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

Neuroimage. 2021 Apr 15;230:117786. doi: 10.1016/j.neuroimage.2021.117786. Epub 2021 Jan 23.


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.

Keywords: Blood-brain barrier permeability; Cerebral small vessel disease; DCE-MRI; Digital reference object; Endothelial dysfunction; Spatio-temporal imaging artefacts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Artifacts
  • Blood-Brain Barrier / diagnostic imaging*
  • Blood-Brain Barrier / metabolism
  • Capillary Permeability / physiology
  • Cerebral Small Vessel Diseases / diagnostic imaging
  • Cerebral Small Vessel Diseases / metabolism
  • Computer Simulation*
  • Contrast Media* / metabolism
  • Humans
  • Image Processing, Computer-Assisted / methods*
  • Magnetic Resonance Imaging / methods*
  • Models, Neurological
  • Motion
  • Neurodegenerative Diseases / diagnostic imaging*
  • Neurodegenerative Diseases / metabolism


  • Contrast Media