UK Renal Imaging Network (UKRIN): Enabling clinical translation of functional MRI for kidney disease

The global burden of kidney disease is significant; 10% of the world's population have chronic kidney disease (CKD). Causes of CKD include acute kidney Injury (AKI), diabetes and high blood pressure. Other risk factors include cardiovascular disease and obesity. CKD confers a large increase in cardiovascular events, cardiovascular mortality or end-stage kidney disease, with an annual estimated cost in England of >£1.5 billion. Treatment options are limited by a lack of validated methods for patient stratification and assessment of response to therapy. Magnetic Resonance Imaging (MRI) has emerged as a promising new approach for assessing, monitoring and managing kidney disease. However, the potential of MRI kidney biomarkers is underestimated and unexplored in both clinical practice and research. Numerous research studies report small numbers of patients and use different MRI methods, making results from different studies difficult to compare or extrapolate into clinical practice.
We propose to work together to tackle the challenges associated with moving renal MRI to clinical use. This Partnership proposal will capitalise on the UK Renal Imaging Network (UKRIN), an existing network of 13 UK renal MRI sites. Through the Partnership grant we aim to develop a renal MRI platform, share expertise, build capacity, and develop a harmonized approach thus enabling data sharing, and accelerating the clinical potential of renal MRI. This will facilitate larger cohort studies, providing a unique contribution to the understanding and treatment of kidney disease. This is a global 1st initiative bringing together patients, leading scientists and clinical researchers, other multidisciplinary experts, Kidney Research UK and industry scanner manufacturers. The Partnership will consolidate the UK's global pioneering role in this field; enable clinical translation of this novel technology; and continue to accelerate new technological advances. This will serve as a platform for future collaborative research programmes, including multi-site clinical studies.
Our specific objectives for the three-year Partnership grant period are to develop a platform to become a national standard for renal MRI:
1) We will share experience in renal MRI that has built up across UK sites.
2) We will organise a series of renal MRI Symposia and Workshops.
3) We will produce a set of optimised scanning protocols for renal imaging that can be used by all the UK sites. These will include: (i) relatively straightforward structural and functional renal imaging methods that can applied quickly; (ii) more advanced cutting-edge methods that require additional development work; (iii) standardised quality assurance protocols that can be used to maintain a high level of scanner performance at all sites.
4) We will develop a national image sharing and analysis platform to develop the capability to share and aggregate data acquired across UKRIN sites, and to develop analysis pipelines that are optimised for renal MRI data. This will follow the template currently employed by the Dementias Platform UK (DPUK), using the open source XNAT informatics software. We will also facilitate links with the UK Renal Registry.
This proposal will establish a standard of renal MRI measures by creating and validating a platform to form the national guide. These new functional non-invasive renal MRI methods will allow various different renal aspects of each kidney to be assessed independently, with results reflecting instantaneous kidney function, rather than the metabolic consequences over time. Imaging the kidney using MRI methods has the potential to improve the management of kidney patients through better diagnosis, better assessment of prognosis and the effect of therapy, and accelerating new drug discovery. The Partnership grant will address key areas of governance, patient engagement, business development and exploitation all supported by an integrated communications plan.

We propose an MRC Partnership to build on the UK's pioneering role in the development and standardisation of renal MRI. This will bring together MR physicists, radiologists, and nephrologists from major UK renal MRI research centres to create a platform for sharing expertise, building capacity, resolving challenges in data acquisition and analysis, and providing support for data sharing. Once established, this will provide technical support and shared databases of normative data to enable clinical validation through multi-centre studies.
The Partnership Grant will allow us to:
1) Build capacity and enhance the UK's expertise in renal MRI, sharing expertise across the three main MR vendor platforms, and delivering a programme of network activities including Workshops and Symposia.
2) Produce a series of optimised and harmonized protocols for renal MRI comprising: (i) "standard" sequences (BOLD R2*, diffusion-weighted imaging, T1 and T2-weighted images, angiography and phase contrast MRI, T1 mapping); (ii) more advanced protocols (such as arterial spin labelling and magnetic resonance elastography); (iii) quality control protocols.
3a) Set up a Data Analysis Centre (DAC) to develop and validate a software framework for processing multi-parametric renal MRI data. This will support future clinical studies using renal MRI in study design and setup, and image quality assurance and processing.
3b) Develop a centralised platform for data sharing and analysis using the framework of the Dementias Platform UK (DPUK) national XNAT-based informatics platform.
4) Demonstrate the Partnership capability by performing a "travelling kidney" study and collecting a normative data set of subjects, providing data for testing within- and between-site reproducibility across the three MR vendors.
5) Ensure that the UK MR research community can exploit investment in renal MRI and provide sustainability through the establishment of the UKRIN Strategy Board.

The MRC has recently invested heavily in MR equipment through the Clinical Research Infrastructure Initiative (CRII) and the Advanced Imaging Centre (AIC) in Leeds, and analysis hubs such as the Leeds MRC Medical Bioinformatics Centre, and the MRC's Dementia Platform UK (DPUK) Imaging Informatics initiative. This Partnership grant will extend the capabilities of these infrastructures in renal MRI, building on the UK's lead in this area to form a sustainable platform for future work. This will impact positively on the UK's medical technology, through working with the MR vendors, pharmaceutical sectors, ultimately leading to benefits for health and well-being.

This Partnership will benefit the following groups:

Project Staff: It will provide training/experience in renal MRI across MR vendor platforms. This will increase employability of the PDRAs, and increase the profile of UK research.

Renal medicine: Through workshops and Symposia we will share expertise across the UKRIN sites, the wider renal community, and specialists in other disciplines such as histopathology and cardiology. This will highlight the potential of renal MRI to clinicians who currently have no expertise in this area. UKRIN collaborates with the UKKRC's Clinical Study Groups (CSGs), ensuring accessibility across the nephrology sub-specialities. Clinicians are members of the Partnership Steering Committee to ensure the needs of the clinical community are met. Results of this Partnership will be published widely on the dedicated website and through specialist and general interest journals.

General Public: We are committed to public engagement as evidenced by the involvement in a wide range of outreach activities by the UKRIN sites. KRUK have many years of experience communicating science to lay groups including patients and patient engagement teams, carers and the general public, and through KRUK's integral role in the Partnership we will widely disseminate our findings. We will disseminate to the general public through a website hosted by KRUK, and via social media (Twitter/Facebook). Patients are also involved as key partners in the development and planning for future research that build on the outputs from this Partnership. KRUK also has an active public affairs programme engaging with parliamentarians and other key healthcare policy influencers.

Diagnostics and pharmaceutical industry: An important outcome of the Partnership is the establishment of a platform providing image acquisition and analysis support for future large, cross-site, clinical trials which will have significant impact upon human health and the pharmaceutical industry. Multi-site studies involving large cohorts are recognized as being essential if meaningful inferences are to be made at a population level. However there are significant barriers to the successful implementation of such studies. By focusing on delivering a portfolio of common protocols, coupled with the tools for data sharing and management, we will produce the infrastructure needed to enable such large scale studies to succeed.

NHS and patients: The Partnership will lead to longer-term potential benefits on patient outcome and sustainability of health care. Improved risk stratification will facilitate targeting of interventions to patients at risk, thereby reducing the proportion requiring renal replacement therapy, the most expensive component of CKD treatment. In addition, stratification of low risk patients will spare them the burden and cost of unnecessary treatment. Improved understanding of pathophysiological changes will generate insights which may lead to new treatments which benefit patients in the long term. Forming partnerships with pharmaceutical industries will help in the evaluation and development of new drugs for kidney disease, potentially allowing drugs to be evaluated in fewer participants and over shorter observation periods, resulting in substantial cost savings.