Analysis of structural effects of sickle cell disease on brain vasculature of mice using three-dimensional quantitative phase imaging.
Analysis of structural effects of sickle cell disease on brain vasculature of mice using three-dimensional quantitative phase imaging.
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DOI：
10.1117/1.jbo.28.9.096501
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发表时间：
2023-09
影响因子：
3.5
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中科院分区：
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虽然镰状细胞病（SCD）的分子起源已被广泛研究，SCD对血管的影响，这可能会影响凝血机制，疼痛危机和中风还没有得到很好的理解。提高这种理解可以深入了解这种毁灭性疾病的机制和广泛影响。我们的目标是证明一种无标记的3D定量相位成像技术，称为定量斜背照明显微镜（qOBM）的能力，以提供深入了解SCD对脑血管系统的影响。使用qOBM，我们定量分析了新鲜切除的，但在其他方面未改变的，整个小鼠大脑的血管。我们使用Townes镰状细胞转基因小鼠作为对照，该小鼠密切概括了人类SCD的病理生理学，而镰状细胞性状小鼠作为对照。研究了两个发育时间点：6周龄小鼠和20周龄小鼠。从高分辨率图像中提取血管的定量结构和生物物理参数（包括与干质量成线性比例的折射率（RI））并进行分析。qOBM揭示了脑血管厚度（对于SCD在特定脑区域中更薄）和血管壁的RI（对于SCD在整个脑中更高并且包含更大的变化）的结构差异。这些变化仅在20周龄的小鼠中显着。此外，在两个时间点在SCD小鼠中观察到血管破裂。在这些破裂点附近的血管壁RI分布，直到远离破裂点，显示出以宽RI变化为特征的不稳定行为。发现血管直径、迂曲度、血管内纹理和结构分形图案无统计学差异。与血管破裂一样，我们也只在患有SCD的小鼠脑中观察到血管阻塞。qOBM提供了对SCD小鼠脑血管生物物理和结构组成的深入了解。数据表明，RI可能是血管刚度、血管强度和/或张力的间接指标，其随SCD而变化。未来的离体和体内qOBM研究可以提高我们对SCD的理解。
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. 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. 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. 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. 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.