[论文解读] Lateral shearing optical diffraction tomography of brain organoid with reduced spatial coherence

Pawel Goclowski, Julianna Winnik+7 more|arXiv (Cornell University)|Jan 27, 2026

Digital Holography and Microscopy被引用 0

一句话总结

该论文提出了横向剪切ODT（LS-ODT），一种常见路径干涉法，结合动态散斑照明，用于重建厚实、异质样本（如脑类器官）的三维折射率，减少多散射影响并提高灵敏度。

ABSTRACT

Optical diffraction tomography (ODT) is a powerful technique for quantitative, label-free reconstruction of the three-dimensional refractive index (RI) distribution of biological samples. While ODT is well established for imaging thin, weakly scattering samples, it encounters significant challenges when applied to heterogeneous, strongly scattering thick samples such as tissues and organoids. In this work, a novel common-path interferometric approach to ODT is presented, specifically designed for the RI reconstruction of heterogeneous and highly scattering samples at high temporal stability. The proposed technique, termed lateral shearing (LS)-ODT, incorporates partial lateral shearing off-axis interferometry to suppress the effects of multiple scattering, similar to the mechanism in differential interference contrast (DIC) microscopy, which is widely used for imaging thick specimens. Additionally, the LS-ODT system uses dynamic speckle illumination to enhance both spatial phase and RI sensitivity compared to laser-based ODT systems. The effectiveness of this method is demonstrated through experiments on a cell phantom. Its robustness and accuracy are further validated across a wide range of samples, including mouse kidney tissue sections and brain organoids derived from human induced pluripotent stem cells (iPSCs), in both thin and thick sections. Furthermore, correlative fluorescence and RI tomography of the organoids highlights the potential of LS-ODT to enhance and support a broad spectrum of biomedical studies, particularly in the field of histology.

研究动机与目标

• 为异质且高度散射的样本（如脑类器官）量身定制一个常见路径的 LS-ODT 方法。
• 抑制多重散射效应，以实现厚样本中的准确 RI 重建。
• 通过动态散斑照明提升空间相位和 RI 灵敏度。
• 在薄片和厚组织切片中展示鲁棒性，并与荧光相关性进行比较。

提出的方法

• 引入部分横向剪切的偏轴干涉来抑制多重散射效应。
• 实施常见路径干涉几何以实现高时间稳定性。
• 结合动态散斑照明以提升相位和 RI 相对于激光基 ODT 的灵敏度。
• 在细胞仿体、鼠肾组织切片和人类 iPSC 来源的脑类器官上验证该方法。
• 进行相关荧光与 RI 断层成像，以展示互补成像能力。

实验结果

研究问题

• RQ1 LS-ODT 能否抑制厚厚异质样本中的多重散射，从而获得准确的三维 RI 重建？
• RQ2 动态散斑照明是否相对于传统激光基 ODT 提高了空间相位和 RI 的灵敏度？
• RQ3 LS-ODT 在不同研究材料类型（细胞仿体、组织切片、类器官）及不同厚度下是否鲁棒？
• RQ4 LS-ODT 在类器官组织学应用中与荧光成像的互补性有多强？

主要发现

• LS-ODT 在常见路径配置中表现出高时间稳定性。
• 动态散斑照明相较于激光基系统提升了空间相位和 RI 的灵敏度。
• 该方法在细胞仿体、鼠肾组织以及人类 iPSC 来源的脑类器官的薄片和厚片中均得到验证。
• 相关荧光与 RI 断层成像显示在整合组织学研究中的潜力。
• 该方法在多种样本类型和厚度范围内表现出鲁棒性。