Quantitative measurement of blood‐brain barrier permeability in human using dynamic contrast‐enhanced MRI with fast T₁ mapping

Abstract

Breakdown of the blood-brain barrier (BBB), occurring in many neurological diseases, has been difficult to measure noninvasively in humans. Dynamic contrast-enhanced magnetic resonance imaging measures BBB permeability. However, important technical challenges remain and normative data from healthy humans is lacking. We report the implementation of a method for measuring BBB permeability, originally developed in animals, to estimate BBB permeability in both healthy subjects and patients with white matter pathology. Fast T 1 mapping was used to measure the leakage of contrast agent Gadolinium diethylene triamine pentaacetic acid (Gd-DTPA) from plasma into brain. A quarter of the standard Gd-DTPA dose for dynamic contrastenhanced magnetic resonance imaging was found to give both sufficient contrast-to-noise and high T 1 sensitivity. The Patlak graphical approach was used to calculate the permeability from changes in 1/T 1 . Permeability constants were compared with cerebrospinal fluid albumin index. The upper limit of the 95% confidence interval for white matter BBB permeability for normal subjects was 3 × 10 −4 L/g min. MRI measurements correlated strongly with levels of cerebrospinal fluid albumin in those subjects undergoing lumbar puncture. Dynamic contrast-enhanced magnetic resonance imaging with low dose Gd-DTPA and fast T 1 imaging is a sensitive method to measure subtle differences in BBB permeability in humans and may have advantages over techniques based purely on the measurement of pixel contrast changes.

Measuring subtle leakage of the blood-brain barrier in cerebrovascular disease with DCE-MRI: Test-retest reproducibility and its influencing factors

“…The leakage rates observed in this study were in accordance with values found in a previous study in patients with white matter pathology (∼2.0·10 −3 min −1 ) and a study in patients with mild cognitive impairment (∼1.0·10 −3 min −1 ), despite differences in image acquisition and analysis methods. The fairly low CVs and moderate to excellent ICCs observed in this study indicate that the reproducibility of measuring subtle leakage is moderate to excellent.…”

“…Recently, DCE‐MRI is increasingly applied to estimate subtle leakage of the BBB in cerebrovascular and neurodegenerative diseases (e.g. cerebral small vessel disease [cSVD] and Alzheimer's disease) . These studies have found increased leakage of the BBB, which confirmed the role of the breakdown of this barrier in the pathophysiology.…”

Bridging barriers: a comparative look at the blood–brain barrier across organisms

“…Studies performed in mice have demonstrated that observations of leakage with MRI using gadolinium reflect leakage patterns observed after injection with exogenous tracers (Nitta et al 2003;Navarathna et al 2013;Li et al 2014). DCE-MRI has been used to show that BBB leakage is a characteristic of several neurodegenerative diseases in humans, including multiple sclerosis (Taheri et al 2010;Gaitán et al 2011;Ingrisch et al 2012;Cramer et al 2015;Montagne et al 2015) and Alzheimer's disease (Montagne et al 2015;van de Haar et al 2016a, b).…”

Characterizing blood–brain barrier perturbations after exposure to human triglyceride‐rich lipoprotein lipolysis products using MRI in a rat model

“…To test this hypothesis, we used MR contrast agent (MRCA)‐assisted MRI as used extensively in assessing BBB injury after stroke both clinically and experimentally . MRCA‐MRI has the advantage of achieving relatively high resolution and being relatively noninvasive, allowing a subject to be monitored over time.…”