Medical imaging relaxes to brighten up

Protein packaging may enhance MRI contrast.

Images of body tissues and organs could soon be brighter and sharper thanks to a technique developed by Italian chemists. They have made the chemical contrast agents used in magnetic resonance imaging (MRI) produce a stronger signal by trapping them in protein cages just 12 millionths of a millimetre (nanometres) or so widesup>1.

Such improvements increase the contrast of the images, so they should reveal more detailed information, enabling doctors to better discriminate between different tissue types. The researchers, Silvio Aime and co-workers at the University of Turin, hope to persuade their protein cages to latch onto particular cells, as this would help them to pinpoint diseased tissues.

One of the best MRI contrast agents is a molecule containing atoms of the element gadolinium. Injected into the bloodstream, the gadolinium compound accumulates in abnormal tissues such as scar tissue and tumours, so they become brighter in MRI scans. The agent is ultimately passed out of the body in urine.

Making gadolinium contrast agents brighter is a subtle business. Gadolinium enhances MRI contrast because it helps water molecules to relax. The MRI signal comes from water molecules that have been stimulated into an excited state by radio waves. The quicker the water molecules return to their normal state, the stronger the signal. Gadolinium assists in this process.

How well gadolinium does its job depends on the molecules around it. Proteins can amplify the relaxation induced by gadolinium because chemicals on their surface interact with water molecules. Aime’s team found they got better MRI contrast by keeping standard gadolinium contrast agents close to proteins.

Nature provided them with a ready-made protein cage in the form of ferritin, a shell of 24 protein molecules with a cavity about 7.5 nanometres across. Liver cells store iron inside ferritin, packing up to 4,500 iron atoms into its hollow interior.

The Italian team used a stripped-down version of ferritin known as apoferritin. They trapped the gadolinium contrast agent inside the cavity by first splitting the capsule open in acid and then reforming it in neutral solution containing the gadolinium compound. Each apoferritin compartment holds about ten of these gadolinium molecules.

Crucially, apoferritin’s walls are riddled with channels that are wide enough to let water in and out but too narrow to let gadolinium through. This exchange of water between the inside and the outside is essential for increasing its relaxation rate. Apoferritin seems to enhance gadolinium’s relaxation about 20-fold, the team reports.

They haven’t yet discovered how this translates into changes in MRI contrast, however. The clinical usefulness of the new approach will depend on many other factors, such as how efficiently apoferritin-bound gadolinium can be transported round the body, and how easily it can be cleared from the bloodstream.

References

1. Aime, S., Frullano, L. & Crich, S.G. Compartmentalization of a gadolinium complex in the apoferritin cavity: a route to obtain high relaxivity contrast agents for mangetic resonance imaging. Angewandte Chemie International Edition, 41, 1017 – 1019, (2002).