New type of molecular tag makes MRI 10,000 times more sensitive
MRI takes advantage of a property called spin, which makes the nuclei in hydrogen atoms act like tiny magnets. By generating a strong magnetic field (such as 3 Tesla) and a series of radio-frequency waves, MRI induces these hydrogen magnets in atoms 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 (such as the brain), blood vessels, and tumors inside the body.
MRI’s ability to track chemical transformations in the body has been limited by the low sensitivity of the technique. That makes it impossible to detect small numbers of molecules (without using unattainably more massive magnetic fields).
So to take MRI a giant step further in sensitivity, the Duke researchers created a new class of molecular “tags” that can track disease metabolism in real time, and can last for more than an hour, using a technique called hyperpolarization.* These tags are biocompatible and inexpensive to produce, allowing for using existing MRI machines.
“This represents a completely new class of molecules that doesn’t look anything at all like what people thought could be made into MRI tags,” said Warren S. Warren, James B. Duke Professor and Chair of Physics at Duke, and senior author on the study. “We envision it could provide a whole new way to use MRI to learn about the biochemistry of disease.”
The new molecular tags open up a new world for medicine and research by making it possible to detect what’s happening in optically opaque tissue instead of requiring expensive positron emission tomography (PET), which uses a radioactive tracer chemical to look at organs in the body and only works for (typically) about 20 minutes, or CT x-rays, according to the researchers.
This research was reported in the March 25 issue of Science Advances. It was supported by the National Science Foundation, the National Institutes of Health, the Department of Defense Congressionally Directed Medical Research Programs Breast Cancer grant, the Pratt School of Engineering Research Innovation Seed Fund, the Burroughs Wellcome Fellowship, and the Donors of the American Chemical Society Petroleum Research Fund.
* For the past decade, researchers have been developing methods to “hyperpolarize” biologically important molecules. “Hyperpolarization gives them 10,000 times more signal than they would normally have if they had just been magnetized in an ordinary magnetic field,” Warren said. But while promising, Warren says these hyperpolarization techniques face two fundamental problems: incredibly expensive equipment, around 3 million dollars for one machine, and most of these molecular “lightbulbs” burn out in a matter of seconds.
“It’s hard to take an image with an agent that is only visible for seconds, and there are a lot of biological processes you could never hope to see,” said Warren. “We wanted to try to figure out what molecules could give extremely long-lived signals so that you could look at slower processes.”
So the researchers synthesized a series of molecules containing diazarines, a chemical structure composed of two 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.
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.