Hyperpolarized Carbon-13 Magnetic Resonance Imaging and Spectroscopy (Volume 3) (Advances in Magnetic Resonance Technology and Applications, Volume 3)

Front Cover
HYPERPOLARIZED CARBON-13 MAGNETIC RESONANCE IMAGING AND SPECTROSCOPY
HYPERPOLARIZED CARBON-13 MAGNETIC RESONANCE IMAGING AND SPECTROSCOPY
Copyright
Series list
Contents
Contributors
Preface
	Organization
	Prerequisites
	Acknowledgments
1 - The physics of dissolution Dynamic Nuclear Polarization
	1.1 Introduction
	1.2 Polarization, magnetization, sensitivity, and hyperpolarization
	1.3 Methods of hyperpolarization
	1.4 Dynamic Nuclear Polarization
		1.4.1 Solid effect
		1.4.2 Cross-effect and thermal mixing
	1.5 The DNP sample: formulation of the imaging agent and the electron paramagnetic agent
	1.6 Dissolution and relaxation
	1.7 Conclusion
	References
2 - Hardware for preparing HP 13C-molecules: from polarizer to patient
	2.1 Requirements for DNP
		2.1.1 The magnet
		2.1.2 Cryogenic environment
		2.1.3 Microwaves
		2.1.4 The sample
	2.2 Monitoring of solid-state 13C polarization
	2.3 Rapid state change
	2.4 Preclinical dDNP
	2.5 Postdissolution
	2.6 Clinical dDNP
		2.6.1 Quality control
	2.7 Future developments
	2.8 Conclusions
	Acknowledgments
	References
3 - HP acquisition methods: pulse sequences, reconstruction, and RF coils
	3.1 Introduction
	3.2 Hyperpolarized imaging considerations
		3.2.1 T1 decay and nonrecoverable magnetization
		3.2.2 RF decay and metabolism
		3.2.3 Chemical shift displacement
	3.3 Pulse sequences and reconstruction
		3.3.1 Nonselective spectroscopy and CSI
		3.3.2 Fast spectroscopic imaging
		3.3.3 IDEAL CSI
		3.3.4 Metabolite-selective imaging
		3.3.5 Pulse sequence summary
	3.4 RF coils
		3.4.1 Surface and volume coils
		3.4.2 Multichannel arrays and coil combination
	3.5 Summary
	References
4 - HP experimental methods: cells and animals
	4.1 Introduction
	4.2 Dissolution—What is in it?
	4.3 Transfer to the magnet—how fast can you run?
	4.4 Delivery—how much and how to?
		4.4.1 How much of the hyperpolarized agent is sufficient?
		4.4.2 How to deliver the hyperpolarized agent?
	4.5 Preclinical model systems for testing of hyperpolarized 13C agents
		4.5.1 Models used for feasibility testing
		4.5.2 Models used for HP agent development for a predetermined biomedical application
		4.5.3 Preclinical animal models used in hyperpolarized NMR
	4.6 Understanding and interpreting the hyperpolarized signals to shed light on the underlying biochemistry of the pathology
	Acknowledgments
	References
	Further study
5 - HP agents and biochemical interactions
	5.1 Introduction
		5.1.1 Main differences between 1H MRI and HP 13C spectroscopy and imaging
		5.1.2 Ideal characteristics of an HP 13C agent
		5.1.3 Carbon-13 magnetic resonance and labeled metabolic substrates
	5.2 Overview of biological HP agents
		5.2.1 [1-13C]pyruvate
		5.2.2 [1,4-13C2]Fumarate
		5.2.3 Carbohydrates
		5.2.4 Fatty acids and ketone bodies
		5.2.5 l-[1-13C]lactate and amino acids
		5.2.6 Redox sensors
		5.2.7 Sensors of pH and other ions
		5.2.8 Urea and other perfusion tracers
	5.3 Formulation of HP 13C agents for dissolution DNP
		5.3.1 The need for formulation
		5.3.2 Essential characteristics of a formulation
		5.3.3 Free radicals
		5.3.4 Glassing
		5.3.5 Doping with additional paramagnetic species
		5.3.6 Chemical stability
		5.3.7 Formulation development and optimization
			5.3.7.1 Glassing
			5.3.7.2 Radical concentration
			5.3.7.3 Microwave frequency
	5.4 Biochemical interactions of HP 13C agents
		5.4.1 Biochemical environment and relaxation dynamics
		5.4.2 Transport to sites of metabolic action
		5.4.3 Enzyme kinetics
		5.4.4 Chemical equilibrium
		5.4.5 Labeled substrates in metabolic pathways
		5.4.6 Fractional enrichment and apparent metabolic rate
		5.4.7 Metabolite identification and assignment
			5.4.7.1 Metabolite production in other compartments
			5.4.7.2 Literature and spectral databases
			5.4.7.3 Practical metabolite assignment experiments
			5.4.7.4 Contaminants
	5.5 Summary and conclusion
	References
6 - Analysis and visualization of hyperpolarized 13C MR data
	6.1 Data extraction
	6.2 Data visualization
	6.3 Kinetic modeling
		6.3.1 Modeling the chemical reaction
		6.3.2 Modeling the biophysical system
		6.3.3 Choosing a model
		6.3.4 Fitting algorithms
	6.4 Model-free metrics
		6.4.1 Metabolite ratios
		6.4.2 Normalized metabolic product amplitudes
		6.4.3 Dynamic metrics
	6.5 Evaluation of metabolism metrics
	6.6 Summary
	References
7 - Integration into cancer studies
	7.1 Metabolic reprogramming is a central hallmark of cancer
	7.2 Metabolic reprogramming can be monitored to provide precision imaging of cancer
	7.3 Imaging oncogenic reprogramming of metabolism using HP 13C MRS/I in preclinical cancer models
		7.3.1 Interrogating the Warburg effect using HP [1-13C]pyruvate
			7.3.1.1 Monitoring tumor burden, aggressiveness, and disease progression
			7.3.1.2 Monitoring tumor response to therapy and development of treatment resistance
		7.3.2 Interrogating glycolysis and the TCA cycle using HP [2-13C]pyruvate
		7.3.3 Interrogating glutamine metabolism using HP [5-13C]glutamine or [1-13C]glutamate
		7.3.4 Interrogating oncometabolism using HP [1-13C]α-KG or [1-13C]glutamine
	7.4 Imaging oncogenic reprogramming of metabolism using HP 13C MRS/I in the clinic
	7.5 Conclusions
	Acknowledgments
	References
8 - Neurological applications of hyperpolarized 13C MR
	8.1 Introduction: an overview of the brain and its metabolism
	8.2 Neurological applications of HP [1-13C]pyruvate
		8.2.1 Healthy brain
			8.2.1.1 Adult
			8.2.1.2 Effects of age and sex
			8.2.1.3 Effects of anesthesia
		8.2.2 Neurological disorders
			8.2.2.1 Cell studies of immunometabolism
			8.2.2.2 Primary brain diseases
				8.2.2.2.1 Multiple sclerosis
				8.2.2.2.2 Traumatic brain injury
				8.2.2.2.3 Stroke and ischemia
			8.2.2.3 Peripheral insults affecting brain metabolism
				8.2.2.3.1 Acute liver failure
				8.2.2.3.2 Diet and diabetes
	8.3 New HP probes for brain applications
		8.3.1 Energy metabolism
			8.3.1.1 Glycolysis
			8.3.1.2 TCA cycle
			8.3.1.3 Glutamine/glutamate metabolism and nitrogen homeostasis
		8.3.2 Oxidative stress
		8.3.3 The case of HP [1-13C]lactate: theranostic and BBB permeability agent
	8.4 Correlation studies for HP 13C data
		8.4.1 In vivo methods
			8.4.1.1 Noninvasive imaging approaches
			8.4.1.2 Genetic studies of animal models
			8.4.1.3 Behavioral studies
		8.4.2 Ex vivo methods
			8.4.2.1 Biochemical assays
			8.4.2.2 Metabolomics
			8.4.2.3 Immunohistochemistry/immunofluorescence
	8.5 Conclusion
	References
9 - Hyperpolarized MR in cardiology: probing the heart of life
	9.1 Fueling the pump: metabolism and the healthy heart
		9.1.1 Fats burn in the fire of carbohydrates: β-oxidation and glycolysis
			9.1.1.1 Glycolysis
			9.1.1.2 β-oxidation
		9.1.2 Oxidative phosphorylation
			9.1.2.1 The TCA cycle
			9.1.2.2 The electron transport chain
		9.1.3 The physiological regulation of metabolism
		9.1.4 Metabolic alterations in disease
			9.1.4.1 Heart failure
			9.1.4.2 Metabolic therapies for heart failure
		9.1.5 Ischemic heart disease
		9.1.6 The value of metabolic imaging in cardiac disease
	9.2 Quantifying cardiac metabolism with MR
		9.2.1 Conventional, thermal equilibrium MR: strengths and limitations
		9.2.2 Hyperpolarized MR spectroscopy: a successful molecular menagerie of hyperpolarized probes
		9.2.3 Hyperpolarized [1-13C]pyruvate
			9.2.3.1 Hyperpolarized [2-13C]pyruvate
			9.2.3.2 Hyperpolarized fatty acids and ketone bodies
			9.2.3.3 Other hyperpolarized probes
		9.2.4 Hyperpolarized perfusion imaging and angiographic applications
	9.3 Imaging hyperpolarized metabolism in the heart
		9.3.1 Cardiac-specific considerations
		9.3.2 Space, time, and chemical specificity: how to slice the cake
		9.3.3 Spectroscopic acquisitions
		9.3.4 Alternative “rapid” imaging approaches
	9.4 Conclusion
	References
10 - Integration of Hyperpolarized 13C MRI into Liver Studies
	10.1 Liver imaging: state of the art
	10.2 Technical challenges of liver HP 13C MRI
	10.3 Liver metabolic pathways accessible via HP imaging
	10.4 Target applications of liver HP 13C MRI
		10.4.1 Liver cancer
		10.4.2 Diffuse liver disease
	10.5 Discussion
	References
Index
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	Z
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