Duke scientists have discovered a new class of inexpensive and long-lived molecular tags that enhance MRI signals by 10,000-fold. To activate the tags, the researchers mix them with a newly developed catalyst (center) and a special form of hydrogen (gray), converting them into long-lived magnetic resonance ‘lightbulbs’ that might be used to track disease metabolism in real time. Credit: Thomas Theis, Duke University
Discovery could enable cheaper, more versatile bioimaging. Duke University researchers have taken a major step towards realizing a new form of MRI that could record biochemical reactions in the body as they happen. A new class of molecular tags enhance MRI signals by 10,000-fold and generate detectable signals that last over an hour. The tags are biocompatible and inexpensive to produce, paving the way for widespread use of MRI to monitor metabolic processes of conditions like cancer and heart disease in real time.
MRI takes advantage of a property called spin, which makes the nuclei in hydrogen atoms act like tiny magnets. Applying a strong magnetic field, followed by a series of radio waves, induces these hydrogen magnets to broadcast their locations. Since most of the hydrogen atoms in the body are bound up in water, the technique is used in clinical settings to create detailed images of soft tissues like organs, blood vessels and tumors inside the body.
But the technique also has the potential to show body chemistry in action, said Thomas Theis, assistant research professor of chemistry at Duke. “With magnetic resonance in general, you have this unique sensitivity to chemical transformations. You can see them and track them in real time.”
MRI’s ability to track chemical transformations in the body has been limited by the low sensitivity of the technique, which makes small numbers of molecules impossible to detect without using unattainably massive magnetic fields. For the past decade, researchers have been developing methods to “hyperpolarize” biologically important molecules, converting them into what Warren calls magnetic resonance “lightbulbs.” With this boosted signal, these “lightbulbs” can be detected even in low numbers.
While promising, Warren says these hyperpolarization techniques face 2 problems: incredibly expensive equipment – 3 million dollars for one machine – and most of these molecular lightbulbs burn out in a matter of seconds.
Jerry Ortiz Jr., a graduate student at Duke synthesized a series of molecules containing diazarines, a chemical structure which is composed of 2 nitrogen atoms bound together in a ring. Diazirines were a promising target for screening because their geometry traps hyperpolarization in a “hidden state” where it cannot relax quickly. Using a simple and inexpensive approach to hyperpolarization called SABRE-SHEATH, in which the molecular tags are mixed with a spin-polarized form of hydrogen and a catalyst, the researchers were able to rapidly hyperpolarize one of the diazirine-containing molecules, greatly enhancing its magnetic resonance signals for over an hour.
“It can be tagged on small molecules, macro molecules, amino acids, without changing the intrinsic properties of the original compound,” said Wang. “We are really interested to see if it would be possible to use it as a general imaging tag.” The scientists believe their SABRE-SHEATH catalyst could be used to hyperpolarize a wide variety of chemical structures at a fraction of the cost of other methods.
“You could envision, in five or ten years, you’ve got the container with the catalyst, you’ve got the bulb with the hydrogen gas. In a minute, you’ve made the hyperpolarized agent, and on the fly you could actually take an image,” Warren said. “That is something that is simply inconceivable by any other method.” http://www.eurekalert.org/pub_releases/2016-03/du-nco032316.php
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