Contrast-Enhanced Magnetic Resonance Microangiography Reveals Remodeling of the Cerebral Microvasculature in Transgenic ArcAβ Mice

Abstract

Amyloid-␤ (A␤) deposition in the cerebral vasculature is accompanied by remodeling which has a profound influence on vascular integrity and function. In the current study we have quantitatively assessed the age-dependent changes of the cortical vasculature in the arcA␤ model of cerebral amyloidosis. To estimate the density of the cortical microvasculature in vivo, we used contrast-enhanced magnetic resonance microangiography (CE-MRA). Three-dimensional gradient echo datasets with 60 m isotropic resolution were acquired in 4-and 24-month-old arcA␤ mice and compared with wild-type (wt) control mice of the same age before and after administration of superparamagnetic iron oxide nanoparticles. After segmentation of the cortical vasculature from difference images, an automated algorithm was applied for assessing the number and size distribution of intracortical vessels. With CE-MRA, cerebral arteries and veins with a diameter of less than the nominal pixel resolution (60 m) can be visualized. A significant age-dependent reduction in the number of functional intracortical microvessels (radii of 20 -80 m) has been observed in 24-month-old arcA␤ mice compared with age-matched wt mice, whereas there was no difference between transgenic and wt mice of 4 months of age. Immunohistochemistry demonstrated strong fibrinogen and A␤ deposition in small-and medium-sized vessels, but not in large cerebral arteries, of 24-monthold arcA␤ mice. The reduced density of transcortical vessels may thus be attributed to impaired perfusion and vascular occlusion caused by deposition of A␤ and fibrin. The study demonstrated that remodeling of the cerebrovasculature can be monitored noninvasively with CE-MRA in mice.

Aminopyrimidine Class Aggregation Inhibitor Effectively Blocks Aβ–Fibrinogen Interaction and Aβ-Induced Contact System Activation

“…This interaction also induces abnormal clot structure and increases clot resistance towards fibrinolysis 15, 18, 27, 28 . In addition, fibrinogen is frequently localized to Aβ deposits around the blood vessels of the brain (cerebral amyloid angiopathy, CAA) and the brain parenchyma in AD patients as well as AD mouse models 15, 29–31 . These findings suggest that the Aβ-fibrinogen interaction could be crucial to the onset and progression of neurovascular damage and cognitive impairment in AD.…”

CHAPTER 5. Increased Sensitivity Using Cryogenic Radiofrequency Coils: Application to In Vivo Phenotyping of Mice

“…Special applications like microstructural imaging and the confection of MRI based digital atlases require even ultrahigh spatial resolution. 3,12 Furthermore, comprehensive phenotyping may involve the acquisition of multiple imaging data sets (multiparametric imaging) with large groups of animals at repeated time points; hence throughput becomes an essential requirement. Substantial efforts have been made to increase the sensitivity as defined by the SNR for imaging applications in mice.…”

“…Quantitative analysis of contrast-enhanced microangiograms revealed a reduction of intracortical microvessels in 24-month-old arcAb mice compared to agematched controls, while no significant differences were seen between arcAb mice and wild-type controls at 4 months of age ( Figure 5.6(a)). 12 In addition to (c) High-resolution horizontal cross-section through mouse brain with a spatial resolution of 52Â52Â170 mm 3 acquired at 9.4 T with a CRP. Data acquisition time was 12 min.…”

“…the microvasculature of the cerebral cortex. 12 2) Longitudinal studies: The potential to carry out high-resolution phenotyping studies in vivo is of particular advantage as animals can be used repetitively e.g. in longitudinal studies, which helps to reduce the number of animals needed for a study.…”

Extracting Vascular Networks under Physiological Constraints via Integer Programming

“…Many diseases affect general properties of the cerebrovascular network, examples are arteriosclerosis and dilative vascular malformations changing vessel shape and diameter, but also Alzheimer's and related neuro-degenerative diseases that are suspected to affect the general vascularity and global network properties [1,2]. While segmenting and tracing tubular structures is a longstanding field of interest in medical image computing [3][4][5][6], we approach here the wider -and somewhat neglected [7] -problem of extracting the full vascular network from image volumes under consideration of global geometric properties of the vascular structure.…”