PET and SPECT in Neurology

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