Fluorine Magnetic Resonance Imaging

Over the past decade, fluorine (19F) magnetic resonance imaging (MRI) has garnered significant scientific interest in the biomedical research community owing to the unique properties of fluorinated materials and the 19F nucleus. Fluorine has an intrinsically sensitive nucleus for MRI. There is negligible endogenous 19F in the body and thus there is no background signal. Fluorine-containing compounds are ideal tracer labels for a wide variety of MRI applications. Moreover, the chemical shift and nuclear relaxation rate can be made responsive to physiology via creative molecular design. This book is an interdisciplinary compendium that details cutting-edge science and medical research in the emerging field of 19F MRI. Edited by Ulrich Flögel and Eric Ahrens, two prominent MRI researchers, this book will appeal to investigators involved in MRI, biomedicine, immunology, pharmacology, probe chemistry, and imaging physics.

Preface... Table of Contents... Contributing Authors... Part I Introduction 1. Recommendations for Preclinical Renal MRI: A Comprehensive Open-Access Protocol Collection to Improve Training, Reproducibility, and Comparability of Studies Andreas Pohlmann, Susan J. Back, Andrea Fekete, Iris Friedli, Stefanie Hectors, Neil Peter Jerome, Min-Chi Ku, Dario Livio Longo, Martin Meier, Jason M. Millward, João S. Periquito, Erdmann Seeliger, Suraj D. Serai, Sonia Waiczies, Steven Sourbron, Christoffer Laustsen, and Thoralf Niendorf Part II Animal Models, Preparation, Monitoring, and Physiological Interventions 2. Animal Models of Renal Pathophysiology and Disease Adam Hosszu, Tamas Kaucsar, Erdmann Seeliger, and Andrea Fekete 3. Preparation and Monitoring of Small Animals in Renal MRI Tamas Kaucsar, Adam Hosszu, Erdmann Seeliger, Henning M. Reimann, and Andrea Fekete 4. Reversible (Patho-)Physiologically Relevant Test Interventions: Rationale and Examples Kathleen Cantow, Mechthild Ladwig-Wiegard, Bert Flemming, Andrea Fekete, Adam Hosszu, Erdmann Seeliger 5. Preparation of Ex Vivo Rodent Phantoms for Developing, Testing, and Training MR Imaging of the Kidney and Other Organs Jason M. Millward, João S. Periquito, Paula Ramos Delgado, Christian Prinz, Thoralf Niendorf, and Sonia Waiczies Part III Basic Concepts of Measurement Techniques 6. Quantitative Assessment of Renal Perfusion and Oxygenation by Invasive Probes: Basic Concepts Kathleen Cantow, Roger G. Evans, Dirk Grosenick, Thomas Gladytz, Thoralf Niendorf, Bert Flemming, and Erdmann Seeliger 7. Ultrasound and Photoacoustic Imaging of the Kidney: Basic Concepts and Protocols Sandra Meyer, Dieter Fuchs, and Martin Meier 8. Hardware Considerations for Preclinical Magnetic Resonance of the Kidney Paula Ramos Delgado, Ekkehard Küstermann, André Kühne, Jason M. Millward, Thoralf Niendorf, Andreas Pohlmann, and Martin Meier 9. MRI Mapping of Renal T1: Basic Concept Stefanie Hectors, Sabrina Doblas, Philippe Garteiser, Gwenaël Pagé, Bernard E. Van Beers, John C. Waterton, and Octavia Bane 10. MRI Mapping of the Blood Oxygenation Sensitive Parameter T2* in the Kidney: Basic Concept Lu-Ping Li, Bradley Hack, Erdmann Seeliger, and Pottumarthi V. Prasad 11. Renal Diffusion Weighted Imaging (DWI) for Apparent Diffusion Coefficient (ADC), Intra Voxel Incoherent Motion (IVIM), and Diffusion Tensor Imaging (DTI): Basic Concept Neil Peter Jerome, Anna Caroli, and Alexandra Ljimani 12. Dynamic Contrast Enhancement (DCE)-MRI Derived Renal Perfusion and Filtration: Basic Concepts Michael Pedersen, Pietro Irrera, Walter Dastrù, Frank G. Zöllner, Kevin M. Bennett, Scott C. Beeman, G. Larry Bretthorst, Joel R. Garbow, and Dario Livio Longo 13. Non-Invasive Renal Perfusion Measurement Using Arterial Spin Labelling (ASL) MRI: Basic Concept Min-Chi Ku, María A. Fernández-Seara, Frank Kober, and Thoralf Niendorf 14. Renal pH Imaging Using Chemical Exchange Saturation Transfer (CEST)-MRI: Basic Concepts Dario Livio Longo, Pietro Irrera, Lorena Consolino, Phillip Zhe Sun, and Michael T. McMahon 15. Sodium (23Na) MRI of the Kidney: Basic Concept James T. Grist, Esben Søvsø Hansen, Frank G. Zöllner, and Christoffer Laustsen 16. Hyperpolarized Carbon (13C) MRI of the Kidneys: Basic Concepts Cornelius von Morze, Galen D. Reed, Zhen J. Wang, Michael A. Ohliger, and Christoffer Laustsen 17. Functional Imaging Using Fluorine (19F) MR Methods: Basic Concepts Sonia Waiczies, Christian Prinz, Ludger Starke, Jason M. Millward, Paula Ramos Delgado, Jens Rosenberg, Marc Nazaré, Helmar Waiczies, Andreas Pohlmann, and Thoralf Niendorf 18. MR Elastography of the Abdomen: Basic Concepts Suraj D. Serai and Meng Yin Part IV Experimental Protocols 19. Monitoring Renal H

Following its well-received predecessor, this book offers an essential guide to chemists for understanding fluorine in spectroscopy. With over 1000 compounds and 100 spectra, the second edition adds new data – featuring fluorine effects on nitrogen NMR, chemical shifts, and coupling constants. • Explains how to successfully incorporate fluorine into target molecules and utilize fluorine substituents to structurally characterize organic compounds • Includes new data on nitrogen NMR, focusing on N-15, to portray the influence of fluorine upon nitrogen NMR chemical shifts and coupling constants • Expands on each chapter from the first edition with additional data and updated discussion from recent findings • "The flawless ordering of material covered in this stand-alone volume is such that information can be found very easily." – Angewandte Chemie review of the first edition, 2010

This open access book describes marked advances in imaging technology that have enabled the visualization of phenomena in ways formerly believed to be completelyimpossible. These technologies have made major contributions to the elucidation of the pathology of diseases as well as to their diagnosis and therapy. The volume presents various studies from molecular imaging to clinical imaging. It also focuses on innovative, creative, advanced research that gives full play to imaging technology inthe broad sense, while exploring cross-disciplinary areas in which individual research fields interact and pursuing the development of new techniques where they fuse together. The book is separated into three parts, the first of which addresses the topic of visualizing and controlling molecules for life. Th e second part is devoted to imaging of disease mechanisms, while the final part comprises studies on the application of imaging technologies to diagnosis and therapy. Th e book contains the proceedings of the 12th Uehara International Symposium 2017, “Make Life Visible” sponsored by the Uehara Memorial Foundation and held from June 12 to 14, 2017. It is written by leading scientists in the field and is an open access publication under a CC BY 4.0 license.

Standard magnetic resonance imaging (MRI) is a prominent clinical imaging modality used to diagnose and study diseases in vivo. It is principally based on the detection of the nuclei of hydrogen atoms (the proton; symbol 1H) in water molecules in tissues. X-nuclei MRI (also called non-proton MRI) is based on the detection of the nuclei of other atoms (X-nuclei) in the body, such as sodium (23Na), phosphorus (31P), chlorine (35Cl), potassium (39K), deuterium (2H), oxygen (17O), lithium (7Li), and fluorine (19F) using modified software and hardware. X-nuclei MRI can provide fundamental, new metabolic information related to cellular energetic metabolism and ion homeostasis in tissues that cannot be assessed using standard hydrogen MRI. This book is an introduction to the techniques and biomedical applications of X-nuclei MRI. It describes the theoretical and experimental basis of X-nuclei MRI, the limitations of this technique, and its potential biomedical applications for the diagnosis and prognosis of many disorders or for quantitative monitoring of therapies in a wide range of diseases. The book is divided into four parts. Part I includes a general description of X-nuclei nuclear magnetic resonance physics and imaging. Part II deals with the MRI of endogenous nuclei such as 23Na, 31P, 35Cl, and 39K; Part III, the MRI of endogenous/exogenous nuclei such as 2H and 17O; and Part IV, the MRI of exogenous nuclei such as 7Li and 19F. The book is illustrated throughout with many representative figures and includes references and reading suggestions in each section. It is the first book to introduce X-nuclei MRI to researchers, clinicians, students, and general readers who are interested in the development of imaging methods for assessing new metabolic information in tissues in vivo in order to diagnose diseases, improve prognosis, or measure the efficiency of therapies in a timely and quantitative manner. It is an ideal starting point for a clinical or scientific research project in non-proton MRI techniques.

Fluorine and Health presents a critical multidisciplinary overview on the contribution of fluorinated compounds to resolve the important global issue of medicinal monitoring and health care. The involved subjects are organized in three thematic parts devoted to Molecular Imaging, Biomedical Materials and Pharmaceuticals. Initially the key-position of partially fluorinated low molecular weight compounds labelled either with the natural 19F-isotope for Magnetic Resonance Imaging (MRI) or labelled with the radioactive [18F]-isotope for Positron Emission Tomography (PET) is highlighted. Both non-invasive methods belong to the most challenging in vivo imaging techniques in oncology, neurology and in cardiology for the diagnosis of diseases having the highest mortality in the industrialized countries. The manifold facets of fluorinated biomaterials range from inorganic ceramics to perfluorinated organic molecules. Liquid perfluorocarbons are suitable for oxygen transport and as potential respiratory gas carriers, while fluorinated polymers are connected to the pathology of blood vessels. Another important issue concerns the application of highly fluorinated liquids in ophthalmology. Moreover, fluorine is an essential trace element in bone mineral, dentine and tooth enamel and is applied for the prophylaxis and treatment of dental caries. The various origins of human exposure to fluoride species is detailed to promote a better understanding of the effect of fluoride species on living organisms. Medicinally relevant fluorinated molecules and their interactions with native proteins are the main focus of the third part. New molecules fluorinated in strategic position are crucial for the development of pharmaceuticals with desired action and optimal pharmacological profile. Among the hundreds of marketed active drug components there are more than 150 fluorinated compounds. The chapters will illustrate how the presence of fluorine atoms alters properties of bioactive compounds at various biochemical steps, and possibly facilitate its emergence as pharmaceuticals. Finally the synthetic potential of a fluorinase, the first C-F bond forming enzyme, is summarized. - New approach of topics involving chemistry, biology and medicinal techniques - Transdisciplinar papers on fluoride products - Importance of fluoride products in health - Updated data on specific topics

The opening chapter of The Essential Guide to Magnetic Resonance presents applications of Fluorine-19 Magnetic Resonance Imaging (19F MRI) in cancer research, tissue metabolomics, quantification of drug delivery, cellular tracking, tissue pH measurements and detection of 19F labeled cells. The authors review in vitro research applying 19F MRI and Magnetic Resonance Spectroscopy (MRS) to facilitate the synthesis, tracking and visualization of new fluorinated drug conjugates. 19F MRI also provides high contrast in vivo images due to the absence of an endogenous 19F signal, 100% natural abundance of 19F, and a chemical shift range of over 400 ppm. Afterwards, examples of current methods of magnetic resonance imaging (MRI) guided photodynamic therapy are presented. Recent development of MRI detectable nanoparticle constructs, magnetic resonance spectroscopy (MRS) sensors, gadolinium based photosensitizers and europium singlet oxygen probes are discussed. In addition, applications of Functional MRI using a blood oxygen dependent level (BOLD) MRI in monitoring photodynamic action are addressed, with the goal of informing researchers about the potential for using MRI guided photodynamic therapy and oxygen dosimetry. The applications of MRI within the sphere of pharmacy are analyzed; in particular, the use of MRI to track pharmaceuticals in vitro and in vivo noninvasively and monitoring their controlled-release. Functional MRI for noninvasive clinical brain imaging is explored as it is applied to studies of autism, schizophrenia, epilepsy Alzheimers disease, Parkinson's disease, traumatic brain injury and blood oxygenation-level dependent (BOLD) imaging of brain function. An overview of the scope of MRI as a diagnostic technique in neurology and in neurosurgery is also provided.