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

Background: 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 betwee...

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Autores principales: Shao, Xingfeng, Jann, Kay, Ma, Samantha J., Yan, Lirong, Montagne, Axel, Ringman, John M., Zlokovic, Berislav V., Wang, Danny J. J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733970/
https://www.ncbi.nlm.nih.gov/pubmed/33328848
http://dx.doi.org/10.3389/fnins.2020.571480
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author Shao, Xingfeng
Jann, Kay
Ma, Samantha J.
Yan, Lirong
Montagne, Axel
Ringman, John M.
Zlokovic, Berislav V.
Wang, Danny J. J.
author_facet Shao, Xingfeng
Jann, Kay
Ma, Samantha J.
Yan, Lirong
Montagne, Axel
Ringman, John M.
Zlokovic, Berislav V.
Wang, Danny J. J.
author_sort Shao, Xingfeng
collection PubMed
description Background: 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(Gad) = Ktrans/Vp) and water exchange rate (kw) in a cohort of elderly subjects at risk of cerebral small vessel disease (cSVD). Methods: Ktrans/k(Gad) 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(Gad) and test-retest kw. In addition, kw and Ktrans/k(Gad) were compared in normal appearing white matter (NAWM), white matter hyperintensity (WMH) lesions and penumbra. Results: Significant correlation was found between kw and Ktrans only in WM (β = 6.7 × 10(4), P = 0.036), caudate (β = 8.6 × 10(4), P = 0.029), and middle cerebral artery (MCA) perforator territory (β = 6.9 × 10(4), P = 0.009), but not in the whole brain, GM or rest 5 brain regions. Significant correlation was found between kw and k(Gad) in MCA perforator territory (β = 1.5 × 10(3), P = 0.049), medial-temporal lobe (β = 3.5 × 10(3), P = 0.032), and hippocampus (β = 3.4 × 10(3), P = 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%, P = 0.026), and k(Gad) was significantly lower in NAWM than in the WMH penumbra (20.8%, P < 0.001). Conclusion: kw provides a measure of water exchange rate across the BBB with good test-retest reproducibility. The BBB mechanism underlying kw and Ktrans/k(Gad) 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(Gad).
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spelling pubmed-77339702020-12-15 Comparison Between Blood-Brain Barrier Water Exchange Rate and Permeability to Gadolinium-Based Contrast Agent in an Elderly Cohort Shao, Xingfeng Jann, Kay Ma, Samantha J. Yan, Lirong Montagne, Axel Ringman, John M. Zlokovic, Berislav V. Wang, Danny J. J. Front Neurosci Neuroscience Background: 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(Gad) = Ktrans/Vp) and water exchange rate (kw) in a cohort of elderly subjects at risk of cerebral small vessel disease (cSVD). Methods: Ktrans/k(Gad) 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(Gad) and test-retest kw. In addition, kw and Ktrans/k(Gad) were compared in normal appearing white matter (NAWM), white matter hyperintensity (WMH) lesions and penumbra. Results: Significant correlation was found between kw and Ktrans only in WM (β = 6.7 × 10(4), P = 0.036), caudate (β = 8.6 × 10(4), P = 0.029), and middle cerebral artery (MCA) perforator territory (β = 6.9 × 10(4), P = 0.009), but not in the whole brain, GM or rest 5 brain regions. Significant correlation was found between kw and k(Gad) in MCA perforator territory (β = 1.5 × 10(3), P = 0.049), medial-temporal lobe (β = 3.5 × 10(3), P = 0.032), and hippocampus (β = 3.4 × 10(3), P = 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%, P = 0.026), and k(Gad) was significantly lower in NAWM than in the WMH penumbra (20.8%, P < 0.001). Conclusion: kw provides a measure of water exchange rate across the BBB with good test-retest reproducibility. The BBB mechanism underlying kw and Ktrans/k(Gad) 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(Gad). Frontiers Media S.A. 2020-11-30 /pmc/articles/PMC7733970/ /pubmed/33328848 http://dx.doi.org/10.3389/fnins.2020.571480 Text en Copyright © 2020 Shao, Jann, Ma, Yan, Montagne, Ringman, Zlokovic and Wang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Shao, Xingfeng
Jann, Kay
Ma, Samantha J.
Yan, Lirong
Montagne, Axel
Ringman, John M.
Zlokovic, Berislav V.
Wang, Danny J. J.
Comparison Between Blood-Brain Barrier Water Exchange Rate and Permeability to Gadolinium-Based Contrast Agent in an Elderly Cohort
title Comparison Between Blood-Brain Barrier Water Exchange Rate and Permeability to Gadolinium-Based Contrast Agent in an Elderly Cohort
title_full Comparison Between Blood-Brain Barrier Water Exchange Rate and Permeability to Gadolinium-Based Contrast Agent in an Elderly Cohort
title_fullStr Comparison Between Blood-Brain Barrier Water Exchange Rate and Permeability to Gadolinium-Based Contrast Agent in an Elderly Cohort
title_full_unstemmed Comparison Between Blood-Brain Barrier Water Exchange Rate and Permeability to Gadolinium-Based Contrast Agent in an Elderly Cohort
title_short Comparison Between Blood-Brain Barrier Water Exchange Rate and Permeability to Gadolinium-Based Contrast Agent in an Elderly Cohort
title_sort comparison between blood-brain barrier water exchange rate and permeability to gadolinium-based contrast agent in an elderly cohort
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733970/
https://www.ncbi.nlm.nih.gov/pubmed/33328848
http://dx.doi.org/10.3389/fnins.2020.571480
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