Signal Amplification in NMR and MRI using hyperpolarised compounds

The NMR Centre and the Neuroimaging Centre at the University of York have conducted a programme of work that has demonstrated that one of the fundamental limitations of conventional Nuclear Magnetic Resonance (NMR) and Magnetic Resonance Imaging (MRI) techniques can be dramatically overcome. NMR is the most popular method for performing analytical and structural chemistry and MRI is the technique of choice for carrying out non-invasive imaging in humans. Even though the global markets for these techniques exceeds 6billion annually, as identified in a recent US report to Congress, both technologies are limited in application due to poor sensitivity. A process termed hyperpolarisation, developed in York throughout the last decade, allows these limitations to be overcome. We have recently shown that 0.5 seconds worth of data collection equates to 58 days on the conventional device.In laymen's terms, both NMR and MRI deal with the probing of the magnetic behaviour of nuclei within molecules. These nuclei behave like bar magnets and therefore can either have a north or south seeking orientation. Parahydrogen is simply a reaction feedstock where rather than having a mixture of such orientations, we start with a pure magnetic form. We have established a new route to utilising this feedstock in MR studies. The parahydrogen simply acts like a radiator which when brought into contact with its surroundings warms the room. In this case, the result is a potential 31,000 increase in detected signal strength. The information obtained through MIR studies is well established as providing critical information related to diagnosis and treatment in the health field. The breakthrough in sensitivity enhancement offers opportunities for a step change in modern healthcare and in high resolution NMR markets. This is achieved without the chemical modification of a material and it can employ substances that are native to the body. We therefore expect that it will not suffer from the toxicological problems associated with gadolinium contrast agents and PET and hence be well received by the medical community and laymen alike.Please see Proposal Form for details

Magnetic resonance imaging (MRI) is widely and powerfully used in front-line healthcare. The importance of MRI to modern medicine is such that any advances which increase its diagnostic availability will lead to major and lasting gains, with improvements in the selectivity and the sensitivity of MRI contrast agents particularly opening up major new healthcare possibilities. Given the multidisciplinary nature of MRI, future advances will rely on teams of scientists, biomedical scientists and clinicians working closely together in an interdisciplinary manner that come from companies and Universities. Here we seek to achieve this by applying a revolutionary new technology developed at the University of York. MRI works by detecting the radio frequency signals which result from nuclei undergoing a magnetic spin state alignment change. These signals, however, are very weak, severely limiting the information available from MRI. Information enhancement can be achieved by using a contrast agent. Indeed, over 1.4 million MRI scans were performed in the NHS in 2008 where almost one third required an injected contrast agent to provide useful clinical information. The contrast agents in current widespread use are based on gadolinium. These agents are relatively sensitive giving clinician's good anatomical information, but offer no biochemical selectivity. They also suffer from potential toxicity issues. There is therefore a widely recognised and urgent need for new contrast agents and, in particular, for new agents offering significant increases in sensitivity. Increases in sensitivity will lead to major benefits in front-line healthcare which include, for example, reductions of the size of MRI scanners which in itself would greatly expand the accessibility and availability of MRI. Advances in contrast agent selectivity and specificity would also give a step change in the quality of clinically useful information available from imaging. In this context, hyperpolarised contrast agents have the potential to revolutionise magnetic resonance methods such as MRI through unrivaled gains in contrast agent sensitivity. Already, hyperpolarised xenon is used medically in lung imaging. For example, while hardware developments such as increasing magnet size in high resolution NMR spectroscopy over the last 20 years have improved the strength of the detected signal by just over one order of magnitude, hyperpolarisation can increase sensitivity by five orders of magnitude in a single step with no changes in the detection hardware. Significantly, the ability to hyperpolarise molecules of biological interest opens up the possibility of major increases in not only sensitivity both also in selectivity. It is here where York has made significant breakthroughs by utilising parahydrogen to generate hyperpolarised contrast agents simply and easily. The advantage of York's new method is that it allows the rapid production of large amounts of hyperpolarised agents without changing their molecular structure (a significant advantage over other hyperpolarisation methods and dynamic nuclear polarisation techniques where the method of contrast agent generation is limited in either amount/speed of sample and/or range of materials that can be hyperpolarised). Using the York technology, the in vivo chemical functionality of the molecule will be retained which offers the potential to create highly sensitive and highly specific contrast agents reliably and inexpensively. The benefits of the hyperpolarisation approach for improving healthcare are not restricted to imaging. In its high resolution version it enables the detailed characterisation of molecules in solution, leading to direct applications for better drug discovery product screening, sample characterisation, stability studies, and enzyme structure determinations. The impact of this methods therefore spans many areas of science, but here we seek to primarily develop the MRI context.