Cellular signals: NMR metabolic profiling

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  • Published: May 15, 2017
  • Author: David Bradley
  • Channels: NMR Knowledge Base
thumbnail image: Cellular signals: NMR metabolic profiling

Novel NMR

A novel NMR technique developed at U of T Scarborough has the potential for noninvasive disease diagnosis using current MRI technology. Credit: University of Toronto Scarborough

A novel NMR technique developed by researchers at the University of Toronto Scarborough, Canada, can for the first time obtain undistorted high-resolution profiles of the molecules and metabolites present within a living organism.

Team leader Andre Simpson explains that, "In a way we've developed this molecular window that can look inside a living system and extract a full metabolic profile." He adds that, "Getting a sense of which molecules are in a tissue sample is important if you want to know if it is cancerous, or if you want to know if certain environmental contaminants are harming cells inside the body."

Until now conventional nuclear magnetic resonance (NMR) spectroscopic techniques have been unable to offer high-resolution profiles of living organisms because samples themselves distort the magnetic field, which leads to the signals getting blured and the molecular information lost. The analogy Simpson gives is that it is like attempting a conversation at an open-air rock concert with a helicopter hovering overhead. Of course, "walkie-talkies" would help solve that problem and Simpson and his team have been able to overcome the magnetic susceptibility distortion problem by opening up communication channels by exploiting long-range dipole interactions between molecules. Specifically, the team describes how "intermolecular single quantum coherence (iSQC) is a technique that breaks the sample's spatial isotropy to form long range dipolar couplings, which can be exploited to extract chemical shift information free of perturbations...using in-phase iSQC (IP-iSQC)."

Metabolic profiling

Simpson's work focuses on environmental NMR spectroscopy but he points out that the potential in biomedical research and medicine itself is enormous now that they have demonstrated proof of principle with this approach. "It could have implications for disease diagnosis and a deeper understanding of how important biological processes work," he explains, pointing out that the technique can be adapted so that it might be programmed into existing magnetic resonance imaging systems, the modern MRI machines used by many hospitals today.

Simpson also suggests that the technique could be used to profile biomarkers for cancer present only in diseased tissue. The new approach holds potential to detect these signatures without the need for surgical examination of an internal lesion or biopsy. The spectra could be used to quickly and accurately determine whether or not a tumour is malignant or benign based on its chemical profile.

The team also hopes that the same techniques might be applicable in brain research. While current functional MRI methods can reveal which parts of the brain "light up" in response to stimuli, the new technique might be used to look deep within those illuminated regions to reveal the biomolecules involved in a given response to stimulus. "This could mark an important step in unravelling the biochemistry of the brain," adds Simpson.

Industrial connection

Simpson and colleagues Ioana Fugariu, Daniel Lane, and Ronald Soong work with Wolfgang Bermel at scientific instruments company Bruker BioSpin, which specializes in NMR technology. The new technique itself builds on the serendipitous discovery in 1995 of the phenomenon of long-range dipole interactions, which were considered implausible at the time they were first reported. The next step will be to test the technique with human samples. Simpson adds that since the technique detects all metabolites equally there is also potential for non-targeted discovery, that is, finding pathologies or processes that were not initially suspected. "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 adds. "You can then determine whether you need further testing or surgery. So the potential for this technique is truly exciting."

Related Links

Angew Chem, 2017, online: "In-Phase Ultra High-Resolution In Vivo NMR"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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