Chu Kengyeh K, Mojahed Diana, Fernandez Courtney M, Li Yao, Liu Linbo, Wilsterman Eric J, Diephuis Bradford, Birket Susan E, Bowers Hannah, Martin Solomon G, Schuster Benjamin S, Hanes Justin, Rowe Steven M, Tearney Guillermo J
Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts.
Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts; Department of Biology, Tufts University, Medford, Massachusetts.
Biophys J. 2016 Sep 6;111(5):1053-63. doi: 10.1016/j.bpj.2016.07.020.
Clinical manifestations of cystic fibrosis (CF) result from an increase in the viscosity of the mucus secreted by epithelial cells that line the airways. Particle-tracking microrheology (PTM) is a widely accepted means of determining the viscoelastic properties of CF mucus, providing an improved understanding of this disease as well as an avenue to assess the efficacies of pharmacologic therapies aimed at decreasing mucus viscosity. Among its advantages, PTM allows the measurement of small volumes, which was recently utilized for an in situ study of CF mucus formed by airway cell cultures. Typically, particle tracks are obtained from fluorescence microscopy video images, although this limits one's ability to distinguish particles by depth in a heterogeneous environment. Here, by performing PTM with high-resolution micro-optical coherence tomography (μOCT), we were able to characterize the viscoelastic properties of mucus, which enables simultaneous measurement of rheology with mucociliary transport parameters that we previously determined using μOCT. We obtained an accurate characterization of dextran solutions and observed a statistically significant difference in the viscosities of mucus secreted by normal and CF human airway cell cultures. We further characterized the effects of noise and imaging parameters on the sensitivity of μOCT-PTM by performing theoretical and numerical analyses, which show that our system can accurately quantify viscosities over the range that is characteristic of CF mucus. As a sensitive rheometry technique that requires very small fluid quantities, μOCT-PTM could also be generally applied to interrogate the viscosity of biological media such as blood or the vitreous humor of the eye in situ.
囊性纤维化（CF）的临床表现源于气道内衬上皮细胞分泌的黏液黏度增加。颗粒追踪微观流变学（PTM）是一种广泛认可的确定CF黏液黏弹性特性的方法，有助于更好地理解这种疾病，并为评估旨在降低黏液黏度的药物治疗效果提供途径。PTM的优点之一是能够测量小体积样本，最近已用于对气道细胞培养形成的CF黏液进行原位研究。通常，颗粒轨迹是从荧光显微镜视频图像中获取的，不过这限制了在异质环境中按深度区分颗粒的能力。在此，通过使用高分辨率显微光学相干断层扫描（μOCT）进行PTM，我们能够表征黏液的黏弹性特性，从而能够同时测量流变学以及我们先前使用μOCT测定的黏液纤毛运输参数。我们准确地表征了葡聚糖溶液，并观察到正常人和CF患者气道细胞培养分泌的黏液黏度存在统计学上的显著差异。我们通过进行理论和数值分析，进一步表征了噪声和成像参数对μOCT-PTM灵敏度的影响，结果表明我们的系统能够在CF黏液特征黏度范围内准确量化黏度。作为一种需要非常少量液体的灵敏流变测量技术，μOCT-PTM还可普遍应用于原位检测生物介质（如血液或眼玻璃体液）的黏度。
