Detection of Cerebrovascular Loss in the Normal Aging C57BL/6 Mouse Brain Using in vivo Contrast-Enhanced Magnetic Resonance Angiography

• Published in: Frontiers 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
• Language: English
• 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
• ISSN: 1663-4365; 1663-4365
• DOI: 10.3389/fnagi.2020.585218

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.