A four-dimensional computational model of dynamic contrast-enhanced magnetic resonance imaging measurement of subtle blood-brain barrier leakage

Jose Bernal, Maria d.C. Valdés-Hernández, Javier Escudero, Anna K. Heye, Eleni Sakka, Paul A. Armitage, Stephen Makin, Rhian M. Touyz, Joanna M. Wardlaw, Michael J. Thrippleton* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)
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Dynamic contrast-enhanced MRI (DCE-MRI) is increasingly used to quantify and map the spatial distribution of blood-brain barrier (BBB) leakage in neurodegenerative disease, including cerebral small vessel disease and dementia. However, the subtle nature of leakage and resulting small signal changes make quantification challenging. While simplified one-dimensional simulations have probed the impact of noise, scanner drift, and model assumptions, the impact of spatio-temporal effects such as gross motion, k-space sampling and motion artefacts on parametric leakage maps has been overlooked. Moreover, evidence on which to base the design of imaging protocols is lacking due to practical difficulties and the lack of a reference method. To address these problems, we present an open-source computational model of the DCE-MRI acquisition process for generating four dimensional Digital Reference Objects (DROs), using a high-resolution brain atlas and incorporating realistic patient motion, extra-cerebral signals, noise and k-space sampling. Simulations using the DROs demonstrated a dominant influence of spatio-temporal effects on both the visual appearance of parameter maps and on measured tissue leakage rates. The computational model permits greater understanding of the sensitivity and limitations of subtle BBB leakage measurement and provides a non-invasive means of testing and optimising imaging protocols for future studies.
Original languageEnglish
Article number117786
Number of pages12
Early online date23 Jan 2021
Publication statusPublished - 15 Apr 2021

Bibliographical note

This work is supported by the MRC Doctoral Training Programme
in Precision Medicine (JB); the Wellcome Trust (patient recruitment, scanning, and primary study - Reference No. WT088134/Z/09/A); the
UK Dementia Research Institute, which receives its funding from DRI
Ltd, funded by the UK MRC, Alzheimer’s Society, and Alzheimer’s Research UK; the Fondation Leducq Network for the Study of Perivascular Spaces in Small Vessel Disease (16 CVD 05); The Row Fogo
Charitable Trust Centre for Research into ageing and the Brain (MVH) (BRO-D.FID3668413); a British Heart Foundation Chair award (RMT) (CH/12/4/29762); and NHS Lothian Research and Development Office (MJT); European Union Horizon 2020, PHC-03-15, project No666881. We thank the participants, their families, radiographers at Edinburgh
Imaging, and the Stroke Research Network at the University of Edinburgh.


  • Digital reference object
  • Blood-brain barrier permeability
  • Spatio-temporal imaging artefacts
  • Endothelial dysfunction
  • Cerebral small vessel disease
  • Neurology
  • Cognitive Neuroscience


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