New Research Could Lead to Enhanced MRI Scans

New research from the University of Southampton could lead to enhanced MRI scans, producing brighter and more precise images, and potentially allowing the detection of cancerous cells before they cause health problems.

Professor Malcolm Levitt of the University of Southampton, and co-workers, have been awarded a grant from the European Research Council of 2.8 million euros to support research into enhanced nuclear magnetic resonance (NMR). NMR is the physical principle underlying MRI scanning, which is used routinely to detect abnormalities such as tumours. The long term aim is that this research will lead to a range of clinical applications, including the early detection of cancer.
NMR signals are inherently very weak. However, methods have been developed recently which lead to substances exhibiting a phenomenon called hyperpolarization, and which give rise to NMR signals that can be more than 100,000 times stronger than normal. The problem is that this incredible enhancement only lasts a short amount of time -- up to one minute in favourable cases.
Research in Southampton has previously demonstrated the existence of quantum states that have very long lifetimes -- up to half an hour in the case of the common substance nitrous oxide, often known as laughing gas. The new research grant has been awarded for a project that involves a combination of the hyperpolarization effect with the long-lived quantum states developed in Southampton. The combination could give the best of both worlds -- enormously enhanced NMR signals, which last long enough to perform an MRI scan. Professor Levitt says:
"This could have benefits for MRI Scanning. If you have strong signals, you can detect smaller amounts of substance that are less concentrated. For example, some substances naturally occur in a cell as part of the metabolism process, but occur in greater amounts in cancerous cells. Through this method, we should be able to detect when these substances are present and cells are potentially cancerous, earlier than ever before.
"Additionally, this method could allow us to detect oxygen levels in cells. When oxygen levels are depleted, this can mean that cells are metabolising more quickly, which can suggest that the cells are cancerous."
In addition to funding the research, the grant will allow for two new pieces of equipment to be installed at the University of Southampton. One will be a polarizer, which will be designed and constructed in Southampton, and which will generate substances exhibiting the hyperpolarization phenomenon. The second piece of equipment will be a NMR spectrometer equipped to perform small-scale MRI experiments, to test out the new concepts in preparation for performing experiments on a clinical MRI scanner. It is hoped that this research, which will run over the next four years, will lead to the development of new tools for clinicians to detect metabolic or anatomical abnormalities in the body.

NMR Used to Determine Whether Gold Nanoparticles Exhibit 'Handedness'

Carnegie Mellon University's Roberto R. Gil and Rongchao Jin have successfully used NMR to analyze the structure of infinitesimal gold nanoparticles, which could advance the development and use of the tiny particles in drug development.
Their approach offers a significant advantage over routine methods for analyzing gold nanoparticles because it can determine whether the nanoparticles exist in a both right-handed and left-handed configuration, a phenomenon called chirality. Determining a nanoparticle's chirality is an important step toward developing them as chiral catalysts -- tools that are highly sought-after by the pharmaceutical industry. Their results are published online at ACS Nano.
Many drugs on the market today contain at least one molecule that is chiral. Often only one of the configurations, or isomers, is effective in the body. In some cases, the other isomer may even be harmful. A striking example is the drug thalidomide, which consisted of two isomers: one of which helped pregnant women control nausea while the other caused damage to the developing fetus. In an effort to create safer, more effective drugs, drug manufacturers are looking for ways to produce purer substances that contain only the left- or right-handed isomer.
Huifeng Qian, a fourth-year graduate student working with Jin, created a gold nanoparticle that has the potential to catalyze chemical reactions that will produce one isomer rather than the other. The nanoparticle is composed of precisely 38 gold atoms and measures a mere 1.4 nanometers. Qian worked diligently for nearly a year to grow the nanoparticles into high-quality crystals so that he could study their structure using x-ray crystallography.
"Growing a pure crystal from nanoparticles is very challenging, and you may not even be able to get a crystal at all," said Jin, an assistant professor of chemistry in CMU's Mellon College of Science. "In the nanoparticle community, the crystal structures of only three nanoparticles have been reported."
In Jin's case, x-ray crystallography revealed that the gold nanoparticle is chiral. Chemists typically probe the internal chiral structure of gold nanoparticles using a technique called circular dichoism spectroscopy. When pure chiral molecules are exposed to circularly polarized light, each isomer absorbs the light differently, resulting in a unique -- and of opposite sign -- spectrum for each isomer. The process of creating the gold nanoparticles, however, often results in a 50/50 mix of each isomer, known as racemates.
"Because the spectrum is of opposite sign for each isomer, they cancel each other out and the net optical response is zero. This makes circular dichoism (CD) spectroscopy useless when it comes to determining the chirality of gold nanoparticles in 50/50 mixtures," said Gil, associate research professor of chemistry and director of the Department of Chemistry's NMR Facility.
Since Jin couldn't use circular dichoism spectroscopy, Gil was able to use NMR to help Jin distinguish between his gold nanoparticles' left- and right-handed isomers.
NMR spectroscopy takes advantage of the physical phenomenon wherein some nuclei wobble and spin like tops, emitting and absorbing a radio frequency signal in a magnetic field. By observing the behavior of these spinning nuclei, scientists can piece together the chemical structure of the compound.
In 1957, scientists observed that the hydrogen atoms of a freely rotating methylene (CH2) group produced two different frequencies if they were close to a chiral center. Jin's gold nanoparticles, which have a chiral core, are cushioned by several chemical groups, including freely rotating methylene groups. Gil reasoned that the nanoparticles' chiral core should induce the methylene group's two hydrogen atoms to give off different frequencies, a phenomenon known as diastereotopicity.
Gil and Jin compared the NMR signal from the hydrogen atoms in a non-chiral gold nanoparticle with the NMR signal from the hydrogen atoms in chiral gold nanoparticle. The non-chiral nanoparticle's NMR spectrum did not reveal any differences, but the chiral nanoparticle's NMR spectrum revealed two different hydrogen signals, providing a simple and efficient way of telling whether the particle is chiral or not, even for a 50/50 mixture of isomers.
"NMR is an alternative -- and very efficient -- method for providing useful information about how the atoms in nanoparticles form the molecular structure. Because NMR can determine chirality in some cases, it can readily be used to determine the purity of a nanoparticle mixture," Jin said.
In current work, Jin and Qian are striving to turn their 50/50 mixture of right- and left-handed isomers into a pure solution of one or the other.

Nuclear Magnetic Resonance With No Magnets

Nuclear magnetic resonance (NMR), a scientific technique associated with outsized, very low-temperature, superconducting magnets, is one of the principal tools in the chemist’s arsenal, used to study everything from alcohols to proteins to such frontiers as quantum computing. In hospitals the machinery of NMR’s cousin, magnetic resonance imaging (MRI), is as loud as it is big, but nevertheless a mainstay of diagnosis for a wide range of medical conditions.
It sounds like magic, but now two groups of scientists at Berkeley Lab and UC Berkeley, one expert in chemistry and the other in atomic physics, long working together as a multidisciplinary team, have shown that chemical analysis with NMR is practical without using any magnets at all.
Dmitry Budker of Berkeley Lab’s Nuclear Science Division, a professor of physics at UC Berkeley, is a protean experimenter who leads a group with interests ranging as far afield as tests of the fundamental theorems of quantum mechanics, biomagnetism in plants, and violations of basic symmetry relations in atomic nuclei. Alex Pines, of the Lab’s Materials Sciences Division and UCB’s Department of Chemistry, is a modern master of NMR and MRI. He guides the work of a talented, ever-changing cadre of postdocs and grad students known as the “Pinenuts” – not only in doing basic research in NMR but in increasing its practical applications. Together the groups have extended the reach of NMR by eliminating the use of magnetic fields at different stages of NMR measurements, and have finally done away with external magnetic fields entirely.