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A magnetic probe for pH and, perhaps, disease

BioPhotonics
Jul 2008
Hank Hogan

There could be a new way to detect disease, researchers say. The technique uses MRI of hyperpolarized bicarbonate to measure tissue pH, which often is low when pathology is present. Because of this, the pH probe could detect disease and also measure treatment response. A team from Cambridge University, Cancer Research UK’s Cambridge Research Institute, GE Healthcare of Amersham, all in the UK, and from Imagnia AB of Malmö, Sweden, demonstrated the technique in a mouse tumor model.

The key isn’t in the MRI scanner itself, said team member and Cambridge biomedical magnetic resonance professor Kevin M. Brindle. “The secret is the hyperpolarization, which offers an enormous gain in sensitivity.”

BNpH_image.jpg

Hyperpolarization increases the magnetic resonance signal of carbon-13-labeled bicarbonate, allowing researchers to map pH in vivo. Because a lower pH is often associated with disease, this could serve to delineate disease. Here a tumor, outlined in white, shows up as a region of lower pH. Courtesy of Kevin M. Brindle, Cambridge University.

Indicative of acid-base balance, pH often changes when disease is present. However, past attempts at developing a clinically useful magnetic-resonance-based pH measurement have suffered from low probe sensitivity or hard-to-interpret results. Some have required injection of problematic contrast agents.

Hyperpolarization and the selection of the right probe can solve these problems. In hyperpolarization, the nuclear spin of a material is forced from a normal state into one that is much more polarized. This results in a substantial magnetic resonance signal increase.

Within the past five years, it has become practical to get the hyperpolarized sample from something just above absolute zero to room temperature very quickly without losing the polarization. This advance, courtesy of team members Klaes Golman and Jan Henrik Ardenkjær-Larsen, makes the pH probe possible.

Using the technique, the group hyperpolarized bicarbonate, selecting it in part because it is a naturally occurring molecule within the body. It also can be infused safely in patients at relatively high concentrations. The ratio of bicarbonate to carbon dioxide is sensitive to pH, making it a suitable probe. The researchers labeled bicarbonate with the nonradioactive carbon 13 isotope and boosted its magnetic resonance signal to detectability.

When they injected hyperpolarized bicarbonate into tubes containing buffers at different pHs, they found that the magnetic resonance results correlated well with those obtained with a pH meter. They then injected the bicarbonate into lymphoma-bearing mice and compared the readings with those from an older magnetic resonance probe, again finding good agreement.

Plans call for transporting the technique into the clinic, with GE Healthcare developing the technology. Brindle cautioned, however, that a great deal of work must be done before that happens. First, it isn’t completely clear yet which diseases would benefit from the pH probe, although it’s likely to be useful for tumor detection and possibly for spotting inflammation. Therefore, work must be done to pin down the circumstances in which the probe would be useful.

Secondly, because the polarization is short-lived, the injection and the imaging must be done rapidly. However, Brindle noted that this should be a solvable problem. “There is already a lot of work going on to develop very fast imaging techniques to detect hyperpolarized substrates,” he said.

Nature, published online May 28, 2008.


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