Zero-Field MRI to Enhance Diagnosis of Neurodegeneration

Neurodegenerative diseases present major public health concerns, with over 0.85m cases in the UK (expected to double by 2040 due to an ageing population) at an annual cost to the economy of >£23bn. There is an urgent need for neuroprotective agents that could be used early to slow disease progression, but none currently exist. The major barrier is the difficulty of early diagnosis (when agents are most likely to be effective) and the lack of robust biomarkers (to measure drug efficacy). Thus the prospect of non-invasive early diagnosis and therapy monitoring using new medical imaging technologies is compelling.

In this project we plan to develop a radically new diagnostic imaging method, called Zero-Field (ZF) MRI. Due to its ability to use interactions that are completely masked at the high magnetic fields used by normal MRI scanners, ZF-MRI should have exquisite sensitivity to molecular changes in brain tissue, bringing the possibility of early diagnosis. The challenge is to develop imaging technology that will enable pre-symptomatic diagnosis of neurodegenerative diseases associated with abnormal protein aggregation, particularly Alzheimer's and Parkinson's diseases.

In our recent research we have developed technology and methods of a new type of MRI called Fast Field-Cycling MRI (FFC-MRI). In this technique (which requires very special magnets, power supplies and control electronics) the magnetic field is switched rapidly between levels, always returning to the same field for signal detection. In ZF-MRI the magnetic field will be held at zero for part of the procedure, during which time the special zero-field interactions will take place. In this manner, the resulting images of the brain will contain information about brain structure and function at the molecular and cellular levels, which has hitherto been invisible to MRI.

Work will be carried out using an existing human-sized FFC-MRI scanner that we have built in our laboratories. In order to employ it for ZF-MRI we will devise methods to cancel the Earth's field within the volume of the scanner, using cancellation coils along with the scanner's shim coils. New techniques will be developed to measure and minimise the residual magnetic field. Several magnetic resonance phenomena are known to exist at zero field and we will develop methods to exploit them for enhanced diagnosis. They include, for example, the tiny magnetic fields generated by atoms within protein molecules. These magnetic fields are insignificant compared to the very strong magnetic fields used in conventional hospital MRI scanners. However, by operating at zero magnetic field (for part of the scanning procedure) ZF-MRI will be exceptionally sensitive to changes in these magnetic fields, and hence to the tissue structure and content.

Tests of ZF-MRI will be carried out using tissue-mimicking test samples made of gels and other chemicals, then protein aggregates of the kind we expect to encounter in patients' brains, followed by pre-clinical studies. This will allow us to determine the sensitivity of ZF-MRI to subtle changes in tissue composition and molecular dynamics. Later in the project we will scan patients (subject to ethical approval) who are known to have neurodegenerative conditions, together with normal volunteers, and will compare the results obtained from ZF-MRI with brain scans obtained on our 3-tesla conventional MRI scanner.

Who will benefit from this research?
* Patients with a range of neurodegenerative medical conditions.
* Hospital radiology departments and neurology departments.
* Universities, research institutes and hospitals conducting research into MRI, neuroradiology and neurodegenerative disease.
* Pharmaceutical companies developing new drugs for the treatment of neurodegenerative conditions.
* Large medical imaging companies which manufacture and supply MRI systems.
* Smaller companies (SMEs) supplying components to medical imaging companies.
* Research staff working on the project.

How will the beneficiaries benefit from this research?
The research has the potential to detect changes in the brain arising from neurodegenerative conditions such as Alzheimer's and Parkinson's diseases, and to do so at a significantly earlier stage of the disease than is possible with present diagnostic imaging technology. Patients will benefit from earlier diagnosis, leading to earlier and more effective treatment. In this way the research will contribute to the health and wellbeing of the general population.
Hospitals will benefit from the ability to diagnose and treat neurodegenerative conditions earlier than before.
Universities and research institutes will benefit from having at their disposal a new method of detecting changes in the brain caused by neurodegenerative disease. This will benefit research into these medical conditions.
Pharmaceutical companies will benefit from the ability to measure biomarkers of neurodegenerative disease, in turn informing them about the effectiveness of neuroprotective agents, or of drugs to halt or reverse neurodegeneration.
Manufacturers of MRI systems will benefit from increased sales of MRI systems. Companies could manufacture dedicated ZF-MRI scanners, and there is also the potential for them to produce add-on hardware to enable ZF-MRI to be implemented on some existing MRI scanners, which are capable of being upgraded by the add-on field-cycling hardware. Companies supplying ZF-MRI scanners would benefit from the increased exposure in the market that association with the novel technique will bring.
Research staff working on the project will benefit from working with novel diagnostic technology, and from direct contacts with clinical and biomedical researchers. The project will enhance research staff members' knowledge, and will make them more employable, in universities, research institutes, hospitals and industry.

When will the benefits arise?
The research staff will benefit throughout the period of the project, and after it has finished due to the extra skills and knowledge gained. MRI manufacturers will benefit as soon as they are able to bring the product to market, typically 2-5 years after the project end. Hospitals and other users of the technology will benefit once the ZF-MRI technology is installed in their institute, 2-5 years after completion of the project. Patients will start to benefit as soon as the technology is installed in hospitals and research institutes, and the benefit to these communities will increase as the number of ZF-MRI scanners increases over the following 5-10 years. With more ZF-MRI scanners in use, knowledge about their benefits will spread among the potential user community, further increasing the number of units sold, to the benefit of manufacturers, users and society at large.