Imaging and metabolism

Foreword for Imaging and Metabolism
Preface: Imaging and Metabolism
Contents
Contributors
Part I: Basic Principles
	1: Molecular Imaging and Molecular Imaging Technologies
		1.1	 Definition of the Field
		1.2	 Molecular Imaging Technologies
			1.2.1	 History
			1.2.2	 Nuclear Imaging
				1.2.2.1	 PET Imaging: Probes and Principles
				1.2.2.2	 SPECT Imaging: Probes and Principles
			1.2.3	 Magnetic Resonance Imaging
			1.2.4	 Ultrasound Imaging
			1.2.5	 Optical Imaging
				1.2.5.1	 Fluorescence Imaging: Probes and Principles
				1.2.5.2	 Bioluminescence Imaging
				1.2.5.3	 Cerenkov Luminescence Imaging
			1.2.6	 Future Perspectives
		References
	2: A Topical Report on the Design Principles of Metabolism
		2.1	 Metabolism: Basic Biochemical Principles and Fundamental Concepts
		2.2	 Cell-Autonomous Metabolism
		2.3	 Systemic Metabolism
		2.4	 How Metabolic Processes Go Wrong Leading to Disease
		2.5	 Concluding Remarks
		References
Part II: Metabolic Imaging Approaches
	3: Overview of Positron-Emission Tomography Tracers for Metabolic Imaging
		3.1	 Introduction
			3.1.1	 Basics of PET Imaging
			3.1.2	 Tracer Principle and Specific Activity
			3.1.3	 Radionuclides
			3.1.4	 Limitations of PET
		3.2	 Carbohydrates
			3.2.1	 Carbohydrate-Based PET Tracers
			3.2.2	 Oncologic Imaging
			3.2.3	 Neuroimaging
			3.2.4	 Cardiac Imaging
			3.2.5	 Brown Adipose Tissue
		3.3	 Amino Acids
			3.3.1	 Neuro-Oncology
			3.3.2	 Prostate Cancer
			3.3.3	 Neuroendocrine Tumors
			3.3.4	 Glutaminolysis
			3.3.5	 Protein Synthesis
		3.4	 Nucleoside Analogs
			3.4.1	 Oncologic Imaging
		3.5	 Fatty Acids
			3.5.1	 Oncologic Imaging
			3.5.2	 Cardiac Imaging
			3.5.3	 Long-Chain Fatty Acid Cardiac Imaging
		3.6	 Membrane Synthesis
			3.6.1	 Oncologic Imaging
		3.7	 Hypoxia
		3.8	 Summary
		References
	4: Introduction: MRI/MRS as Metabolic Imaging Tools
		4.1	 Basics of MRI/MRS Techniques
			4.1.1	 Magnetic Resonance
			4.1.2	 Relaxation and Tissue Contrast
			4.1.3	 Spatial Encoding and MRI
			4.1.4	 Combining Spatial Encoding and Chemical Information: MR Spectroscopic Imaging
			4.1.5	 Magnetic Resonance Spectroscopy Beyond Protons
		4.2	 Magnetic Resonance Spectroscopy: Clinical Application and Innovation
			4.2.1	 First Application: Nuclei In Situ
			4.2.2	 Ramping Up the Signal: Hyperpolarized MRS
		4.3	 Chemical Exchange Saturation Transfer (CEST)
		4.4	 Metabolic Imaging: Other MR Techniques
		References
	5: Metabolic Imaging Approaches: Optical Imaging
		5.1	 Imaging Oxygenation
			5.1.1	 Deep-Tissue Optical Imaging of Oxygenation
				5.1.1.1	 Introduction
				5.1.1.2	 Diffuse Optical Imaging and Spectroscopy
				5.1.1.3	 Diffuse Optics for Monitoring Metabolic Tumor Response to Chemotherapy in Breast Cancer
				5.1.1.4	 Diffuse Optics for Tracking Oxygenation Levels in the Brain
				5.1.1.5	 Diffuse Optics for Small Animal Imaging
			5.1.2	 High-Resolution Imaging of Blood Oxygenation In Vivo
				5.1.2.1	 Photoacoustic Microscopy
				5.1.2.2	 Two-Photon and Confocal Microscopy
				5.1.2.3	 Optical Coherence Tomography
		5.2	 Autofluorescence Microscopy of Metabolism
			5.2.1	 Introduction
			5.2.2	 NADH and FAD Autofluorescence Properties
			5.2.3	 Role of NADH and FAD in Cellular Respiration
			5.2.4	 Physiological Origins of Variations in NADH and FAD
			5.2.5	 Instrument Requirements for Redox Ratio Imaging
			5.2.6	 Instrumentation Requirements for FLIM Imaging
			5.2.7	 Summary
		5.3	 Optical Metabolic Contrast Agents
			5.3.1	 Introduction
			5.3.2	 Relative Uptake of Nutrients
			5.3.3	 Enzyme Activity
			5.3.4	 Local Chemical Environment
			5.3.5	 Cell Signaling
		References
Part III: Metabolic Diseases
	6: Cancer Metabolism
		6.1	 Introduction
			6.1.1	 The Warburg Effect Is a Hallmark of Cancer Cells
			6.1.2	 Cancer-Associated Alterations in Glycolysis
			6.1.3	 Cancer-Associated Alterations in Amino Acid Metabolism
			6.1.4	 Cancer Cells Reprogram One-Carbon Metabolism
		6.2	 Oncogenic Reprogramming of Metabolism
			6.2.1	 PI3K/AKT/mTOR Pathway Rewires Metabolism in Glioblastomas (GBMs)
			6.2.2	 Isocitrate Dehydrogenase Is Mutated in Gliomas
			6.2.3	 MYC Is a Central Metabolic Regulator in Many Tumors
			6.2.4	 Renal Carcinomas Show Mutations in Metabolic Regulators
		6.3	 Therapeutic Targeting of Cancer Metabolism
			6.3.1	 Targeting Glucose Uptake and Glycolysis
			6.3.2	 Inhibiting Glutamine Metabolism
			6.3.3	 Mutant IDH Inhibitors
		6.4	 Targeting Pyruvate Dehydrogenase
		6.5	 Alternative Strategies to Modulate Cancer Metabolism
		6.6	 Summary
		References
	7: Inflammation and Immune Metabolism
		7.1	 Introduction
			7.1.1	 Biology and Function of Inflammation
				7.1.1.1	 Step 1: Triggering Inflammatory Responses
				7.1.1.2	 Step 2: Activation of the Innate Immune System
				7.1.1.3	 Step 3: Recruitment of Immune Cells
				7.1.1.4	 Step 4: Involvement of the Adaptive Immune System
				7.1.1.5	 Step 5: Systemic Inflammatory Responses
			7.1.2	 Requirements to Image Inflammation
				7.1.2.1	 The Unique Features of Inflammation
				7.1.2.2	 Choice of Target
		7.2	 Metabolism in Relation to Immune Cell Function
			7.2.1	 Lymphocytes
			7.2.2	 Macrophages
			7.2.3	 Neutrophils
		7.3	 Targets for Imaging Immune Cell Metabolism
			7.3.1	 Imaging Cell-Surface Receptors and Transporters
				7.3.1.1	 Translocator Protein
				7.3.1.2	 Iron-Binding Proteins
				7.3.1.3	 Scavenger Receptor
				7.3.1.4	 Folate Receptor
				7.3.1.5	 Endocytosis
			7.3.2	 Imaging Specific Metabolic Substrates
				7.3.2.1	 Glucose Metabolism
				7.3.2.2	 DNA Synthesis
				7.3.2.3	 Lipid Synthesis
				7.3.2.4	 Amino Acid Metabolism
			7.3.3	 Imaging Enzyme Activity
				7.3.3.1	 Myeloperoxidase Activity
				7.3.3.2	 Cyclooxygenase Activity
				7.3.3.3	 Elastase and Matrix Metalloproteinase Activity
			7.3.4	 Imaging Metabolites
		7.4	 Future Developments
			7.4.1	 Integrative Analysis of Multiscale Data
			7.4.2	 Manipulation of Immune Cell Metabolism
			7.4.3	 Hyperpolarized MR
			7.4.4	 Hybrid PET/MR Imaging
		References
	8: Imaging in Diabetes
		8.1	 Introduction
			8.1.1	 Physiology of the Pancreas/Islets
			8.1.2	 Disease Background
			8.1.3	 Role of Imaging in Diabetes
		8.2	 Imaging Modalities in Diabetes
		8.3	 Imaging Limitations and Design Considerations for Pancreatic Imaging
			8.3.1	 MRI
			8.3.2	 PET/SPECT
				8.3.2.1	 Targeted Molecular Imaging
				8.3.2.2	 Nuclear Imaging of Insulitis
			8.3.3	 Fluorescence
				8.3.3.1	 Fluorescence Imaging for Molecular Probe Design
			8.3.4	 Ultrasonography and Computed Tomography
			8.3.5	 Multimodal Imaging
		8.4	 Molecular Imaging Outside the Pancreas in Diabetes
		8.5	 Conclusions and Future Directions
		References
	9: Brain Disorders
		9.1	 Introduction and Scope
		9.2	 History
		9.3	 Description of Modern Imaging Approaches
		9.4	 Categories of Metabolic Disorders
			9.4.1	 Central Energy Metabolism
			9.4.2	 Urea Cycle Disorders
			9.4.3	 Cholesterol Synthesis Disorders
			9.4.4	 Amino Acid Metabolism Disorders
			9.4.5	 Organic Acidosis Disorders
			9.4.6	 Peroxisome Disorders
			9.4.7	 Lysosomal Storage Disorders
		9.5	 Multifactorial Disorders and Neurodegenerative Diseases
			9.5.1	 Alzheimer’s Disease
			9.5.2	 Parkinson’s Disease
			9.5.3	 Differential Diagnosis of PD Based on Imaging
			9.5.4	 Diabetes
			9.5.5	 Depression
		9.6	 Concluding Remarks
		References
	10: Fatty Liver Disease
		10.1	 Introduction
		10.2	 Ultrasound
			10.2.1	 Typical B-Mode Ultrasound Imaging
			10.2.2	 Measuring Liver Stiffness with Ultrasound
		10.3	 Computed Tomography
		10.4	 Magnetic Resonance
			10.4.1	 1H MRS and Fat Fraction
			10.4.2	 Fat Imaging and the Dixon Method
			10.4.3	 Magnetic Resonance Elastography
			10.4.4	 Other MRI-Based Techniques
		10.5	 Preclinical and Investigational Imaging
			10.5.1	 Magnetic Resonance
			10.5.2	 Positron Emission Tomography (PET)
			10.5.3	 Optical Imaging
		10.6	 Summary
		References
	11: Imaging Myocardial Metabolism
		11.1	 Introduction
		11.2	 Energy Production and Related Metabolic Pathways
			11.2.1	 Acetyl-CoA from β-Oxidation of Ketones and Fatty Acids
			11.2.2	 Pyruvate and Lactate
			11.2.3	 Glucose and Glycogen
			11.2.4	 Anaplerosis
			11.2.5	 Compartmentation of Pyruvate Metabolism
		11.3	 Radionuclide Methods to Image Metabolism
			11.3.1	 Single Photon Emission Computed Tomography
			11.3.2	 Positron Emission Tomography
			11.3.3	 Myocardial Oxygen Consumption
			11.3.4	 Carbohydrate Metabolism
			11.3.5	 Fatty Acid Metabolism
		11.4	 Hyperpolarized 13C
			11.4.1	 Probes and Pathways
			11.4.2	 Pyruvate
			11.4.3	 Lactate
			11.4.4	 Acetate and Butyrate: Substrates That Bypass PDH
			11.4.5	 Substrate Competition in Hyperpolarization Exams
		11.5	 Complementary Information
			11.5.1	 Methodologic Advances
			11.5.2	 Applications and Potential Synergies
				11.5.2.1	 Myocardial Ischemia
					PET and SPECT
					13C Hyperpolarization
					Potential Synergies
				11.5.2.2	 Myocardial Hypertrophy and Cardiomyopathies
					SPECT and PET
					13C Hyperpolarization
					Potential Synergies
				11.5.2.3	 Obesity, Insulin Resistance, and Diabetes
					PET
					HP MR
					Potential Synergies
		11.6	 The Future: Validation and the Potential of Combined PET and 13C-HP
		References
	12: Other Metabolic Syndromes
		12.1	 Introduction
		12.2	 Neonatal-Onset Metabolic Disease
			12.2.1	 Acute Toxicity: Aminoacidopathies, Organic Acidemias, and Urea Cycle Disorders
				12.2.1.1	 Aminoacidopathies
					Maple Syrup Urine Disease (MSUD)
					MSUD: Imaging
					Nonketotic Hyperglycinemia (NKH)
					NKH: Imaging
				12.2.1.2	 Organic Acidemias
					Methylmalonic Acidemia (MMA)
					MMA: Imaging
					Propionic Academia (PA)
					Glutaric Aciduria Type I
					Glutaric Aciduria Type I: Imaging
				12.2.1.3	 Urea Cycle Disorders
					Urea Cycle Defects: Imaging
		12.3	 Chronic Encephalopathies of Infancy
			12.3.1	 Aminoacidopathies, Peroxisomal Disorders, Mitochondrial Disorders, Lysosomal Disorders, and Lipidoses
				12.3.1.1	 Aminoacidopathies
					Phenylketonuria (PKU)
					PKU: Imaging
				12.3.1.2	 Peroxisomal Disorders
					Zellweger Syndrome
					Zellweger Syndrome: Imaging
					X-Linked ALD
					X-Linked ALD: Imaging
				12.3.1.3	 Mitochondrial Disorders
		12.4	 Focal Lesions in Deep Gray Matter Structures
			12.4.1	 Leigh Disease
		12.5	 Strokes Crossing Vascular Territories
		12.6	 White Matter Changes
		12.7	 Pyruvate Dehydrogenase Deficiency
			12.7.1	 Lysosomal Disorders
				12.7.1.1	 Neuronal Ceroid Lipofuscinoses
				12.7.1.2	 Neuronal Ceroid Lipofuscinoses: Imaging
				12.7.1.3	 Sphingolipidoses
					Krabbe’s Disease
					Krabbe’s Disease: Imaging
				12.7.1.4	 Metachromatic Leukodystrophy
				12.7.1.5	 Metachromatic Leukodystrophy: Imaging
				12.7.1.6	 Gangliosidoses
				12.7.1.7	 Tay-Sachs: Imaging
				12.7.1.8	 Gaucher Disease
				12.7.1.9	 Gaucher Disease: Imaging
				12.7.1.10	 Niemann-Pick Type C
				12.7.1.11	 NPC: Imaging
			12.7.2	 Lipid Storage Disorders
				12.7.2.1	 Mucolipidosis
				12.7.2.2	 Mucolipidosis: Imaging
					Mucolipidosis Type II (I-Cell Disease)
					Mucolipidosis Type IV
				12.7.2.3	 CPT II Deficiency
				12.7.2.4	 CPT II Deficiency: Imaging
			12.7.3	 Mucopolysaccharidoses
		12.8	 Brain Injury due to Substrate Depletion
			12.8.1	 Creatine Deficiency
			12.8.2	 Creatine Deficiency Disorders
			12.8.3	 Cerebral Creatine Deficiency: Imaging
			12.8.4	 Molybdenum Cofactor Deficiency
			12.8.5	 Molybdenum Cofactor Deficiency: Imaging
		12.9	 Other Disorders
			12.9.1	 Rett Syndrome (RS)
			12.9.2	 Rett Syndrome: Imaging
			12.9.3	 Smith-Lemli-Opitz Syndrome
			12.9.4	 Smith-Lemli-Opitz Syndrome: Imaging
			12.9.5	 Alexander Disease
			12.9.6	 Alexander: Imaging
			12.9.7	 Biotinidase Deficiency
			12.9.8	 Biotinidase Deficiency: Imaging
		References
Index