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Blood-brain barrier permeability measured using dynamic contrast-enhanced magnetic resonance imaging: a validation study

Blood-brain barrier permeability measured using dynamic contrast-enhanced magnetic resonance imaging: a validation study
Blood-brain barrier permeability measured using dynamic contrast-enhanced magnetic resonance imaging: a validation study
Blood–brain barrier (BBB) leakage can be measured using dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) as the influx constant Ki. To validate this method we compared measured Ki with biological expectations, namely (1) higher Ki in healthy individual grey matter (GM) versus white matter (WM), (2) GM/WM cerebral blood volume (CBV) ratio close to the histologically established GM/WM vascular density ratio, (3) higher Ki in visibly enhancing multiple sclerosis (MS) lesions versus MS normal appearing white matter (NAWM), and (4) higher Ki in MS NAWM versus healthy individual NAWM. We recruited 13 healthy individuals and 12 patients with MS and performed whole‐brain 3D DCE‐MRI at 3 T. Ki and CBV were calculated using Patlak modelling for manual regions of interest (ROI) and segmented tissue masks. Ki was higher in control GM versus WM (P = 0.001). CBV was higher in GM versus WM (P = 0.005, mean ratio 1.9). Ki was higher in visibly enhancing MS lesions versus MS NAWM (P = 0.002), and in MS NAWM versus controls (P = 0.014). Bland–Altman analysis showed no significant difference between ROI and segmentation methods (P = 0.638) and an intra‐class correlation coefficient showed moderate single measure consistency (0.610). Ki behaves as expected for a compound marker of permeability and surface area. The GM/WM CBV ratio measured by this technique is in agreement with the literature. This adds evidence to the validity of Ki measured by DCE‐MRI as a marker of overall BBB leakage.
0022-3751
699-709
Varatharaj, Aravinthan
33d833af-9459-4b21-8489-ce9c0b6a09e0
Liljeroth, Maria
30815318-3434-4a70-9010-957799172516
Darekar, Angela
f7b566e5-3568-4c27-aed9-a5275f7a5cf5
Larsson, Henrik B.W.
e6a4213a-310b-4928-8f07-4e2e53be51ae
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Cramer, Stig P.
ed3fe479-8e5e-4e38-bc02-bac30263db63
Varatharaj, Aravinthan
33d833af-9459-4b21-8489-ce9c0b6a09e0
Liljeroth, Maria
30815318-3434-4a70-9010-957799172516
Darekar, Angela
f7b566e5-3568-4c27-aed9-a5275f7a5cf5
Larsson, Henrik B.W.
e6a4213a-310b-4928-8f07-4e2e53be51ae
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Cramer, Stig P.
ed3fe479-8e5e-4e38-bc02-bac30263db63

Varatharaj, Aravinthan, Liljeroth, Maria, Darekar, Angela, Larsson, Henrik B.W., Galea, Ian and Cramer, Stig P. (2019) Blood-brain barrier permeability measured using dynamic contrast-enhanced magnetic resonance imaging: a validation study. The Journal of Physiology, 597 (3), 699-709. (doi:10.1113/JP276887).

Record type: Article

Abstract

Blood–brain barrier (BBB) leakage can be measured using dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) as the influx constant Ki. To validate this method we compared measured Ki with biological expectations, namely (1) higher Ki in healthy individual grey matter (GM) versus white matter (WM), (2) GM/WM cerebral blood volume (CBV) ratio close to the histologically established GM/WM vascular density ratio, (3) higher Ki in visibly enhancing multiple sclerosis (MS) lesions versus MS normal appearing white matter (NAWM), and (4) higher Ki in MS NAWM versus healthy individual NAWM. We recruited 13 healthy individuals and 12 patients with MS and performed whole‐brain 3D DCE‐MRI at 3 T. Ki and CBV were calculated using Patlak modelling for manual regions of interest (ROI) and segmented tissue masks. Ki was higher in control GM versus WM (P = 0.001). CBV was higher in GM versus WM (P = 0.005, mean ratio 1.9). Ki was higher in visibly enhancing MS lesions versus MS NAWM (P = 0.002), and in MS NAWM versus controls (P = 0.014). Bland–Altman analysis showed no significant difference between ROI and segmentation methods (P = 0.638) and an intra‐class correlation coefficient showed moderate single measure consistency (0.610). Ki behaves as expected for a compound marker of permeability and surface area. The GM/WM CBV ratio measured by this technique is in agreement with the literature. This adds evidence to the validity of Ki measured by DCE‐MRI as a marker of overall BBB leakage.

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Accepted/In Press date: 7 November 2018
e-pub ahead of print date: 12 November 2018
Published date: 1 February 2019

Identifiers

Local EPrints ID: 426019
URI: http://eprints.soton.ac.uk/id/eprint/426019
ISSN: 0022-3751
PURE UUID: 98088a80-cbcc-4e93-9820-052e03f9cb13
ORCID for Aravinthan Varatharaj: ORCID iD orcid.org/0000-0003-1629-5774
ORCID for Ian Galea: ORCID iD orcid.org/0000-0002-1268-5102

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Date deposited: 09 Nov 2018 17:30
Last modified: 16 Mar 2024 07:15

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Contributors

Author: Maria Liljeroth
Author: Angela Darekar
Author: Henrik B.W. Larsson
Author: Ian Galea ORCID iD
Author: Stig P. Cramer

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