Introduction

Abstract

Electron paramagnetic resonance imaging and Overhauser imaging are magnetic resonance techniques for detecting paramagnetic substances (i.e. molecules which have one or more unpaired electron(s) in their outer orbitals). The main impetus for developing these techniques is the intriguing possibility of detecting and imaging the distribution of free radicals in the body. Naturally occurring free radicals are widely believed to be involved in the early development of many diseases, so the ability to localize and quantify them in vivo would have profound implications for many areas of biomedical research. Stable free radicals can also be used as `contrast agents', and following their fate in the body can give useful insights into organ function. Some free radicals and paramagnetic solids have the ability to probe the chemical and physical nature of their surroundings, also offering a wide variety of potential applications, in particular the measurement of oxygen concentrations in tissues. Electron paramagnetic resonance (EPR) was first demonstrated in 1945, the same year that nuclear magnetic resonance (NMR) experiments were first carried out. EPR and NMR are very closely related at the fundamental level, differing mainly in the fact that EPR involves a magnetic resonance experiment on unpaired electrons in the sample, while NMR uses atomic nuclei with non-zero spin. On a practical level, the techniques are also closely related, despite the fact that most EPR experiments are continuous-wave, while virtually all NMR is carried out using pulsed, Fourier-transform methods. Overhauser-based techniques combine both flavours of magnetic resonance in EPR/NMR double-resonance experiments. While NMR has found a valuable place in clinical practice, in the form of magnetic resonance imaging (MRI), biomedical EPR is still in its relative infancy, with about twenty research groups world-wide having the capability to use EPR spectroscopy or imaging to study small animals in vivo. It may appear to the casual observer that progress in the field of EPR is much slower than in NMR, but this is not actually the case: EPR is technically much more demanding than NMR, due to the six orders-of-magnitude shorter relaxation times encountered in EPR. Indeed, considerable progress has been made in the technology and applications of EPR-based methods over the last five years, and the field has now developed sufficiently to enable useful biomedical applications to be investigated. The papers presented in this topical issue represent a broad cross-section of the work being carried out in developing and applying EPR and Overhauser techniques in biology and medicine. A number of papers describe recent advances in technology and methods, including continuous-wave, longitudinally detected and pulsed EPR, and Overhauser imaging. Others focus on applications including those using both endogenous and exogenous free radicals. Two of the most promising areas are in the detection of nitric oxide, a ubiquitous, naturally occurring free radical, and in the measurement of local oxygen concentrations by EPR. Both of these topics are covered in this issue. It is both timely and appropriate that Physics in Medicine and Biology, with its strong reputation in the field of physics applied to medicine and biology, should publish a topical issue on this subject, at a time when rapid improvements in technology are being made, and when useful applications are starting to emerge. The guest editors hope that this summary of the state-of-the-art will act as a comprehensive reference work for those in the field, and will encourage others to develop new applications for the techniques, which we believe have a valuable role to play in biomedical research. David J Lurie Antonello Sotgiu Guest Editors