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

TY - JOUR

T1 - Blood-brain barrier permeability measured using dynamic contrast-enhanced magnetic resonance imaging

T2 - a validation study

AU - Varatharaj, Aravinthan

AU - Liljeroth, Maria

AU - Darekar, Angela

AU - Larsson, Henrik B W

AU - Galea, Ian

AU - Cramer, Stig P

N1 - © 2018 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - KEY POINTS: The blood-brain barrier (BBB) is an important and dynamic structure which contributes to homeostasis in the central nervous system. BBB permeability changes occur in health and disease but measurement of BBB permeability in humans is not straightforward. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be used to model the movement of gadolinium contrast into the brain, expressed as the influx constant Ki . Here evidence is provided that Ki as measured by DCE-MRI behaves as expected for a marker of overall BBB leakage. These results support the use of DCE-MRI for in vivo studies of human BBB permeability in health and disease.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.

AB - KEY POINTS: The blood-brain barrier (BBB) is an important and dynamic structure which contributes to homeostasis in the central nervous system. BBB permeability changes occur in health and disease but measurement of BBB permeability in humans is not straightforward. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be used to model the movement of gadolinium contrast into the brain, expressed as the influx constant Ki . Here evidence is provided that Ki as measured by DCE-MRI behaves as expected for a marker of overall BBB leakage. These results support the use of DCE-MRI for in vivo studies of human BBB permeability in health and disease.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.

U2 - 10.1113/JP276887

DO - 10.1113/JP276887

M3 - Journal article

C2 - 30417928

SN - 0022-3751

VL - 597

SP - 699

EP - 709

JO - The Journal of Physiology

JF - The Journal of Physiology

IS - 3

ER -