Exposure to exogenous particles is of increasing concern to human health. Characterizing the concentrations, chemical species, distribution, and involvement of the stimulus with the tissue microanatomy is essential in understanding the associated biological response. However, no single imaging technique can interrogate all these features at once, which confounds and limits correlative analyses. Developments of synchronous imaging strategies, allowing multiple features to be identified simultaneously, are essential to assess spatial relationships between these key features with greater confidence. Here, we present data to first highlight complications of correlative analysis between the tissue microanatomy and elemental composition associated with imaging serial tissue sections. This is achieved by assessing both the cellular and elemental distributions in three-dimensional space using optical microscopy on serial sections and confocal X-ray fluorescence spectroscopy on bulk samples, respectively. We propose a new imaging strategy using lanthanide-tagged antibodies with X-ray fluorescence spectroscopy. Using simulations, a series of lanthanide tags were identified as candidate labels for scenarios where tissue sections are imaged. The feasibility and value of the proposed approach are shown where an exposure of Ti was identified concurrently with CD45 positive cells at sub-cellular resolutions. Significant heterogeneity in the distribution of exogenous particles and cells can be present between immediately adjacent serial sections showing a clear need of synchronous imaging methods. The proposed approach enables elemental compositions to be correlated with the tissue microanatomy in a highly multiplexed and non-destructive manner at high spatial resolutions with the opportunity for subsequent guided analysis.

中文翻译：

---

通过同步成像策略解决外源颗粒与组织显微解剖学相关成像的不确定性。

暴露于外源颗粒对人类健康日益引起关注。表征浓度、化学种类、分布以及刺激与组织显微解剖的关系对于理解相关的生物反应至关重要。然而，没有一种成像技术可以同时询问所有这些特征，这混淆并限制了相关分析。同步成像策略的发展，允许同时识别多个特征，对于更有信心地评估这些关键特征之间的空间关系至关重要。在这里，我们提供的数据首先强调与连续组织切片成像相关的组织显微解剖学和元素组成之间的相关分析的并发症。这是通过分别使用连续切片上的光学显微镜和大块样品上的共焦 X 射线荧光光谱来评估三维空间中的细胞和元素分布来实现的。我们提出了一种使用镧系元素标记抗体和 X 射线荧光光谱的新成像策略。通过模拟，一系列镧系元素标签被确定为组织切片成像场景的候选标签。在亚细胞分辨率下同时鉴定 Ti 暴露和 CD45 阳性细胞时，显示了所提出方法的可行性和价值。紧邻的连续切片之间可能存在外源颗粒和细胞分布的显着异质性，这表明明显需要同步成像方法。