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Improving Diagnosis by Fast Field-Cycling MRI

Periodic Reporting for period 2 - IDentIFY (Improving Diagnosis by Fast Field-Cycling MRI)

Reporting period: 2017-07-01 to 2018-12-31

"Much of the power of MRI arises from disease-induced changes in the nuclear magnetic resonance (NMR) ""T1 relaxation time"". However, it is not always possible to detect subtle changes in tissues, such as may occur during the early stages of disease, or those occurring at the periphery of an abnormality.
Experiments on tissue samples have indicated that the way in which T1 changes with magnetic field strength (“T1-dispersion”) could be a marker of disease, but this is invisible to conventional MRI scanners because each operates at a fixed field. T1-dispersion is measured using “Fast Field-Cycling” (FFC), which involves altering the magnetic field during the measurements. Despite its use in laboratory studies of small samples (about 1 millilitre) for many years, FFC has only recently been applied to MRI, with prototype human-scale FFC-MRI scanners having been built by Partner 1.
Promising results have been obtained, indicating FFC-MRI as a new diagnostic technique. Nevertheless, there remain significant hurdles to be overcome before FFC-MRI can be adopted as a clinical tool.
The overall objectives are as follows:
1. To improve the technology of FFC-MRI. Precise control of the scanner’s magnetic field is needed, and will be addressed by developing improved sensors, control systems, and electronics. Environmental magnetic fields around a scanner can have adverse effects, even though they may be weak. The project will investigate better ways of measuring environmental fields and correcting them.
2. To improve our understanding of the new information generated by FFC. The link between disease-induced tissue modification and the T1-dispersion shape is poorly understood. A theoretical framework will be developed and then employed within a software tool to extract disease markers from FFC data. Optimum ways will be developed of presenting the T1-dispersion-derived information to end-users.
3. To develop contrast agents, tailored for use with FFC-MRI. The diagnostic potential of FFC-MRI might be enhanced through the injection of a contrast agent, which would need to emphasise differences in T1-dispersion curves between normal and diseased tissues. We will investigate whether existing contrast agents (already approved for human use) have the necessary characteristics and will also study new classes of substance which may ultimately form the basis of improved FFC-MRI contrast agents.
4. To perform tests of FFC on human tissue samples and on small numbers of patients. This will demonstrate the effectiveness of FFC-MRI for discriminating between normal and diseased tissues, as well as providing comparisons between FFC-MRI and standard MRI. Tissue will be obtained from tissue banks and during surgical procedures at two of the project partners. FFC-MRI scanning on patients will be carried out at the University of Aberdeen. Procedures take place only after ethical approval has been obtained and with the consent of patients.
The project will bring FFC-MRI close to the stage where it can be considered as a valuable diagnostic tool for use, ultimately, in research centres and in hospitals. Benefits to society will accrue, due to improved diagnosis leading to better health outcomes, as well as to better understanding by researchers of disease processes. Manufacturers of medical imaging equipment and associated electronic devices will benefit from the ability to produce and market new devices."
Work has been carried out to improve magnetic field stability in FFC. Improved sensors of electric current and magnetic field were needed; a magnetic field sensor (NMR type) and a new current sensor have been built and tested. The outputs of multiple sensors will be combined within a feedback loop. A computer simulation has been developed, so that a “virtual instrument” can be tested prior to physical construction.
A new FFC-NMR relaxometer prototype has been constructed. It includes a new type of power supply, designed in the project. The new relaxometer is amenable to automatic correction of environmental magnetic fields, under development. Existing relaxometers within the consortium have been upgraded to facilitate cross-partner working; one has been fitted with a wide-bore magnet and surface-coil to expand its range of applications.
FFC-MRI needs to operate at extremely low magnetic fields. For operation below the Earth’s magnetic field, instrumentation has been developed for accurate measurement of environmental magnetic fields and their cancellation. Environmental field maps, aided by a mathematical model, have produced optimised methods to cancel unwanted external magnetic fields.
Control hardware and software have been improved so that the prototype FFC-MRI scanner is more flexible, easier to operate, and less prone to image artefacts. Improvements in image quality have arisen from better radiofrequency coils and associated electronics. Methods to speed up FFC-MRI have been implemented, so that a patient-imaging protocol takes only 45 minutes.
Theoretical models of low-field relaxation have been developed which predict the shapes of dispersion curves, under different conditions. User-friendly computer programs have been written for the analysis of dispersion data. Results indicate that this approach can generate reliable “biomarkers” of disease.
Work has been carried out to investigate the potential of contrast agents for FFC-MRI, exploiting the characteristics of dispersion at low field. Studies of new FFC-MRI contrast agents containing manganese were carried out, while the potential of novel agents exploiting quadrupolar relaxation effects has been investigated. Studies on model tumours have investigated how low-field dispersion measurements of existing MRI contrast agents are changed altered by tumour environment.
Studies have investigated the ability of FFC-NMR to differentiate between normal and diseased tissues; many diseased tissues (for example brain cancers) exhibit significantly different dispersion curves than their normal counterparts.
Studies of patients have begun, representing the world's first-ever clinical use of FFC-MRI, using the prototype scanner in Partner 1. This study has shown that the stroke-affected brain tissue can be seen very clearly by FFC-MRI, especially when the scanner is switched to its lowest values of magnetic field (barely higher than the Earth's magnetic field).
Publications arising from the project are listed at http://www.identify-project.eu/publications/
The technology of FFC-MRI has improved, with better magnetic field control and faster image acquisition.
The theory describing nuclear magnetic resonance relaxation phenomena at low field has been developed, and employed in new data-analysis environments.
A range of tissues has been studied by FFC-NMR relaxometry. It has been shown that disease-induced changes in tissues are reflected in the measured T1-dispersion curves, providing promise for the diagnostic potential of FFC-MRI.
FFC-MRI has been used to study disease-affected tissue in living patients, for the first time.
The new medical scanning technology will provide enhanced, non-invasive diagnosis. FFC-MRI will lead to better staging of disease and improved monitoring of treatment, enhancing personalised medicine. There will be positive impacts on treatment outcomes and on the wellbeing of individual patients, with economic benefits for individuals, for hospitals and for employers.