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.

Publications

10 25 50
 
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 04/2016 
End 03/2019
 
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 06/2014 
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 09/2011 
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 09/2015 
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 10/2012 
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 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 07/2016 
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 07/2016 
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 06/2017 
End 05/2018
 
Description Image Quality Transfer
Amount £60,000 (GBP)
Organisation Microsoft Research 
Sector Private
Country Global
Start 10/2015 
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 05/2013 
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 04/2014 
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 06/2010 
End 05/2015
 
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 06/2015 
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 07/2014 
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 06/2014 
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 08/2014 
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 09/2015 
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 07/2012 
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