Detection of Cerebrovascular Loss in the Normal Aging C57BL/6 Mouse Brain Using in vivo Contrast-Enhanced Magnetic Resonance Angiography
Microvascular rarefaction, or the decrease in vascular density, has been described in the cerebrovasculature of aging humans, rats, and, more recently, mice in the presence and absence of age-dependent diseases. Given the wide use of mice in modeling age-dependent human diseases of the cerebrovascul...
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Frontiers Media S.A.
2020-10-01
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Series: | Frontiers in Aging Neuroscience |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2020.585218/full |
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author | Lindsay K. Hill Lindsay K. Hill Lindsay K. Hill Lindsay K. Hill Dung Minh Hoang Dung Minh Hoang Luis A. Chiriboga Thomas Wisniewski Thomas Wisniewski Thomas Wisniewski Martin J. Sadowski Martin J. Sadowski Martin J. Sadowski Youssef Z. Wadghiri Youssef Z. Wadghiri |
author_facet | Lindsay K. Hill Lindsay K. Hill Lindsay K. Hill Lindsay K. Hill Dung Minh Hoang Dung Minh Hoang Luis A. Chiriboga Thomas Wisniewski Thomas Wisniewski Thomas Wisniewski Martin J. Sadowski Martin J. Sadowski Martin J. Sadowski Youssef Z. Wadghiri Youssef Z. Wadghiri |
author_sort | Lindsay K. Hill |
collection | DOAJ |
description | Microvascular rarefaction, or the decrease in vascular density, has been described in the cerebrovasculature of aging humans, rats, and, more recently, mice in the presence and absence of age-dependent diseases. Given the wide use of mice in modeling age-dependent human diseases of the cerebrovasculature, visualization, and quantification of the global murine cerebrovasculature is necessary for establishing the baseline changes that occur with aging. To provide in vivo whole-brain imaging of the cerebrovasculature in aging C57BL/6 mice longitudinally, contrast-enhanced magnetic resonance angiography (CE-MRA) was employed using a house-made gadolinium-bearing micellar blood pool agent. Enhancement in the vascular space permitted quantification of the detectable, or apparent, cerebral blood volume (aCBV), which was analyzed over 2 years of aging and compared to histological analysis of the cerebrovascular density. A significant loss in the aCBV was detected by CE-MRA over the aging period. Histological analysis via vessel-probing immunohistochemistry confirmed a significant loss in the cerebrovascular density over the same 2-year aging period, validating the CE-MRA findings. While these techniques use widely different methods of assessment and spatial resolutions, their comparable findings in detected vascular loss corroborate the growing body of literature describing vascular rarefaction aging. These findings suggest that such age-dependent changes can contribute to cerebrovascular and neurodegenerative diseases, which are modeled using wild-type and transgenic laboratory rodents. |
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language | English |
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spelling | doaj.art-ddf77610c3994948b381abf519ebcfd82022-12-21T21:46:59ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652020-10-011210.3389/fnagi.2020.585218585218Detection of Cerebrovascular Loss in the Normal Aging C57BL/6 Mouse Brain Using in vivo Contrast-Enhanced Magnetic Resonance AngiographyLindsay K. Hill0Lindsay K. Hill1Lindsay K. Hill2Lindsay K. Hill3Dung Minh Hoang4Dung Minh Hoang5Luis A. Chiriboga6Thomas Wisniewski7Thomas Wisniewski8Thomas Wisniewski9Martin J. Sadowski10Martin J. Sadowski11Martin J. Sadowski12Youssef Z. Wadghiri13Youssef Z. Wadghiri14Department of Chemical and Biomolecular Engineering, NYU Tandon School of Engineering, Brooklyn, NY, United StatesDepartment of Radiology, Center for Advanced Imaging Innovation and Research (CAI2R), NYU Grossman School of Medicine, New York, NY, United StatesDepartment of Radiology, Bernard and Irene Schwartz Center for Biomedical Imaging, NYU Grossman School of Medicine, New York, NY, United StatesDepartment of Biomedical Engineering, SUNY Downstate Medical Center, Brooklyn, NY, United StatesDepartment of Radiology, Center for Advanced Imaging Innovation and Research (CAI2R), NYU Grossman School of Medicine, New York, NY, United StatesDepartment of Radiology, Bernard and Irene Schwartz Center for Biomedical Imaging, NYU Grossman School of Medicine, New York, NY, United StatesDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, United StatesDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, United StatesDepartment of Neurology, NYU Grossman School of Medicine, New York, NY, United StatesDepartment of Psychiatry, NYU Grossman School of Medicine, New York, NY, United StatesDepartment of Neurology, NYU Grossman School of Medicine, New York, NY, United StatesDepartment of Psychiatry, NYU Grossman School of Medicine, New York, NY, United StatesDepartment of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY, United StatesDepartment of Radiology, Center for Advanced Imaging Innovation and Research (CAI2R), NYU Grossman School of Medicine, New York, NY, United StatesDepartment of Radiology, Bernard and Irene Schwartz Center for Biomedical Imaging, NYU Grossman School of Medicine, New York, NY, United StatesMicrovascular rarefaction, or the decrease in vascular density, has been described in the cerebrovasculature of aging humans, rats, and, more recently, mice in the presence and absence of age-dependent diseases. Given the wide use of mice in modeling age-dependent human diseases of the cerebrovasculature, visualization, and quantification of the global murine cerebrovasculature is necessary for establishing the baseline changes that occur with aging. To provide in vivo whole-brain imaging of the cerebrovasculature in aging C57BL/6 mice longitudinally, contrast-enhanced magnetic resonance angiography (CE-MRA) was employed using a house-made gadolinium-bearing micellar blood pool agent. Enhancement in the vascular space permitted quantification of the detectable, or apparent, cerebral blood volume (aCBV), which was analyzed over 2 years of aging and compared to histological analysis of the cerebrovascular density. A significant loss in the aCBV was detected by CE-MRA over the aging period. Histological analysis via vessel-probing immunohistochemistry confirmed a significant loss in the cerebrovascular density over the same 2-year aging period, validating the CE-MRA findings. While these techniques use widely different methods of assessment and spatial resolutions, their comparable findings in detected vascular loss corroborate the growing body of literature describing vascular rarefaction aging. These findings suggest that such age-dependent changes can contribute to cerebrovascular and neurodegenerative diseases, which are modeled using wild-type and transgenic laboratory rodents.https://www.frontiersin.org/articles/10.3389/fnagi.2020.585218/fullmagnetic resonance (MR) angiographyblood pool agentmouse brain agingcerebral blood volume (CBV)rarefactionMRI |
spellingShingle | Lindsay K. Hill Lindsay K. Hill Lindsay K. Hill Lindsay K. Hill Dung Minh Hoang Dung Minh Hoang Luis A. Chiriboga Thomas Wisniewski Thomas Wisniewski Thomas Wisniewski Martin J. Sadowski Martin J. Sadowski Martin J. Sadowski Youssef Z. Wadghiri Youssef Z. Wadghiri Detection of Cerebrovascular Loss in the Normal Aging C57BL/6 Mouse Brain Using in vivo Contrast-Enhanced Magnetic Resonance Angiography Frontiers in Aging Neuroscience magnetic resonance (MR) angiography blood pool agent mouse brain aging cerebral blood volume (CBV) rarefaction MRI |
title | Detection of Cerebrovascular Loss in the Normal Aging C57BL/6 Mouse Brain Using in vivo Contrast-Enhanced Magnetic Resonance Angiography |
title_full | Detection of Cerebrovascular Loss in the Normal Aging C57BL/6 Mouse Brain Using in vivo Contrast-Enhanced Magnetic Resonance Angiography |
title_fullStr | Detection of Cerebrovascular Loss in the Normal Aging C57BL/6 Mouse Brain Using in vivo Contrast-Enhanced Magnetic Resonance Angiography |
title_full_unstemmed | Detection of Cerebrovascular Loss in the Normal Aging C57BL/6 Mouse Brain Using in vivo Contrast-Enhanced Magnetic Resonance Angiography |
title_short | Detection of Cerebrovascular Loss in the Normal Aging C57BL/6 Mouse Brain Using in vivo Contrast-Enhanced Magnetic Resonance Angiography |
title_sort | detection of cerebrovascular loss in the normal aging c57bl 6 mouse brain using in vivo contrast enhanced magnetic resonance angiography |
topic | magnetic resonance (MR) angiography blood pool agent mouse brain aging cerebral blood volume (CBV) rarefaction MRI |
url | https://www.frontiersin.org/articles/10.3389/fnagi.2020.585218/full |
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