Towards Reliable Diffusion MRI of Moving Organs

Lead Research Organisation: University College London
Department Name: Medical Physics and Biomedical Eng

Abstract

Diffusion Magnetic Resonance Imaging (DMRI) is a clinical imaging technique that has the unique potential to provide clinically-relevant information without the use of ionising radiation or invasive procedures. Although DMRI is often used in brain imaging, it is not currently widely used in other parts of the body because of a series of technical challenges that this grant will address. Our approach will be to describe the challenges in a unified mathematical framework and solve this using new acquisition and image reconstruction techniques. The intensities in diffusion weighted MR images originate from the distances that water molecules can diffuse. These diffusion distances are affected by the local cellular environment and changes in the environment are reflected in images. Diffusion MRI can reveal the directionality of structures, such as the orientation of cardiac muscle cells and changes in cell density and organisation due to cancerous tumours. Cardiac disease and cancer are very significant health issues worldwide for which DMRI may provide key diagnostic or therapeutic information. Cardiac disease is the main cause of death (ca.30% worldwide), and cancer the third (ca.12%) with lung and liver cancer among the most common.The correct functioning of the cardiac muscle is dependent on the complex orientations of the fibres within the heart wall. Being able to image these in-vivo could lead to enhanced diagnosis, treatment and surgery planning for conditions such as heart failure, congenital defects or remodelling following a heart attack. In cancer, DMRI has the potential to improve diagnosis, aid localisation and grading of tumours, support treatment selection, better identify residual and recurrent disease following treatment, and even predict treatment outcome and reduce diagnostic errors. However, DMRI currently has a limited role outside of the brain because of five main technological restrictions; motion of organs, magnetic field variations due to the different magnetic properties of tissues such as fat, bone and air, magnetic field inaccuracies due to inherent MR scanner imperfections, long scan durations and the question of how to interpret the data. Previously we have described the effect of complex non-rigid motion on MR images using a clear mathematical framework and used this to correct for motion. In this grant, we propose to extend these methods to include the challenges limiting DMRI. Taking this general view allows the challenges to be solved collectively rather than sequentially. The techniques will improve the reliability of DMRI and thus widen its clinical uptake. At the same time, the techniques permit more efficient use of scan time, either to encode more information or to shorten scan durations. A general formalism provides a new way of viewing the problem and lends itself to making use of the tools available from other branches of computational mathematics. To support this approach, we will need measurements of magnetic field imperfections caused by MRI scanner inaccuracies. These will be provided by field mapping hardware, which will be installed for the first time in the UK. In addition, novel techniques such as compressed sensing and new models of tissue diffusion will be explored to reduce overall scan times, improve accuracy and provide better interpretation of data.

Publications

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Inati SJ (2017) ISMRM Raw data format: A proposed standard for MRI raw datasets. in Magnetic resonance in medicine

 
Description We developed Magnetic Resonance sequences that can show us the directions of the muscle fibres within the in-vivo heart. The fibre directions are important because these muscle fibres are responsible for the beating of the heart and the pumping of blood around the body and do change in various relevant cardiovascular diseases. We were able to produce 3D visualizations of these cardiac muscle fibres of the in-vivo human heart for the first time.

For the kidney, we modified sequences to achieve high resolution diffusion imaging of the kidney during free breathing. Diffusion imaging in the kidney has the potential to provide information about the microstructural environment and health of the kidney.

With colleagues from the UCL Centre for Medical Image Computing, we developed diffusion sequences that reveal micro structural information about prostate cancer.

As well as developing novel sequences, we have provided insight into how to handle the inherent noise in diffusion scans and built models linking diffusion and other MR properties to histological findings in prostate cancer.

To elucidate microstructural changes in relation to cardiac remodelling in congenital and acquired heart diseases, we translated our imaging tools into the clinical setting and acquired data in patients with systemic right ventricles and in patients with dilated cardiomyopathies in cooperation with cardiology colleagues at KCL. Marked differences of cardiac muscle architecture was detected relative to data from healthy subjects indicating the potential of our method to improve the diagnosis of cardiac patients.

Beyond the visualisation and quantification of cardiac muscle architecture, we also explored the possibility to image tissue perfusion in the heart using diffusion weighted imaging. Such an approach may allow to replace contrast agent based perfusion imaging in the future.

We had access to one of the first commercial field cameras for the highly accurate mapping of magnetic fields within an MRI scanner. Using this we were able to characterise and publish some of the unwanted fields that compromise the accuracy of diffusion imaging. We further showed that knowledge of unwanted fields permits the correction of biases to yield accurate diffusion metrics.

With the availability of detailed information on in-vivo human cardiac muscle architecture, computer-based biomechanical modelling can be taken to the next level. To this end, collaborations with modelling experts at KCL have been initiated. It is expected that this work will lead to new insights regarding the mechanisms of congenital and failing hearts in the future.
Exploitation Route The MR sequences and acquisition strategies that we developed for imaging of the heart and kidney may be taken forward by other academic centres and industry, using the information that we have published. The 'INNOVATE' single centre trial of 360 prostate cancer patients has started using the diffusion imaging scheme we helped to develop. An EU COST action on kidney imaging led by Leeds University has been funded. The distortion reduction methods have formed the basis of a Cancer Research UK grant awarded to UCL, in this case applied to prostate cancer imaging.

Our published findings using the field camera will inform academic and industrial development. Newer generations of the camera are being marketed by Skope Magnetic Resonance Technologies and benefiting researchers worldwide, including in the UK, Oxford and Nottingham Universities.

The measurement and reconstruction methods we developed for cardiac diffusion tensor imaging provide journal publications and datasets that will be available from a public repository. These will inform models of heart structure and function in disease that could provide new insights into cardiac disease mechanisms.
Sectors Healthcare

 
Description This was a highly technical project requiring persistence from skilled people to acquire, process and interpret data. In addition, considerable efforts were spent to translate the imaging technology into the experimental and clinical setting and provide first evidence of the value of diffusion imaging in patients. As a result of the work a number of tangible projects have been launched: * a single centre trial on 20 patients with aortic stenosis and 12 patients with dilated cardiomyopathy has started to reveal structural remodelling of the heart and its recovery after intervention. * a single centre trial of 360 patients on prostate cancer diagnosis was started. This trial uses a diffusion imaging acquisition developed by the PostDoc on this grant. Promising results have been published in Radiology. * we expect the information we published on diffusion imaging from moving kidneys to become part of the normative data on healthy kidneys. * we are due to launch a cardiac atlas that will be available publicly providing data for in-depth analysis of cardiac mechanics. * we have initiated collaborations with cardiac modelling experts to gain further insights into the mechanisms leading to cardiac remodelling. * partly as a consequence of this work, we have contributed to the diffusion component of the developing international standard for MRI raw data that is independent of vendor. * some of the methods developed in this grant for the reduction of distortions in cardiac imaging have formed part of a successful grant application to Cancer Research UK for distortion correction in prostate MR imaging - something that frequently hampers cancer diagnosis. * the methods developed for imaging the heart have formed the basis to successfully recruit funding for investigating the efficacy of stem-cell based cardiac repair.
Sector Healthcare
Impact Types Societal

 
Description London Cancer - prostate
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Participation in a advisory committee
 
Description COST ACTION
Amount € 400,000 (EUR)
Funding ID CA16103 
Organisation European Union 
Sector Public
Country European Union (EU)
Start 04/2017 
End 04/2021
 
Description CRUK Multidisciplinary Project Award
Amount £389,793 (GBP)
Funding ID C35706/A21099 
Organisation Cancer Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2016 
End 03/2019
 
Description ISMRM Educational Stipend
Amount £270 (GBP)
Organisation International Society for Magnetic Resonance in Medicine (ISMRM) 
Sector Charity/Non Profit
Country United States
Start 04/2013 
End 05/2013
 
Description ISMRM Educational Stipend
Amount £270 (GBP)
Organisation International Society for Magnetic Resonance in Medicine (ISMRM) 
Sector Charity/Non Profit
Country United States
Start 04/2013 
End 05/2013
 
Title Cardiac atlas 
Description We are assembling a cardiac atlas (database of cardiac fibre directions inferred from diffusion MRI). 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact Database is not yet live. 
 
Description King's College London 
Organisation King's College London
Country United Kingdom 
Sector Academic/University 
Start Year 2007
 
Description PHILIPS HEALTHCARE 
Organisation Philips Healthcare
Country Netherlands 
Sector Private 
PI Contribution Feedback of our research results to the collaborator. Feedback on the collaborator's clinical and research products.
Collaborator Contribution Scientific advice, access to clinical scientists with knowledge of MRI hardware and software. Provision of pulse programming software environment and works in progress packages to enable clinical research.
Impact This collaboration enables the research we do using Philips MR systems.
 
Description SKOPE 
Organisation Skope
Country Switzerland 
Sector Private 
PI Contribution Feedback of experience using early version of field camera
Collaborator Contribution Supply of field camera, advice, software.
Impact Publication using field camera: Chan et al, J Magn Reson 244 pp74-84 (2014)
Start Year 2011
 
Description UK Renal Imaging Network 
Organisation Institute of Cancer Research UK
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise in kidney renal diffusion imaging.
Collaborator Contribution Partners have formed the UK Renal Imaging network to bring together research in kidney imaging and promote best clinical practice.
Impact Mailing list, network meetings, support funding from Kidney Research UK.
Start Year 2015
 
Description UK Renal Imaging Network 
Organisation King's College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise in kidney renal diffusion imaging.
Collaborator Contribution Partners have formed the UK Renal Imaging network to bring together research in kidney imaging and promote best clinical practice.
Impact Mailing list, network meetings, support funding from Kidney Research UK.
Start Year 2015
 
Description UK Renal Imaging Network 
Organisation Newcastle University
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise in kidney renal diffusion imaging.
Collaborator Contribution Partners have formed the UK Renal Imaging network to bring together research in kidney imaging and promote best clinical practice.
Impact Mailing list, network meetings, support funding from Kidney Research UK.
Start Year 2015
 
Description UK Renal Imaging Network 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise in kidney renal diffusion imaging.
Collaborator Contribution Partners have formed the UK Renal Imaging network to bring together research in kidney imaging and promote best clinical practice.
Impact Mailing list, network meetings, support funding from Kidney Research UK.
Start Year 2015
 
Description UK Renal Imaging Network 
Organisation University of Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise in kidney renal diffusion imaging.
Collaborator Contribution Partners have formed the UK Renal Imaging network to bring together research in kidney imaging and promote best clinical practice.
Impact Mailing list, network meetings, support funding from Kidney Research UK.
Start Year 2015
 
Description UK Renal Imaging Network 
Organisation University of Leeds
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise in kidney renal diffusion imaging.
Collaborator Contribution Partners have formed the UK Renal Imaging network to bring together research in kidney imaging and promote best clinical practice.
Impact Mailing list, network meetings, support funding from Kidney Research UK.
Start Year 2015
 
Description UK Renal Imaging Network 
Organisation University of Manchester
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise in kidney renal diffusion imaging.
Collaborator Contribution Partners have formed the UK Renal Imaging network to bring together research in kidney imaging and promote best clinical practice.
Impact Mailing list, network meetings, support funding from Kidney Research UK.
Start Year 2015
 
Description UK Renal Imaging Network 
Organisation University of Nottingham
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise in kidney renal diffusion imaging.
Collaborator Contribution Partners have formed the UK Renal Imaging network to bring together research in kidney imaging and promote best clinical practice.
Impact Mailing list, network meetings, support funding from Kidney Research UK.
Start Year 2015
 
Description UK Renal Imaging Network 
Organisation University of Sheffield
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise in kidney renal diffusion imaging.
Collaborator Contribution Partners have formed the UK Renal Imaging network to bring together research in kidney imaging and promote best clinical practice.
Impact Mailing list, network meetings, support funding from Kidney Research UK.
Start Year 2015
 
Title INNOVATE Trial 
Description This is a 360-subject prospective cohort study combining serum and urinary biomarkers with novel diffusion-weighted magnetic resonance imaging for the prediction and characterization of prostate cancer. It is funded by Prostate Cancer UK. INNOVATE is registered on ClinicalTrials.gov, with reference NCT02689271. 
Type Diagnostic Tool - Imaging
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2017
Development Status Under active development/distribution
Clinical Trial? Yes
Impact Pilot work led to a publication in Investigative Radiology 50 (4), 218-227 (2015). 
URL https://clinicaltrials.gov/show/NCT02689271
 
Title ISMRMRD 
Description ISMRMRD is a raw data format for MR image reconstruction. The format is specified in a publication (see DOI below), and in the code available from GitHub. The license used is the NIH Open Source license. Development is still active [March 2017] with regular collaborative meetings using Google Hangouts. 
Type Of Technology Software 
Year Produced 2015 
Open Source License? Yes  
Impact This is a new international standard aimed at facilitating the sharing and validation of reconstruction algorithms for MRI data. 
URL https://github.com/ismrmrd