The processes described above - hyperpolarizing the xenon, caging it in biosensors, and building up depolarized xenon in the immediate vicinity of the target through chemical exchange and selective bursts of rf radiation - led to the development of Hyper-CEST MRI. But until now, Hyper-CEST MRI has only been tested at room temperature.
Using biosensor cages as temperature-controlled molecular depolarization gates makes Hyper-CEST MRI possible at a range of higher-than-room temperatures. Because the technique regulates the exchange rate of hyperpolarized-to-depolarized nuclei through the cages, biosensors regulated this way have been nicknamed "transpletors," by analogy to the transistors that act as gates for the flow of electrons from source to drain in electronic systems.
Hyper-CEST at a range of temperatures has many advantages. Most basic is that biomedical MRI must operate at body temperature. Aside from this practical consideration, temperature determines the rates at which different kinds of cryptophane- cage hosts react with their xenon-atom guests. And increasing temperature dramatically increases chemical exchange rates.
The ability to achieve high-contrast images, multiplexed to identify a range of molecular targets, and to do so in a short time, offers many benefits to patients and physicians.
"Doctors attempting to characterize tumors very often have to take biopsies, and that's painful for the patient, so they usually prefer to take only one biopsy," says Schroeder. "But then they have to run all their tests on this very little tissue. So they would be happy with a method where you have a toolbox of sensors, you throw them all in and wait to let them bind, and then do your tests at the different frequencies and you see what sensors are present, detecting the different proteins. We showed that the exchange rate is so high at increased temperature that you can use a very selective rf pulse."
Enabling fast, sensitive, molecule-specific NMR and MRI in humans and other living subjects is perhaps the most evident advantage of the new technique, but possible applications don't end there. For example, the method offers a better way to study chemical exchange in nanostructures like zeolites, which are important in catalysis, or in versatile carbon nanotubes. Temperature-controlled depolarization is a breakthrough for NMR and MRI that will find uses in a variety of fields.
This research was supported by the Department of Energy's Office of Science, Office of Basic Energy Sciences; by the Deutsche Forschungsgemeinschaft; and by the University of California's Biotechnology Research and Education Program.
Berkeley Lab is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research and is managed by the University of California. Visit our website at http://www.lbl.gov.
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