1 Principles 12.2.2 Utility in MCI 12.2.3 Combined Use of MRI and Other Biomarkers 12.3 Functional MRI and Diffusion Tensor Imaging 12.3.1 Blood-Oxygen-Level-Dependent (BOLD) Functional MRI (fMRI) Principles 12.3.2 Utility in MCI 12.3.3 Diffusion Tensor Imaging (DTI) Principles 12.3.4 Utility in MCI 12.3.5 Combined Use of DTI and Other Biomarkers 12.4 SPECT 12.4.1 Principles 12.4.2 Utility in MCI 12.4.3 Combined Use of SPECT and Other Biomarkers 12.5 18 F-FDG-PET 12.5.1 Principles 12.5.2 Utility in MCI 12.5.3 Combined Use of 18 F-FDG-PET and Other Biomarkers 12.6 Amyloid PET 12.6.1 Principles 12.6.2 Utility in MCI 12.6.3 Combined Use of Amyloid PET and Other Biomarkers 12.7 Receptor Imaging 12.8 Conclusions and Perspectives References 13: Impact of the IWG/Dubois Criteria for Alzheimer’s Disease in Imaging Studies 13.1 The NINCDS-ADRDA Concept of AD 13.2 A New Concept for AD 13.3 Further Refinements of the 2007 Criteria 13.3.1 Refinements of Clinical Entities 13.3.2 Refinements in Biomarkers 13.4 Added Value of the New Criteria 13.5 The NIA-AA Criteria Glossary References 14: Perfusion SPECT: Its Role in the Diagnosis and Differential Diagnosis of Alzheimer’s Disease, with Particular Emphasis on Guidelines 14.1 Introduction 14.2 Guidelines 14.3 Accuracy of the Clinical Diagnosis of Alzheimer’s Disease 14.4 Perfusion Pattern in AD 14.5 Accuracy of Perfusion SPECT for Alzheimer’s Disease 14.6 SPECT in the Differential Diagnosis of Alzheimer’s Disease 14.7 Status Praesens References 15: Nuclear Imaging in Frontotemporal Dementia 15.1 Introduction 15.2 Nuclear Imaging 15.2.1 Regional Cerebral Blood Flow and Glucose Metabolism 15.2.2 Brain Perfusion 15.2.3 Brain Glucose Metabolism 15.2.4 Environmental Factors 15.2.5 Pharmacological Treatments 15.2.6 Longitudinal Studies 15.2.7 Correlation with Behaviour 15.3 Pathologic Markers 15.4 Neurotransmitter Systems 15.4.1 Serotonergic System 15.4.2 Dopaminergic System 15.4.3 Cholinergic System Conclusions References 16: Parkinson Dementia: PET Findings 16.1 Introduction 16.2 Glucose Metabolic Changes in Parkinson Dementia 16.3 Dopaminergic PET Imaging in Parkinson Dementia 16.4 Cholinergic PET Imaging in Parkinson Dementia 16.5 Fibrillary β-Amyloid PET Imaging in Parkinson Dementia 16.6 Multitracer PET Imaging Studies: Dopaminergic and Cholinergic Imaging Studies in PD and Parkinson Dementia 16.7 Discussion References 17: SPECT/PET Findings in Lewy Body Dementia 17.1 Introduction: SPECT/PET Findings in Lewy Body Dementia 17.2 Metabolism in DLB 17.2.1 Hypometabolism and Differential Diagnosis of DLB Versus AD 17.2.2 Differential Diagnosis of DLB and Other Clinical Syndromes 17.2.3 Hypometabolism and Different Symptomatology 17.2.4 Correlation Between Hypometabolism and Pathology 17.2.5 Conclusion 17.3 Cerebral Perfusion in DLB 17.3.1 Studies Using 99m Tc-Hexamethylpropylene Amine Oxime 17.3.2 Studies Using 99m Tc-Ethyl Cysteinate Dimer (ECD) 17.3.3 Studies Using N -isopropyl-p- 123 iodoamphetamine 17.3.4 Conclusion 17.4 Amyloid Deposition in DLB 17.4.1 Amyloid Frequency and Distribution 17.4.2 Amyloid Deposition Relative to Other Disorders and Healthy Controls 17.4.3 Amyloid and Clinical Correlates 17.4.4 Conclusion 17.5 Microglial Activation 17.5.1 In Vitro Studies of DLB Patients 17.5.2 In Vivo Microglial Activation Studies Parkinson’s Disease Alzheimer’s Disease Mild Cognitive Impairment 17.5.3 Other Ligands 17.5.4 Conclusion 17.6 Dopaminergic Degeneration in DLB 17.6.1 Dopamine Transporter Imaging in DLB Discrimination of DLB Against AD DLB Compared to PD and PDD DLB Compared to FTD Diagnostic Accuracy in DLB Versus Other Imaging Techniques Correlation with Clinical Measures in DLB 17.6.2 Dopamine Turnover 17.6.3 Vesicular Monoamine Transporter Type 2 Imaging 17.6.4 Postsynaptic Dopaminergic Receptors 17.6.5 Conclusion 17.7 Cholinergic Deficits in DLB 17.7.1 Imaging Acetylcholinesterase Activity 17.7.2 Imaging Muscarinic Receptors 17.7.3 Imaging Nicotinic Receptors 17.7.4 Treatment Related 17.7.5 Conclusion 17.8 Perspectives Conclusion References 18: Vascular Dementia 18.1 Vascular Dementia 18.2 Multi-Infarct Dementia 18.2.1 Introduction 18.2.2 PET and SPECT in MID 18.3 Strategic Infarct Dementia 18.3.1 Introduction 18.3.2 FDG-PET and SPECT in SID 18.4 Subcortical Vascular Dementia 18.4.1 Introduction 18.4.2 PET and SPECT in SVaD 18.4.3 Amyloid PET in SVaD 18.5 Hereditary Vascular Dementia 18.5.1 CADASIL Introduction PET and SPECT in CADASIL References 19: Value of MIBG in the Differential Diagnosis of Neurodegenerative Disorders 19.1 Introduction 19.2 Evaluation of Cardiac Sympathetic Nerve Activity 19.3 Pathology in Lewy Body Disease 19.4 Meta -iodobenzylguanidine Imaging in Lewy Body Disease 19.4.1 Parkinson’s Disease 19.4.2 Dementia with Lewy Bodies 19.4.3 Pure Autonomic Failure 19.5 Differential Diagnosis of Lewy Body Disease Using 123 I-MIBG Cardiac Scintigraphy Conclusion References 20: Linking Molecular Neurobiology to Therapeutic Approaches for Alzheimer’s Disease with PET 20.1 AD as First Described by Alois Alzheimer 20.2 Introduction 20.3 The Amyloid Cascade Hypothesis 20.4 Amyloid Neurotoxicity 20.5 Combating Amyloid Plaque Load: The Way to Go? 20.6 Novel Anti-amyloid Approaches 20.7 Aβ Production and Clearance Mechanisms of Aβ 20.8 Aβ Clearance and Transport Over the Blood–brain Barrier 20.9 Microvascular Breakdown in Ageing and AD 20.10 Microvascular Cholinergic Innervation in the Cortex in Alzheimer’s Disease 20.11 Loss of Cholinergic Innervation in Alzheimer’s Disease 20.12 Neuroinflammation and AD 20.13 Neuroinflammation, Depression, and Alzheimer’s Disease References Part III: Cerebrovascular Disorders 21: PET and SPECT Studies of Ageing and Cardiovascular Risk Factors for Alzheimer’s Disease 21.1 Introduction 21.2 Cardiovascular Risk Factors and Cognitive Decline 21.3 Cardiovascular Risk Factors and Functional Brain Deficits: PET and SPECT Imaging Evidence 21.3.1 The Impact of Combined Cardiovascular Risk Factors on Brain Functioning 21.3.2 Influence of APOE Gene Polymorphisms on the Relationship Between Cardiovascular Risk Factors and Functional Brain Deficits 21.3.3 Methodological Aspects in Functional Neuroimaging Studies of Cardiovascular Risk: The Impact of Partial Volume Effects 21.4 Microstructural and Molecular Mechanisms Underlying Cardiovascular Risk-Related Brain Functioning Deficits 21.5 Conclusions and Future Directions References 22: Carotid Plaque Imaging with SPECT/CT and PET/CT 22.1 Introduction 22.2 Background of Plaque Vulnerability 22.3 Functional Imaging of Carotid Artery Plaque with SPECT/CT and PET/CT 22.3.1 Inflammation 22.3.2 Lipid Accumulation 22.3.3 Proteolysis 22.3.4 Apoptosis 22.3.5 Angiogenesis 22.3.6 Thrombosis 22.3.7 Plaque Calcification 22.4 Future Perspectives References 23: PET in Brain Arteriovenous Malformations and Cerebral Proliferative Angiopathy 23.1 Introduction 23.2 Brain Arteriovenous Malformation 23.2.1 Clinical Presentation 23.2.2 Natural History 23.2.3 Treatment Options 23.3 Cerebral Proliferative Angiopathy 23.3.1 Clinical Presentation 23.3.2 Natural History 23.3.3 Treatment Options 23.4 Radiological Imaging 23.4.1 Cross-Sectional Imaging 23.4.2 Cerebral Catheter Angiography 23.5 PET Imaging of Brain AVM 23.5.1 Cerebral Blood Flow (CBF) 23.5.2 Cerebral Blood Volume (CBV) 23.5.3 Cerebral Metabolic Rate for Oxygen (CRMO 2) 23.5.4 Oxygen Extraction Factor (OEF) 23.5.5 Cerebral Metabolic Rate for Glucose (CMRGlc) 23.5.6 Effect of Treatment of BAVMs 23.5.7 Conclusion of the PET Imaging Findings 23.6 PET for Differentiation Between BAVM and CPA 23.6.1 Glucose Metabolism 23.6.2 Inflammation 23.6.3 Angiogenesis References 24: Transient Ischaemic Attack (Neuroimaging Findings) 24.1 Introduction 24.1.1 Pathophysiology of TIA 24.1.2 Clinical Assessment of TIA 24.1.3 Clinical Management After TIA 24.2 Brain Imaging with SPECT 24.3 Vascular Imaging with PET and SPECT 24.3.1 Atherosclerosis Imaging with SPECT 24.3.2 Imaging Inflammation with 18 F-fluorodeoxyglucose(FDG) 24.3.3 Prognostic Implications of Vascular FDG Uptake 24.3.4 Emerging Indications for FDG PET 24.3.5 Limitations of FDG PET 24.3.6 Imaging Vascular Calcification Conclusions References 25: PET Reveals Pathophysiology in Ischemic Stroke 25.1 The Concept of the Ischemic Penumbra in Patients with Ischemic Stroke 25.2 Penumbra Defined by PET 25.3 Comparison of PET and PW/DW MRI 25.4 PET as a Surrogate Marker for Treatment Efficiency 25.5 PET for Prediction of “Malignant Infarction” 25.6 Microglia Activation as an Indicator of Inflammation 25.7 Complex Activation Studies Conclusion References Part IV: Movement Disorders 26: Parkinson’s Disease 26.1 Introduction 26.1.1 Parkinson’s Disease Burden 26.1.2 Clinical Manifestations 26.1.3 Brain Pathology 26.1.4 Neurochemical Pathology Consequences of Dopaminergic Dysfunction Cholinergic Dysfunction Serotonergic Dysfunction 26.1.5 Differential Diagnosis and Diagnostic Pitfalls 26.2 Imaging PD with Brain PET and SPECT Dopaminergic Tracers 26.2.1 Targeting Dopaminergic Function Tracers for the Assessment of Presynaptic Dopamine Function L-Aromatic Acid Decarboxylase (L-AADC) Vesicular Monoamine Transporter Type 2 (VMAT2) Dopamine Transporter (DAT) Tracers for the Assessment of Postsynaptic Dopamine Function 26.2.2 Tracking Disease Progression 26.2.3 Monitoring Therapeutic Effects References 27: SPECT Imaging for Idiopatic M. Parkinson and Parkinsonian Syndromes: Guidelines and Comparison with PET and Recent Developments 27.1 Introduction 27.2 Dopamine Transporter Imaging 27.2.1 Indications 27.2.2 Tracers and Nuclear Imaging Protocols Procedure Data Acquisition Interpretation and Quantification 27.2.3 SPECT Versus PET 18 F-FDOPA PET Imaging Comparing the Two Modalities 27.3 Postsynaptic D2 Receptor Ligands 27.3.1 Indications 27.3.2 Tracer and Nuclear Imaging Protocol Procedure Data Acquisition Interpretation and Quantification 27.3.3 SPECT Versus PET 11 C-Raclopride PET Imaging Comparing the Two Modalities 27.4 Recent Developments 27.4.1 18 F-FDG PET and Its Role in the Differential Diagnoses of Parkinsonism 27.4.2 123 I-MIBG: Looking Outside of the Brain for Answers 27.5 Summary and Conclusion References 28: PET and SPECT Imaging in Parkinsonian Syndromes 28.1 Parkinsonian Syndromes 28.1.1 Clinical Features 28.1.2 Structural Imaging 28.2 Functional Imaging 28.2.1 SPECT 28.2.2 PET Metabolic Imaging Differential Diagnosis Microglial Imaging 28.3 Future Directions References 29: Amyotrophic Lateral Sclerosis 29.1 Introduction 29.2 Single-Photon Emission Computed Tomography 29.3 PET 29.3.1 Blood Flow and Metabolism 29.3.2 Ligand Studies An Inhibitory Interneuronal Deficit Neuroinflammation Serotonergic Neuronal Involvement Parkinsonian Overlap 29.3.3 The Future References 30: PET in Huntington’s Disease 30.1 Introduction 30.2 Clinical Features and Neuropathology of HD 30.3 Structural Defects Are Associated with Metabolic Defects 30.4 Receptor Imaging: Means to Establish Neuronal Integrity? 30.5 Inflammation as an Indicator of Neurodegeneration 30.6 PET Imaging as a Biomarker in Experimental Therapeutics Conclusions References 31: PET and SPECT Imaging in Dystonia 31.1 General Introduction 31.1.1 Historical Background 31.1.2 Epidemiology 31.1.3 Classification, Clinical Features, and Etiology 31.1.4 Pathophysiology 31.1.5 Treatment 31.2 Imaging with PET and SPECT in Different Forms of Dystonia 31.3 Primary Focal Dystonia 31.3.1 Glucose Metabolism PET 31.3.2 Regional Cerebral Blood Flow Activation PET 31.3.3 Receptor Imaging with PET and SPECT 31.3.4 Similarities Between Different Forms of Focal Dystonia 31.4 Hereditary Generalized Dystonia 31.4.1 Glucose Metabolism and Regional Cerebral Blood Flow 31.4.2 Receptor Imaging with PET Dopamine-Responsive Dystonia Myoclonus-Dystonia Rapid-Onset Dystonia-Parkinsonism Paroxysmal Dystonia Conclusion References 32: PET and SPECT Imaging in Hyperkinetic Movement Disorders 32.1 General Introduction 32.2 Tremor 32.2.1 Historical Background 32.2.2 Classification, Clinical Features, Etiology, and Pathophysiology 32.2.3 Treatment 32.2.4 Imaging with PET and SPECT Essential Tremor Regional Cerebral Blood Flow and Glucose Metabolism Receptor Imaging Orthostatic Tremor 32.3 Gilles de la Tourette Syndrome and Tics 32.3.1 Historical Background 32.3.2 Clinical Features and Etiology 32.3.3 Pathophysiology 32.3.4 Treatment 32.3.5 Imaging with PET and SPECT Glucose Metabolism Regional Cerebral Blood Flow Receptor Imaging 32.4 Myoclonus 32.4.1 Historical Background 32.4.2 Classification, Clinical Features, and Etiology 32.4.3 Pathophysiology 32.4.4 Treatment 32.4.5 Imaging Epileptic Myoclonus Degenerative Diseases Prion Disease Posthypoxic Myoclonus Opsoclonus-Myoclonus Syndrome General Remarks on Imaging in Patients with Myoclonus 32.5 Restless Legs Syndrome and Periodic Limb Movements in Sleep 32.5.1 Historical Background 32.5.2 Clinical Features and Etiology 32.5.3 Pathophysiology 32.5.4 Treatment 32.5.5 Imaging 32.6 General Conclusion References 33: Clinical Applications of [ 123 I]FP-CIT SPECT Imaging 33.1 Introduction 33.2 Dopamine Transporter Imaging in Healthy Controls with [ 123 I]FP-CIT SPECT 33.3 [ 123 I]FP-CIT SPECT Imaging in Parkinson’s Disease and Atypical Parkinsonian Syndromes 33.3.1 [ 123 I]FP-CIT SPECT Imaging in Parkinson’s Disease 33.3.2 [ 123 I]FP-CIT SPECT Imaging in Multiple System Atrophy and Progressive Supranuclear Palsy 33.3.3 [ 123 I]FP-CIT SPECT Imaging in Corticobasal Degeneration 33.3.4 [ 123 I]FP-CIT SPECT Imaging in Vascular Parkinsonism 33.3.5 [ 123 I]FP-CIT SPECT Imaging in DLB 33.4 Methods to Analyse [ 123 I]FP-CIT SPECT Studies in Routine Clinical Practice 33.5 Extrastriatal [ 123 I]FP-CIT Binding 33.6 Concluding Remarks References Part V: Inflammatory Disorders 34: PET Imaging of Microglia Activation in Neuropsychiatric Disorders with Potential Infectious Origin 34.1 General Introduction 34.2 Establishment of CNS Infection 34.2.1 Neuroinvasive Species 34.2.2 Neuroinvasion Mechanisms 34.2.3 Pathogen Reservoirs 34.2.4 Response to Pathogens 34.3 Inflammatory Response to CNS Infection 34.3.1 Functions of the Blood-Brain Barrier 34.3.2 Functions of Microglia 34.3.3 Microglia Activation: Imaging with [ 11 C]PK11195 34.4 Microglia Activation in Neuropsychiatric Disorders 34.4.1 Neurodegenerative Disorders 34.4.2 Vitamin Deficiency 34.4.3 Encephalopathy 34.4.4 Psychiatric Disorders 34.5 Microglia Activation in Neuroinfectious Disorders 34.5.1 Herpes Simplex Virus Infection 34.5.2 HIV 34.5.3 Neuroborreliosis 34.6 Neuroinfection Imaging 34.7 Clinical Note Conclusion References 35: PET Imaging in Multiple Sclerosis: Focus on the Translocator Protein 35.1 Introduction 35.2 Neuroimaging Hallmarks of MS 35.3 The 18 kDA Translocator Protein 35.3.1 Rationale for Imaging of Activated Microglia in MS 35.3.2 TSPO Imaging Studies in MS Autoradiography Studies PET Studies in MS Patients [ 11 C]PK11195 Studies Novel TSPO PET Radioligands Limitations of Current TSPO PET Tracers Signal-to-Noise Ratio Variation in Binding Affinities Using Second-Generation TSPO PET Radioligands Methods for Quantification of Radioligand Uptake 35.4 Non-TSPO Targets for PET Imaging in MS Conclusions References 36: PET and SPECT Imaging of Neurotoxicity 36.1 Introduction 36.1.1 Exposure to Neurotoxins 36.1.2 Developmental Neurotoxicity 36.1.3 Assessment of Neurotoxicity 36.1.4 Imaging of Neurotoxicity 36.2 Intrauterine Imaging of Exposure to Xenobiotics 36.2.1 Imaging of the Blood–Placenta Barrier 36.2.2 Imaging Intrauterine Fetal Accumulation of Neurotoxins 36.2.3 Imaging Pharmacological Response to Intrauterine Fetal Exposure 36.3 Developmental Neurotoxicity After Maternal Exposure to Xenobiotics 36.3.1 Methodology 36.3.2 Methylazoxymethanol 36.3.3 Methylmercury 36.4 Neurotoxicity After Adulthood Intoxication 36.4.1 Organic Solvents 36.4.2 Metals 36.5 Neurotoxicity in Suicide Survivors 36.6 Concluding Remarks References 37: PET and SPECT in Hepatic and Uraemic Encephalopathy 37.1 Introduction 37.2 Hepatic Encephalopathy 37.2.1 Pathophysiology 37.2.2 Regional Cerebral Blood Flow: SPECT and PET 37.2.3 Ammonia: PET 37.2.4 Energy Metabolism: PET 37.2.5 Neuroinflammation: PET 37.2.6 Neurotransmission: PET and SPECT 37.2.7 Open Questions: PET and SPECT in Hepatic Encephalopathy 37.3 Uraemic Encephalopathy 37.3.1 Pathophysiology and Symptomatology 37.3.2 Blood Flow: SPECT and PET 37.3.3 Energy Metabolism: PET 37.3.4 Open Questions: PET and SPECT in Uraemic Encephalopathy References Part VI: Epilepsy 38: PET in Epilepsy 38.1 Clinical Impact of PET in Epilepsy 38.2 Impact of Novel PET Ligands 38.2.1 Imaging GABAergic Neurotransmission 38.2.2 Imaging Serotonergic Neurotransmission 38.2.3 Imaging Opioid Neurotransmission 38.2.4 Imaging P-gp Function 38.3 Outlook References 39: SISCOM (Subtraction Ictal SPECT Coregistered to MRI) 39.1 Introduction 39.2 Image Processing for SISCOM 39.3 Interpretation of SISCOM 39.4 Clinical Significance and Research Applications of SISCOM References 40: Nuclear Medicine Neuroimaging and Electromagnetic Source Localization in Nonlesional Drug-Resistant Focal Epilepsy 40.1 Introduction 40.2 Nuclear Medicine Neuroimaging in Nonlesional Drug- 40.3 Nuclear Medicine Neuroimaging and Electromagnetic Source Localization Conclusions References Part VII: Tumors of the Nervous System 41: Gliomas 41.1 Introduction 41.2 Glioma Grading 41.2.1 Vascular Changes Amino Acid Tracers Blood-Brain Barrier Breakdown 41.2.2 Metabolic Changes FDG FLT Choline 41.2.3 Biopsy Targeting 41.3 Diagnosing Recurrent Glioma 41.4 Guiding and Monitoring Therapy 41.4.1 Resection and Radiotherapy Planning Amino Acid Tracers Selection of Patients for Radio- and Chemotherapy Monitoring of Therapy 41.5 Summary and Conclusion References 42: Single-Photon Emission Computed Tomography [Neuro-SPECT] Imaging of Brain Tumors 42.1 Introduction 42.2 SPECT Radiotracers 42.3 Clinical Applications 42.3.1 Characterization of Intracranial Masses: Differentiation of Brain Tumors from Nonneoplastic Lesions 42.3.2 Differentiate Glioma Recurrence from Treatment-­Induced Necrosis (TIN) 42.3.3 Assessment of Glioma Aggressiveness 42.3.4 Assessment of Meningioma Aggressiveness 42.3.5 Assessment of Patient Prognosis Conclusion References 43: The Value of 11 C-Methionine PET in the Differential Diagnosis Between Brain Tumor Recurrence and Radionecrosis 43.1 Introduction 43.1.1 Primary Brain Tumors 43.1.2 Recurrent Brain Tumors 43.1.3 Brain Metastases 43.2 Neuroimaging: Role and Dilemma 43.2.1 Role 43.2.2 Dilemma 43.3 11 C-Methionine PET 43.4 The Role of MET-PET in General in Gliomas and Metastases 43.5 The Role of MET-PET in the Differentiation Between Tumor Recurrence and Radiation Necrosis Conclusions References 44: Imaging Brain Metastases of Neuroendocrine Tumors 44.1 Introduction 44.2 Incidence 44.3 Origin of Neuroendocrine Brain Metastases 44.4 Growth Patterns of Neuroendocrine Brain Metastases 44.5 Clinical Presentation 44.6 Imaging 44.7 Somatostatin Receptor Imaging 44.8 Metabolic Imaging 44.9 Catecholamine Pathway 44.10 Serotonin Pathway Conclusion References Part VIII: Other Subjects 45: Traumatic Brain Injury: Nuclear Medicine Neuroimaging 45.1 Introduction 45.2 PET 45.2.1 18 F-FDG PET in the Acute Phase of Brain Trauma 15 O 2 -PET 45.2.2 18 F-FDG PET in the Chronic Phase of Brain Trauma 45.2.3 PET Imaging of Specific Cellular Process in Brain Trauma PET Imaging of Neuroinflammation 45.3 Single-Photon Emission Computed Tomography (SPECT) Conclusions References 46: Whiplash, Real or Not Real? A Review and New Concept 46.1 Introduction 46.2 Biomechanical Context of the Whiplash Trauma 46.2.1 Pathological Considerations 46.2.2 Facet Joint and Capsular Ligament 46.2.3 Ligaments and Intervertebral Disk 46.2.4 Dorsal Root Ganglion 46.2.5 Neck Muscles 46.3 Imaging Studies 46.3.1 Neck Imaging 46.3.2 Brain Imaging: Perfusion and Metabolism 46.3.3 Other Brain Imaging Studies 46.4 Close Interaction Between the Neck and Midbrain 46.5 Discussion and Conclusions References 47: PET Imaging in Altered States of Consciousness: Coma, Sleep, and Hypnosis 47.1 Introduction 47.2 Disorders of Consciousness Following a Brain Injury 47.3 PET Scan and Disorders of Consciousness 47.3.1 Measuring the Brain at “Rest” 47.3.2 Measuring the Brain During Sensory Stimulation 47.4 PET Scan and Sleep 47.5 PET Scan and Hypnosis Conclusion References 48: Anaesthesia and PET of the Brain 48.1 Introduction 48.2 Consciousness and Unconsciousness 48.3 Definition of Anaesthesia 48.4 Why Study Anaesthesia? 48.5 Available Tools for Studying Anaesthesia 48.6 Early Theories of the Molecular Mechanism of Anaesthetic Action 48.7 Current Theories of the Molecular Mechanism of Anaesthetic Action 48.8 Early PET Studies of the Global and Regional Changes in Cerebral Glucose Metabolism Caused by Anaesthetic Agents 48.9 PET and Propofol 48.10 PET and Ketamine 48.11 PET and Alpha2 Agonists 48.12 PET and the Volatile Anaesthetic Agents 48.13 PET and Nitrous Oxide 48.14 PET and Xenon 48.15 Summary and Conclusion References 49: Modulation of Brain Functioning by Deep Brain Stimulation: Contributions from PET Functional Imaging 49.1 Introduction 49.2 Materials and Methods 49.2.1 Summary of the Different Radiotracers Used 49.3 PET Functional Imaging of DBS in Parkinson’s Disease 49.3.1 Subthalamic Nucleus (STN) DBS Effect of STN-DBS at Rest Effect of STN-DBS During Movement Effect of STN-DBS During Speech Effect of STN-DBS on Cognition, Emotion, and Behavior Effect of STN-DBS on Dopamine Release 49.3.2 Internal Globus Pallidus (GPi) DBS 49.3.3 Pedunculopontine Nucleus (PPN) DBS 49.4 PET Functional Imaging of DBS in Dystonia 49.5 PET Functional Imaging of DBS in Tremor 49.6 PET Functional Imaging of DBS in Affective Disorders 49.6.1 Depression 49.6.2 Obsessive-Compulsive Disorders (OCD) 49.6.3 Alzheimer Disease 49.7 Interest and Limitations of PET Functional Imaging for Understanding the Mechanism of Action of DBS Conclusion References 50: Radionuclide Imaging Studies in Pediatric Neurology 50.1 Introduction 50.2 Epileptic Disorders 50.2.1 Epilepsy Temporal Lobe Epilepsy Extratemporal Lobe Epilepsy 50.2.2 Pediatric Epilepsy Syndromes Infantile Spasms or West Syndrome Tuberous Sclerosis Lennox-Gastaut Syndrome Sturge-Weber Syndrome Hemimegalencephaly Rasmussen’s Encephalitis and Epilepsy of Suspected Inflammatory Origin 50.3 Other Neurological Disorders 50.3.1 Perinatal Hypoxic Ischemic Brain Injury and Cerebral Palsy 50.3.2 Autism 50.3.3 Developmental Dyslexia 50.3.4 Landau-Kleffner Syndrome 50.3.5 Tourette Syndrome 50.3.6 Neuronal Ceroid Lipofuscinosis or Spielmeyer-Vogt (or Batten) Disease References The Editors Guest Editor List of Reviewers Anthology of Apologies Index