A biophysical simulation framework for magnetic resonance microstructure imaging

Lead Research Organisation: University College London
Department Name: Computer Science

Abstract

This project develops a simulation system for the MR signal in biological tissue and its dependence on molecular dynamics as influenced by tissue microarchitecture and composition. The system is an essential tool in the development of next-generation non-invasive imaging techniques. Specifically, it underpins the development and translation of the emerging paradigm of microstructure imaging. The paradigm uses mathematical models, which relate the MR signal to underlying tissue properties, to estimate and map those properties by fitting the models voxel-by-voxel to combinations of appropriately sensitised image data. The approach provides much greater biological specificity than standard MRI, thus enhancing diagnosis and treatment planning.

The current generation of microstructure-imaging techniques is now starting to find widespread application in clinical studies. Prominent examples include NODDI for neuroimaging and VERDICT for cancer imaging, both developed by the investigators on this project. Those techniques are based entirely on diffusion MRI and their extension and refinement within that single contrast mechanism continues rapidly. However, a new generation of microstructure-imaging technique is just beginning to emerge that draws on multiple sources of MR contrast, for example combining diffusion MRI with relaxometry, susceptibility, etc. Such techniques offer great promise in the decades to come for the realisation of 'virtual histology' avoiding invasive procedures, such as biopsy, across a wide range of medical applications.

EPSRC grant EP/E064280/1, which finished in 2011, developed the current state-of-the-art simulation system within the Camino toolkit. That system underpinned the early development of the microstructure-imaging paradigm, which led to current techniques like NODDI and VERDICT. However, the current system is insufficient to evaluate even current microstructure imaging techniques, because it excludes key effects that influence the diffusion MR signal. Moreover, its implementation limits the simulation to molecular diffusion as the only source of MR contrast, which fundamentally prevents its extension for validation of next-generation techniques.

The new simulation system will use more sophisticated underlying models of tissue geometry and MR signal generation enabling it to support both modern diffusion-based microstructure-imaging applications and future multi-modal techniques. It provides a unique and invaluable validation tool allowing us to realise the full potential of quantitative non-invasive imaging in medicine and beyond. Within the project we demonstrate the new system by evaluating the performance of NODDI and VERDICT under a wide range of conditions. We also test two early examples of multi-modal microstructure imaging techniques paving the way for their robust development and eventual clinical translation.

Planned Impact

Impact of the project arises through facilitation of the development of accurate and well-validated microstructure-imaging techniques.

Microstructure imaging promises advances in understanding and management of some of the biggest challenges facing 21st century healthcare; most directly: neurological diseases and cancer. The UK dementia platform estimates annual socioeconomic costs of dementia in Britain at around £17B. A treatment prolonging independent life of the average dementia patient by just one year would save around £1B per year in care costs as well as boosting the UK economy through revenue from the treatment if realised through its pharmaceutical industry and thriving community of related SMEs. The potential of microstructure imaging is to detect and classify disease earlier, enabling appropriate and early intervention, and to stage disease more accurately supporting effective treatment development and deployment. Annual costs of cancer have similar scale. Microstructure imaging promises rapid, non-invasive, and specific early diagnosis, supporting precision medicine and treatment delivery with similar socio-economic impact.

Current microstructure-imaging techniques are rapidly becoming part of the mainstream battery of imaging techniques used routinely in clinical studies and exams. NODDI is a key component in large-scale data-collection initiatives, such as the 1946-cohort imaging project (~1000 subjects), and most current large-scale brain imaging projects, such as the UK Biobank (100,000 subjects) and the Human Connectome Project (1000s of subjects), use protocols designed to support the technique. The more recent VERDICT technique is already a key component of large-scale prostate-cancer imaging initiatives at UCLH, such as the PROMIS (1000s of subjects) and INNOVATE (100s of subjects) projects, and other institutions are preparing to follow suit.

Despite their success, intense debate continues in the technical imaging-science community about t mathematical models and acquisition protocols at the heart of the techniques. The debate arises from incomplete understanding of both the biophysical sources of MR contrast and the effects of simplifying modelling assumptions that are essential to make stable front-line techniques. The simulation tool we propose here advances our understanding in these key questions providing confidence in the conclusions drawn from large-scale studies and clinical trials, as well as highlighting areas of weakness in current techniques to ameliorate for future generations.

Publications

10 25 50
 
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 Academic/University
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 Academic/University
Country United Kingdom
Start 06/2014 
End 05/2017
 
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 Academic/University
Country United Kingdom
Start 01/2018 
End 12/2020
 
Description Direction measurements of microstructure from MRI
Amount £1,600,000 (GBP)
Funding ID EP/G007748/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 10/2008 
End 09/2014
 
Description Enabling Clinical Decisions From Low-power MRI In Developing Nations Through Image Quality Transfer
Amount £1,035,545 (GBP)
Funding ID EP/R014019/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 02/2018 
End 01/2021
 
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 Academic/University
Country United Kingdom
Start 06/2015 
End 05/2020
 
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 Academic/University
Country United Kingdom
Start 07/2014 
End 06/2019
 
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 Academic/University
Country United Kingdom
Start 08/2014 
End 07/2019
 
Description Workshop on diffusion MRI meets diffusion MRS. Combining DW-MRI and DW-MRS: a multi-scale approach to microstructure imaging 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Title: Diffusion MRI meets diffusion MRS. Combining DW-MRI and DW-MRS: a multi-scale approach to microstructure imaging

Organizers: Marco Palombo and Hui Zhang

Topic: development of new methods for brain microstructure non-invasive imaging

Aim: to create a stimulating forum where experts in diffusion-weighted MRI (DW-MRI) and spectroscopy (DW-MRS) techniques can discuss the best way to combine two techniques of complementary scale to improve the non-invasive brain tissue microstructure characterization. To scope out the key research challenges and opportunities associated with this multi-scale approach to microstructure imaging.

Motivation: Up to now, diffusion-weighted magnetic resonance community has been working primarily on the development of either DW-MRI or DW-MRS techniques separately, without exploiting the complementarity between them to create a new unified technique which can perform much better than both on their own. We want to push the community to change its point of view, considering combining the two techniques of complementary scale to improve the non-invasive brain tissue microstructure characterization.

Key invitees: Prof. F Barkhof (ION/UCH, UK); Dr. S Bisdas (ION/UCH, UK); Dr. S Punwani (ION/UCH, UK); Prof. S. Lehéricy (ICM, France); Dr. F Branzoli (ICM, France); Prof. I Ronen (LUMC, Netherlands); Dr. M Nilsson (Lund University, Sweden); Dr. J Valette (CEA/MIRCen, France).

Attendees: over 50 students, researchers and professors from UCL; KCL; Cambridge University; Oxford University; Imperial College; Crick's Institute; NHS.

Outcomes:

1) Review paper on the combination of DW-MRI and DW-MRS, in collaboration with Julien Valette (CEA Fontenay-aux-Roses in Paris, France), Itamar Ronen (LUMC in Leiden, the Netherlands) and Noam Shemesh (Champalimaud Centre for the Unknown in Lisbon, Portugal), published on NeuroImage 2017 (https://doi.org/10.1016/j.neuroimage.2017.11.028); 

2) Collaboration with Francesca Branzoli and Stephane Lehericy (ICM in Paris, France): two abstracts submitted to ISMRM 2018; two papers in preparation; consolidation of long-term collaboration. 

3) Collaboration with Noam Shemesh (Champalimaud Centre for the Unknown in Lisbon, Portugal): two abstracts submitted at the ISMRM 2018; two papers in preparation; establishment of new long-term collaboration. 

4) Invited speaker at an equivalent workshop on combining DW-MRI and DW-MRS, 10-12 October 2018, in ICM in Paris, France, organized by Julien Valette, Itamar Ronen and Francesca Branzoli. The aim of the meeting will be to consolidate the collaborations established in the UCL's workshop and to discuss future projects.
Year(s) Of Engagement Activity 2017