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HYPER-CEST MRI Breaks New Ground in Molecular Imaging


In a paper published in the October 20, 2006 issue of the journal Science, the team of researchers report on a technique in which xenon atoms that have been hyperpolarized with laser light to enhance their MRI signal, incorporated into a biosensor and linked to specific protein or ligand targets.  These hyperpolarized xenon biosensors generate highly selective contrast at sites where they are bound, dramatically boosting the strength of the MRI signal and resulting in spatial images of the chosen molecular or cellular target.

This research was led by Alexander Pines and David Wemmer, who both hold joint appointments with Berkeley Lab and UC Berkeley.  Their paper is entitled Molecular Imaging Using a Targeted Magnetic Resonance Hyperpolarized Biosensor.  Co-authoring the paper with Pines and Wemmer were Leif Schröder and Thomas Lowery, plus Christian Hilty.

“Our HYPER-CEST molecular MRI technique makes optimum use of hyperpolarized xenon signals by creating a strong signal in regions where the biosensor is present, allowing for easy non-invasive determination of the target molecule,” said Pines, one of the world’s leading authorities on NMR/MRI technology, who holds a joint appointment as a chemist with Berkeley Lab’s Materials Sciences Division and with UC Berkeley, where he is the Glenn T. Seaborg Professor of Chemistry. “This approach should be broadly applicable, potentially overcoming many shortcomings of currently used strategies for molecular imaging.”

Added Wemmer, a chemist with Berkeley Lab’s Physical Biosciences Division and UC Berkeley chemistry professor,  “Other molecular MRI contrast agents provide small changes in big MRI signals, making the changes difficult to detect when the amount of contrast agent binding is small. Our HYPER-CEST contrast agent provides a big change in the xenon MRI signal, which means it is much easier to detect even though the xenon MRI signals are rather small.”

In addition to its intrinsically higher contrast, another advantage with the HYPER-CEST technique is that its effects can be “multiplexed,” meaning that the polarized xenon biosensors can be targeted to detect different proteins at the same time in a single sample. This capability, which is not shared by most conventional molecular MRI contrast agents, opens up a number of possibilities for future diagnostics.

Explained co-author Schröder, a member of the Pines’ research group who is affiliated with Berkeley Lab’s Materials Sciences Division, “For example, as a diagnostic tool for the detection of cancer, with HYPER-CEST, we could perform multiple virtual biopsies on a single tissue sample, using different biosensors to screen for each potential form of cancer.”

As a diagnostic tool for cancer, HYPER-CEST would be extremely sensitive, Schröder says, able to detect the presence of cancer-related proteins at micromolar (parts per million) concentrations.  The sooner that the presence of cancerous cells is detected, the better the chances are for successful treatment.  In addition to high sensitivity and target specificity, HYPER-CEST MRI is also unique from other molecular imaging techniques in that it provides both spatial and biochemical information.  This points to a wide range of biomedical applications far beyond cancer diagnostics.