Doctors could see real-time images of the effects of their treatments in unprecedented detail

A technique that significantly boosts the sensitivity of magnetic resonance imaging (MRI) is on the verge of clinical trials which, if successful, could allow doctors to assess the effects of cancer drugs on a tumour within hours.

Kevin Brindle of the University of Cambridge, UK, says that his method improves the signal to noise ratio of an MRI scan by up to 10000 times. This sharpens MRI images enough to reveal rapidly whether cells in a tumour are dying in response to a particular drug, essential when doctors now have a range to different treatments to choose from. ’This will go into human clinic trials with healthy volunteers within the next year, and into clinical trials with cancer patients within the next two years,’ said Brindle.

His technique involves injecting patients with a biochemical called pyruvate, which is normally converted quickly into lactate by healthy cells. But this process is much slower in dying cells, allowing pyruvate to linger long enough to be tracked by MRI, highlighting regions where anticancer drugs are taking effect.

Absolute zero

MRI produces images by measuring how certain atomic nuclei, such as 1H and 13C, interact with an external magnetic field. Each nucleus is a spinning charge, which acts like a tiny bar magnet and can either align itself with or against the field. A burst of radio waves from the MRI machine flips the nuclei between these two states, leaving more nuclei in a higher-energy state. As these nuclei relax and lose their energy, they re-emit radio waves which are detected by receiver coils in the MRI scanner. Since nuclei in different types of tissue relax at different rates, this can produce a detailed scan of the patient’s internal organs.

However, the signal detected by the machine depends on the difference between the number of nuclei in the two states - and under normal conditions, this difference is tiny. ’But you can improve the population difference by lowering the temperature,’ explained Brindle. In fact, at temperatures close to absolute zero (-273?C), all the nuclei will be in the lower of the two energy states - the sample is said to be spin polarised.

But injecting pyruvate at absolute zero into a patient clearly isn’t an option. The answer, developed in collaboration with Buckinghamshire-based diagnostics firm Amersham (now part of GE Healthcare), turned out to be ’incredibly simple,’ said Brindle. ’You just blast your sample out with hot water, which quickly brings it from about 1K to room temperature.’ 

This makes it suitable for injection, while keeping most of the nuclei in their lower-energy state for long enough to take a high-quality snapshot of the patient’s tissue. ’The agent circulates around the body within a few seconds, so you can take images within five seconds of injecting it,’ said Brindle, who described the technique on 3 October at the LAB conference and laboratory equipment exhibition at London’s ExCel centre.

Acid diagnosis

Brindle is now working on a similar approach to create a MRI probe for pH. Bicarbonate molecules normally react rapidly in the body with acid to form carbon dioxide. So injecting spin-polarised bicarbonate and then using imaging to check the ratio of the two compounds reveals the pH of the tissue, a useful diagnostic for disease. ’Disease is usually associated with inflamed tissue, which has a low pH, and tumours also have a low pH,’ Brindle pointed out.

The technique is currently limited to the few molecules that can retain polarisation for particularly long time periods. Using carbon nuclei, this means finding a molecule with a carbon atom at least three or four bonds away from the nearest hydrogen - otherwise, coupling between the nuclei means a rapid loss of polarisation. 

John van Duynhoven, NMR specialist with consumer product multinational Unilever, told Chemistry World that the polarisation technique might work with a few carefully chosen molecules, but there would be further work to do before it could be used more generally. 

James Mitchell Crow

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