scholarly journals Imaging intact human organs with local resolution of cellular structures using hierarchical phase-contrast tomography

2021 ◽  
Author(s):  
C. L. Walsh ◽  
P. Tafforeau ◽  
W. L. Wagner ◽  
D. J. Jafree ◽  
A. Bellier ◽  
...  

AbstractImaging intact human organs from the organ to the cellular scale in three dimensions is a goal of biomedical imaging. To meet this challenge, we developed hierarchical phase-contrast tomography (HiP-CT), an X-ray phase propagation technique using the European Synchrotron Radiation Facility (ESRF)’s Extremely Brilliant Source (EBS). The spatial coherence of the ESRF-EBS combined with our beamline equipment, sample preparation and scanning developments enabled us to perform non-destructive, three-dimensional (3D) scans with hierarchically increasing resolution at any location in whole human organs. We applied HiP-CT to image five intact human organ types: brain, lung, heart, kidney and spleen. HiP-CT provided a structural overview of each whole organ followed by multiple higher-resolution volumes of interest, capturing organotypic functional units and certain individual specialized cells within intact human organs. We demonstrate the potential applications of HiP-CT through quantification and morphometry of glomeruli in an intact human kidney and identification of regional changes in the tissue architecture in a lung from a deceased donor with coronavirus disease 2019 (COVID-19).

2021 ◽  
Author(s):  
C. Walsh ◽  
P. Tafforeau ◽  
Willi L. Wagner ◽  
D. J. Jafree ◽  
A. Bellier ◽  
...  

ABSTRACTHuman organs are complex, three-dimensional and multiscale systems. Spatially mapping the human body down through its hierarchy, from entire organs to their individual functional units and specialised cells, is a major obstacle to fully understanding health and disease. To meet this challenge, we developed hierarchical phase-contrast tomography (HiP-CT), an X-ray phase propagation technique utilising the European Synchrotron Radiation Facility’s Extremely Brilliant Source: the world’s first high-energy 4th generation X-ray source. HiP-CT enabled three-dimensional and non-destructive imaging at near-micron resolution in soft tissues at one hundred thousand times the voxel size whilst maintaining the organ’s structure. We applied HiP-CT to image five intact human parenchymal organs: brain, lung, heart, kidney and spleen. These were hierarchically assessed with HiP-CT, providing a structural overview of the whole organ alongside detail of the organ’s individual functional units and cells. The potential applications of HiP-CT were demonstrated through quantification and morphometry of glomeruli in an intact human kidney, and identification of regional changes to the architecture of the air-tissue interface and alveolar morphology in the lung of a deceased COVID-19 patient. Overall, we show that HiP-CT is a powerful tool which can provide a comprehensive picture of structural information for whole intact human organs, encompassing precise details on functional units and their constituent cells to better understand human health and disease.


2018 ◽  
Vol 115 (27) ◽  
pp. 6940-6945 ◽  
Author(s):  
Mareike Töpperwien ◽  
Franziska van der Meer ◽  
Christine Stadelmann ◽  
Tim Salditt

To quantitatively evaluate brain tissue and its corresponding function, knowledge of the 3D cellular distribution is essential. The gold standard to obtain this information is histology, a destructive and labor-intensive technique where the specimen is sliced and examined under a light microscope, providing 3D information at nonisotropic resolution. To overcome the limitations of conventional histology, we use phase-contrast X-ray tomography with optimized optics, reconstruction, and image analysis, both at a dedicated synchrotron radiation endstation, which we have equipped with X-ray waveguide optics for coherence and wavefront filtering, and at a compact laboratory source. As a proof-of-concept demonstration we probe the 3D cytoarchitecture in millimeter-sized punches of unstained human cerebellum embedded in paraffin and show that isotropic subcellular resolution can be reached at both setups throughout the specimen. To enable a quantitative analysis of the reconstructed data, we demonstrate automatic cell segmentation and localization of over 1 million neurons within the cerebellar cortex. This allows for the analysis of the spatial organization and correlation of cells in all dimensions by borrowing concepts from condensed-matter physics, indicating a strong short-range order and local clustering of the cells in the granular layer. By quantification of 3D neuronal “packing,” we can hence shed light on how the human cerebellum accommodates 80% of the total neurons in the brain in only 10% of its volume. In addition, we show that the distribution of neighboring neurons in the granular layer is anisotropic with respect to the Purkinje cell dendrites.


2007 ◽  
Vol 52 (23) ◽  
pp. 6923-6930 ◽  
Author(s):  
F Pfeiffer ◽  
O Bunk ◽  
C David ◽  
M Bech ◽  
G Le Duc ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Shengkun Yao ◽  
Yunbing Zong ◽  
Jiadong Fan ◽  
Zhibin Sun ◽  
Huaidong Jiang

X-ray imaging techniques significantly advanced our understanding of materials and biology, among which phase contrast X-ray microscopy has obvious advantages in imaging biological specimens which have low contrast by conventional absorption contrast microscopy. In this paper, three-dimensional microstructure of arthropod with high contrast has been demonstrated by synchrotron X-ray in-line phase contrast tomography. The external morphology and internal structures of an earthworm were analyzed based upon tomographic reconstructions with and without phase retrieval. We also identified and characterized various fine structural details such as the musculature system, the digestive system, the nervous system, and the circulatory system. This work exhibited the high efficiency, high precision, and wide potential applications of synchrotron X-ray phase contrast tomography in nondestructive investigation of low-density materials and biology.


2012 ◽  
Vol 67 (3) ◽  
pp. 261-264 ◽  
Author(s):  
Alexander Kostenko ◽  
Hemant Sharma ◽  
E. Gözde Dere ◽  
Andrew King ◽  
Wolfgang Ludwig ◽  
...  

2011 ◽  
Vol 5 (1) ◽  
pp. 19-25 ◽  
Author(s):  
Lu Zhang ◽  
Shuqian Luo

The current imaging methods have a limited ability to visualize microstructures of biological soft tissues. Small lesions cannot be detected at the early stage of the disease. Phase contrast imaging (PCI) is a novel non-invasive imaging technique that can provide high contrast images of soft tissues by the use of X-ray phase shift. It is a new choice in terms of non-invasively revealing soft tissue details. In this study, the lung and hepatic fibrosis models of mice and rats were used to investigate the ability of PCI in microstructures observation of soft tissues. Our results demonstrated that different liver fibrosis stages could be distinguished non-invasively by PCI. The three-dimensional morphology of a segment of blood vessel was constructed. Noteworthy, the blood clot inside the vessel was visualized in three dimensions which provided a precise description of vessel stenosis. Furthermore, the whole lung airways including the alveoli were obtained. We had specifically highlighted its use in the visualization and assessment of the alveoli. To our knowledge, this was the first time for non-invasive alveoli imaging using PCI. This finding may offer a new perspective on the diagnosis of respiratory disease. All the results confirmed that PCI will be a valuable tool in biological soft tissues imaging.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sara Stabile ◽  
Francesca Palermo ◽  
Inna Bukreeva ◽  
Daniela Mele ◽  
Vincenzo Formoso ◽  
...  

AbstractAncient Herculaneum papyrus scrolls, hopelessly charred in the 79 A.D. Vesuvius eruption, contain valuable writings of the Greek philosophers of the day, including works of the Epicurean Philodemus. X-ray phase contrast tomography has recently begun unlocking their secrets. However, only small portions of the text hidden inside the scroll have been recover. One of the challenging tasks in Herculaneum papyri investigation is their virtual unfolding because of their highly complicated structure and three-dimensional arrangement. Although this procedure is feasible, problems in segmentation and flattening hinder the unrolling of a large portion of papyrus. We propose a computational platform for the virtual unfolding procedure, and we show the results of its application on two Herculaneum papyrus fragments. This work paves the way to a comprehensive survey and to further interpretation of larger portions of text hidden inside the carbonized Herculaneum papyri.


2010 ◽  
Vol 654-656 ◽  
pp. 2322-2325 ◽  
Author(s):  
Sheridan Mayo ◽  
Andrew Stevenson ◽  
Stephen Wilkins ◽  
Da Chao Gao ◽  
Steven Mookhoek ◽  
...  

X-ray phase-contrast imaging and tomography add an additional dimension to conventional x-ray methods by exploiting the x-ray refraction effects in addition to x-ray absorption in forming an image. This greatly enhances the visibility of edges, voids and boundaries within a sample. It also makes it possible to characterise weakly x-ray absorbing samples which would produce little or no contrast in conventional x-ray imaging. Here we described the application of a laboratory-based x-ray phase-contrast microscope to x-ray micro-tomography of a self-healing polymer system and the quantitative analysis of the resulting three dimensional (3D) datasets to better understand the healing and ageing processes.


Lex Russica ◽  
2020 ◽  
pp. 100-107
Author(s):  
D. S. Ksenofontova

Modern breakthrough scientific ideas in the field of introduction and development of biomedical technologies have led to a significant objectification of the human body. The paper analyzes the trend of commodification of the human body and its parts from the standpoint of bioethics and law, which determines the consideration of these as goods that participate in economic turnover and have their own price. The problems of insufficiency of human organs suitable for transplantation, the risk of rejection of the transplant by the recipient’s immune system, as well as the need to ensure the safety of donor organs and tissues can be leveled by creating artificial human organs and tissues, including through the use of advanced additive technologies (3D bioprinting), creating a three-dimensional model of a human organ on a cellular basis, which is subject to subsequent transplantation to a recipient in need. The development of 3D-bioprinting allows us to resolve bioethical and legal contradictions caused by the actual inclusion of human organs and tissues in civil (economic) turnover, while international acts enshrine the principle of inadmissibility of commercialization of the human body, by virtue of which the human body and its parts should not be a source of financial benefit. The author summarizes that 3D bioprinting is able to significantly smooth out the negative manifestations of the human body commodification trend. The peculiarity of applying the principle of non-commercialization of the human body is due to the fact that in this case the emphasis is placed on obtaining cellular material for creating a bioprinted human organ. First of all, the principle of non-commercialization of the human body should remain in effect when providing cell material by a third party (donor), even if only in terms of determining the legal regime of cell material and created bioprinted human organs and tissues. If the recipient’s own cells are used, this principle loses its meaning.


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