Field-cycling is used in a technique that we developed in Aberdeen called FC-PEDRI, with the aim of imaging the distribution of free radicals in biological samples and tissues. Indeed, our involvement with Field-Cycling magnetic resonance dates back to 1989, when we started to use it in this context.

Free Radical Imaging

Free radicals are defined as molecules with one or more unpaired electron in their outer orbital. Because of this property, they tend to be quite reactive. Free radicals are involved in normal metabolism, and are always present in the human body, but normally at very low concentrations. There is considerable interest in free radicals among the medical research community, because changes in their concentrations are believed to be involved in the early stages of many diseases, including cancer, inflammatory disease, heart disease and many more. Our aim is to design, build and use "scanners" to show where these free radicals are within the body, and to view the response of these free radicals to various forms of treatment. 

PEDRI

PEDRI (Proton-Electron Double-Resonance Imaging) is a technique for imaging the distribution of free radicals within the body. PEDRI is able to detect low concentrations of free radicals and can also produce very high quality images, showing the distribution of free radicals in large samples. PEDRI makes use of a double resonance magnetic resonance technique called the Overhauser Effect.

The Overhauser Effect is essentially a combination of nuclear magnetic resonance (NMR) and electron spin resonance (ESR). The NMR signal is obtained in the usual way, by applying pulses of radiowaves at the NMR frequency. At the same time, the free radical's unpaired electrons are irradiated by applying an irradiation (radiowave or microwave) at the ESR frequency. If there is good magnetic coupling between the unpaired electrons and the water hydrogen nuclei, the ESR irradiation can cause a transfer of polarisation from the electrons to the nuclear spins, resulting in an amplification or "enhancement" of the measured NMR signal. In theory, the enhancement can be up to 330-fold, though in practice enhancement factors of 10- to 50-fold are more commonly observed.

NMR FIDs
NMR FIDs from solution of TEMPOL free radical, at different EPR irradiation powers

PEDRI is the imaging version of the Overhauser experiment. The ESR resonance of the free radicals of interest is irradiated during the collection of an MR image. The Overhauser effect causes an enhancement of the NMR signal in parts of the sample containing the free radical, and these regions "light up" in the resulting image, showing the distribution of the free radical.

PEDRI pulse sequence
PEDRI pulse sequence

 

   
Left: diagram of free radical phantom (diameter 2 cm); Middle: 0.02 tesla EPR-off image of phantom; Right: 0.02 tesla EPR-on image, showing Overhauser enhancement in regions containing free radical.

PEDRI imagers normally use low-field magnets with magnetic fields of about 0.01 tesla (as opposed to the 1 tesla or so used in clinical MRI systems). This is because the ESR frequency is 659 times the NMR frequency in a given magnetic field. So, in a 1 tesla magnet, the ESR frequency would be 28 GHz, well into the microwave part of the electromagnetic spectrum, which would cook any biological sample being imaged! Reducing the magnetic field to 0.01 tesla brings the ESR frequency to a more manageable 280 MHz.

Field-Cycled PEDRI (FC-PEDRI)

The down side of using a low magnetic field is that the image quality suffers (high fields are used in clinical MRI to improve the images). The ideal would be to irradiate the ESR at low field - hence low frequency and no cooking (!) - and to detect the NMR signals at high field - to give good image quality. This is what we do in Field-Cycled PEDRI. In the field-cycled PEDRI (FC-PEDRI) experiment the magnetic field is switched between two levels. The magnetic field starts at a low value (called the "evolution" field, typically 0.004 tesla), and the ESR irradiation is applied at about 120 MHz. Then the field is switched to a high value (called the "detection" field, 0.06 tesla in our prototype system), at which the imaging gradients are applied and the NMR signals detected.

PEDRI pulse sequence
FC-PEDRI pulse sequence

An advantage of PEDRI over "direct" ESR-based free radical imaging techniques is that the image formation is entirely by NMR, as opposed to ESR. This means that the spatial resolution is independent of the ESR linewidth of the free radical under study. Another related advantage is that PEDRI can make use of standard MRI pulse sequences, including rapid imaging techniques.

In our whole-body system, the detection magnetic field is provided by a whole-body sized permanent magnet which generates a vertical field of 59 mT. Just inside the bore of the permanent magnet is a resistive magnet, made from copper conductor in a saddle configuration. When electric current is sent through the resistive magnet windings they generate a field of up to 59 mT, in opposition to the permanent magnet's field. In this way, switching on and off the current switches the total field in the centre of the magnet down and up in value, and the precise field value can be selected by choosing the correct current to send through the resistive magnet coils.

FC-PEDRI scanner
Whole-body FC-MRI scanner, which is also used for FC-PEDRI

In addition to the usual transmit/receive radiofrequency (RF) coil needed in MRI, FC-PEDRI also requires hardware to generate and apply the RF for ESR irradiation. The NMR transmit/receive coil and the ESR coil/resonator are usually combined into a double-resonance coil assembly. Because the NMR and ESR frequencies are usually far apart (even when field cycling is used), separate resonant structures are usually used. The figure below shows a double-resonant coil assembly, comprising a solenoidal NMR coil (2.5 MHz) and a birdcage resonator for ESR irradiation (51 MHz).

RF coils
FC-PEDRI RF coil assembly, comprising split-solenoid NMR transmit/receive coil, and birdcage resonator for ESR irradiation. Assembly is mounted inside a cylindrical RF shield made of copper foil on a Perspex former.