Upscaling X-ray nanoimaging to macroscopic specimens

Abstract

Upscaling X-ray nanoimaging to macroscopic specimens has the potential for providing insights across multiple length scales, but its feasibility has long been an open question. By combining the imaging requirements and existing proof-of-principle examples in large-specimen preparation, data acquisition and reconstruction algorithms, the authors provide imaging time estimates for howX-ray nanoimaging can be scaled to macroscopic specimens. To arrive at this estimate, a phase contrast imaging model that includes plural scattering effects is used to calculate the required exposure and corresponding radiation dose. The coherent X-ray flux anticipated from upcoming diffraction-limited light sources is then considered. This imaging time estimation is in particular applied to the case of the connectomes of whole mouse brains. To image the connectome of the whole mouse brain, electron microscopy connectomics might require years, whereas optimized X-ray microscopy connectomics could reduce this to one week. Furthermore, this analysis points to challenges that need to be overcome (such as increased X-ray detector frame rate) and opportunities that advances in artificial-intelligence-based `smart' scanning might provide. While the technical advances required are daunting, it is shown that X-ray microscopy is indeed potentially applicable to nanoimaging of millimetre- or even centimetre-size specimens.

A multiscale X-ray phase-contrast tomography dataset of a whole human left lung

“…At synchrotron facilities, systematic upgrades 13 , 14 in the X-ray source and imaging techniques over the past decades provide the means to tackle biological questions across meaningful scales and resolution 11 , 15 – 20 . Although synchrotron-based X-ray imaging can access finer anatomical detail than laboratory micro-CT 19 , 21 – 23 , many bioimaging scenarios require further upscaling of the imaging throughput and accommodation of large sample size while maintaining microscopic resolution 24 , 25 .…”

A multiscale X-ray phase-contrast tomography dataset of whole human left lung

“…At synchrotron facilities, systematic upgrades 11,12 in the X-ray source and imaging techniques over the past decades provide the means to tackle biological questions on meaningful scales and resolution [13][14][15][16][17][18][19] . Although synchrotron-based X-ray imaging can access finer anatomical detail than laboratory micro-CT 18,[20][21][22] , many bioimaging scenarios require further upscaling of the imaging throughput and accommodation of large sample size while maintaining microscopic resolution 23,24 . Thanks to the high X-ray photon flux and coherence achieved at modern fourth-generation synchrotron sources and careful design of the imaging protocol, it is now possible to image complete, large, partially dehydrated human organs in their entirety at micrometer resolution using hierarchical phase-contrast tomography (HiP-CT) 25 .…”

Demonstration of an AI-driven workflow for autonomous high-resolution scanning microscopy

“…Fine-resolution large-field-of-view scanning experiments, however, come with some significant drawbacks: the volume of data generated and the probe-induced damage to the sample can be prohibitively large. For example, it is now routinely possible to perform x-ray imaging of 1 mm 3 volumes at ≈10 nm resolution, but this generates ≈ 10 15 voxels of data 7,8 and requires a commensurately high probe dose 9 . Meanwhile, the information of interest in these experiments is often concentrated in sparse regions that contain interfaces, defects, or other specific structural elements.…”