Electron spin resonance imaging: a functional imaging tool for biomedical science

Modern medicine relies upon a variety of body scanners with which to visualise the internal structures of our bodies. Similar instruments are used by research scientists to study materials of significance across the whole range of the biological and medical sciences. For many purposes, however, anatomical or other structural information is not enough: we seek functional imaging methods that report on the processes that are taking place. Our project is concerned with the development of such a functional imaging method of exceptionally broad applicability: electron spin resonance imaging. It is the electrons furthest away from the atomic nucleus, the so-call 'valence' electrons, which confer most of the chemical and physical properties on atoms, ions, molecules and materials, since it is these electrons that interact most strongly with the environment. When an odd number of valence electrons are present (or in some special cases an even number) the electrons impart a net magnetic moment onto the atom/molecule/material. Electron spin resonance is a sensitive and precise method of measuring this magnetism. It is possible to relate these measurements to the environment of the valence electrons and hence use it to report on chemical structure and dynamics, and ultimately to provide functional information on chemical and other dynamical processes. Electron spin resonance determines the magnetic properties of electrons by measuring the applied magnetic field that is required to allow resonant absorption of microwave radiation. Spatial information is obtained by applying different magnetic fields to different parts of the object under investigation. If the microwave absorption is measured in a large number of magnetic field gradients a three-dimensional image of the magnetic properties of the object can be calculated. This overall approach is similar to that employed in nuclear magnetic resonance imaging (MRI). However, electron spin resonance imaging is technically much more challenging because valence electrons interact much more strongly with their environment than do nuclei. This important difference means that new, extremely sensitive and efficient, methods of measuring microwave absorption are required. Our project is focused on the necessary technologies. The sensitivity of an electron spin resonance imaging instrument should properly be expressed as the number of electrons that can be detected in a spatially resolved volume element in a given time. Thus an instrument with substantially improved sensitivity will also be able to make higher resolution images and/or faster measurements. Insufficient resolution and speed have been limiting factors in earlier approaches. The motivation behind our project is the extraordinary range of important applications to which ESR imaging can potentially be put. This work will enable substantial advances in our understanding of major human diseases such as cardio-vascular disease, cancer, diabetes, and septic shock, and also allow the efficacy of new therapies for these conditions to be assessed.

The goal of this work is to advance dramatically our ability to visualise paramagnetic molecular species in a living organism - especially in small laboratory animals such as mice. This will be an important enabling technology for basic biomedical research concerned with cardio-vascular disease (heart-attack, stroke), diabetes, arthritis, septic shock, and cancer. Quantitative, non-invasive measurements of oxygen, nitric oxide and reactive oxygen species will allow the efficacy of new therapies to be assessed, and the underlying biochemical processes elucidated. The labelling of both the active and 'helper' components of pharmaceutical preparations with paramagnetic 'spin' labels will allow mechanisms of drug delivery to be observed and optimised. In principle, electron spin resonance imaging (ESRi) has the sensitivity, spatial resolution and speed required to perform these measurements. However, the current generation of instruments have only partially delivered on this promise. Although they have clearly demonstrated the potential and scientific relevance of ESRi, frustratingly, many important measurements lie outside their capabilities. Our project is a 'first principles' examination of the measurement methods employed in ESRi instruments. We have identified aspects of the microwave circuit, the signal recovery method and the data analysis where innovative technologies offer scope for dramatic advance. A sensitivity improvement in excess of two orders of magnitude is realistically achievable. In practical experiments this fundamental improvement can be used to provide up to four orders of magnitude more spatial information or temporal resolution. Advances of this magnitude have the potential to make ESRi a mainstream research tool. We seek funds to construct a prototype instrument to optimise the new technology and assess its potential in biomedical applications.