Developing a rapid MRI technique for simultaneous structural and functional susceptibility mapping

1) Brief description of the context of the research including potential impact
MRI is indispensable in the diagnosis of neurodegenerative diseases. These are poorly understood while their prevalence and socio-economic burden continue to rise. Structural and functional Magnetic Resonance Imaging (MRI) can provide biomarkers for early diagnosis and potential therapeutic intervention in neurodegenerative diseases. The vision for this research is to optimise MRI methods for simultaneous structural and functional mapping of tissue magnetic susceptibility as quantitative susceptibility mapping (QSM) has shown promise for neuroimaging, revealing changes in brain tissue composition in diseases such as Parkinson's and Alzheimer's disease (AD). Functional QSM may provide even more accurate localisation of brain activity than standard functional MRI but is extremely challenging, requiring specialised physiological noise removal. The rapid, efficient integrated scan developed in this research will be ideal for AD patients. It has the potential to provide a rich set of novel, multimodal MRI contrasts (including conductivity mapping) to allow development of new combined structural and functional biomarkers for early diagnosis of AD and other diseases.

2) Aims and Objectives
To optimise MRI acquisition and QSM processing methods to provide simultaneous structural and functional susceptibility maps in a much shorter time than typical gradient-echo MRI pulse sequences used for QSM. The MRI pulse sequence will be designed so that it can also be used for electrical conductivity mapping.
The specific objectives are to:
- Design and build a phantom (MRI test object) with several compartments with known tissue equivalent magnetic susceptibilities
- Develop and test rapid MRI pulse sequences such as multi-echo echo-planar imaging (ME-EPI) suitable for both structural and functional QSM
- Develop and optimise structural QSM techniques for ME-EPI data acquired in healthy volunteers: this may involve incorporating new regularisation methods for this inverse problem and deep-learning based techniques.
- Develop and test image processing techniques for resting-state functional QSM
- Develop and optimise physiological noise removal methods for functional QSM
The ultimate goal is to apply the optimised sequence and processing techniques in a cohort of early AD patients and age-matched controls to observe whether any differences can be detected between these groups. The optimisation of MRI acquisition pulse sequences and QSM algorithms will be carried out in both phantoms and healthy volunteers. The student will work primarily at the 3 Tesla Prisma MRI system at the National Hospital for Neurology and Neurosurgery. QSM is based on the phase (time-evolution ) of the complex MRI signal so the phase (offset) can be used for conductivitymapping and the magnitude signal (used for conventional imaging) is still available and can be utilised for standard T2*-weighted imaging and standard functional MRI with no extra scan time cost.

3)Novelty of Research Methodology
The student will develop rapid acquisition and processing techniques optimised for both accurate structural and functional QSM. Novel MRI pulse sequences will be developed and tested incorporating new image acceleration techniques. Resting-state functional QSM is extremely challenging so we will develop novel techniques for correction of artifacts due to e.g. motion and /or geometric image distortion as well as physiological noise removal techniques. Novel QSM reconstruction methods / algorithms will be developed to process the resulting images to produce accurate structural and functional susceptibility maps.

4)Alignment to strategies and research areas
Healthcare technologies (aims to accelerate and translate research to healthcare applications). The specific research area is Medical Imaging and potentially artificial intelligence technologies.
5) No collaborators.

The critical mass of scientists and engineers that i4health will produce will ensure the UK's continued standing as a world-leader in medical imaging and healthcare technology research. In addition to continued academic excellence, they will further support a future culture of industry and entrepreneurship in healthcare technologies driven by highly trained engineers with deep understanding of the key factors involved in delivering effective translatable and marketable technology. They will achieve this through high quality engineering and imaging science, a broad view of other relevant technological areas, the ability to pinpoint clinical gaps and needs, consideration of clinical user requirements, and patient considerations. Our graduates will provide the drive, determination and enthusiasm to build future UK industry in this vital area via start-ups and spin-outs adding to the burgeoning community of healthcare-related SMEs in London and the rest of the UK. The training in entrepreneurship, coupled with the vibrant environment we are developing for this topic via unique linkage of Engineering and Medicine at UCL, is specifically designed to foster such outcomes. These same innovative leaders will bolster the UK's presence in medical multinationals - pharmaceutical companies, scanner manufacturers, etc. - and ensure the UK's competitiveness as a location for future R&D and medical engineering. They will also provide an invaluable source of expertise for the future NHS and other healthcare-delivery services enabling rapid translation and uptake of the latest imaging and healthcare technologies at the clinical front line. The ultimate impact will be on people and patients, both in the UK and internationally, who will benefit from the increased knowledge of health and disease, as well as better treatment and healthcare management provided by the future technologies our trainees will produce.

In addition to impact in healthcare research, development, and capability, the CDT will have major impact on the students we will attract and train. We will provide our talented cohorts of students with the skills required to lead academic research in this area, to lead industrial development and to make a significant impact as advocates of the science and engineering of their discipline. The i4health CDT's combination of the highest academic standards of research with excellent in-depth training in core skills will mean that our cohorts of students will be in great demand placing them in a powerful position to sculpt their own careers, have major impact within our discipline, while influencing the international mindset and direction. Strong evidence demonstrates this in our existing cohorts of students through high levels of conference podium talks in the most prestigious venues in our field, conference prizes, high impact publications in both engineering, clinical, and general science journals, as well as post-PhD fellowships and career progression. The content and training innovations we propose in i4health will ensure this continues and expands over the next decade.