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【技术产业】分子影像新纪元:HYPER-CEST MRI

http://www.lbl.gov/Science-Articles/Archive/MSD-HYPER-CEST.html
HYPER-CEST MRI Breaks New Ground in Molecular Imaging
Contact: Lynn Yarris (510) 486-5375, lcyarris@lbl.gov

BERKELEY, CA — Researchers with the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California at Berkeley have developed a new technique for Magnetic Resonance Imaging (MRI) that allows detection of signals from molecules present at 10,000 times lower concentrations than conventional MRI techniques. Called HYPER-CEST, for hyperpolarized xenon chemical exchange saturation transfer, this new technique holds great promise for molecular imaging, in which the spatial distribution of specific molecules is detected within an organism. Ultimately, HYPER-CEST could become a valuable tool for medical diagnosis, including the early detection of cancer.



From left, Thomas Lowery, holding an imaging phantom, Leif Schröder and David Wemmer were members of a collaboration with Alexander Pines (not shown) that developed a promising new technique called HYPER-CEST for MRI 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.



Set against the two-compartment phantom is a diagram of how HYPER-CEST works. Selective saturation of biosensor-encapsulated xenon (green) and subsequent chemical exchange with the free xenon (blue) allows accumulation of depolarized nuclei (red). This procedure corresponds to continuous depolarization of cage-related magnetization that can be measured indirectly after several cycles by the difference between initial and final bulk magnetization.

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作者:admin@医学,生命科学    2010-12-06 17:11
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