Near Field ptychography with a laboratory x-ray source: a new tool for brain tissue studies and beyond

本项目旨在开发一种新的、基于实验室的x射线定量相衬成像（QPI）技术，即近场全息成像（NFPty），它非常适合于弱吸收分层样品（如生物组织）的多尺度成像。NFPty提供了通过其他基于实验室的QPI技术提供的分辨率桥接，以及相干衍射成像方法的高分辨率。x射线成像（XI）是非破坏性研究物质的有力工具，其应用包括生命科学和物理科学。同步加速器是执行XI的最佳工具；然而，它们的数量少使得获取具有竞争力，它可以用于基础科学研究，但不能用于日常应用。为了服务于更大的社区，从学术界到工业界，必须通过开发方法来解决x射线束质量下降的问题，将同步加速器产生的x射线成像技术转化为实验室来源。x射线相衬成像（XPCI）是x射线成像的一个子集，它允许成像弱吸收标本和具有相似吸收特性的鉴别材料。不同的实现存在：从最简单的直线全息术到边缘照明，光栅干涉术，近场和远场全息术。这些成像工具可以在同步加速器设施中使用，其中一些，例如边缘照明，光栅干涉测量，已经成功地适应于实验室光源。NFPty尚未出口到实验室，但它是一个很有前途的候选者：NFPty需要简单的设置，放宽x射线束质量要求，并受益于强大的重建算法。这个项目将把NFPty转换到实验室环境中，使它可以为大型用户社区使用。该项目通过模拟和实验使该方法适应实验室源的低通量和x射线质量，并开发出专用仪器。该项目将在伦敦大学学院的高级x射线成像小组内进行，该小组的活动重点是为实验室源开发新的x射线成像技术。在伦敦大学学院，不同的x射线源（从标准的旋转阳极到新型的液态金属射流）将用于实验。为了使该项目的影响最大化，该研究将以脑成像的案例研究为动力，最终目的是展示该技术在这一重要领域的潜力。通过与该领域的专家（来自卡迪夫大学的Palombo博士，来自伦敦大学学院的Parker教授和来自CNR-Nanotec罗马的Fratini博士）密切合作，基于实验室的nffpty将被应用于脑组织和脑幻影成像，并使用获得的数据来验证扩散磁共振成像（dMRI）。dMRI是脑研究和诊断的重要工具。然而，由于任务的多尺度性质，dMRI信号的解释和分析的验证具有挑战性。验证依赖于离体样本、软件模型或物理模型的数据。物理幻影的优点是既真实又可控，同时又能防止动物祭祀。然而，创建有用的大脑仿生模型需要在微米级分辨率下对模型结构进行精确的表征，并对细胞结构进行特定的对比。这些信息可以通过在同步加速器上使用多尺度高分辨率XPCI直接获得，但是对这些设施的有限访问限制了可用的统计数据。该项目将使使用nffpty在标准实验室中获取这些数据成为可能。该计划将生产一种新的仪器，其视野范围从100微米到毫米（神经元排列和典型MRI体素的尺度），具有亚微米分辨率（细胞/亚细胞结构的尺度）。获得的数据将有助于理解大脑结构，指导更好的幻影的发展，并推动dMRI的验证。

This project aims to develop a new, laboratory-based, x-ray quantitative phase contrast imaging (QPI) technique, namely near-field ptychography (NFPty), ideal for multi-scale imaging of weakly absorbing hierarchical samples, such as biological tissues. NFPty offers resolution bridging that available through other lab-based QPI techniques, and the high resolution of coherent diffraction imaging methods.X-ray imaging (XI) is a powerful tool for investigating matter non-destructively, with applications encompassing the life and physical sciences. Synchrotrons are the best instruments for performing XI; however, their small number makes access competitive, it enables fundamental science studies but not everyday applications. To serve a larger community, from academia to industry, it is essential to translate the x-ray imaging techniques born at synchrotrons to laboratory sources, by developing ways to work around the degraded quality of the x-ray beam. X-ray phase contrast imaging (XPCI) is a subset of x-ray imaging that allows imaging weakly absorbing specimens and differentiating materials with similar absorption properties. Different implementations exist: from the simplest in-line holography to edge illumination, grating interferometry, near and far-field ptychography. These imaging tools are available at synchrotron facilities and some of them, e.g. edge illumination, grating interferometry, have been successfully adapted to laboratory sources. NFPty has not yet been exported to laboratory but it is a promising candidate: NFPty requires a simple setup, has relaxed x-ray beam quality requirements, and benefits from robust reconstruction algorithms.This project will translate NFPty into the lab-environment to make it available to a large user community. The project uses simulations and experiments to adapt the method to the lower flux and x-ray quality of the laboratory sources and develop a dedicated instrument. The project will be based at UCL, within the Advanced X-ray Imaging Group whose activity is focused on developing new x-ray imaging techniques for laboratory sources. At UCL different x-ray sources (from standard rotating anode to the novel Liquid Metal Jet) will be available for the experiments.To maximise the impact of the project, the research will be driven by a case study in brain imaging, with the ultimate aim of demonstrating the technique's potential in that important area. By working closely with experts in the field (Dr Palombo from Cardiff University, Prof Parker from UCL and, Dr Fratini from CNR-Nanotec Rome), the lab-based NFPty will be applied to image brain tissue and brain phantoms and use the acquired data to validate diffusion Magnetic Resonance Imaging (dMRI). dMRI is a key tool for brain study and diagnosis. However, the interpretation of dMRI signal and the validation of the analysis are challenging because of the multiscale nature of the task. The validation relies on data from ex-vivo samples, software phantoms or physical phantom. Physical phantoms have the advantage of being realistic and controllable while preventing animal sacrifice. Nevertheless, the creation of useful brain biomimetic phantoms requires accurate characterization of the phantom structure at micrometric resolution and specific contrast for cellular structures. This information can be directly obtained by using multiscale high-resolution XPCI at synchrotrons, but the limited access to these facilities limits the available statistics. This project will make it possible to acquire these data in a standard laboratory by using NFPty. The programme will produce a new instrument with adjustable field of view from 100s of microns to millimetres (scale of the neuron's arrangements and typical MRI voxel), with sub-micron resolution (scale of the cellular/sub-cellular structures). The acquired data will be instrumental in understanding brain structure, guiding the development of better phantoms, and driving the validation of dMRI.