AUTHOR=Shao Xingfeng , Jann Kay , Ma Samantha J. , Yan Lirong , Montagne Axel , Ringman John M. , Zlokovic Berislav V. , Wang Danny J. J. 

TITLE=Comparison Between Blood-Brain Barrier Water Exchange Rate and Permeability to Gadolinium-Based Contrast Agent in an Elderly Cohort

JOURNAL=Frontiers in Neuroscience

VOLUME=14

YEAR=2020

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2020.571480

DOI=10.3389/fnins.2020.571480

ISSN=1662-453X

ABSTRACT=<p><bold>Background:</bold> Dynamic contrast-enhanced (DCE) MRI using intravenous injection of gadolinium-based contrast agents (GBCAs) is commonly used for imaging blood-brain barrier (BBB) permeability. Water is an alternative endogenous tracer with limited exchange rate across the BBB. A direct comparison between BBB water exchange rate and BBB permeability to GBCA is missing. The purpose of this study was to directly compare BBB permeability to GBCA (Ktrans and k<sub>Gad</sub> = Ktrans/Vp) and water exchange rate (kw) in a cohort of elderly subjects at risk of cerebral small vessel disease (cSVD).</p><p><bold>Methods:</bold> Ktrans/k<sub>Gad</sub> and kw were measured by DCE-MRI and diffusion prepared pseudo-continuous arterial spin labeling (DP-pCASL), respectively, at 3 Tesla in 16 elderly subjects (3 male, age = 67.9 ± 3.0 yrs) at risk of cSVD. The test-retest reproducibility of kw measurements was evaluated with repeated scans ~6 weeks apart. Mixed effects linear regression was performed in the whole brain, gray matter (GM), white matter (WM), and 6 subcortical brain regions to investigate associations between Ktrans/k<sub>Gad</sub> and test-retest kw. In addition, kw and Ktrans/k<sub>Gad</sub> were compared in normal appearing white matter (NAWM), white matter hyperintensity (WMH) lesions and penumbra.</p><p><bold>Results:</bold> Significant correlation was found between kw and Ktrans only in WM (β = 6.7 × 10<sup>4</sup>, <italic>P</italic> = 0.036), caudate (β = 8.6 × 10<sup>4</sup>, <italic>P</italic> = 0.029), and middle cerebral artery (MCA) perforator territory (β = 6.9 × 10<sup>4</sup>, <italic>P</italic> = 0.009), but not in the whole brain, GM or rest 5 brain regions. Significant correlation was found between kw and k<sub>Gad</sub> in MCA perforator territory (β = 1.5 × 10<sup>3</sup>, <italic>P</italic> = 0.049), medial-temporal lobe (β = 3.5 × 10<sup>3</sup>, <italic>P</italic> = 0.032), and hippocampus (β = 3.4 × 10<sup>3</sup>, <italic>P</italic> = 0.038), but not in the rest brain regions. Good reproducibility of kw measurements (ICC=0.75) was achieved. Ktrans was significantly lower inside WMH than WMH penumbra (16.2%, <italic>P</italic> = 0.026), and k<sub>Gad</sub> was significantly lower in NAWM than in the WMH penumbra (20.8%, <italic>P</italic> &lt; 0.001).</p><p><bold>Conclusion:</bold> kw provides a measure of water exchange rate across the BBB with good test-retest reproducibility. The BBB mechanism underlying kw and Ktrans/k<sub>Gad</sub> is likely to be different, as manifested by correlations in only three brain regions for each pair of comparison between kw and Ktrans or k<sub>Gad</sub>.</p>