Non-contrast assessment of blood-brain barrier permeability to water in mice: An arterial spin labeling study at cerebral veins

Zhiliang Wei; Hongshuai Liu; Zixuan Lin; Minmin Yao; Ruoxuan Li; Chang Liu; Yuguo Li; Jiadi Xu; Wenzhen Duan; Hanzhang Lu

NeuroImage (Mar 2023)

Non-contrast assessment of blood-brain barrier permeability to water in mice: An arterial spin labeling study at cerebral veins

Zhiliang Wei,
Hongshuai Liu,
Zixuan Lin,
Minmin Yao,
Ruoxuan Li,
Chang Liu,
Yuguo Li,
Jiadi Xu,
Wenzhen Duan,
Hanzhang Lu

Affiliations

Zhiliang Wei: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 600N. Wolfe Street, Park 326, Baltimore, MD 21287, USA; F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, USA; Corresponding author at: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 600N. Wolfe Street, Park 326, Baltimore, MD 21287, USA.
Hongshuai Liu: Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC 8-121, Baltimore, MD 21287, USA
Zixuan Lin: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 600N. Wolfe Street, Park 326, Baltimore, MD 21287, USA
Minmin Yao: Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC 8-121, Baltimore, MD 21287, USA
Ruoxuan Li: Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC 8-121, Baltimore, MD 21287, USA
Chang Liu: Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC 8-121, Baltimore, MD 21287, USA
Yuguo Li: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 600N. Wolfe Street, Park 326, Baltimore, MD 21287, USA; F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, USA
Jiadi Xu: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 600N. Wolfe Street, Park 326, Baltimore, MD 21287, USA; F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, USA
Wenzhen Duan: Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC 8-121, Baltimore, MD 21287, USA; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Corresponding author at: Department of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC 8-121, Baltimore, MD 21287, USA.
Hanzhang Lu: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 600N. Wolfe Street, Park 326, Baltimore, MD 21287, USA; F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Journal volume & issue: Vol. 268
p. 119870

Abstract

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Blood-brain barrier (BBB) plays a critical role in protecting the brain from toxins and pathogens. However, in vivo tools to assess BBB permeability are scarce and often require the use of exogenous contrast agents. In this study, we aimed to develop a non-contrast arterial-spin-labeling (ASL) based MRI technique to estimate BBB permeability to water in mice. By determining the relative fraction of labeled water spins that were exchanged into the brain tissue as opposed to those that remained in the cerebral veins, we estimated indices of global BBB permeability to water including water extraction fraction (E) and permeability surface-area product (PS). First, using multiple post-labeling delay ASL experiments, we estimated the bolus arrival time (BAT) of the labeled spins to reach the great vein of Galen (VG) to be 691.2 ± 14.5 ms (N = 5). Next, we investigated the dependence of the VG ASL signal on labeling duration and identified an optimal imaging protocol with a labeling duration of 1200 ms and a PLD of 100 ms. Quantitative E and PS values in wild-type mice were found to be 59.9 ± 3.2% and 260.9 ± 18.9 ml/100 g/min, respectively. In contrast, mice with Huntington's disease (HD) revealed a significantly higher E (69.7 ± 2.4%, P = 0.026) and PS (318.1 ± 17.1 ml/100 g/min, P = 0.040), suggesting BBB breakdown in this mouse model. Reproducibility studies revealed a coefficient-of-variation (CoV) of 4.9 ± 1.7% and 6.1 ± 1.2% for E and PS, respectively. The proposed method may open new avenues for preclinical research on pathophysiological mechanisms of brain diseases and therapeutic trials in animal models.

Published in NeuroImage

ISSN: 1053-8119 (Print); 1095-9572 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neuroimage

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