MRI measurements of Blood-Brain Barrier function in dementia: A review of recent studies

Abstract

Blood-brain barrier (BBB) separates the systemic circulation and the brain, regulating transport of most molecules to protect the brain microenvironment. Multiple structural and functional components preserve the integrity of the BBB. Several imaging modalities are available to study disruption of the BBB. However, the subtle changes in BBB leakage that occurs in vascular cognitive impairment and Alzheimer's disease have been less well studied. Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is the most widely adopted non-invasive imaging technique for evaluating BBB breakdown. It is used as a significant marker for a wide variety of diseases with large permeability leaks, such as brain tumors and multiple sclerosis, to more subtle disruption in chronic vascular disease and dementia. DCE-MRI analysis of BBB includes both model-free parameters and quantitative parameters using pharmacokinetic modelling. We review MRI studies of BBB breakdown in dementia. The challenges in measuring subtle BBB changes and the state of the art techniques are initially examined. Subsequently, a systematic review comparing methodologies from recent in-vivo MRI studies is presented. Various factors related to subtle BBB permeability measurement such as DCE-MRI acquisition parameters, arterial input assessment, T1 mapping and data analysis methods are reviewed with the focus on finding the optimal technique. Finally, the reported BBB permeability values in dementia are compared across different studies and across various brain regions. We conclude that reliable measurement of low-level BBB permeability across sites remains a difficult problem and a standardization of the methodology for both data acquisition and quantitative analysis is required. This article is part of the Special Issue entitled 'Cerebral Ischemia'.

Keywords: Blood-brain barrier permeability; Dementia; Dynamic contrast enhanced MRI; Vascular cognitive impairment.

Copyright © 2017 Elsevier Ltd. All rights reserved.

Figures

Figure 1

The DCE-MRI method consists of five steps. During data acquisition we choose the contrast agent (CA) type and dosage and the MRI sequence for T1 mapping. T1 and CA concentrations are then calculated from the data. Next we have to make a choice of the tracer-kinetic model to use. Patlak model is one such example. The model parameters are finally calculated.

Figure 2

The tissue model within a voxel is described for the tracer-kinetic model described by Equation [1]. The voxel is divided into extravascular extracellular space (EES) with a volume fraction ve (blue), and the intravascular space (light red). The EES space excludes the brain cells (yellow) and the plasma (light red) with volume fraction vp excludes the blood cells (red). The model parameters to be estimated are volume transfer constant Ktrans, rate constant for back flow kep, and the volume fractions vp and ve.

Figure 3

The flow diagram summarizes the search strategy and inclusion-exclusion criteria.

Figure 4

A majority of increased permeability (red) is within a penumbra (green) marked around the white matter hyper-intensity. Image (B) is an enlarged version of the image (A).