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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 (3d) histology based on x-ray computed tomography (μ- and nanoCT) in direct vicinity of hospitals and biomedical research institutions. Combining advanced x-ray generation and detection techniques with phase reconstruction algorithms, 3d 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. Here, we investigate to which extent 3d histology of neuronal tissue can exploit the cone-beam geometry at high magnification M using a nanofocus transmission x-ray tubes (nanotube) with 300 nm minimal spot size (Excillum), combined with a single-photon counting camera. Tightly approaching the source spotwith the biopsy punch,we achieve highM ≈ 10¹-10², 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 cyto-architecture 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. at low-M geometry, reveals similar to slightly superior data quality for the nanotube setup. Besides its compactness, reduced power consumption by a factor of 10³ and shorter scan duration, the particular advantage of the nanotube setup also lies in its suitability with pixel detector technology, enabling an increased range of opportunities for applications in laboratory phase-contrast x-ray tomography. Conclusions: The phase retrieval scheme utilized here mixes amplitude and phase contrast, with results being robust with respect to reconstruction parameters. Structural information content is comparable 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 progress in pixel detector technology is particularly beneficial. Further progress is thus likely to bring 3d virtual histology to the performance in scan time and throughput required for clinical practice in neuropathology. [ABSTRACT FROM AUTHOR]

This chapter reviews recent progress in propagation-based phase-contrast imaging and tomography of biological matter. We include both inhouse µ-CT results recorded in the direct-contrast regime of propagation imaging (large Fresnel numbers F), as well as nanoscale phase contrast in the holographic regime with synchrotron radiation. The current imaging capabilities starting from the cellular level all the way to small animal imaging are illustrated by recent examples of our group, with an emphasis on 3D histology. [ABSTRACT FROM AUTHOR]

An appendix is presented of topics including fourier transform and Convolution.

The article presents the conclusion to the thesis which pertains to performing propagation-based phase-contrast tomography for the conduction of three-dimensional (3D) virtual histology of neuronal tissue. It outlines the evaluation of experimental setups, phase-retrieval algorithms and sample preparations for the purpose. It describes the method for increasing tissue contrast with the help of radiocontrast agents and embedded media.

The article offers insights on the application of propagation-based phase-contrast tomography for the purpose of conducting three-dimensional (3D) imaging of the structural changes which occur during neurodegenerative diseases like multiple sclerosis, Alzheimer's disease and ischemic stroke. Details on the methodology and results of the experiments that were conducted for these individual diseases, are presented.

The article presents a quantitative analysis of the three-dimensional (3D) cytoarchitecture of a human cerebellum which has been embedded in paraffin. Topics discussed include study of the cerebellum at both synchrotron and laboratory setups and details on the experimental setup and parameters. Details on the experiment's results are presented with the observation of automated cellular segmentation.

The article discusses the method for enhancing the contrast during the imaging of neuronal structures with the help of various embedding media. Topics discussed include the preparation for the evaporation-of-solvent method and experiments with regard to mouse cerebellum which has been embedded in ethanol and cerebellum embedded in paraffin. The results of the experiments are presented.

The article discusses the method for enhancing the contrast during the imaging of neuronal structures with the use of radiocontrast metals for staining. It outlines information on the anatomies of the mouse retina which has been strained by osmium and the hippocampus stained by Golgi-Cox. Details on the methods, parameters and results of the mouse experiments are presented.

The article discusses the method of imaging an unstained hydrated cerebellum of a mouse. Topics discussed include the the cerebellum's anatomy with details regarding its various layers, sample preparation and the setup for the experiment. Topics including data analysis with involved phase retrieval and tomographic imaging results are also discussed.

The article discusses the experimental realization of propagation-based x-ray phase-contrast tomography. Topics discussed include use of x-ray detectors like fiber and lens-coupled detectors, setup of Göttingen Instrument for Nano Imaging with coherent X-rays (GINIX) and the concept of empty-beam correction. The laboratory setup for the experiment is discussed in detail.

The article discusses the concept of computed tomography. It describes the aim of the concept which is the reconstruction of the three-dimensional (3D) distribution of the refractive index decrement and extinction coefficient. Topics discussed include filtered backprojection, cone-beam tomography and misaligned rotation axis. Topics including ring, motion and geometry artifacts along with the concept of beam hardening are discussed.

The article discusses the method of overcoming the phase issue in two-dimensional propagation-based phase-contrast x-ray imaging. Topics discussed include direct-contrast regime, modified Bronnikov algorithm and Bronnikov-aided correction. The holographic regime of the process is discussed, with details on phase retrieval based on contrast transfer function.

The article discusses the concept of two-dimensional propagation-based phase-contrast x-ray imaging. Topics discussed include Maxwell's equations, free-space propagation and paraxial approximation. Topics including interactions of x-rays with matter and the concept of contrast formation are discussed, with details on intensity transport, contrast transfer function and imaging regimes.

An introduction is presented which discusses the use of the x-ray computed tomography (CT) technique for the visualization of cytoarchitecture of neuronal tissues for the purpose of detecting structural changes in neurodegenerative diseases.