(G-265) Sickle Cell Disease Mediated Remodeling of Cerebral Arteries Imaged with Microcomputed Tomography

Sickle Cell Disease (SCD) is a genetic disease that causes hemoglobin polymerization inside of red blood cells under deoxygenated conditions. As a consequence, there are many severe health complications with one of them being pediatric strokes. Strokes are cardiovascular complications of larger arteries with oxygenated blood. Our lab has previously shown accelerated elastin and collagen damage in the carotid artery walls due to SCD. This work is investigating the effects of SCD on the cerebral arteries, implicated in stroke pathology. We used the Townes transgenic mouse model of SCD study and imaged the morphology and architecture of the cerebral vasculature by micro computed tomography (uCT). We hypothesized that mice with SCD would have larger diameters and altered vessel geometries, with a focus on Interior carotid artery (ICA), middle cerebral artery (MCA), and anterior cerebral artery (ACA).

We examined 5-month-old Townes sickle cell mice that were either homozygous for β-globin S mutation (SS) or heterozygous (AS).  After sacrifice, and cannulating the thoracic aorta, a radiopaque polymer (Microfil) was injected into the cerebral arterial vascular via thoracic aorta and allowed to cure/harden.  The brains were then carefully removed and placed in 10% Formalin for long term preservation and scanned using a Bruker SKYSCAN 1272 at 17µm resolution.  Data was uploaded into Analyze 14.0 software and a reconstruction of the vasculature generated, thresholder, and segmented to isolate the arteries of interest (ICA, MCA and ACA). We then measured vessel segment angles, diameters, volumes, and surface area.

Angle measurements were made between the artery branches and there was no significant difference between AS and SS. For angle between ACA and MCA, SS and AS had average of 85.75 degree and 84 degrees, respectively. Diameters showed the greatest difference in absolute values, but a t-test demonstrated they were not statistically significant. The average diameter for the bottom of ICA were 0.23mm for SS mice, and 0.19mm for AS mice. The volume and surface area measurements also did not show statistically significant difference between AS and SS mice. The volume of right-side main arteries were 0.24mm³ for mice with SS, and 0.25mm³ for AS. The area of right main arteries in SS were 14.27mm² and 14.56mm² in AS.

Although the results from the measurements did not yield statistically significant differences between AS and SS mice in the cerebral arteries. However, this lab’s previous results do show differences in area and volume for carotid arteries so there may be a difference between these two large arteries and their sickle cell mediated expansive remodeling. Those other measurements were made with magnetic resonance angiography (MRA) or histological methods, different from uCT used here. Multiple modalities will be useful for appropriate comparisons.