A novel technique developed by University of Toronto researchers can now produce high-resolution profiles of molecules present inside living organisms.
Until now, traditional nuclear magnetic resonance (NMR) hasn’t been able to provide high-resolution profiles of living organisms because of magnetic distortions in the sample.
Andre Simpson, professor of physical and environmental sciences at U of T Scarborough, likens it to being in a helicopter and trying to talk to people at a concert below. It’s difficult to communicate because of the noise distortion, but if you give both a walkie-talkie, it makes communication much easier, Simpson says.
Simpson and his team were able to overcome the magnetic distortion problem by creating tiny communication channels based on something called long-range dipole interactions between molecules. The new NMR technique allows them to get a complete chemical makeup of molecules within the object.
Simpson’s work focuses on environmental NMR, but he says there’s great medical potential for the new technique in medical imaging.
“In a way we’ve developed this molecular window that can look inside a living system and extract a full metabolic profile,” says Simpson, who led research into developing the technique.
“Getting a sense of which molecules are in a tissue sample is important if you want to know if it’s cancerous, or if you want to know if certain environmental contaminants are harming cells inside the body. It could have implications for disease diagnosis and a deeper understanding of how important biological processes work.”
NMR technology is able to generate a magnetic field that is so powerful that atomic nuclei can be made to absorb and reemit energy in distinct patterns, revealing a unique molecular signature.
Simpson says the new technique is easily programmable and can be translated to work on existing modern MRI systems found in hospitals.
He points to specific molecules called cancer biomarkers that are unique to diseased tissue. The new approach holds potential to detect these signatures without resorting to surgery and determine whether a growth is cancerous or benign directly from the MRI alone.
It also has the potential to tell us how the brain works, he says. Current MRI methods can tell which part of the brain “lights up” in response to stimuli like fear or happiness, but those just indicate which part of the brain is responsible. The new technique can potentially be used to look inside those locations and reveal the chemicals actually causing the response.
“It could mark an important step in unraveling the biochemistry of the brain,” says Simpson.
Simpson has been working on perfecting the technique for more than three years with colleagues at Bruker BioSpin, a scientific instruments company that specializes in developing NMR technology. The technique is based on some unexpected scientific concepts that were discovered in 1995, which at the time were described as impossible by many researchers.
The technique developed by Simpson and his team, which includes PhD student Ioana Fugariu, builds upon these early discoveries and is published in the journal Angewandte Chemie. The work was supported by Mark Krembil of the Krembil Foundation and the Natural Sciences Engineering Research Council of Canada (NSERC).
Simpson says the next step for the research is to test it on human samples. He adds that since the technique detects all metabolites equally, there’s also potential for non-targeted discovery like finding pathologies or processes you weren’t even looking for in the first place.
“Since you can see metabolites in a sample that you weren’t able to see before, you can now identify molecules that may indicate there’s a problem,” he says.
“You can then determine whether you need further testing or surgery. The potential for this technique is truly exciting.”