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This Basic Technology will literally represent a step-change in the way in which magnetic resonance imaging (MRI) is implemented, resulting in new, information-rich contrast mechanisms becoming available for the first time. The proposed work is cross-disciplinary, bringing together physicists/engineers, chemists, biologists and medical scientists. We will break the first law of magnetic resonance imaging (MRI) - that the applied magnetic field must be held constant during image acquisition. By doing so we will gain access to radically new types of image contrast, with the potential to gain insight into disease processes at the molecular level. This new Basic Technology is called Fast Field-Cycled MRI (FFC-MRI).Since its inception in the 1970s, enormous advances have been made in every aspect of MRI, including hardware, techniques and applications. There has been a trend towards developing and using MRI at ever-increasing magnetic fields: 1.5 tesla MRI systems are now the norm, and whole-body systems up to 7 tesla are being installed in research centres. Existing MRI systems operate at one, and only one magnetic field strength, and the normal imaging process demands that the magnetic field be absolutely stable over time. The very fact that the field is fixed, however, denies access to a truly fundamental contrast mechanism, namely the dependence of the sample's (or patient's) nuclear magnetic resonance (NMR) relaxation times on the applied magnetic field. (In MRI, it is differences in the relaxation times that provide contrast between tissue types, and between normal and diseased tissue.) Any conventional MRI system can only provide information about the sample's relaxation times at one, fixed, magnetic field. In FFC-MRI the scanner's magnet will be switched rapidly (hence the Fast in FFC-MRI) between levels during the collection of an image, allowing the NMR-sensitive nuclei to evolve at the chosen magnetic field (or at a range of field values). The magnetic field will always be returned to a fixed magnetic field, however, in order to read out the NMR signals. In this way, the image contrast (arising from relaxation time differences) will be that appropriate to the chosen field, rather than to the readout magnetic field.By obtaining FFC-MR images at a range of switched fields, it will be possible to optimise the endogenous contrast contained in the variation of relaxation times with magnetic field strength - something that is completely hidden from normal, fixed-field MRI, no matter what that field strength is. Another contrast mechanism that is accessible to FFC-MRI (but inaccessible to standard MRI) is an effect called the quadrupole-dip , which provides quantitative information related specifically to protein concentration and dynamics. The ubiquity of proteins in the body, and their role in disease, makes the latter particularly attractive.FFC-MRI also offers radically new possibilities for exogenous contrast, via injected contrast agents. Another vital unifying strand of the new Basic Technology is the design of contrast agents that are precisely tailored for the new FFC-MRI instruments, in order to improve sensitivity and specificity by at least an order of magnitude compared to conventional contrast-enhanced MRI. The improved sensitivity and specificity will enable molecular imaging applications to be developed.In order to develop the basic technology of FFC-MRI, we will work closely with our Collaborators in the areas of magnets, MRI control systems and contrast agents. So that we can demonstrate the utility of FFC-MRI, we will explore applications that are likely to benefit from the method, from basic bio-medical science through sports science to potential clinical applications, as well as other areas, including the food industry. This proposal will create the potential to revolutionise the way that MRI is carried out, in the bio-medical research laboratory, in the clinic, and elsewhere.
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