News | Magnetic Resonance Imaging (MRI) | March 28, 2016

New Class of Molecular Lightbulbs Illuminate MRI

Duke researchers synthesize molecular tags that generate significantly stronger signal for longer to track biochemical reactions

Duke University study, molecular lightbulbs, MRI imaging agent

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. Image courtesy of Thomas Theis, Duke University.

March 28, 2016 — Duke University researchers have taken a major step towards realizing a new form of magnetic resonance imaging (MRI) that could record biochemical reactions in the body as they happen.

In the March 25 issue of Science Advances, they report the discovery of a new class of molecular tags that 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.

“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.”

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 and co-lead author on the paper. “With magnetic resonance in general, you have this unique sensitivity to chemical transformations. You can see them and track them in real time,” Theis said.

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. “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.

While promising, Warren says these hyperpolarization techniques face two fundamental problems: incredibly expensive equipment — around $3 million 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.”

Jerry Ortiz Jr., a graduate student at Duke and co-lead author on the paper, synthesized a series of molecules containing diazarines, a chemical structure which is 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.

Qiu Wang, assistant professor of chemistry at Duke and co-author on the paper, said this structure is a particularly exciting target for hyperpolarization because it has already been demonstrated as a tag for other types of biomedical imaging.

“It can be tagged on small molecules, macromolecules, 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.”

Other authors include Angus W. J. Logan, Kevin E. Claytor, Yesu Fang, William P. Huhn, Volker Blum and Steven J. Malcolmson of Duke University and Eduard Y. Chekmenev of Vanderbilt University.

This research was supported by the National Science Foundation (CHE-1058727, CHE-1363008, CHE-1416268), the National Institutes of Health (1R21EB018014), the Department of Defense Congressionally Directed Medical Research Programs Breast Cancer grant (W81XWH-12-1-0159/BC112431), 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 more information: www.scienceadvances.org

Related Content

Ingenia Ambition X 1.5T MR. This innovation is the latest advance in the Ingenia MRI portfolio, which comprises fully-digital MRI systems, healthcare informatics and a range of maintenance and life cycle services for integrated solutions that empower a faster, smarter, and simpler path to enabling a confident diagnosis
News | Magnetic Resonance Imaging (MRI) | September 14, 2018
Philips, a global leader in health technology, launched the Ingenia Ambition X 1.5T MR.
Gadolinium contrast agents (GBCAs) are partly retained in the brain, raising safety concerns, as seen in this MRI.

Gadolinium contrast agents (GBCAs) are partly retained in the brain, raising safety concerns, as seen in this MRI.

News | Contrast Media | September 12, 2018
In February 2018, a workshop was held at the National Institutes of Health (NIH) in Bethesda, Maryland, to explore co
Veye Chest version 2
News | Lung Cancer | September 11, 2018
Aidence, an Amsterdam-based medical AI company, announced that Veye Chest version 2, a class IIa medical device, has
Sponsored Content | Case Study | Magnetic Resonance Imaging (MRI) | September 07, 2018 | By Sabine Sartoretti, M.D.
As soon as the Compressed SENSE technology became available to the MRI team at Kantonsspital Winterthur (Switzerland),...

Image courtesy of Philips Healthcare

Feature | Magnetic Resonance Imaging (MRI) | September 06, 2018 | By Melinda Taschetta-Millane
According to the Prescient & Strategic Intelligence report, “Global Magnetic Resonance Imaging (MRI) Market Size,...
Brain Iron Levels May Predict Multiple Sclerosis Disabilities
News | Neuro Imaging | August 31, 2018
A new, highly accurate magnetic resonance imaging (MRI) technique can monitor iron levels in the brains of multiple...
Study Finds Multiple Sclerosis Drug Slows Brain Shrinkage

An NIH-funded clinical trial suggested that the anti-inflammatory drug ibudilast may slow brain shrinkage caused by progressive MS. Image courtesy of Robert J. Fox, M.D., Cleveland Clinic.

News | Neuro Imaging | August 30, 2018
August 30, 2018 — Results from a clinical...
Rapid Cardiac MRI Technique May Cut Costs, Boost Care in Developing World
News | Magnetic Resonance Imaging (MRI) | August 29, 2018
A newly developed rapid imaging protocol quickly and cheaply diagnosed heart ailments in patients in Peru, according to...
iSchemaView RAPID Technology Now Installed in More Than 500 Stroke Centers
News | Neuro Imaging | August 27, 2018
iSchemaView announced that more than 575 stroke centers in 22 countries have selected the RAPID advanced imaging...
Radiation Therapy Affects Event Recall for Children With Brain Tumors
News | Radiation Therapy | August 24, 2018
Children with certain types of brain tumors who undergo radiation treatment are less likely to recall the specifics of...
Overlay Init