Direct Measurements of Microstructure from MRI
Lead Research Organisation:
University College London
Department Name: Computer Science
Abstract
The research will produce a new imaging paradigm called active imaging . Traditional imaging techniques are designed by physicists; medical or biological researchers use them if they provide useful contrast between different types of material or correlate with interesting effects. Recent trends in medical imaging are towards quantitative imaging techniques that combine biophysical models of tissue with traditional imaging techniques to provide more specific information relevant to particular applications. Active imaging extends this idea to exploit biophysical models more completely to design the imaging techniques themselves. More specifically, the technique uses optimization algorithms to search for combinations of images that provide the most information about the biophysical model and the best estimates of biologically relevant quantities.For example, Alzheimer's diseaseattacks and destroys brain cells. It leaves holes in brain tissue and deposits of unusual proteins. Brain tissue from Alzheimer's patients looks very different to normal tissue under a microscope, but the differences are not apparent on images from standard techniques like magnetic resonance imaging (MRI). Even techniques like diffusion-tensor MRI, which has acute sensitivity to tissue microstructure, show only moderate contrast. A broader class of technique, called diffusion MRI, measures the scattering of water molecules in tissue. The tissue microstructure controls the scatter pattern and so diffusion MRI provides information about the microstructure. Diffusion-tensor MRI provides only particular features of the scatter pattern that happen to be insensitive to the microstructural changes in Alzheimer's. However, we can tune the sensitivity of diffusion MRI in an almost infinite number of other ways. Active imaging will use a model of the microstructural changes in Alzheimer's to find the precise combination of diffusion MRI measurements that is most sensitive to those changes and discriminates them most successfully from normal tissue or other diseases.The project considers three diseases: Alzheimer's, multiple sclerosis and focal cortical dyplasia (a common cause of epilepsy). Each has characteristic abnormalities in brain tissue microstructure that current imaging techniques do not reveal reliably. The project will construct biophysical models of the abnormalities and use active imaging to devise diffusion MRI techniques that reveal them. The project will also use active imaging to tune diffusion MRI to reveal specific microstructural features of normal brain tissue, such as size and density of axons in white matter. No current technique can image these features in live subjects, but the information would provide fundamental new information about the structure and function of the brain. The active-imaging paradigm extends to almost any other imaging technique including other MRI techniques, X-ray or optical tomography or positron-emission tomography (PET). Although the project focusses on active imaging for diffusion MRI, it also aims to initiate follow-on projects to explore applications to other diseases (such as cancers) and other imaging techniques.
Organisations
- University College London (Lead Research Organisation)
- Aarhus University (Collaboration)
- Champalimaud Foundation (Collaboration)
- Frenchay Hospital (Project Partner)
- University College Hospital (Project Partner)
- Philips Research Laboratories (Project Partner)
- GlaxoSmithKline (United Kingdom) (Project Partner)
People |
ORCID iD |
Daniel Alexander (Principal Investigator) |
Publications
Grussu F
(2018)
Relevance of time-dependence for clinically viable diffusion imaging of the spinal cord
in Magnetic Resonance in Medicine
Slator PJ
(2018)
Placenta microstructure and microcirculation imaging with diffusion MRI.
in Magnetic resonance in medicine
Ganepola T
(2018)
Using diffusion MRI to discriminate areas of cortical grey matter.
in NeuroImage
Battiston M
(2018)
Fast and reproducible in vivo T1 mapping of the human cervical spinal cord.
in Magnetic resonance in medicine
Battiston M
(2018)
An optimized framework for quantitative magnetization transfer imaging of the cervical spinal cord in vivo.
in Magnetic resonance in medicine
Ianus A
(2018)
Incomplete initial nutation diffusion imaging: An ultrafast, single-scan approach for diffusion mapping.
in Magnetic resonance in medicine
Graham MS
(2018)
A supervised learning approach for diffusion MRI quality control with minimal training data.
in NeuroImage
Alfaro-Almagro F
(2018)
Image processing and Quality Control for the first 10,000 brain imaging datasets from UK Biobank.
in NeuroImage
Ianus A
(2018)
Accurate estimation of microscopic diffusion anisotropy and its time dependence in the mouse brain.
in NeuroImage
Alexander DC
(2019)
Imaging brain microstructure with diffusion MRI: practicality and applications.
in NMR in biomedicine
Description | This project developed the paradigm of microstructure imaging, which infers microscopic tissue features from macroscopic MRI measurements. The work has led to several key imaging techniques: - ActiveAx for mapping axon diameter and density in nervous tissue. - NODDI (Neurite orientation dispersion and density imaging) also for brain and central nervous system tissue, but offering a clinically viable alternative to ActiveAx. - AMICO (Accelerated microstructure imaging through convex optimisation), which estimates model parameters very quickly enabling high throughput on large data sets such as the UK Biobank imaging data set. - SMT (Spherical mean technique), which ameliorates some of the simple modelling assumptions in NODDI. - VERDICT (vascular extracellular and restricted diffusion for cytometry in tumours) for cancer imaging. A clinical trial into the use of VERDICT in prostate cancer management (Johnston Radiology 2019) recently demonstrated its utility as the first non-invasive imaging technique to provide significant discrimination between Gleason grade 3 and grade 4 cancers - a key decision currently driven by biopsy and histology. |
Exploitation Route | Research and application of microstructure imaging is a very active topic in neuroimaging, cancer imaging, and a range of other areas. |
Sectors | Healthcare Pharmaceuticals and Medical Biotechnology |
URL | http://mig.cs.ucl.ac.uk/index.php?n=Main.Projects |
Description | Microstructure imaging techniques, such as NODDI and VERDICT, are being used in an increasing diversity of clinical studies to highlight structural brain differences associated with particular disorders. NODDI is a neuroimaging technique that is now widely used in clinical studies of diseases that affect brain microstructure and in studies of brain tumours. VERDICT is a cancer imaging technique that is now undergoing a clinical trial for use in prostate cancer - the Prostate Cancer UK Innovate trial - that trial reports positive results in the ability of VERDICT to differentiate Gleason grade 3 and grade 4 lesions, which is a key clinical decision previously impossible non-invasively. More experimental techniques such as ActiveAx have motivated the development of next-generation MRI hardware that potentially make the techniques clinically viable. In particular, it is a key motivator for the EPSRC-funded National Microstructure Imaging Facility in Cardiff. |
First Year Of Impact | 2012 |
Sector | Healthcare |
Impact Types | Societal |
Description | A biophysical simulation framework for magnetic resonance microstructure imaging |
Amount | £665,423 (GBP) |
Funding ID | EP/N018702/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2016 |
End | 03/2019 |
Description | AI-powered brain microstructure imaging |
Amount | £1,076,148 (GBP) |
Funding ID | MR/T020296/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 06/2020 |
End | 06/2021 |
Description | Anatomy driven brain connectivity mapping |
Amount | £775,427 (GBP) |
Funding ID | EP/L022680/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 05/2014 |
End | 05/2017 |
Description | Axon and myelin damage assessed using advanced diffusion imaging: from mathematical models to clinical applications |
Amount | £815,568 (GBP) |
Funding ID | EP/I027084/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 08/2011 |
End | 08/2014 |
Description | CDS QUAMRI: A Clinical Decision Support system based on Quantitative multimodal brain MRI for personalized treatment in neurological and psychiatric disorders |
Amount | € 3,200,000 (EUR) |
Funding ID | 634541 |
Organisation | European Commission |
Department | Horizon 2020 |
Sector | Public |
Country | European Union (EU) |
Start | 08/2015 |
End | 08/2020 |
Description | CONNECT: Consortium of NeuroImagers for the Non-invasive Exploration of Brain Connectivity and Tractography |
Amount | £1,600,000 (GBP) |
Funding ID | 238292 |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start | 01/2010 |
End | 10/2012 |
Description | Computational PLatform for Assessment of Cognition In Dementia (C-PLACID) |
Amount | £1,500,000 (GBP) |
Funding ID | EP/M006093/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2015 |
End | 12/2017 |
Description | Computational models of neurodegenerative disease progression |
Amount | £599,868 (GBP) |
Funding ID | EP/J020990/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2012 |
End | 09/2015 |
Description | Developing single cell resolution 3D models of immune surveillance in cancer |
Amount | £165,263 (GBP) |
Funding ID | NS/A000069/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2018 |
End | 12/2020 |
Description | Developing single-cell resolution 3D models of immune surveillance in cancer |
Amount | £487,000 (GBP) |
Funding ID | NS/A000069/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2018 |
End | 12/2020 |
Description | EPSRC Centre for Doctoral Training in Intelligent, Integrated Imaging In Healthcare (i4health) |
Amount | £6,034,274 (GBP) |
Funding ID | EP/S021930/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 08/2019 |
End | 03/2028 |
Description | EPSRC Doctoral Prize (UCL) |
Amount | £110,000 (GBP) |
Funding ID | Andrada Ianus - two year post-doc fellowship |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2016 |
End | 12/2017 |
Description | EPSRC Doctoral Prize PhD Plus |
Amount | £15,000 (GBP) |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2011 |
End | 01/2012 |
Description | EPSRC Early Career Fellowship |
Amount | £982,000 (GBP) |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 06/2016 |
End | 07/2021 |
Description | EPSRC Early career fellowship |
Amount | £1,000,000 (GBP) |
Funding ID | EP/N021967/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 06/2016 |
End | 06/2021 |
Description | Enabling clinical decisions from low-power MRI in developing nations through image quality transfer |
Amount | £1,020,000 (GBP) |
Funding ID | EP/R014019/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 02/2018 |
End | 01/2021 |
Description | Gold-standard assessment of prostate cancer MRI accuracy |
Amount | $25,000 (AUD) |
Organisation | Sydney Catalyst |
Sector | Charity/Non Profit |
Country | Australia |
Start | 05/2017 |
End | 05/2018 |
Description | Image Quality Transfer |
Amount | £60,000 (GBP) |
Organisation | Microsoft Research |
Sector | Private |
Country | Global |
Start | 09/2015 |
End | 09/2018 |
Description | Imaging research to facilitate new treatments for multiple sclerosis |
Amount | £1,350,000 (GBP) |
Funding ID | H001-12.4 |
Organisation | Multiple Sclerosis Society |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 04/2013 |
End | 04/2018 |
Description | In vivo microstructural neuroimaging in infants at risk of developing neurocognitive delay or neurobehavioural disorders |
Amount | £794,544 (GBP) |
Funding ID | MR/L011530/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2014 |
End | 03/2019 |
Description | Intelligent imaging: motion form and function across scale |
Amount | £5,600,000 (GBP) |
Funding ID | EP/H046410/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 05/2010 |
End | 05/2015 |
Description | JPND: Stratification of presymptomatic amyotrophic lateral sclerosis: the development of novel imaging biomarkers |
Amount | € 1,600,000 (EUR) |
Funding ID | MR/T046473/1 |
Organisation | JPND Research |
Sector | Academic/University |
Country | Global |
Start | 06/2020 |
End | 07/2023 |
Description | Learning MRI and histology image mappings for cancer diagnosis and prognosis |
Amount | £774,000 (GBP) |
Funding ID | EP/R006032/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 12/2017 |
End | 01/2020 |
Description | Medical image computing for next-generation healthcare technology |
Amount | £1,500,000 (GBP) |
Funding ID | EP/M020533/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 05/2015 |
End | 05/2020 |
Description | Medical imaging markers of cancer initiation, progression and therapeutic response in the breast based on tissue microstructure |
Amount | £812,350 (GBP) |
Funding ID | EP/K020439/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2013 |
End | 12/2015 |
Description | National facility for in vivo MRI of human tissue microstructure |
Amount | £2,900,000 (GBP) |
Funding ID | EP/M00855X/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 06/2014 |
End | 06/2019 |
Description | Neurite orientation dispersion and density imaging - a new approach to understanding cellular pathology in Motor Neurone Disease |
Amount | £118,000 (GBP) |
Funding ID | Leigh/Apr14/824-791 |
Organisation | Motor Neurone Disease Association (MND) |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 05/2014 |
End | 12/2015 |
Description | Next generation MRI brain imaging platform for dementia research: from microstructure to function |
Amount | £1,500,000 (GBP) |
Funding ID | MR/M009106/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 07/2014 |
End | 07/2019 |
Description | Placenta Imaging Project |
Amount | $3,229,581 (USD) |
Funding ID | 1U01HD087202-01 |
Organisation | National Institutes of Health (NIH) |
Sector | Public |
Country | United States |
Start | 08/2015 |
End | 09/2018 |
Description | Robust graph analysis of brain connectivity |
Amount | £416,856 (GBP) |
Funding ID | EP/J016292/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 06/2012 |
End | 06/2015 |
Description | Collaboration with Champalimaud Foundation |
Organisation | Aarhus University |
Country | Denmark |
Sector | Academic/University |
PI Contribution | Computational and theoretical expertise on data analysis and MRI pulse sequence design and implementation. |
Collaborator Contribution | Laboratory environment and expertise for designing and using novel imaging MRI sequences on pre-clinical scanners. Collaborators from Aarhus University are also bringing theoretical expertise. |
Impact | - Ianus, A., Shemesh, N., Alexander, D.C., Drobnjak, I. Double Oscillating Diffusion Encoding (DODE) and sensitivity to microscopic anisotropy. Magnetic Resonance in Medicine (2016) - Ianus, A., Shemesh, N., Alexander, D.C., Drobnjak, I. Impact of sequence parameters on the sensitivity of DDE and DODE sequences to microscopic anisotropy 24th Meeting of the International Society for Magnetic Resonance in Medicine (2016) - Ianus, A., S. Jespersen, Alexander, D.C., Drobnjak, I., N. Shemesh Time dependence of microscopic anisotropy in the mouse brain measured with double oscillating diffusion encoding 25th Meeting of the International Society for Magnetic Resonance in Medicine (2017) - Ianus, A. and Shemesh, N.Incomplete initial nutation diffusion imaging: An ultrafast, single-scan approach for diffusion mapping |
Start Year | 2016 |
Description | Collaboration with Champalimaud Foundation |
Organisation | Champalimaud Foundation |
Department | Champalimaud Centre for the Unknown |
Country | Portugal |
Sector | Academic/University |
PI Contribution | Computational and theoretical expertise on data analysis and MRI pulse sequence design and implementation. |
Collaborator Contribution | Laboratory environment and expertise for designing and using novel imaging MRI sequences on pre-clinical scanners. Collaborators from Aarhus University are also bringing theoretical expertise. |
Impact | - Ianus, A., Shemesh, N., Alexander, D.C., Drobnjak, I. Double Oscillating Diffusion Encoding (DODE) and sensitivity to microscopic anisotropy. Magnetic Resonance in Medicine (2016) - Ianus, A., Shemesh, N., Alexander, D.C., Drobnjak, I. Impact of sequence parameters on the sensitivity of DDE and DODE sequences to microscopic anisotropy 24th Meeting of the International Society for Magnetic Resonance in Medicine (2016) - Ianus, A., S. Jespersen, Alexander, D.C., Drobnjak, I., N. Shemesh Time dependence of microscopic anisotropy in the mouse brain measured with double oscillating diffusion encoding 25th Meeting of the International Society for Magnetic Resonance in Medicine (2017) - Ianus, A. and Shemesh, N.Incomplete initial nutation diffusion imaging: An ultrafast, single-scan approach for diffusion mapping |
Start Year | 2016 |
Title | ActiveAx implementation in Camino |
Description | ActiveAx is the non-invasive axon diameter mapping technique that emerged from the fellowship project. Originally reported in (Alexander et al Neuroimage 2010) and extended in (Zhang et al Neuroimage 2011; Dyrby et al Magnetic Resonance in Medicine 2013). The software enabling wide application of the technique is now available in the free and open-source Camino toolkit www.camino.org.uk. Specific page documenting the module is here:http://cmic.cs.ucl.ac.uk/camino//index.php?n=Tutorials.ActiveAx. |
Type Of Technology | Software |
Year Produced | 2010 |
Open Source License? | Yes |
Impact | Highly cited technique that helped motivate the development of next generation MRI hardware such as the Boston Connectom scanner, The Cardiff National Microstructure Imaging Facility, and Siemens' latest Prisma scanner. |
URL | http://cmic.cs.ucl.ac.uk/camino//index.php?n=Tutorials.ActiveAx |
Title | MISST - Microstructure Imaging Sequence Simulation ToolBox |
Description | Microstructure Imaging Sequence Simulation Toolbox (MISST) is a practical diffusion MRI simulator for development, testing, and optimisation of novel MR pulse sequences for microstructure imaging. MISST is based on a matrix method approach and simulates the signal for a large variety of pulse sequences and tissue models. Its key purpose is to provide a deep understanding of the restricted diffusion MRI signal for a wide range of realistic, fully flexible scanner acquisition protocols, in practical computational time. |
Type Of Technology | Software |
Year Produced | 2015 |
Open Source License? | Yes |
Impact | MISST has been used in several research studies presented at recent conferences. |
Title | NODDI matlab toolbox |
Description | NODDI is another microstructure imaging technique emerging from the fellowship project. It requires short enough acquisition time to be viable for clinical studies and as such has received a lot of attention since its first publication in 2012. This software makes the technique widely available to the research community. The original technique is documented in (Zhang et al Neuroimage 2012). The URL for the toolbox is here: http://cmic.cs.ucl.ac.uk/mig/index.php?n=Tutorial.NODDImatlab. |
Type Of Technology | Software |
Year Produced | 2012 |
Open Source License? | Yes |
Impact | Increasingly widely used in neuroimaging studies. |
URL | http://cmic.cs.ucl.ac.uk/mig/index.php?n=Tutorial.NODDImatlab |
Title | Spherical Mean Technique |
Description | It implements a model-based imaging technique for deriving microstructural maps from MRI. |
Type Of Technology | Software |
Year Produced | 2016 |
Open Source License? | Yes |
Impact | It's quite new, but already being used in a range of clinical studies. Impact will come and we'll report back when it does. |
URL | https://ekaden.github.io |