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

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 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 gadoliniumbearing 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.

Aging reduces calreticulin expression and alters spontaneous calcium signals in astrocytic endfeet of the mouse dorsolateral striatum

“…6 ). In line with our finding are studies showing no change in striatal BV density between young and aged mice 62 , 63 . However, numerous reports confirm decreased cortical BV density with aging 64 – 66 ; indicating that BV density loss in the aging brain is likely region specific.…”

Fluorescently-tagged magnetic protein nanoparticles for high-resolution optical and ultra-high field magnetic resonance dual-modal cerebral angiography

“…Recent studies have reported visualization of cerebral vasculature through MRA methods on ultra-high (≥7 T) magnetic fields. 1,[70][71][72][73] Pastor et al reported an optimized protocol for visualization of cerebral microvessels of rats using a repetition time of 60 ms and achieved an isotropic resolution up to 62 µm in 98 min of total imaging time at 11.7 T using 3D TOF angiograms. This protocol seems promising for cerebral MRA at ultra-high field MRI, however the time required to visualize the microvessels was surprisingly high which may introduce a challenge the need to keep animals under anesthesia for a prolonged scan.…”

“…The cerebral vasculature plays a critical role in maintaining normal brain function and cognition, providing an uninterrupted supply of oxygen and nutrients, and thus alterations to blood supply could contribute to brain pathologies. 1,2 Cerebral angiography can help diagnose and track effective therapies for neurovascular diseases, and may eliminate the need for surgery. 3,4 A critical barrier to understanding cerebrovascular pathophysiology is the ability to accurately visualize microvas-cular networks and/or blood perfusion.…”

Neuronal deletion of MnSOD in mice leads to demyelination, inflammation and progressive paralysis that mimics phenotypes associated with progressive multiple sclerosis

“…A coronal axial multi-slice DWI sequence covering the entire brain was performed with the following parameters: TR = 3000 ms, TE = 32.5 ms, matrix size = 96 × 96, slice thickness = 0.75 mm. Apparent diffusion coefficient (ADC) values were acquired by placing four circular regions-of-interest (ROIs) within various brain and spinal cord regions, with values averaged [ 80 ].…”