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应用布里渊显微镜和光相干断层扫描技术测量颅神经管闭合过程中的组织生物力学。

Tissue biomechanics during cranial neural tube closure measured by Brillouin microscopy and optical coherence tomography.

机构信息

Fischell Department of Bioengineering, University of Maryland, Maryland.

Department of Biomedical Engineering, University of Houston, Houston, Texas.

出版信息

Birth Defects Res. 2019 Aug 15;111(14):991-998. doi: 10.1002/bdr2.1389. Epub 2018 Sep 21.

Abstract

BACKGROUND

Embryonic development involves the interplay of driving forces that shape the tissue and the mechanical resistance that the tissue offers in response. While increasing evidence has suggested the crucial role of physical mechanisms underlying embryo development, tissue biomechanics is not well understood because of the lack of techniques that can quantify the stiffness of tissue in situ with 3D high-resolution and in a noncontact manner.

METHODS

We used two all-optical techniques, optical coherence tomography (OCT) and Brillouin microscopy, to map the longitudinal modulus of the tissue from mouse embryos in situ.

RESULTS

We acquired 2D mechanical maps of the neural tube region of embryos at embryonic day (E) 8.5 (n = 2) and E9.5 (n = 2) with submicron spatial resolution. We found the modulus of tissue varied distinctly within the neural tube region of the same embryo and between embryos at different development stages, suggesting our technique has enough sensitivity and spatial resolution to monitor the tissue mechanics during embryonic development in a noncontact and noninvasive manner.

CONCLUSIONS

We demonstrated the capability of OCT-guided Brillouin microscopy to quantify tissue longitudinal modulus of mouse embryos in situ, and observed distinct change in the modulus during the closure of cranial neural tube. Although this preliminary work cannot provide definitive conclusions on biomechanics of neural tube closure yet as a result of the limited number of samples, it provides an approach of quantifying the tissue mechanics during embryo development in situ, thus could be helpful in investigating the role of tissue biomechanics in the regulation of embryonic development. Our next study involving more embryo samples will investigate systematic changes in tissue mechanics during embryonic development.

摘要

背景

胚胎发育涉及塑造组织的驱动力和组织提供的机械阻力之间的相互作用。虽然越来越多的证据表明物理机制在胚胎发育中起着关键作用,但由于缺乏能够以非接触方式定量测量组织原位 3D 高分辨率硬度的技术,组织生物力学仍未得到很好的理解。

方法

我们使用两种全光学技术,光学相干断层扫描(OCT)和布里渊显微镜,原位映射组织的纵向模量。

结果

我们以亚微米空间分辨率获得了胚胎发育第 8.5 天(n=2)和第 9.5 天(n=2)的神经管区域的 2D 力学图。我们发现,同一胚胎的神经管区域内以及不同发育阶段的胚胎之间,组织的模量明显不同,这表明我们的技术具有足够的灵敏度和空间分辨率,可以非接触和非侵入性地监测胚胎发育过程中的组织力学。

结论

我们证明了 OCT 引导的布里渊显微镜在原位定量测量小鼠胚胎组织纵向模量的能力,并观察到颅神经管闭合过程中模量的明显变化。虽然由于样本数量有限,这项初步工作尚不能对神经管闭合的生物力学提供明确的结论,但它提供了一种在胚胎发育过程中定量测量组织力学的方法,因此有助于研究组织生物力学在胚胎发育调控中的作用。我们的下一项研究将涉及更多的胚胎样本,以研究胚胎发育过程中组织力学的系统变化。

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