Dementias Platform UK MR-PET Partnership

Imaging has become the most informative technology for our understanding and diagnosis of brain changes that underlie and likely cause dementia. It has also undergone very rapid technological progress, making it possible to obtain scans within about 30 min with little discomfort for patients and volunteers in dementia research. However, in order to obtain complete information up to now two different types of scans, magnetic resonance imaging (MRI) and positron emission tomography (PET), are required for instance in clinical trials of new drugs against Alzheimer's disease and in research studies to ultimately prevent dementia. Very recent new technology now allows acquiring both, MRI and PET, simultaneously in a single scanning session in one hybrid MR-PET scanner. The dementias platform UK (DPUK) has been successful in acquiring a capital grant to build a unique national dementia imaging network based on seven closely collaborating MR-PET scanners located at universities across the UK. This partnership grant will ensure that these centres work closely together to ensure that scans are being recorded and analysed everywhere to the same highest standards. Thus, the network will provide a unique and world-leading homogeneous platform for dementia research in much larger cohorts of patients and volunteers than possible until now, enabling clinical trials and research studies at an unprecedented scale.

We are seeking support for four task forces in this grant. The first task force will ensure effective communication between all partners and DPUK, but also beyond to engage with all relevant stakeholders, including patient advocacy and support groups, research organisations, scientific societies, and pharmaceutical industry. The second task force will ensure proper staff training. This is particularly relevant because traditionally training for technical MRI and PET staff has been organised in separate curricula with little interaction, and also because there are two different manufactures of MR-PET scanners with their own technical specifications and training schedules. These borders will be overcome by systematic cross training in MRI and PET on MR-PET scanners of both manufacturers. The third task force will perform a pilot study to actually harmonise scanning and image reconstruction across all centres and manufacturers. This will ensure that studies will be conducted by all partners to the same standards. The fourth task force will deal with regulatory aspects which are highly relevant for the further development of PET methods, which depend on new imaging agents (tracers). These new agents will often need to undergo clinical trials, similar to new therapeutic agents, and we envisage that this collaboration would provide an excellent opportunity to facilitate this process.

This partnership grant aims at providing coherent and harmonised operations of the DPUK MR-PET network. It will tightly be managed within the DPUK imaging platform, where it relates primarily to the work package on clinical governance which is led by Prof. Karl Herholz. We will also closely cooperate with the DPUK imaging work packages on radiochemistry, data analysis, and IT. This will be ensured by the composition of the executive team, representation of all disciplines in the steering committee, and by overlap between network task force leadership with the broader work package leadership of the DPUK imaging platform.
The imaging platform will comprise seven MR-PET scanners from two different vendors. Thus, one obvious priority is minimising differences in image quality and quantification, while still maximising the benefits of MR-PET over separate MR and PET scanning. This will be addressed by investigation into the technical characteristics of the scanning and image reconstruction, but also by providing appropriate cross-training of staff, and by devising harmonised SOPs. Initially we will concentrate on harmonising established MR protocols and tracers, in particular to provide the current standard set of imaging biomarkers for dementia research. We will also facilitate implementation of research studies using other tracers and MR techniques.
Four major tasks have been identified to reach these goals. Task force 1 is providing the essential means for effective communication and reporting, task force 2 will organise training, and task force 3 will conduct the harmonisation scanning study. An additional task force (#4) will address governance, regulations and business development to ensure continuous growth of activities for long-term sustainability. Task forces will adhere to a detailed project plan with specific deliverables and annual reporting to the DPUK management board.

DPUK is engaging in a very large population study for dementia research, including patients with dementia but also large cohorts of individuals at risk of dementia. Imaging plays a central role in modern dementia research as MRI and PET not only demonstrate brain atrophy and other changes that are secondary to degeneration, but also can identify functional changes that precede the onset of dementia and may even play a causal role for disease progression. Until recently imaging techniques were technically complicated, expensive and of very limited availability and therefore could not be used in population based dementia research. The installation of 7 dedicated MR-PET scanners across the UK has the potential to induce a huge step change in dementia research by making comprehensive advanced imaging available for this type of research. However, this cannot be realised within a heterogeneous environment where each scanner is operated by local research groups according to local research interests and expertise.

This application is providing the basis for homogeneous scanner operations across all 7 partners. It therefore is an essential first step for delivering the huge advance in dementia research that has been envisaged by installation of these scanners. Ultimately, this will allow unprecedented longitudinal population-based studies in combination which, in combination with genetics, proteomics, and clinical phenotyping, is expected to identify the pathophysiological mechanisms that determine disease initiation and progression. It will also provide a platform for large-scale clinical trials to modify disease progression and ultimately even prevent the progression of mild cognitive deficits to dementia. Thus, its potential impact for improvement of public health and reduction of the huge socio-economic costs associated with dementia can hardly be overestimated.