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Improving Diagnosis by Fast Field-Cycling MRI

Periodic Reporting for period 3 - IDentIFY (Improving Diagnosis by Fast Field-Cycling MRI)

Reporting period: 2019-01-01 to 2019-12-31

Much of the power of MRI arises from disease-induced changes in the nuclear magnetic resonance (NMR) "T1 relaxation time". But subtle or early changes may not be visible.
Before IDentIFY, experiments on tissue samples showed that the way in which T1 changes with magnetic field strength (“T1-dispersion”) could be a disease marker, but this is invisible to conventional MRI scanners. T1-dispersion is measured using “Fast Field-Cycling” (FFC), by altering the magnetic field while scanning. Despite its use in small-sample laboratory studies for decades, FFC has only recently been applied to MRI, with prototype FFC-MRI scanners built by Partner 1.
Promising results had been obtained before this project, showing the diagnostic potential of FFC-MRI. Nevertheless, significant hurdles remained to be overcome before FFC-MRI could be adopted clinically.
The objectives were as follows:
1. Improve FFC-MRI technology. Precise control of the scanner’s magnetic field was needed, and was addressed by developing improved sensors, control systems, and electronics. Magnetic fields around a scanner can have adverse effects on measurements; the project resulted in better ways of measuring and correcting for environmental fields.
2. Improve our understanding of the new information generated by FFC. A theoretical framework was developed, in order to elucidate the link between disease-induced tissue modification and the T1-dispersion shape. Software was developed to extract disease markers from FFC data and from FFC-MRI images. Methods of presenting the T1-dispersion-derived information to end-users were investigated.
3. Development of contrast agents, tailored for FFC-MRI. FFC-MRI might be enhanced through the injection of a contrast agent, to emphasise differences in T1-dispersion curves between normal and diseased tissues. The project investigated whether already-approved contrast agents had the necessary characteristics; IDentIFY also studied new classes of substance as 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 was aimed at demonstrating the effectiveness of FFC-MRI for discriminating between normal and diseased tissues, and to provide comparisons between FFC-MRI and standard MRI. Tissue samples were obtained from tissue banks and during surgical procedures. FFC-MRI scanning on patients was carried out at the University of Aberdeen. Procedures took place only after ethical approval had been obtained and with the consent of patients.
Conclusions of the project (the “action”): The project has brought FFC-MRI closer to the stage where it can be considered as a valuable diagnostic tool for use, ultimately, in research centres and hospitals. This has occurred because (a) the FFC technology is more reliable and less susceptible to external interference; (b) a better understanding of the FFC “signals” and methods of data and image analysis has enabled FFC markers of disease to be identified and exploited; (c) studies in the partner laboratories have demonstrated the effectiveness of FFC in measuring disease-related changes in human tissue samples and in images of patients using FFC-MRI.
Work was done to improve magnetic field stability in FFC. A new magnetic field sensor (NMR type) and a new electric current sensor were built and tested, for use in a magnet-control feedback loop. Computer simulations allowed optimisation of the control parameters on a “virtual instrument”.
A new FFC-NMR relaxometer prototype was constructed, incorporating a new type of power supply. The relaxometer is compatible with new methods for automatic correction of environmental magnetic fields, developed during the project. Existing relaxometers within the consortium were upgraded to facilitate cross-partner working; one was 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 was developed for accurate measurement of environmental magnetic fields and their cancellation. Magnetic field maps, aided by a mathematical model, resulted in optimised methods to cancel unwanted environmental fields.
Control hardware and software were 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 electronics. Methods to speed up FFC-MRI were implemented, allowing a patient to be scanned in 45 minutes.
Theoretical models of low-field relaxation were developed to predict the shapes of dispersion curves, under different conditions. Computer programs were written for the analysis of dispersion data; this approach generated reliable, quantitative “biomarkers” of disease.
Work was carried out to investigate the potential of contrast agents for FFC-MRI, exploiting the 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 was investigated. Studies on model tumours have investigated how low-field dispersion measurements of existing agents, already approved for human use, are altered by the tumour environment.
Studies investigated the ability of FFC-NMR to differentiate between normal and diseased tissues; many diseased tissues (e.g. brain cancers and colorectal cancers) exhibit significantly different dispersion curves than their normal counterparts.
Studies of patients took place, representing the world's first-ever clinical use of FFC-MRI, using the prototype scanner in Partner 1. These studies showed that stroke-affected brain tissue can be seen very clearly by FFC-MRI, when the scanner is switched to its lowest magnetic field (barely higher than the Earth's field). Studies of patients with brain cancer and patients with breast cancer have also been carried out.
The project has resulted in 22 peer-reviewed publications, 3 book chapters and 86 presentations at scientific conferences. Two one-day Symposia on FFC-MRI were organised and a wide range of public-engagement activities took place during IDentIFY. All outputs from the project are listed at http://www.identify-project.eu/.
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 has been employed in new data- and image-analysis environments.
A wide range of tissues has been studied by FFC-NMR relaxometry, confirming that disease-induced changes in tissues are reflected in the measured T1-dispersion curves. This provides 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, for the medical imaging industry and for employers.
Prototype human-sized FFC-MRI scanner at the Partner 1 laboratory