Heye, A.K., Thrippleton, M.J, Armitage, P.A. et al. (5 more authors) (2016) Tracer kinetic modelling for DCE-MRI quantification of subtle blood–brain barrier permeability. NeuroImage, 125. pp. 446-455. ISSN 1053-8119
Abstract
There is evidence that subtle breakdown of the blood–brain barrier (BBB) is a pathophysiological component of several diseases, including cerebral small vessel disease and some dementias. Dynamic contrast-enhanced MRI (DCE-MRI) combined with tracer kinetic modelling is widely used for assessing permeability and perfusion in brain tumours and body tissues where contrast agents readily accumulate in the extracellular space. However, in diseases where leakage is subtle, the optimal approach for measuring BBB integrity is likely to differ since the magnitude and rate of enhancement caused by leakage are extremely low; several methods have been reported in the literature, yielding a wide range of parameters even in healthy subjects. We hypothesised that the Patlak model is a suitable approach for measuring low-level BBB permeability with low temporal resolution and high spatial resolution and brain coverage, and that normal levels of scanner instability would influence permeability measurements. DCE-MRI was performed in a cohort of mild stroke patients (n = 201) with a range of cerebral small vessel disease severity. We fitted these data to a set of nested tracer kinetic models, ranking their performance according to the Akaike information criterion. To assess the influence of scanner drift, we scanned 15 healthy volunteers that underwent a “sham” DCE-MRI procedure without administration of contrast agent. Numerical simulations were performed to investigate model validity and the effect of scanner drift. The Patlak model was found to be most appropriate for fitting low-permeability data, and the simulations showed vp and KTrans estimates to be reasonably robust to the model assumptions. However, signal drift (measured at approximately 0.1% per minute and comparable to literature reports in other settings) led to systematic errors in calculated tracer kinetic parameters, particularly at low permeabilities. Our findings justify the growing use of the Patlak model in low-permeability states, which has the potential to provide valuable information regarding BBB integrity in a range of diseases. However, absolute values of the resulting tracer kinetic parameters should be interpreted with extreme caution, and the size and influence of signal drift should be measured where possible.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | Blood–brain barrier; Dynamic contrast-enhanced MRI; Tracer kinetic modelling; Cerebral small vessel disease |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Infection, Immunity and Cardiovascular Disease |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 02 Nov 2016 11:33 |
Last Modified: | 02 Nov 2016 11:33 |
Published Version: | http://dx.doi.org/10.1016/j.neuroimage.2015.10.018 |
Status: | Published |
Publisher: | Elsevier |
Refereed: | Yes |
Identification Number: | 10.1016/j.neuroimage.2015.10.018 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:106413 |