The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging.
Title:
The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging.
Author:
Merbach, Andre S.
ISBN:
9781118503676
Personal Author:
Edition:
2nd ed.
Physical Description:
1 online resource (665 pages)
Contents:
Cover -- Title Page -- Copyright -- Contents -- List of Contributors -- Preface -- Chapter 1 General Principles of MRI -- 1.1 Introduction -- 1.2 Theoretical basis of NMR -- 1.2.1 Short description of NMR -- 1.2.2 Relaxation times -- 1.2.3 Saturation transfer -- 1.2.4 Concept of localization by magnetic field gradients -- 1.3 Principles of magnetic resonance imaging -- 1.3.1 Spatial encoding -- 1.4 MRI pulse sequences -- 1.4.1 Definition -- 1.4.2 k-Space trajectory -- 1.4.3 Basic pulse sequences -- 1.5 Basic image contrast: Tissue characterization without injection of contrast agents (main contrast of an MRI sequence: Proton density (P), T_1 and T_2, T_2^*) -- 1.5.1 Proton density weighting -- 1.5.2 T1 weighting -- 1.5.3 T2 weighting -- 1.5.4 T2* weighting -- 1.6 Main contrast agents -- 1.6.1 Gadolinium (Gd) complex agents -- 1.6.2 Iron oxide (IO) agents -- 1.6.3 CEST agents -- 1.7 Examples of specialized MRI pulse sequences for angiography (MRA) -- 1.7.1 Time of flight angiography: No contrast agent -- 1.7.2 Angiography using intravascular contrast agent (Blood pool CA) injection -- 1.7.3 DSC DCE MRI -- References -- Chapter 2 Relaxivity of Gadolinium(III) Complexes: Theory and Mechanism -- 2.1 Introduction -- 2.2 Inner-sphere proton relaxivity -- 2.2.1 Hydration number and hydration equilibria -- 2.2.2 Gd-H distance -- 2.2.3 Proton/water exchange -- 2.2.4 Rotation -- 2.3 Second- and outer-sphere relaxation -- 2.4 Relaxivity and NMRD profiles -- 2.4.1 Fitting of NMRD profiles -- 2.4.2 Relaxivity of low-molecular-weight Gd(III) complexes -- 2.4.3 Relaxivity of macromolecular MRI contrast agents -- 2.4.4 Contrast agents optimized for application at high magnetic field -- 2.5 Design of high relaxivity agents: Summary -- References.
Chapter 3 Synthesis and Characterization of Ligands and their Gadolinium(III) Complexes -- 3.1 Introduction-general requirements for the ligands and complexes -- 3.2 Contrast agents employing linear polyamine scaffold -- 3.2.1 Synthesis of linear polyamine backbone -- 3.2.2 N-functionalization of linear polyamine scaffold -- 3.3 Contrast agents employing cyclen scaffold -- 3.3.1 Synthesis of the macrocyclic skeleton -- 3.3.2 N-functionalization of macrocyclic scaffold -- 3.4 Other types of ligands -- 3.4.1 H4TRITA and related ligands -- 3.4.2 H3PCTA and related ligands -- 3.4.3 TACN derivatives -- 3.4.4 Ligands with HOPO coordinating arms and related groups -- 3.4.5 H4AAZTA and related ligands -- 3.5 Bifunctional ligands and their conjugations -- 3.6 Synthesis and characterization of the Ln(III) complexes -- 3.6.1 General synthetic remarks -- 3.6.2 Characterization of the complexes -- List of Abbreviations -- References -- Chapter 4 Stability and Toxicity of Contrast Agents -- 4.1 Introduction -- 4.2 Equilibrium calculations -- 4.2.1 Constants that characterize metal ligand interactions (protonation constants of the ligands, stability constants of the complexes, conditional stability constants, ligand selectivity, and concentration of free Gd^3+: pM) -- 4.2.2 A brief overview of the programs used in equilibrium calculations (calculation of protonation constants, stability constants, and equilibrium speciation diagrams) -- 4.3 Stability of metal-ligand complexes -- 4.3.1 Stability of complexes of open chain ligands (EDTA, DTPA, EGTA, and TTHA) -- 4.3.2 Stability of complexes of tripodal and AAZTA ligands -- 4.3.3 Stability of complexes of macrocyclic ligands -- 4.3.4 Ternary complexes formed between the Ln(L) complexes and various bio-ligands -- 4.3.5 Mn2+-based contrast agents.
4.4 Kinetics of M(L) complex formation -- 4.4.1 Formation kinetics of DOTA complexes -- 4.4.2 Formation kinetics of complexes of simple DOTA-tetraamides -- 4.5 Dissociation of M(L) complexes -- 4.5.1 Inertness of complexes of open chain ligands (EDTA, DTPA, and AAZTA) -- 4.5.2 Decomplexation of DOTA complexes -- 4.5.3 Decomplexation of DOTA-tetraamide complexes -- 4.6 Biodistribution and in vivo toxicity of Gd3+-based MRI contrast agents -- 4.6.1 Osmolality and hydrophobicity of Gd3+-based MRI contrast agents -- 4.6.2 Biodistribution -- 4.6.3 In vivo toxicity -- 4.6.4 Predicting in vivo toxicity of Gd3+-based contrast agents using thermodynamic conditional stability constants -- 4.6.5 The role of kinetic inertness in determining in vivo toxicity -- 4.6.6 Kinetic inertness combined with thermodynamic stability is the best predictor of in vivo toxicity -- 4.6.7 Nephrogenic systemic fibrosis (NSF) -- 4.7 Concluding remarks -- Acknowledgements -- References -- Chapter 5 Structure, Dynamics, and Computational Studies of Lanthanide-Based Contrast Agents -- 5.1 Introduction -- 5.2 Computational methods -- 5.3 Lanthanide-induced NMR shifts -- 5.3.1 Bulk magnetic susceptibility shifts -- 5.3.2 Diamagnetic shifts -- 5.3.3 Contact shifts -- 5.3.4 Pseudocontact shifts -- 5.3.5 Evaluation of bound shifts -- 5.3.6 Separation of shift contributions -- 5.4 Lanthanide-induced relaxation rate enhancements -- 5.4.1 Evaluation of bound relaxation rates -- 5.4.2 Inner-sphere relaxation -- 5.4.3 Outer-sphere relaxation -- 5.5 Anisotropic hyperfine interactions on the first coordination sphere water molecules -- 5.6 Evaluation of geometries by fitting NMR parameters -- 5.7 Two-dimensional NMR -- 5.8 139La and 89Y NMR -- 5.9 Water hydration numbers.
5.10 Chirality of lanthanide complexes of polyaminocarboxylates -- 5.11 Complexes of non-macrocyclic polyaminocarboxylates -- 5.11.1 DTPA and derivatives -- 5.11.2 TTHA -- 5.11.3 EGTA -- 5.11.4 DTTA -- 5.11.5 Tripodal complexes -- 5.12 Complexes of macrocyclic ligands -- 5.12.1 DOTA and derivatives -- 5.12.2 DO3A and derivatives -- 5.12.3 PCTA and derivatives -- 5.12.4 TETA -- 5.12.5 DOTP -- 5.12.6 Phosphinates and phosphonate esters -- 5.12.7 Cationic macrocyclic lanthanide complexes -- 5.12.8 AAZTA -- 5.13 Fullerenes -- References -- Chapter 6 Electronic Spin Relaxation and Outer-Sphere Dynamics of Gadolinium-Based Contrast Agents -- 6.1 Introduction -- 6.2 Theory of electronic spin relaxation of Gd^3+ ions -- 6.2.1 Classical approach: Bloch equations -- 6.2.2 Quantum approach: Electronic time correlation functions -- 6.2.3 The zero-field splitting Hamiltonian -- 6.2.4 The density matrix formalism -- 6.2.5 The Redfield approximation -- 6.2.6 The Swedish super-operator approaches -- 6.2.7 Monte-Carlo simulation of the Gd3+ electronic relaxation: The Grenoble method -- 6.3 Outer-sphere dynamics -- 6.3.1 Standard theory neglecting the electronic relaxation -- 6.3.2 Analytical hard-sphere models -- 6.3.3 The general case of anisotropic polyatomic molecules -- 6.3.4 Experimental determination of the dipolar time correlation function -- 6.4 Relaxivity quenching by the electronic spin relaxation -- 6.4.1 The various field regimes -- 6.4.2 Outer-sphere relaxivity -- 6.4.3 Inner- and second-sphere relaxivities -- 6.4.4 Application to a cyclodecapeptide Gd3+ complex -- 6.5 Various experimental approaches of the electronic spin relaxation -- 6.5.1 Outer-sphere relaxivity profiles -- 6.5.2 EPR spectroscopy -- 6.6 Conclusion and perspectives.
6.A Appendix: Similar evolutions of the macroscopic magnetization of the electronic spin and of its correlation functions -- References -- Chapter 7 Targeted MRI Contrast Agents -- 7.1 Introduction -- 7.2 Serum albumin -- 7.3 Fibrin -- 7.4 Type I collagen -- 7.5 Elastin -- 7.6 Sialic acid -- 7.7 αVβ3 integrin -- 7.8 Folate receptor -- 7.9 Matrix metalloproteinases (MMP) -- 7.10 E-selectin -- 7.11 Fibrin-fibronectin complex -- 7.12 Alanine aminopeptidase (CD13) -- 7.13 Carbonic anhydrase -- 7.14 Interleukin 6 receptor -- 7.15 Estrogen and progesterone receptors -- 7.16 Contrast agents based on natural products -- 7.17 Messenger RNA (mRNA) -- 7.18 Myelin -- 7.19 DNA -- 7.20 Conclusions -- References -- Chapter 8 Responsive Probes -- 8.1 Introduction -- 8.2 Probes responsive to physiological parameters -- 8.2.1 Temperature responsive probes -- 8.2.2 pH sensing -- 8.2.3 Redox responsive probes -- 8.2.4 Sensing of biologically relevant ions -- 8.2.5 Enzyme responsive probes -- 8.3 Conclusions -- References -- Chapter 9 Paramagnetic CEST MRI Contrast Agents -- 9.1 Introduction -- 9.2 Theoretical and practical considerations on CEST response -- 9.2.1 NMR/chemical properties of CEST site(s) -- 9.2.2 NMR properties of the wat site -- 9.2.3 Instrumental variables -- 9.2.4 Variables dependent on the sample -- 9.2.5 Spectroscopic versus imaging detection of CEST response -- 9.2.6 Characterization of a CEST agent and its quantification -- 9.3 Diamagnetic versus paramagnetic CEST agents -- 9.4 Paramagnetic CEST agents -- 9.4.1 ParaCEST agents -- 9.4.2 SupraCEST agents -- 9.4.3 NanoCEST agents -- 9.5 Other exchange-mediated contrast modes accessible for paramagnetic CEST agents -- 9.6 Concluding remarks -- References -- Chapter 10 Superparamagnetic Iron Oxide Nanoparticles for MRI -- 10.1 Introduction.
10.2 Synthesis of iron oxide nanoparticles.
Abstract:
Magnetic Resonance Imaging (MRI) is one of the most important tools in clinical diagnostics and biomedical research. The number of MRI scanners operating around the world is estimated to be approximately 20,000, and the development of contrast agents, currently used in about a third of the 50 million clinical MRI examinations performed every year, has largely contributed to this significant achievement. This completely revised and extended second edition: Includes new chapters on targeted, responsive, PARACEST and nanoparticle MRI contrast agents. Covers the basic chemistries, MR physics and the most important techniques used by chemists in the characterization of MRI agents from every angle from synthesis to safety considerations. Is written for all of those involved in the development and application of contrast agents in MRI. Presented in colour, it provides readers with true representation and easy interpretation of the images. A word from the Authors: Twelve years after the first edition published, we are convinced that the chemistry of MRI agents has a bright future. By assembling all important information on the design principles and functioning of magnetic resonance imaging probes, this book intends to be a useful tool for both experts and newcomers in the field. We hope that it helps inspire further work in order to create more efficient and specific imaging probes that will allow materializing the dream of seeing even deeper and better inside the living organisms. Reviews of the First Edition: "...attempts, for the first time, to review the whole spectrum of involved chemical disciplines in this technique..."-Journal of the American Chemical Society "...well balanced in its scope and attention to detail...a valuable addition to the library of MR scientists..."-NMR in Biomedicine.
Local Note:
Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, 2017. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries.
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