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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Published inFrontiers in aging neuroscience Vol. 12; p. 585218
Main Authors Hill, Lindsay K, Hoang, Dung Minh, Chiriboga, Luis A, Wisniewski, Thomas, Sadowski, Martin J, Wadghiri, Youssef Z
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Research Foundation 20.10.2020
Frontiers Media S.A
Subjects
Age
Aging
Angiography
Blood
blood pool agent
Brain
Cerebral blood flow
cerebral blood volume (CBV)
Gadolinium
Immunohistochemistry
Laboratory animals
Lipids
magnetic resonance (MR) angiography
Medical imaging
Microscopy
Microvasculature
mouse brain aging
MRI
Neurodegenerative diseases
Neuroimaging
Neuroscience
Polyethylene glycol
rarefaction
Vascular diseases
United States > US
cerebral blood volume (CBV)
magnetic resonance (MR) angiography
mouse brain aging
rarefaction
MRI
blood pool agent
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Abstract 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 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 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.
AbstractList 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.
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 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 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.
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.
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 in establishing the baseline changes that occur with aging. In order 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 similarity in detected vascular loss corroborates the growing body of literature describing vascular rarefaction in aging and suggests that such age-dependent changes can contribute to cerebrovascular and neurodegenerative diseases, which are modeled using wild-type and transgenic laboratory rodents.
Author Hoang, Dung Minh
Chiriboga, Luis A
Wisniewski, Thomas
Wadghiri, Youssef Z
Sadowski, Martin J
Hill, Lindsay K
AuthorAffiliation 5 Department of Pathology, NYU Grossman School of Medicine , New York, NY , United States
4 Department of Biomedical Engineering, SUNY Downstate Medical Center , Brooklyn, NY , United States
8 Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine , New York, NY , United States
2 Department of Radiology, Center for Advanced Imaging Innovation and Research (CAI2R), NYU Grossman School of Medicine , New York, NY , United States
7 Department of Psychiatry, NYU Grossman School of Medicine , New York, NY , United States
6 Department of Neurology, NYU Grossman School of Medicine , New York, NY , United States
1 Department of Chemical and Biomolecular Engineering, NYU Tandon School of Engineering , Brooklyn, NY , United States
3 Department of Radiology, Bernard and Irene Schwartz Center for Biomedical Imaging, NYU Grossman School of Medicine , New York, NY , United States
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– name: 4 Department of Biomedical Engineering, SUNY Downstate Medical Center , Brooklyn, NY , United States
– name: 7 Department of Psychiatry, NYU Grossman School of Medicine , New York, NY , United States
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Copyright Copyright © 2020 Hill, Hoang, Chiriboga, Wisniewski, Sadowski and Wadghiri.
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Keywords cerebral blood volume (CBV)
magnetic resonance (MR) angiography
mouse brain aging
rarefaction
MRI
blood pool agent
Language English
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ORCID: Lindsay K. Hill orcid.org/0000-0002-1833-8574 Dung Minh Hoang orcid.org/0000-0001-7613-7167 Luis A. Chiriboga orcid.org/0000-0002-2028-6873 Thomas Wisniewski orcid.org/0000-0002-3379-8966 Martin J. Sadowski orcid.org/0000-0002-3830-1779 Youssef Z. Wadghiri orcid.org/0000-0001-7175-9397
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Snippet Microvascular rarefaction, or the decrease in vascular density, has been described in the cerebrovasculature of aging humans, rats, and, more recently, mice in...
Microvascular rarefaction, or the decrease in vascular density, has been described in the cerebrovasculature of aging humans, rats and, more recently, mice in...
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StartPage 585218
SubjectTerms Age
Aging
Angiography
Blood
blood pool agent
Brain
Cerebral blood flow
cerebral blood volume (CBV)
Gadolinium
Immunohistochemistry
Laboratory animals
Lipids
magnetic resonance (MR) angiography
Medical imaging
Microscopy
Microvasculature
mouse brain aging
MRI
Neurodegenerative diseases
Neuroimaging
Neuroscience
Polyethylene glycol
rarefaction
Vascular diseases
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Title Detection of Cerebrovascular Loss in the Normal Aging C57BL/6 Mouse Brain Using in vivo Contrast-Enhanced Magnetic Resonance Angiography
URI https://www.ncbi.nlm.nih.gov/pubmed/33192479
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Volume 12
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