Free radical imaging.

Abstract

Mention medical imaging and most radiologists and medical physicists will think of CT, MRI, ultrasound and nuclear medicine, the techniques that form the backbone of diagnostic radiology. Nevertheless, there are a number of other methods currently under development that are potentially capable of producing extremely valuable functional information. One of these up-andcoming areas is free radical imaging. Although the techniques used are based on MRI, free radical imaging is sufficiently different that many MR physicists and radiologists may be unaware of the methodology and of its potential uses. This commentary describes the techniques currently in use or under development and will highlight some of the biomedical applications for which they have been used and for which they may be used in the future. Free radicals are molecules with one or more unpaired electron in their outer orbitals. A number of related MR methods are used for imaging free radicals, all of which make use of the fact that a free radical’s unpaired electron exhibits a quantum-mechanical spin and therefore has a magnetic moment. This means that an MR signal can be generated in a manner exactly analogous to the detection of hydrogen nuclei (protons) by nuclear magnetic resonance (NMR) in conventional MRI. MR of unpaired electrons is called electron spin resonance (ESR). Substances that have unpaired electrons are termed paramagnetic, thus ESR is also referred to as electron paramagnetic resonance (EPR). The mass of an electron is about three orders of magnitude smaller than that of a proton, therefore the MR properties of the two particles are rather different. In a given strength of applied magnetic field, the ESR frequency is 659 times that of proton NMR. For example, in a magnetic field of 1 T (a common field strength for clinical MRI), the NMR frequency is 42.6 MHz while the ESR frequency would be 28 GHz, well into the microwave part of the electromagnetic spectrum, with strong absorption by conducting samples such as tissue. Owing to this, most biomedical free radical imaging by ESR is carried out using much lower magnetic field strengths, usually between 10 mT and 40 mT, with resonant frequencies between 250 MHz and 1 GHz, which can penetrate a few centimetres into tissues allowing at least small animals to be studied. Another difference between ESR and NMR is that the electron relaxation times of free radicals are very short, typically between 0.1 ms and 1 ms, a million times shorter than those encountered in clinical MRI. As a result, most ESR spectroscopy and imaging is done using ‘‘continuous wave’’ (CW) detection methods. Instead of applying a pulse of radiowave energy and waiting for the transient response, as in clinical MRI, in CW ESR the sample is continuously irradiated with low intensity electromagnetic radiation and the resonant response of the unpaired electrons is measured by slowly increasing the strength of the applied magnetic field. When an ESR is encountered, the combined effect of the unpaired electrons (the ‘‘electron magnetization’’) alters the electrical properties of the resonator used to apply the radiowaves and a reflected signal can be measured. To obtain spatial information about the sample, a magnetic field gradient is applied continuously during the magnetic field sweep. An image is built up by back-projecting a series of one-dimensional projections of the sample, obtained by measuring the ESR signal repeatedly, with the direction of the applied magnetic field gradient stepped in small increments [1]. Perhaps the greatest technical difficulty of the CW ESR method is its extreme sensitivity to physiological motion of the animal under study, which results in both increased noise and image artefacts. One solution is to use sophisticated electronics to correct for changes brought about by animal motion, but in fact the problem can be almost completely alleviated by using an alternative detection scheme called longitudinallydetected ESR (LODESR). In this method, the sample is irradiated with electromagnetic radiation close to the desired resonant frequency (say 300 MHz), the intensity of which is modulated at a much lower frequency (say 0.5 MHz). This causes the unpaired electron magnetization to Received 29 November 2000 and accepted 25 May 2001. The British Journal of Radiology, 74 (2001), 782–784 E 2001 The British Institute of Radiology