Related Experiment Video
Updated: Jul 16, 2025
Quantification of Cerebral Vascular Architecture using Two-photon Microscopy in a Mouse Model of HIV-induced Neuroinflammation
Published on: January 12, 2016
Analysis of structural effects of sickle cell disease on brain vasculature of mice using three-dimensional
Caroline Filan1, Hannah Song2,3, Manu O Platt2,3
1Georgia Institute of Technology, George W. Woodruff School of Mechanical Engineering, Atlanta, Georgia, United States.
Insights
Quantitative oblique back-illumination microscopy (qOBM) reveals significant changes in brain vasculature of sickle cell disease (SCD) mice, including thinner vessels and altered refractive index, offering new insights into disease mechanisms.
Area of Science:
- Biomedical imaging
- Vascular biology
- Disease pathology
Background:
- Sickle cell disease (SCD) molecular origins are studied, but vascular effects remain unclear.
- Understanding SCD's vascular impact is crucial for addressing pain crises and strokes.
Purpose of the Study:
- To demonstrate quantitative oblique back-illumination microscopy (qOBM) for analyzing SCD's effects on brain vasculature.
- To provide insight into the biophysical and structural changes in brain blood vessels due to SCD.
Main Methods:
- Utilized label-free 3D qOBM on freshly excised whole mouse brains from Townes sickle transgenic mice and controls.
- Analyzed quantitative structural and biophysical parameters, including refractive index (RI), at 6 and 20 weeks of age.
Main Results:
- Observed thinner brain blood vessels and altered vessel wall RI in SCD mice, particularly at 20 weeks.
- Detected vessel breakages and blockages exclusively in SCD mice, with erratic RI near breaks.
- Found no significant differences in vessel diameter, tortuosity, texture, or fractal patterns.
Conclusions:
- qOBM effectively reveals SCD-induced biophysical and structural changes in brain vasculature.
- RI variations may indicate altered vessel rigidity, strength, or tension in SCD.
- Further qOBM studies can enhance understanding of SCD's vascular complications.
Significance:
Although the molecular origins of sickle cell disease (SCD) have been extensively studied, the effects of SCD on the vasculature-which can influence blood clotting mechanisms, pain crises, and strokes-are not well understood. Improving this understanding can yield insight into the mechanisms and wide-ranging effects of this devastating disease.
Aim:
We aim to demonstrate the ability of a label-free 3D quantitative phase imaging technology, called quantitative oblique back-illumination microscopy (qOBM), to provide insight into the effects of SCD on brain vasculature.
Approach:
Using qOBM, we quantitatively analyze the vasculature of freshly excised, but otherwise unaltered, whole mouse brains. We use Townes sickle transgenic mice, which closely recapitulate the pathophysiology of human SCD, and sickle cell trait mice as controls. Two developmental time points are studied: 6-week-old mice and 20-week-old mice. Quantitative structural and biophysical parameters of the vessels (including the refractive index (RI), which is linearly proportional to dry mass) are extracted from the high-resolution images and analyzed.
Results:
qOBM reveals structural differences in the brain blood vessel thickness (thinner for SCD in particular brain regions) and the RI of the vessel wall (higher and containing a larger variation throughout the brain for SCD). These changes were only significant in 20-week-old mice. Further, vessel breakages are observed in SCD mice at both time points. The vessel wall RI distribution near these breaks, up to away from the breaking point, shows an erratic behavior characterized by wide RI variations. Vessel diameter, tortuosity, texture within the vessel, and structural fractal patterns are found to not be statistically different. As with vessel breaks, we also observe blood vessel blockages only in mice brains with SCD.
Conclusions:
qOBM provides insight into the biophysical and structural composition of brain blood vessels in mice with SCD. Data suggest that the RI may be an indirect indicator of vessel rigidity, vessel strength, and/or tensions, which change with SCD. Future ex vivo and in vivo studies with qOBM could improve our understanding of SCD.
