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...

Full description

Bibliographic Details
Main Authors: Lindsay K. Hill, Dung Minh Hoang, Luis A. Chiriboga, Thomas Wisniewski, Martin J. Sadowski, Youssef Z. Wadghiri
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-10-01
Series:Frontiers in Aging Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnagi.2020.585218/full
_version_ 1831571859598999552
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.
first_indexed 2024-12-17T13:16:10Z
format Article
id doaj.art-ddf77610c3994948b381abf519ebcfd8
institution Directory Open Access Journal
issn 1663-4365
language English
last_indexed 2024-12-17T13:16:10Z
publishDate 2020-10-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Aging Neuroscience
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
work_keys_str_mv AT lindsaykhill detectionofcerebrovascularlossinthenormalagingc57bl6mousebrainusinginvivocontrastenhancedmagneticresonanceangiography
AT lindsaykhill detectionofcerebrovascularlossinthenormalagingc57bl6mousebrainusinginvivocontrastenhancedmagneticresonanceangiography
AT lindsaykhill detectionofcerebrovascularlossinthenormalagingc57bl6mousebrainusinginvivocontrastenhancedmagneticresonanceangiography
AT lindsaykhill detectionofcerebrovascularlossinthenormalagingc57bl6mousebrainusinginvivocontrastenhancedmagneticresonanceangiography
AT dungminhhoang detectionofcerebrovascularlossinthenormalagingc57bl6mousebrainusinginvivocontrastenhancedmagneticresonanceangiography
AT dungminhhoang detectionofcerebrovascularlossinthenormalagingc57bl6mousebrainusinginvivocontrastenhancedmagneticresonanceangiography
AT luisachiriboga detectionofcerebrovascularlossinthenormalagingc57bl6mousebrainusinginvivocontrastenhancedmagneticresonanceangiography
AT thomaswisniewski detectionofcerebrovascularlossinthenormalagingc57bl6mousebrainusinginvivocontrastenhancedmagneticresonanceangiography
AT thomaswisniewski detectionofcerebrovascularlossinthenormalagingc57bl6mousebrainusinginvivocontrastenhancedmagneticresonanceangiography
AT thomaswisniewski detectionofcerebrovascularlossinthenormalagingc57bl6mousebrainusinginvivocontrastenhancedmagneticresonanceangiography
AT martinjsadowski detectionofcerebrovascularlossinthenormalagingc57bl6mousebrainusinginvivocontrastenhancedmagneticresonanceangiography
AT martinjsadowski detectionofcerebrovascularlossinthenormalagingc57bl6mousebrainusinginvivocontrastenhancedmagneticresonanceangiography
AT martinjsadowski detectionofcerebrovascularlossinthenormalagingc57bl6mousebrainusinginvivocontrastenhancedmagneticresonanceangiography
AT youssefzwadghiri detectionofcerebrovascularlossinthenormalagingc57bl6mousebrainusinginvivocontrastenhancedmagneticresonanceangiography
AT youssefzwadghiri detectionofcerebrovascularlossinthenormalagingc57bl6mousebrainusinginvivocontrastenhancedmagneticresonanceangiography