A National Centre for Translational Hyperpolarised Magnetic Resonance

Lead Research Organisation: University of Leeds
Department Name: School of Medicine

Abstract

We have developed a new imaging method that has the potential to increase the signal in a magnetic resonance (MR) image by up to 100,000 fold. This method can potentially be used on any hospital MR scanner. Our method works by magnetically labelling substances we seek to probe without affecting their molecular structure and is therefore non-toxic. With this method it is possible to label both drugs and substances that occur naturally in the body, making the method widely applicable. In previously and currently funded work, we are developing the technical aspects of this method and seek to test it in healthy subjects. As part of the current grant application, we will create the infrastructure needed to apply this method in patients within 5 years, focussing on patients with heart disease, cancer and joint disease. Our new method has the potential to speed up and improve MR imaging in a very wide range of diseases and help in the development of new drugs.

Technical Summary

The technique of "spin hyperpolarised" Magnetic Resonance (MR) has the potential to provide a safe and uniquely versatile high-sensitivity tool for medical research, drug discovery and clinical diagnostics. By employing the "Signal Amplification by Reversible Exchange" ("SABRE") method, developed in York, spin hyperpolarisation is delivered in seconds in a continuous low-cost mode to 1H, 31P, 19F, 13C and 15N nuclei, which are ubiquitous to drugs, metabolites and biomarkers, offering distinct advantages over other hyperpolarisation methods. The in vivo detection of these biochemical probes through relatively low-cost, in-vivo molecular MR measurement in conventional hospital scanners can empower both clinical diagnosis and improve treatment in a wide range of conditions. In this joint bid, the Universities of Leeds and York, supported by clinical and industry partners, aim to establish a National Centre for Translational Hyperpolarised Magnetic Resonance to take SABRE hyperpolarisation from bench to bedside within 5 years. Target conditions in the areas of cancer, cardiovascular and musculoskeletal disease, all areas of international excellence in Leeds, will be investigated. Challenges of clinical compound generation and delivery will be addressed with close MHRA oversight and in collaboration with partners working on alternative hyperpolarisation methods, especially Dynamic Nuclear Polarisation, which is already entering clinical trials. Achieving our aim of clinical translation of the SABRE hyperpolarisation method would significantly advance the UK's prominence in exploring new areas in clinical research and address major scientific challenges relating to both the stratification of diseases and experimental studies in man.

Planned Impact

Hyperpolarised MR has unique potential as a new research and clinical diagnostic tool for basic scientific discovery, drug development and targeted therapy, which could deliver the state of the art technology for metabolic imaging and pharmacological studies of the near future.

The SABRE hyperpolarisation method developed here has the capability to revolutionise MR methods through unrivalled gains in sensitivity without the need for modification of the chemical target and should be implementable on all standard clinical scanners operating in the UK.

With SABRE, a very wide range of substances can be polarised, including endogenous biomarkers, role-specific imaging agents and drugs. Our aim is to take this method to first clinical application within 5 years and continue to provide novel agents following the completion of this proposal.

Beneficiaries of this proposal will include researchers in basic science (through NMR applications of SABRE) and clinical science (through MRI application of the method). Within the life-time of this proposal, SABRE will allow them to address major scientific challenges relating to both the stratification of diseases and experimental studies in man.

Our proposal will benefit the pharmaceutical industry within 5-10 years by providing a novel tool for drug development that allows unprecedented and safe (non-ionising) drug discovery and product screening. Patients will benefit from these developments by having access within 5-10 years to a novel method for diagnosis and therapy.

The technology has resulted in new intellectual property protected by patents filed on behalf of UK universities and an independent review has indicated that there are good commercial opportunities that could be taken up by UK and global industrial partners who are part of the application.

Publications

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Iali W (2019) Hyperpolarising Pyruvate through Signal Amplification by Reversible Exchange (SABRE). in Angewandte Chemie (International ed. in English)

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Manoharan A (2019) Catalyst-Substrate Effects on Biocompatible SABRE Hyperpolarization. in Chemphyschem : a European journal of chemical physics and physical chemistry

 
Description BHF Programme grant
Amount £912,067 (GBP)
Funding ID RG/16/1/32092 
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2017 
End 01/2022
 
Description BHF Project grant. Multidimensional diffusion encoding MRI: Novel imaging biomarkers of tissue microstructure in hypertrophic cardiomyopathy
Amount £291,000 (GBP)
Funding ID PG/19/1/34076 
Organisation University of Leeds 
Sector Academic/University
Country United Kingdom
Start 04/2019 
End 04/2022
 
Description Hyperpolarised MRI 
Organisation University of York
Country United Kingdom 
Sector Academic/University 
PI Contribution New collaboration to explore the clinical translation of SABRE Hyperpolarisation in Magnetic Resonance. MRC grant awarded for a new centre across the two universities. We will provide the clinical pull through.
Collaborator Contribution Our partners in York have invented the SABRE method and are carrying out the preclinical development to first in man.
Impact MRC grant awarded.
Start Year 2014
 
Description Quantitative perfusion MRI 
Organisation National Institutes of Health (NIH)
Country United States 
Sector Public 
PI Contribution Evaluate methods in a clinical environment.
Collaborator Contribution Provide software for the quantification of myocardial blood flow.
Impact not yet
Start Year 2016
 
Title SABRE hyperpolarisation 
Description A new method for hyperpolarised MRI developed by collaborators in York. 
Type Diagnostic Tool - Imaging
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2014
Development Status Under active development/distribution
Impact SABRE is expected to have wide research and clinical application. An MRC funded grant supports its clinical translation. 
 
Description Media interviews and online coverage of opening of MRC funded Advanced Imaging Centre 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Several media interviews.
Year(s) Of Engagement Activity 2017