Non-contrast assessment of blood-brain barrier permeability to water in mice: An arterial spin labeling study at cerebral veins
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | NeuroImage |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1053811923000198 |
| _version_ | 1811169478552059904 |
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| author | Zhiliang Wei Hongshuai Liu Zixuan Lin Minmin Yao Ruoxuan Li Chang Liu Yuguo Li Jiadi Xu Wenzhen Duan Hanzhang Lu |
| author_facet | Zhiliang Wei Hongshuai Liu Zixuan Lin Minmin Yao Ruoxuan Li Chang Liu Yuguo Li Jiadi Xu Wenzhen Duan Hanzhang Lu |
| author_sort | Zhiliang Wei |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T16:43:05Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1095-9572 |
| language | English |
| last_indexed | 2024-04-10T16:43:05Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage |
| spelling | doaj.art-3eaa71ad1aff4a44894599b6621898022023-02-08T04:16:29ZengElsevierNeuroImage1095-95722023-03-01268119870Non-contrast assessment of blood-brain barrier permeability to water in mice: An arterial spin labeling study at cerebral veinsZhiliang Wei0Hongshuai Liu1Zixuan Lin2Minmin Yao3Ruoxuan Li4Chang Liu5Yuguo Li6Jiadi Xu7Wenzhen Duan8Hanzhang Lu9The 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.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, USAThe Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 600N. Wolfe Street, Park 326, Baltimore, MD 21287, USADivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC 8-121, Baltimore, MD 21287, USADivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC 8-121, Baltimore, MD 21287, USADivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC 8-121, Baltimore, MD 21287, USAThe 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, USAThe 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, USADivision 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.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, USABlood-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.http://www.sciencedirect.com/science/article/pii/S1053811923000198Blood-brain barrierPermeability surface-area productWater extractionArterial spin labelingMouseMRI |
| spellingShingle | Zhiliang Wei Hongshuai Liu Zixuan Lin Minmin Yao Ruoxuan Li Chang Liu Yuguo Li Jiadi Xu Wenzhen Duan Hanzhang Lu Non-contrast assessment of blood-brain barrier permeability to water in mice: An arterial spin labeling study at cerebral veins NeuroImage Blood-brain barrier Permeability surface-area product Water extraction Arterial spin labeling Mouse MRI |
| title | Non-contrast assessment of blood-brain barrier permeability to water in mice: An arterial spin labeling study at cerebral veins |
| title_full | Non-contrast assessment of blood-brain barrier permeability to water in mice: An arterial spin labeling study at cerebral veins |
| title_fullStr | Non-contrast assessment of blood-brain barrier permeability to water in mice: An arterial spin labeling study at cerebral veins |
| title_full_unstemmed | Non-contrast assessment of blood-brain barrier permeability to water in mice: An arterial spin labeling study at cerebral veins |
| title_short | Non-contrast assessment of blood-brain barrier permeability to water in mice: An arterial spin labeling study at cerebral veins |
| title_sort | non contrast assessment of blood brain barrier permeability to water in mice an arterial spin labeling study at cerebral veins |
| topic | Blood-brain barrier Permeability surface-area product Water extraction Arterial spin labeling Mouse MRI |
| url | http://www.sciencedirect.com/science/article/pii/S1053811923000198 |
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