Non-Invasive Physiology and Pharmacology Using ¹⁹F Magnetic Resonance

MRI has become the technology of choice for radiology and detection of many diseases. Clinical MRI uses almost exclusively the proton nucleus of the hydrogen atom, which occurs naturally in tissue water. Thus, there is a particularly strong signal, which is sensitive to tissue status and provides exquisite indications of soft tissue anatomy. Increasingly, the development of specific contrast agents and selective pulse sequences allows more detailed analysis of tissue properties such as diffusion, flow, and changes in vascular oxygenation. ¹⁹F provides a powerful tool for nuclear magnetic resonance (NMR) investigations. It has been widely exploited for both spectroscopic studies and increasingly for magnetic resonance imaging (MRI). The 19F atom has high NMR sensitivity while there is essentially no background signal in the body. Many diverse reporter molecules have been designed, which exploit the unique sensitivity of the fluorine atom to its microenvironment and these cover such diverse aspects as pO₂, pH, metal ion concentrations (e.g., calcium, magnesium), gene reporter molecules, hypoxia reporters, vascular flow, and volume. To date, clinical application is hindered by the lack of availability of clinical ¹⁹F NMR, but manufacturers are increasingly recognizing the value of including such capability. Given that ¹⁹F NMR offers the potential to investigate many diverse parameters, it will become increasingly available and useful in the future. This chapter examines the properties of the fluorine atom that make it an ideal tool for NMR, consider the many properties that are available for interrogation and examine applications.