Statistical dynamics of flowing red blood cells by morphological image processing.

Statistical dynamics of flowing red blood cells by morphological image processing.
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DOI:
10.1371/journal.pcbi.1000288
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发表时间:
2009-02
影响因子:
4.3
通讯作者:
Mahadevan L
Mahadevan L
中科院分区:
生物学2区
文献类型:
--
作者:
Higgins JM;Eddington DT;Bhatia SN;Mahadevan L

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血液是一种具有独特重要性的柔软非布朗细胞的稠密悬浮液。生理性血流涉及血细胞彼此之间以及与环境之间的复杂相互作用,这是由于变化的细胞浓度、细胞形态、细胞流变学和限制的综合作用。我们使用计算形态图像分析和机器学习算法来分析这些相互作用,以量化细胞速度在最小的准二维微流体环境中的非平衡波动,从而实现血细胞流动的高分辨率时空测量。特别是,我们测量血细胞的有效流体动力学扩散率,并分析其与宏观性质,如体积流速和密度的关系。我们还使用有效的悬浮液温度来区分正常红细胞和病理性镰状红细胞的流动,并建议,这个温度可能有助于表征血液凝固和血栓形成的魏尔啸三联征中的停滞倾向。从远处看,流动的血液看起来像一种均匀的流体,但近距离观察,血液中的细胞会改变它们的位置和速度。这些单个细胞运动可能在营养和气体运输、凝血和正常过程出错的疾病的生理学和病理生理学中发挥作用。为了描述这些随机运动,我们需要在一个非常拥挤的悬浮液中跟踪单个细胞-细胞通常占据血液体积的三分之一以上。我们已经开发出了计算机软件,可以在人群中分离单个细胞,并在它们流动时跟踪它们。我们使用这个软件来分析细胞水平的血流,并发现健康患者的血液和镰状细胞病患者的血液之间新的和可能重要的差异,镰状细胞病是一种血细胞变得僵硬并经常停止流动的疾病。我们提供的证据表明,镰状细胞病患者的血液显示随机细胞运动减少,并表明这种差异可能为镰状细胞病闭塞风险增加提供了物理基础。
Blood is a dense suspension of soft non-Brownian cells of unique importance. Physiological blood flow involves complex interactions of blood cells with each other and with the environment due to the combined effects of varying cell concentration, cell morphology, cell rheology, and confinement. We analyze these interactions using computational morphological image analysis and machine learning algorithms to quantify the non-equilibrium fluctuations of cellular velocities in a minimal, quasi-two-dimensional microfluidic setting that enables high-resolution spatio-temporal measurements of blood cell flow. In particular, we measure the effective hydrodynamic diffusivity of blood cells and analyze its relationship to macroscopic properties such as bulk flow velocity and density. We also use the effective suspension temperature to distinguish the flow of normal red blood cells and pathological sickled red blood cells and suggest that this temperature may help to characterize the propensity for stasis in Virchow's Triad of blood clotting and thrombosis. Viewed from a distance, flowing blood looks like a uniform fluid, but up close the cells in the blood change their position and speed somewhat heterogeneously. These individual cell movements may play a role in the physiology and pathophysiology of nutrient and gas transport, clotting, and diseases where normal processes go wrong. To characterize these random motions, we need to follow individual cells in a very crowded suspension—cells usually occupy more than one-third of the volume in blood. We have developed computer software that can separate individual cells in a crowd and track them as they flow. We use this software to analyze blood flow at the level of the cell and find new and possibly important differences between the blood from healthy patients and the blood from patients with sickle cell disease, a disorder in which blood cells become stiff and often stop flowing. We provide evidence that blood from patients with sickle cell disease shows decreased random cellular motions and suggest that this difference may provide a physical basis for the increased risk of occlusion in sickle cell disease.
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发表时间: 2007-12-18
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