Patient-specific MRI sequence design using Direct Signal Control

Lead Research Organisation: King's College London
Department Name: Imaging & Biomedical Engineering


Magnetic Resonance Imaging is a powerful and versatile means for visualizing the inner workings of the human body, for clinical diagnosis or for medical research. Image quality from MRI has dramatically improved through the years and continues to do so as technology and the methods we use are refined. One avenue for this improvement has been to develop scanners that are based on stronger magnets - the signal strength in our images increases with the magnetic field used and this has lead to a move from scanners with 1.5T magnets to 3T with some research systems using 7T magnets and beyond. The use of such strong magnetic fields allows us to make images with very high resolution and to gain functional information, such as brain activation much more accurately. Unfortunately high field strength magnets do have a disadvantage: MRI uses rapidly oscillating magnetic fields to produce signals from within the patient, which are then turned into images. The frequency of oscillation required is proportional to the magnetic field strength used, and so strong magnets require high frequency fields. Because the oscillation frequency is up in the radio frequency range, these are known as radio frequency or RF fields. The problem is that high frequency RF fields do not penetrate the human body in a uniform manner - they create strong and weak spots causing bright and dark regions in the images produced, making them hard to interpret. This effect is difficult to overcome because the location and strength of the bright and dark patches varies a lot depending on the size and composition (fat-muscle-organ balance) of the person placed within the scanner.

Parallel transmission technology has been developed as a way of overcoming these problems. This involves modifying the way in which the scanner produces RF fields so that rather than having a single source, it uses multiple sources in parallel (hence 'parallel transmission') and the aim is to produce interference that leads to images with uniform properties. The parallel sources give the scanner the ability to adapt itself to the specific person placed within it. Parallel transmission is a new concept and only a few research MRI systems around the world have the capacity to do this with a large number of parallel sources. These systems offer huge flexibility and can create highly controllable RF field patterns that vary in complex ways. So far this flexibility has been mostly used to try to tailor the field patterns to make them as uniform as possible within the body, with limited success.

In this project we will take an alternative route and investigate methods for producing images with desired properties by focusing on how applied fields interact with the subject during the entire image formation process. MRI is such a successful technique because it is possible to generate images with a huge variety of different contrast properties by using different sequences of RF pulses and magnetic field gradients; these are known as 'pulse sequences'. The subject of the proposed research is the idea that entire pulse sequences should be adapted on a patient specific basis to achieve optimal image quality for each specific subject. This is fundamental change in the way in which MRI examinations are usually carried out, and will require considerable mathematical and computational methods to allow it to be feasible in practice. The research will be undertaken primarily at St. Thomas' Hospital where a prototype parallel transmission MRI scanner has recently been installed. Some aspects will also be carried out in conjunction with researchers at Utrecht University at their 7T MRI facility. Early pilot work has proven to be successful leading to new ideas about how to work with parallel transmission systems. In this project we aim to develop these ideas to create comprehensive methods and to demonstrate the resulting improvements across a range of imaging applications.

Planned Impact

Parallel transmission is a new development that marks a serious departure in the way in which MRI machines operate, with the potential to lead to new imaging capabilities and large improvements in current techniques. The United Kingdom has historically played a key role in the development of MRI and the proposed research, which aims to harness this new technological benefit, will contribute to maintaining this national position.

The proposed research will be of relevance to a wide range of potential beneficiaries. Most directly there are range of academic beneficiaries, as outlined more clearly in the eponymous section of this proposal. The project aims to develop new methods for improving the performance of cutting edge magnetic resonance imaging using parallel transmission, and will thus be relevant to others conducting research with similar technology. Indirectly it will also benefit clinical or biological research scientists using such technology in their work. These benefits could be expected to be realized in a relatively short timescale, perhaps concurrently or within 3 years of the projects' end. In addition to immediate scientific benefits, the project will result in the training of a postdoctoral research fellow with specialized skills for working at the forefront of imaging research, which will benefit the community as a whole. The benefits of this training may extend beyond the immediate scope of high field MRI, since the numerical and analytic skills, and the experience of working with specialized and complex hardware, are transferable to other academic or industrial pursuits.

The rapid development of magnetic resonance imaging has been driven by both academia and industry. The ideas and intellectual property generated by this project will be of interest to the commercial sector. MRI manufacturers could benefit from this work; Philips Healthcare have expressed their support for the project but it is also likely that benefits could be spread to a wider range of third party manufacturers who build RF coils for use with MRI. We have already been in discussion with one such (UK based) company over designing and building a 'next generation' coil for this type of work. While benefiting industry may be seen as a goal in itself, industrial uptake of new methods generated by academia is an important pathway for propagating new developments to the wider public. Improvements in diagnostic medical imaging technology are ultimately intended to improve the health of the nation. For the proposed work, current patients will benefit via improved diagnostic quality of improved scanning methods, and future patients will also benefit indirectly from the improved understanding that will be the result of medical research at high field MRI facilities using improved techniques. It could be expected that new scanning methods will be taken up by manufacturers within a 5-year time-scale and that these could then start to benefit patients scanned at high field MRI facilities thereafter. The current prevailing technical issues with ultra high field strength MRI mean that it is used almost exclusively for research only. The considerable advantages of high resolution and stronger contrast are thus unavailable to wider clinical patient groups. If successful, parallel transmission MRI using the direct signal control methodology outlined in this proposal could lead to large improvements in image quality and enable use by a wider range of beneficiaries.


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Description The project proposed to further develop methods for adapting MRI imaging protocols to given patients, in order to maximise image quality and reliability. We have now developed new mathematical ways of approaching this adaptation process that make the calculations much faster - the result is that the process could now be incorporated into the software that controls MRI scanners. Subsequent work has also shown that it is possible to use these methods to make whole-brain 3D imaging possible on new 7T MRI scanners - although these scanners offer excellent resolution and image contrast, they do otherwise suffer from areas of low signal so struggle to image the whole brain in one go. This innovation is of increasing value particularly to the UK neuroimaging community with the recent proliferation of sites that have been funded to purchase 7T MRI systems.

An unexpected offshoot of this work is an application that improves efficiency of cardiac MRI. This has the potential to become more widely useful by reducing scan times.
Exploitation Route MRI scanner manufacturers or third party companies could offer this method as a means for optimizing MRI, particularly on high field strength (7T) MRI scanners that can suffer from issues with variable and sub-optimal image quality. Software that allows implementation of all of the innovations produced in this project has been made publicly available, and other researchers can take the findings forwards or use the methods in their own studies.
Sectors Healthcare

Description The grant has funded development of patient-specific sequences for MRI, which are increasingly important for new ultra high field (UHF) MRI scanners. The impact of this work will be felt mainly in the future, however in the last years the number of UHF MRI scanners in the UK has increased sharply, and KCL will imminently be installing one. The methods we have developed will allow for better and more reliable image quality on these systems, which will benefit patient groups as activity on all of the new sites across the UK is increased. Recently (early 2018) we produced high quality whole brain 3D fluid suppressed (FLAIR) MRI images with our collaborators in Utrecht; these images are a promising tool for investigation of multiple sclerosis. Software to use these methods more widely has been developed by spin out company MR Code from the Netherlands and is now installed on multiple sites worldwide. We are also developing a pre-product version with support from Siemens (the market leader with the most installed 7T MRI systems) with the objective of achieving wider uptake of the methods in the coming year. The increased knowledge and experience from this work is contributing to the UK's leadership position in medical imaging technology, which also helps patient groups by ensuring that they have access to cutting edge technology.
First Year Of Impact 2017
Sector Healthcare
Impact Types Societal,Economic

Description Masters course
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Influenced training of practitioners or researchers
Description Collaboration Award in Science
Amount £4,000,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2017 
End 12/2021
Description MRC Development Pathway Funding Scheme
Amount £554,587 (GBP)
Funding ID MR/N027949/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 07/2016 
End 05/2019
Description UMC Utrecht 
Organisation University Medical Center Utrecht (UMC)
Country Netherlands 
Sector Academic/University 
PI Contribution The Utrecht group are a world leading high field MRI site and the RCUK grant funds collaboration with them (via travel funding support). My team has contributed to joint scientific endeavour.
Collaborator Contribution Utrecht have directly supported the work by providing free access to their advanced MRI facilities normally charged at €700/hour (I estimate at least 20 hours of usage in 2015 alone). They have also collaborated scientifically on a core aspect of the project, in particular by dedicating the time of a talented mathematician (Alessandro Sbrizzi). Sbrizzi and Malik (the PI of the RCUK grant) jointly developed advanced software tools that will make the application of the direct signal control methods - that are the subject of the grant - accessible and simple to perform for other users. The method has now been published ('Optimal control design of turbo spin-echo sequences with applications to parallel-transmit systems') and the software is available on our software dissemination website: This is a key deliverable from the project. UMC have expanded the collaboration by sending a student to work with us for 3 months in 2015, and we are now also collaborating on joint technology development programme that is directly funded by an MRC grant.
Impact Publication: Optimal control design of turbo spin-echo sequences with applications to parallel-transmit systems, doi:10.1002/mrm.26084 Software output:
Start Year 2012
Title Publically available Research Software Resource 
Description An issue in the MRI physics field is that new ideas are often described in publications at a highly technical level, meaning that there is a high cost to other groups wishing to replicate results or take research forwards. This new project - - is aimed to remove this barrier. All output from my group is now provided in open source form with detailed usage instructions, and will be linked from all new publications. 
Type Of Technology Software 
Year Produced 2015 
Open Source License? Yes  
Impact It is hoped that this will lead to new users and a higher profile of the research. Early impressions from others has been positive and partners in Utrecht have also hosted software on the same platform. This website hosts multiple software projects, new projects are added at the same time as methods are published in order to facilitate uptake by the research community. Software and data associated with all of the publications associated with this project (plus many others) are hosted on this website - it is the primary method that we use for promoting open access to data and software.