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

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 K_i. This paper provides evidence that K_i 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

Background

Blood‐brain barrier (BBB) leakage can be measured using dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) as the influx constant K_i. To validate this method we compared measured K_i with biological expectations, namely (1) higher K_i 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 K_i in visibly‐enhancing multiple sclerosis (MS) lesions versus MS normal appearing white matter (NAWM), and (4) higher K_i in MS NAWM versus healthy individual NAWM.

Methods

We recruited 13 healthy individuals and 12 patients with MS and performed whole‐brain 3D DCE‐MRI at 3 Tesla. K_i and CBV were calculated using Patlak modelling for manual regions of interest (ROI) and segmented tissue masks. Results: K_i was higher in control GM versus WM (p = 0.001). CBV was higher in GM versus WM (p = 0.005, mean ratio 1.9). K_i 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).

Conclusions

K_i 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 K_i measured by DCE‐MRI as a marker of overall BBB leakage.

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