New nuclear magnetic resonance technique offers ‘molecular window’ for live disease diagnosis

May 7, 2017

University of Toronto Scarborough researchers have developed a new “molecular window” technology based on nuclear magnetic resonance (NMR) that can look inside a living system to get a high-resolution profile of which specific molecules are present, and extract a full metabolic profile.

“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,” says Professor Andre Simpson, who led research in developing the new technique.*

[+]

An NMR spectrometer generates a powerful magnetic field that causes atomic nuclei to absorb and re-emit energy in distinct patterns, revealing a unique molecular signature — in this example: the chemical ethanol. (credit: adapted from the Bruker BioSpin “How NMR Works” video at http://www.theresonance.com/nmr-know-how)

Simpson says there’s great medical potential for this new technique, since it can be adapted to work on existing magnetic resonance imaging (MRI) systems found in hospitals. “It could have implications for disease diagnosis and a deeper understanding of how important biological processes work,” by targeting specific biomarker molecules that are unique to specific diseased tissue.

The new approach could detect these signatures without resorting to surgery and could determine, for example, whether a growth is cancerous or benign directly from the MRI alone.

The technique could also provide highly detailed information on how the brain works, revealing the actual chemicals involved in a particular response. “It could mark an important step in unraveling the biochemistry of the brain,” says Simpson.

Overcoming magnetic distortion

Until now, traditional NMR techniques haven’t been able to provide high-resolution profiles of living organisms because of magnetic distortions from the tissue itself.  Simpson and his team were able to overcome this problem by creating tiny communication channels based on “long-range dipole interactions” between molecules.

The next step for the research is to test it on human tissue samples, says Simpson. Since the technique detects all cellular metabolites (substances such as glucose) equally, there’s also potential for non-targeted discovery.

“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 explains. “You can then determine whether you need further testing or surgery. So the potential for this technique is truly exciting.”

The research results are published in the journal Angewandte Chemie.

* 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, called “in-phase intermolecular single quantum coherence” (IP-iSQC), is based on some unexpected scientific concepts that were discovered in 1995, which at the time were described as impossible and “crazed” by many researchers. The technique developed by Simpson and his team builds upon these early discoveries. The work was supported by Mark Krembil of the Krembil Foundation and the Natural Sciences Engineering Research Council of Canada (NSERC).


Abstract of In-Phase Ultra High-Resolution In Vivo NMR

Although current NMR techniques allow organisms to be studied in vivo, magnetic susceptibility distortions, which arise from inhomogeneous distributions of chemical moieties, prevent the acquisition of high-resolution NMR spectra. 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. While this approach holds vast potential, present practical limitations include radiation damping, relaxation losses, and non-phase sensitive data. Herein, these drawbacks are addressed, and a new technique termed in-phase iSQC (IP-iSQC) is introduced. When applied to a living system, high-resolution NMR spectra, nearly identical to a buffer extract, are obtained. The ability to look inside an organism and extract a high-resolution metabolic profile is profound and should find applications in fields in which metabolism or in vivo processes are of interest.

Scientists Have Made a Huge Breakthrough In Cryogenics

March 30, 2017

Cryopreservation

Cryopreservation is the process of freezing organs and tissues at very low temperatures in order to preserve them. While it sounds simple in theory, only a handful of cells and tissues have survived this method. This is because while science has successfully developed ways to cool organs to the very low temperatures required for preservation, thawing them out has proven far more difficult. As the specimen thaws, it forms ice crystals, which can damage the tissue and render organs unusable.

Right now, the process is only a viable option for small samples, such as sperm or embryos. Previous efforts using slow warming techniques have proven to be effective on samples of that size, but haven’t worked for larger tissue samples, like whole human organs. The inability to safely thaw the tissue has also precluded the theoretical concept of cryogenically preserving entire human bodies, with the intention of reanimating them later. The concept has roots in cryogenic technology, but is actually referred to as “cryonics”, and the scientific community generally considers it to be more science fiction than science fact — at least for the time being.

A recent study has made a significant breakthrough which may well begin closing that gap even more. Using a new technique, scientists were able to cryopreserve human and pig samples, then successfully rewarm it without causing any damage to the tissue.

As lead researcher John Bischof from the University of Minnesota notes:

This is the first time that anyone has been able to scale up to a larger biological system and demonstrate successful, fast, and uniform warming of hundreds of degrees Celsius per minute of preserved tissue without damaging the tissue.

By using nanoparticles to heat the tissues at an equal rate, scientists were able to prevent the formation of those destructive ice crystals. The researchers mixed silica-coated iron oxide nanoparticles in a solution and applied an external magnetic field to generate heat. The process was tested on several human and pig tissue samples, and it showed that nanowarming achieves the same speed of thawing as the use of traditional convection techniques.

Preserving Organs and Saving Lives

One theoretical application for this discovery would be, of course, bringing cryogenic life-extension techniques out of the realm of science fiction and into reality. But we’re not quite there yet.

A more practical application for the technique would be to safely preserve and store organs for extended periods, thus improving the logistical challenges behind organ transplantation.

According to statistics from the United Network for Organ Sharing, 22 people die every day in the US while waiting for organ transplants. Contrary to popular belief, this isn’t because there is a shortage of organs being donated — it’s because organs cannot be preserved for more than a few hours. So, while there are available organs ready to be transplanted, the time it takes to find a matching recipient and transport the organ safely to their location often exceeds the window of time in which the organ remains viable for transplant.

Over half of donated hearts and lungs are thrown out each year because they don’t make it to patients in time. They can only be kept on ice for four hours, and while some organs can last longer than others without a blood supply during transport, it’s still not a long enough in many cases.

“If only half of these discarded organs were transplanted, then it has been estimated that wait lists for these organs could be extinguished within two to three years,” Bischof adds. With the help of cryopreservation technology, we may be well on our way to keeping donated organs viable for longer — meaning they could be transported to patients who need them even if distance and time stands between them.

https://futurism.com/4-scientists-have-found-a-way-to-rapidly-thaw-cryopreserved-tissue-without-damage/