Motion Corrected Reconstruction for 3D Cardiac Simultaneous PET-MR Imaging: Towards Efficient Assessment of Coronary Artery Disease

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

Abstract

Coronary artery disease (CAD) is the leading single cause of morbidity and mortality in the Western world. CAD reduces the blood supply to the cardiac muscle and can lead to chest pain (angina) or heart attack. CAD diagnosis is currently performed by a wide range of invasive and non-invasive tests. However in current practice a non-negligible number of patients that may not need the intervention are referred to invasive, ionizing, and potentially harmful x-ray cardiac catheterization procedures. Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) are two very promising non-invasive imaging technologies for early risk assessment, guidance of therapy and treatment monitoring of CAD. Both technologies provide complementary information, thus the recent introduction of simultaneous PET-MR systems offers great potential for accurate interpretation of findings of PET and MR images and new perspectives for better CAD diagnosis and treatment. For example three-dimensional fusion of PET perfusion images with non-invasive coronary MR images may allow the exact localization of stenosis, causing ischemia, to guide required interventions. However, inevitable patient motion (such as that caused by breathing and heart beating) during the acquisition degrades the image quality of both PET and MR images. Currently, commercial simultaneous PET-MR scanners do not feature technology for efficient and accurate correction of such motion.

Current research developments that deal with the motion problem in cardiovascular PET-MR concentrate mainly on improving the quality of PET images based on MR information. Moreover these approaches do not allow truly simultaneous PET and MR acquisitions leading to prolonged scan times, since diagnostic MR images need to be acquired after the simultaneous PET-MR acquisition. The reason is that dedicated MR acquisitions need to be performed concurrently with the PET imaging in order to correct for motion in the PET data. This means that MR is being used as an expensive motion-correction device limiting its diagnostic utility. In this proposal we aim to develop, implement and test the clinical feasibility of an efficient PET-MR acquisition and reconstruction framework that enables truly simultaneous acquisition of complementary PET and MR diagnostic information. We hypothesize that this can be achieved using synergistic information of both modalities i.e. functional, anatomic and motion MR information, and quantitative perfusion PET data in a motion corrected reconstruction approach. The proposed approach is foreseen as an important step towards clinical adoption of PET-MR cardiovascular imaging and lastly towards an efficient and accurate non-invasive assessment of CAD.

Planned Impact

The beneficiaries of this research will be patients with suspected or known coronary artery disease, who will benefit from efficient and accurate non-invasive diagnostic tests. Secondary beneficiaries will be clinicians involved in the diagnosis and treatment of CAD. Complementary information provided by both imaging technologies will enable more reliable diagnosis. In the long term this project will also help reducing NHS healthcare costs by a) reducing the number of examinations: both PET and MR images will be acquired in a single-test, in a shorter scan time (from 60 min each scan to ~30 min for the simultaneous PET-MR) and will require one integrated reporting from the clinicians; and b) improving hospital discharge rates by providing more accurate diagnosis. Moreover the technology developed in this project may also have an impact in PET-MR cancer imaging where respiratory motion is a known major challenge. Through commercialisation, the research will be of benefit to the imaging manufacturers and subsequently to the healthcare system by improving patient management through improved treatment outcome and reduced healthcare costs on a national and international level.

Our goal is to maximise the impact of our work through dissemination of our ideas and results to the academic and clinical communities and potential industrial partners. The scientific methodology results from this research will be output as research publications in high-impact journals in the field of medical imaging. A large amount of phantom and in-vivo PET-MR data will be generated during the lifetime of the grant. After the studies are published in scientific journals, and after they are patented if patenting is a viable option, this data will be made publicly available for research use. We also plan to use the data to organise a "Motion Correction Challenger" in relevant Scientific Conferences. Moreover the data and reconstruction codes generated during the lifetime of the grant will be used in different teaching, networking and software development activities planned within the EP/M022587/1 "Computational Collaborative Project in Synergistic PET-MR Reconstruction" grant. Dr. Prieto (PI of this proposal) and Dr. Reader (CoI of this proposal) are both CoIs in this recently awarded Computational Collaborative Project PET-MR grant.

Clinical simultaneous PET-MR systems have been available for only a few years with two installations in the UK, one of them at the Division of Imaging Sciences at KCL. However, the UK government is expected to announce funding for five new PET-MR systems. Current commercial PET-MR scanners do not feature advanced techniques to deal with the problem of motion in cardiovascular imaging, therefore this project is foreseen as an important step towards clinical translation and validation of cardiovascular PET-MR. At the completion of this project we plan to work closely together with industrial partner to transfer the developed methodology into the product software to allow wide spread clinical use of this research.

Publications

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Hajhosseiny R (2019) Molecular and Nonmolecular Magnetic Resonance Coronary and Carotid Imaging. in Arteriosclerosis, thrombosis, and vascular biology

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Ginami G (2017) 3D whole-heart phase sensitive inversion recovery CMR for simultaneous black-blood late gadolinium enhancement and bright-blood coronary CMR angiography. in Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance

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Clough JR (2020) Weighted Manifold Alignment using Wave Kernel Signatures for Aligning Medical Image Datasets. in IEEE transactions on pattern analysis and machine intelligence

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Aizaz M (2020) PET/MRI of atherosclerosis. in Cardiovascular diagnosis and therapy

 
Description Coronary artery disease (CAD) is the leading single cause of morbidity and mortality in the Western world. CAD reduces the blood supply to the cardiac muscle and can lead to chest pain (angina) or heart attack CAD diagnosis is currently performed by a wide range of invasive and non-invasive tests. However in current practice a non-negligible number of patients that may not need the intervention are referred to invasive, ionizing, and potentially harmful x-ray cardiac catheterization procedures. Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) are two very promising non-invasive imaging technologies for early risk assessment, guidance of therapy and treatment monitoring of CAD. Both technologies provide complementary information, thus the recent introduction of simultaneous PET-MR systems offers great potential for accurate interpretation of findings of PET and MR images and new perspectives for better CAD diagnosis and treatment. However, inevitable patient motion (such as that caused by breathing and heart beating) during the acquisition degrades the image quality of both PET and MR images.

Through the research funded on this grant we have developed a new framework that allows to correct for respiratory motion in both PET and MR images, enabling better quality PET images, faster MR acquisitions and full co-registration between both datasets to facilitate fusion of the images. We have tested the feasibility of the proposed approach in a small cohort of oncology patients and have a establish collaborations with: 1) the Department of Nuclear Medicine in the Technical University of Munich, 2) the University of Edinburgh and 3) the Department of Nuclear Medicine and Radiology of the University of Maastrich to test the feasibility of the method in a small cohort of patients with cardiovascular disease.

In a parallel study we have developed a novel MR sequence that allows simultaneous acquisition of bright blood and black blood whole heart images to enable visualisation of coronary lumen and coronary thrombus/hemorrhage. The acquisition is efficient as correct for respiratory motion and provides fully co-registered datasets to facilitate analysis. This sequence is currently being tested in a small cohort of patients with Cardiovascular disease at St Thomas' Hospital.
Exploitation Route We are currently working in close collaboration with Siemens to generate a work-in-progress version of the framework which can be distributed to collaborators in other sites to evaluate the performance of the method. The work-in-progress package is ready and has been distributed to collaborators for MR scanners only, a version for hybrid PET-MR scanners is currently under development.
Sectors Healthcare

URL https://kclcvmimaging.wordpress.com/
 
Description Through the research funded on this grant we have developed a new framework that allows to correct for respiratory motion in both PET and MR cardiac images, enabling better quality PET images, faster MR acquisitions and full co-registration between both datasets to facilitate fusion of the images. We have tested the feasibility of the proposed approach in a small cohort of oncology patients and have a establish collaborations with: 1) the Department of Nuclear Medicine in the Technical University of Munich, 2) the University of Edinburgh and 3) the Department of Nuclear Medicine and Radiology of the University of Maastrich to test the feasibility of the method in other cohorts of with cardiovascular disease. Collaborations are still ongoing. As a continuation of this grant we are currently testing the proposed framework in a pilot study for cardiac sarcoidosis patients, considering quantification of inflammation with simultaneous MR and PET images. We have further improved the PET reconstruction considering motion corrected and MR-guided reconstruction. We have also extended the proposed approach to enable quantitative T2 mapping, which is currently being evaluated in cardiac sarcoidosis patients.
First Year Of Impact 2022
Sector Healthcare
Impact Types Societal

 
Description 2018 IEEE NSS-MIC Trainee Grant
Amount $655 (AUD)
Organisation Institute of Electrical and Electronics Engineers (IEEE) 
Sector Learned Society
Country United States
Start 11/2018 
End 11/2018
 
Description ISMRM Educational Stipend 2017
Amount $900 (USD)
Organisation International Society for Magnetic Resonance in Medicine (ISMRM) 
Sector Charity/Non Profit
Country United States
Start 04/2017 
End 04/2017
 
Description ISMRM Educational Stipend 2018
Amount $1,815 (USD)
Organisation International Society for Magnetic Resonance in Medicine (ISMRM) 
Sector Charity/Non Profit
Country United States
Start 06/2018 
End 06/2018
 
Description NIHR Pump-Prime
Amount £66,757 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 03/2020 
End 11/2020
 
Description SCMR 2019 Travel Award (3 people)
Amount € 1,500 (EUR)
Organisation Society for Cardiovascular Magnetic Resonance (SCMR) 
Sector Charity/Non Profit
Country United States
Start 02/2019 
End 02/2019
 
Description SMRA 2018
Amount $550 (USD)
Organisation Society for Magnetic Resonance Angiography (SMRA) 
Sector Learned Society
Country Canada
Start 08/2018 
End 08/2018
 
Title BOOST Magnetic Resonance Imaging Sequence 
Description We have developed an acquisition and reconstruction framework that simultaneously generated 3D whole-heart bright- and black-blood Magnetic Resonance images of the heart. This framework can be applied to a broad range of cardiac pathologies and is being currently clinically validated locally. The package will be distributed to other academic institution and broader clinical validation is foresee. 
Type Of Material Improvements to research infrastructure 
Year Produced 2017 
Provided To Others? Yes  
Impact This framework can be applied to a broad range of cardiac pathologies and is being currently clinically validated locally. The package will be distributed to other academic institution and broader clinical validation is foresee. 
 
Title Motion Corrected PET-CMRA 
Description We have developed a motion corrected PET-CMRA (Positron Emission Tomography-Coronary Magnetic Resonance Angiography) framework that correct for respiratory motion in simultaneously acquired PET and MR images of the heart. This framework can be applied to a broad range of cardiac pathologies and is being currently clinically validated locally and with 3 external collaborators. The package will be distributed to other academic institution and broader clinical validation is foresee. 
Type Of Material Improvements to research infrastructure 
Year Produced 2017 
Provided To Others? Yes  
Impact This framework can be applied to a broad range of cardiac pathologies and is being currently clinically validated locally and with 3 external collaborators. The package will be distributed to other academic institution and broader clinical validation is foresee. 
 
Description Imperial College London CMRA 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Established a collaborative project with Imperial College London to clinically validate a new coronary cardiac MR sequence that includes our under sampled and motion compensated reconstruction developments with intravascular optical coherence tomography in patients with acute coronary syndrome for the simultaneous non-contrast free breathing 3D high resolution magnetic resonance coronary artery angiography and high-risk plaque imaging. Ethical approval for the project has been obtained, an NIHR Pump-Prime award worth (£66,757.50) has been competitively secured and a British Heart Foundation Clinical Research Fellowship grant application has been submitted (currently under assessment).
Collaborator Contribution Access to facilities and patients.
Impact NIHR Pump-Prime award worth (£66,757.50) has been competitively secured and a British Heart Foundation Clinical Research Fellowship grant application has been submitted (currently under assessment).
Start Year 2019
 
Description Maastricht University Medical Center Cardiac PET-MR 
Organisation Maastricht University Medical Center+
Country Netherlands 
Sector Academic/University 
PI Contribution We have developed a framework for efficient free-breathing simultaneous whole-heart coronary magnetic resonance angiography (CMRA) and cardiac positron emission tomography (PET) on a 3T PET-MR system. The acquisition and reconstruction methods are implemented inline in the scanner software. Validation of the proposed framework in patients with cardiovascular disease is being performed in collaboration with Dr. Eline Kooi at the Maastricht University Medical Center .
Collaborator Contribution Dr Eline Kooi and Dr Rik Moonen will be acquiring clinical data to validate the proposed framework.
Impact No outcomes yet. The collaboration involves Physicists experts in Magnetic Resonance Imaging and Nuclear Medicine and clinicians, both cardiologists and radiologists.
Start Year 2017
 
Description TUM (Technische Universität München) Cardiac PET-MR 
Organisation Technical University of Munich
Department Department of Nuclear Medicine
Country Germany 
Sector Academic/University 
PI Contribution We have developed a framework for efficient free-breathing simultaneous whole-heart coronary magnetic resonance angiography (CMRA) and cardiac positron emission tomography (PET) on a 3T PET-MR system. The acquisition and reconstruction methods are implemented inline in the scanner software. Validation of the proposed framework in patients with cardiovascular disease is being performed in collaboration with Dr. Stephan Nekolla Head of Multimodal Cardiac Imaging at the Department of Nuclear Medicine in Munich.
Collaborator Contribution Karl Kunze, PhD student from TUM Munich, spent two weeks at KCL to learn how to use the framework and acquire the data. Currently he is acquiring data on patients in TUM.
Impact The collaboration involves Physicists experts in Magnetic Resonance Imaging and Nuclear Medicine and clinicians, both cardiologists and radiologists. From this collaboration two abstracts were accepted for the international conference ISMRM in 2017. The journal article "Motion-corrected whole-heart PET-MR for the simultaneous visualisation of coronary artery integrity and myocardial viability: an initial clinical validation" is currently under revision in EJNMMI.
Start Year 2016
 
Description University of Edinburgh Cardiac PET-MR 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution We have developed a framework for efficient free-breathing simultaneous whole-heart coronary magnetic resonance angiography (CMRA) and cardiac positron emission tomography (PET) on a 3T PET-MR system. The acquisition and reconstruction methods are implemented inline in the scanner software. Validation of the proposed framework in patients with cardiovascular disease is being performed in collaboration with Dr Mark Dweck and Dr Scott Semple at the University of Edinburgh.
Collaborator Contribution Dr Mark Dweck and Dr Scott Semple will be acquiring clinical data to validate the proposed framework.
Impact No outcomes yet. The collaboration is multidisciplinary as involves Physicists experts in Magnetic Resonance Imaging and Nuclear Medicine and clinicians, both cardiologists and radiologists.
Start Year 2017
 
Title METHOD AND APPARATUS FOR RECONSTRUCTING MAGNETIC RESONANCE IMAGE DATA 
Description In a method for reconstructing magnetic resonance (MR) image data from k-space data, k-space data of an image region of a subject are provided to a computer that is also provided with multiple navigator signals for the image region of the subject. The computer sorts the k-space data into multiple bins, the multiple bins representing different motion states of the subject. For each of the multiple bins, the computer executes a compressed sensing procedure to reconstruct the MR image data from the k-space data in the respective bin. Execution of the compressed sensing procedure includes solving an optimization problem comprising a data consistency component and a transform sparsity component. Motion information is incorporated by the computer into at least one of the data consistency component and the transform sparsity component of the optimization problem. 
IP Reference US2019317172 
Protection Patent application published
Year Protection Granted 2019
Licensed No
Impact Pre-product software for Siemens MRI scanners
 
Title METHOD OF PERFORMING MAGNETIC RESONANCE IMAGING AND A MAGNETIC RESONANCE APPARATUS 
Description In a method of performing magnetic resonance (MR) imaging, an MR apparatus, and a computer-readable medium during a first cardiac cycle of a subject, a first imaging sequence is generated for application to a subject. The first imaging sequence has a preparatory pulse and an inversion recovery pulse following the preparatory pulse. First signals emitted from the subject in response to the first imaging sequence are detected, and first image data are generated based on the first signals. During a second cardiac cycle following the first cardiac cycle, a second imaging sequence is generated for application to the subject. The second imaging sequence has a preparatory pulse. Second signals emitted from the subject in response to the second imaging sequence are detected, and second image data are generated based on the second signals. 
IP Reference US2019064299 
Protection Patent application published
Year Protection Granted 2019
Licensed No
Impact 20190064299
 
Description Royal Society Summer Science Exhibition 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact From July 4th until the 9th the Royal Society held a Summer Science Festival where the School of Biomedical Engineering and Imaging Sciences from King's College London has a stand. The Royal Society was founded in 1690 and has been actively involved in promoting, encouraging and engaging science development. During the Summer Festival, different universities and companies showed some of the work that they have been involved and were trying to raise awareness for important issues e.g. global warming, how technology can be used to prevent and treat diseases, how to create energy from solar power, among others. This year, more than 14,000 people visited!

Together with many other colleagues from the School our group (Dr Teresa Correia, Camila Munoz, Giovanna Nordio, Isabel Ramos and Dr Arna van Engelen), has been helping in engaging the public to the "Heart in your Hands" project. The objective of this project was to answer the question "How do we better engage the public about engineering research in the heart?". A multidisciplinary team was involved in answering it. The School of Biomedical Engineering and Imaging Sciences at KCL holds a multidisciplinary environment where scientists, doctors, physicist, computer programmers and engineers work together trying to understand how the heart works. They produce mathematical and computer models which replicates the heart and by using 3D printing technology they can develop physical heart models. These models can be used for different purposes: they can be used to help diagnosing a disease, to customize and plan a patient-orientated surgery, or to use these models as a show-case. In this Summer Festival the hands-on exhibition had three stands: (1) the heart viewer, where a range of different 3D printed hearts were available with the possibility to see how magnetic resonance imaging can be used to understand their unique function; (2) CardioSync, with a 3D printed heart controller to drive computational simulations of heart function and learn how to put a pacemaker in its correct place and (3) Hold a soft robotic heart in your hands that beats in time with your own heart, and discover its surprising biomechanical function.
Year(s) Of Engagement Activity 2017
 
Description Symposium of Slovene researchers abroad 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Undergraduate students
Results and Impact PhD student Alina Schneider presented at the 6th symposium of Slovene researchers abroad on the 20th of December 2020 participating in a panel about imagining, introducing PET/MR imaging to approx. 40 students in Slovenia. (https://www.drustvovtis.si/si/koledar/simpozij2021)
Year(s) Of Engagement Activity 2020
URL https://www.drustvovtis.si/si/koledar/simpozij2021