Diagnoses of cancer, heart disease, stroke and rheumatoid arthritis could happen faster with technology being developed by a Wayne State University researcher.
Matthew Allen, Ph.D., assistant professor of chemistry in the College of Liberal Arts and Sciences, is seeking to commercialize a class of contrast agents that can enhance the effectiveness of magnetic resonance imaging (MRI) scans.
Contrast agents are injectable “drugs” containing a paramagnetic element that creates temporary magnetic differences between similar tissues, enabling them to appear differently in an MRI scan. Of about 60 million annual MRI scans worldwide, 40 to 50 percent currently use contrast agents; the rest can show tissue differences without them.
Current technology uses a class of contrast agents based on the element gadolinium, but it fails at higher magnetic field strengths. As a result, scientists cannot take advantage of hardware advances that could shorten scan times and produce higher-resolution images using higher field strengths.
Allen pointed to a recent study that found 93 percent of cortical brain lesions in samples from multiple sclerosis patients with a high-field magnet, compared to just 30 percent with a lower-field magnet.
One of his projects, “Evaluation of the Toxicity of New Content Agents for Ultra-High Field Strength Magnetic Resonance Imaging,” focuses on the rare earth element europium as a basis for contrast agents. Like gadolinium, however, europium by itself is toxic to humans and therefore must chemically “caged” before being injected. Allen’s research team will try to do that in laboratory tests during the first portion of the project before testing the new contrast agents.
In a related project, “Interaction of Biphenyl-functionalized EU 2+-Containing Cryptate with Albumin: Implications to Contrast Agents in Magnetic Resonance Imaging,” supported with $530,000 from the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (grant R00EB007129), Allen’s team is looking at how to make changes in the cages around europium, thereby changing its properties relative to MRI.
The property Allen is most interested in is making those cages tumble more slowly within a solution, allowing more time for magnets to conduct scans.
“One way to do that is to attach the cages to something really big,” he said. “We’re targeting a protein called human serum albumin (HSA), the most abundant protein in the blood.
“Basically we have modified the cage, or cryptand, of the group we thought should interact with albumin. We showed that it does, and that it slows down tumbling.”
Allen’s team is working to address an unintended consequence of adding a biphenyl group to side of HSA — the displacement of a water molecule — which complicates the scanning process.
He expects the contrast agents that eventually result from his work will be very similar to currently marketed gadolinium in toxicity and safety because of their proximity on the periodic table of elements. Allen noted, however, that the unique nature of the europium nucleus allows it to demonstrate significantly better contrast at higher field strengths while being nearly as effective as gadolinium at lower field strengths.
Utilizing those properties, he said, should result in higher-resolution images that can help clinicians spot medical issues sooner than is currently possible.
“This gives us the chance to diagnose diseases at earlier stages, and if you can catch things earlier, treatments are usually more successful,” Allen said.
Allen’s research is supported in part by a grant from the Michigan Initiative for Innovation and Entrepreneurship.
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