Phase-contrast x-ray tomography of neuronal tissue at laboratory sources with submicron resolution

Abstract

Purpose: Recently, progress has been achieved in implementing phase-contrast tomography of soft biological tissues at laboratory sources. This opens up opportunities for three-dimensional (3-D) histology based on x-ray computed tomography (μ-and nanoCT) in the direct vicinity of hospitals and biomedical research institutions. Combining advanced x-ray generation and detection techniques with phase reconstruction algorithms, 3-D histology can be obtained even of unstained tissue of the central nervous system, as shown, for example, for biopsies and autopsies of human cerebellum. Depending on the setup, i.e., source, detector, and geometric parameters, laboratory-based tomography can be implemented at very different sizes and length scales.We investigate the extent to which 3-D histology of neuronal tissue can exploit the cone-beam geometry at high magnification M using a nanofocus transmission x-ray tube (nanotube) with a 300 nm minimal spot size (Excillum), combined with a single-photon counting camera. Tightly approaching the source spot with the biopsy punch, we achieve high M ≈ 10 1 − 10 2 , high flux density, and exploit the superior efficiency of this detector technology.Approach: Different nanotube configurations such as spot size and flux, M, as well as exposure time, Fresnel number, and coherence are varied and selected in view of resolution, field of view, and/or phase-contrast requirements. Results:The data show that the information content for the cytoarchitecture is enhanced by the phase effect. Comparison of results to those obtained at a microfocus rotating-anode x-ray tomography setup with a high-resolution detector, i.e., in low-M geometry, reveals similar to slightly superior data quality for the nanotube setup. In addition to its compactness, reduced power consumption by a factor of 10 3 , and shorter scan duration, the particular advantage of the nanotube setup also lies in its suitability for pixel detector technology, enabling an increased range of opportunities for applications in laboratory phase-contrast x-ray tomography. Conclusions:The phase retrieval scheme utilized mixes amplitude and phase contrast, with results being robust with respect to reconstruction parameters. Structural information content is comparable to slightly superior to previous results achieved with a microfocus rotating-anode setup but can be obtained in shorter scan time. Beyond advantages as compactness, lowered power consumption, and flexibility, the nanotube setup's scalability in view of the progress in pixel detector technology is particularly beneficial. Further progress is thus likely to bring 3-D virtual histology to the performance in scan time and throughput required for clinical practice in neuropathology.

X-ray phase tomography with near-field speckles for three-dimensional virtual histology

“…Although conventional laboratory sources will not enable the spatial and density resolution of synchrotron data, due to the reduced coherence properties, the shorter propagation distances, and increased blurring by the source, the quality of the results will be sufficiently high for many applications. Moreover, recently developed specialized x-ray sources with submicrometer spot sizes have shown to be a promising instrument for high-resolution x-ray virtual histology [48,49].…”

3D analysis of the myenteric plexus of the human bowel by X-ray phase-contrast tomography – a future method?

“…Nevertheless, while the cost of the laboratory setups is high, they are made with commercially available equipment, which in the future will become more affordable and more powerful. Also, it was already demonstrated that laboratory setups can be implemented in a way that requires less space, strongly reduces scan durations and is flexible in choice of field-of-view and resolution, achieving a resolution below 1 mm [23]. If beam time is available, the GINIX endstation portfolio has also been recently expanded by a parallel-beam configuration, allowing for fast overview scans with slightly enhanced resolution and contrast compared to the ones presented in this work, but with scan times as short as $70 s [24].…”

3d phase‐contrast nanotomography of unstained human skin biopsies may identify morphological differences in the dermis and epidermis between subjects

“…At the same time, specific volume stains could bring pivotal added benefit. Finally, recent developments in laboratory phase‐contrast nanoCT may lead to a translation from synchrotron to innovative, yet relatively cheap and compact instrumentation, which could become accessible for clinical practice in the future 31 …”