Enhancement of Sensitivity in the MRI of Hyperpolarised Noble Gases

Lead Research Organisation: University of Sheffield
Department Name: Radiology

Abstract

MRI of hyperpolarised (HP) noble gases (3He and 129Xe) shows much promise for imaging ventilation in lungs. Laser hyperpolarisation of gas atoms (with optical pumping) provides ample signal for gas MRI in the lungs. The methodological work carried out to date by the applicant with 3He, has established the University of Sheffield internationally in the area of HP gas MRI. The principle aims of this project, which will be carried out in Sheffield are: 1. Study the effects of magnetic field strength in HP gas MRI. This will make use of a dedicated lung imaging system operating at 0.2 T designed to image the lungs in the upright position, the 1.5 T whole body MRI scanner currently in use and a new 3 T whole body MRI system. The work would be of benefit to the international HP gas MRI research community and MR manufacturers in helping determine the optimum configuration of gas and field strength for performing this exciting new method of functional lung imaging. 2. Development of pulse sequences and radio frequency hardware for parallel imaging with HP gases. These methods will help reduce the amounts of gas needed for imaging through optimisation of polarisation usage. This is important if HP gas MRI is to become widely used in clinical practice since these gases are expensive limited resources. 3. Extend capability to the MRI of HP 129Xe and perform experiments to investigate the NMR physics of the two gases in the lung and to determine their potential sensitivity for functional lung imaging. The ultimate goal is to develop the technology to quantify lung function with as high spatial resolution as possible without the use of harmful ionising radiation as is currently used in the clinical standard lung imaging modalities / CT and nuclear scintigraphy. The potential applications in biomedicine, physical science and industrial research are numerous. The project will involve multiple collaborations with world leqading laboratories and industry working in the area and will help strengthen existing international inter-disciplinary collaborations [www.phil.ens.fr]. This prestigous award would allow the applicant to focus on his area of research expertise and will help consolidate Sheffield and the UK at the forefront of international research in this field..

Publications

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De Zanche N (2008) Asymmetric quadrature split birdcage coil for hyperpolarized 3He lung MRI at 1.5T. in Magnetic resonance in medicine

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Deppe MH (2009) Susceptibility effects in hyperpolarized (3)He lung MRI at 1.5T and 3T. in Journal of magnetic resonance imaging : JMRI

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Parnell S (2009) Study of spin-exchange optically pumped 3He cells with high polarisation and long lifetimes in Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment

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Ireland RH (2010) Detection of radiation-induced lung injury in non-small cell lung cancer patients using hyperpolarized helium-3 magnetic resonance imaging. in Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

 
Description Design, construction and evaluation of novel RF coils for transmit-receive and receiver arrays for 3He and 129Xe in the lungs. Some of this work was done with international academic and industrial collaborators. The designs represent state of the art for imaging inhaled gases in the lungs MRM in terms of performance for transmit homogeneity and receive sensitivity. The theory and designs have been published in three peer-reviewed articles and have been copied by various other parties.

The first B0 field strength comparisons of 3He and 129Xe MRI at field strengths of 1.5T and 3T. We observed comparable SNR at 1.5T and 3T for 3He lung MRI with slightly higher SNR (25%) for 129Xe lung MRI at 3T. Development of rapid acquisition strategies using Compressed Sensing and parallel imaging methods for rapid imaging of inhaled hyperpolarised gases.

Design, construction, testing and regulatory approval of a custom laser polariser for in house 3He and 129Xe MRI production. The high power tuneable external cavity laser design developed has been extremely effective for spin exchange optical pumping of Rb for 129Xe lung MRI. With this polariser 129Xe lung images were obtained with a quality comparable to 3He lung MRI with just 300ml of inhaled 129Xe.

Measuring and modelling the lung diffusion signal; influenced by effects of diffusion, gas mixture, field strength and field gradients. We have developed finite difference models of gas diffusion in the alveolar geometry and experimental validation. We also observed a systematically higher 3He diffusion coefficient at 3T than at 1.5T. these findings challenge existing analytical models of lung gas diffusion in geometrical models of alveolar networks.

Development of novel methods for synchronous detection for the signal from 1H and 3He in the lungs at the same time. the techniques allow simultaneous co-registered acquisition of anatomical and functional data from the two nuclei.

We have made further impact with translational clinical research with the methods developed. My group is the only site in the UK to have conducted HP 3He and 129Xe inhaled gas lung MRI in a clinical setting.
Exploitation Route The work would be of benefit to the international HP gas MRI research community and MR manufacturers in helping determine the optimum configuration of gas and field strength.

Development of pulse sequences and radio frequency hardware for parallel imaging (PI). These methods will help reduce the amounts of gas needed for imaging through optimisation of polarisation usage.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description Understanding of the fundamental science of HP gas MRI is vital if the technique is to make the transition from scientific research method to accepted clinical imaging modality in the future. This project will help European researchers stay at the forefront of implementing this transition. Applications in physical science: There is much potential for NMR polarisation transfer experiments to probe chemical reactions and metabolic pathways. The ability to perform 129Xe NMR would open up new avenues of scientific collaboration for the group in tandem with the bio-medical applications that will be ongoing. The proposed methods of optimised polarisation usage will be of interest to groups in a diverse range of fields that use MRI to image hyperpolarised gases, these include solid state analysis, surface science, porous media, geology/soil science, plant science, gas flow and MR physics and engineering. The applicant has already worked with Fluid Dynamicists who have been modelling the flow of air in the lungs with a view to targeting inhaled drug therapies (www.cophit.co.uk). These applications of the work will be relevant to innovative EU industries, such as aeronautics, oil exploration and pharmaceuticals. Furthermore, the MR engineering focus of the project is technically challenging and the novel ideas proposed will be of interest to this research community and the MRI scanner manufacturers and RF coil manufacturers. Bio-medical applications: Lung diseases are of growing concern. Not only is mortality of importance, but lung diseases are also responsible for considerable morbidity, hospital and treatments costs and affect the quality of life of patients of all ages. HP gas MRI will result in improved assessment of airway anatomy, respiratory mechanics, lung function (oxygen uptake) and ventilation distribution. Specific groups who could benefit from this technology include: Lung cancer, asthma, cystic fibrosis, chronic obstructive pulmonary disease (COPD), emphysema, smokers and industrial diseases. It has been suggested that this new technology could result in earlier diagnosis of emphysema. Furthermore, it is anticipated that this technology will assist surgical decision making in selecting patients for resection of lung cancer and therefore earlier treatment, with an aim of maintaining lung function and quality of life. Long-term follow up studies are viable due to the non-invasive and non-ionising nature of the technique. Health care professionals will benefit from increased information on lung function, thus allowing better founded decision-making regarding therapy. An increased basic knowledge of lung diseases and lung physiology is to be expected, which could lead to advanced drug and therapy development. The NHS will benefit from this work by improving the quality of life and therapeutic options in patients with lung diseases and also patients with systemic diseases that can be treated with novel inhaled medication.
Sector Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Societal

 
Description AirPROM
Amount £1,303,550 (GBP)
Funding ID 128209 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 04/2011 
End 03/2016
 
Description CRUK and EPSRC Cancer Imaging Centre
Amount £166,316 (GBP)
Funding ID C1276/A10345 
Organisation Cancer Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 12/2008 
End 11/2009
 
Description Combination of lung MR imaging with physiological assessment to identify and monitor ventilation heterogeneity in early CF lung disease.
Amount £80,000 (GBP)
Funding ID PJ 555 
Organisation Cystic Fibrosis Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2011 
End 08/2013
 
Description EPSRC (Research Council/Research Council Institute)
Amount £52,420 (GBP)
Funding ID Doctoral Training Award 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 08/2007 
End 09/2010
 
Description EPSRC (research Council/Research Council Institute)
Amount £10,000 (GBP)
Funding ID University of Sheffield Knowledge Trasnfer Grant 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 05/2011 
End 09/2011
 
Description EU Framework 7 (Overseas Institute)
Amount £2,510,841 (GBP)
Funding ID ITN-PEOPLE 
Organisation European Commission 
Department Seventh Framework Programme (FP7)
Sector Public
Country European Union (EU)
Start 11/2010 
End 10/2014
 
Description GE Healthcare UK ltd (Research Institute)
Amount £400,000 (GBP)
Funding ID 3He polariser loan 
Organisation GE Healthcare Limited 
Sector Academic/University
Country United Kingdom
Start 01/2007 
End 01/2011
 
Description GlaxoSmithKline R&D Ltd (Industrial/Commercial)
Amount £272,705 (GBP)
Funding ID Industrial grant for 3He MRI study 
Organisation GlaxoSmithKline (GSK) 
Department Biopharm R&D
Sector Private
Country United Kingdom
Start 07/2010 
End 06/2012
 
Description Medical Research Council (Research Council/Research Council Institute)
Amount £99,893 (GBP)
Funding ID CASE-PhD studentship 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 08/2011 
End 09/2015
 
Description Sheffield Human Magnetic Resonance Facility
Amount £1,000,000 (GBP)
Funding ID 094834 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2011 
End 09/2017
 
Title Portable xenon polariser 
Description Development of a portable xenon polariser that can be taken to novice sites waiting to access the technology for clinical lung imaging 
Type Of Material Improvements to research infrastructure 
Year Produced 2017 
Provided To Others? Yes  
Impact Lung images acquired with xenon at papworth hospital 
 
Description Xenon clinical trails consortium 
Organisation Cincinnati Children's Hospital Medical Center
Department Division of Rheumatology
Country United States 
Sector Hospitals 
PI Contribution Founding member of consortium for development , evaluation and standardisation of imaging methods for outcome measures for clinical trials of respiratory therapeutics
Collaborator Contribution evaluation and standardisation of imaging methods for outcome measures for clinical trials of respiratory therapeutic
Impact none yet
Start Year 2015
 
Description Plenary lecture ISMRM 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Plenary lecture on xenon MRI at ISMRM meeting
Year(s) Of Engagement Activity 2016