Phase-contrast X-ray tomography resolves the terminal bronchioles in free-breathing mice

Shaker, Kian; Häggmark, Ilian; Reichmann, Jakob; Arsenian-Henriksson, Marie; Hertz, Hans M.

doi:10.1038/s42005-021-00760-8

Cited by 11 publications

(5 citation statements)

References 41 publications

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“…3D imaging of lung by XPCT is a case in point. The applicability of XPCT has been demonstrated across a spectrum of scales, ranging from the macroscopic to the microscopic [4][5][6][7][8][9][10][11][12][13], and even including in-vivo lung imaging. With its intricate 3D networks of airways and vasculature, alveolar ducts, spaces and septae, 3D imaging is desirable and at the same time facilitated by strong contrast based on the density contrast of tissue and empty space filled by air or the embedding medium.…”

Section: Introductionmentioning

confidence: 99%

Cytoarchitecture of SARS-CoV-2 infected hamster lungs by X-ray phase contrast tomography: imaging workflow and classification for drug testing

Reichmann,

Sarrazin,

Schmale

et al. 2024

Preprint

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X-ray Phase Contrast Tomography (XPCT) based on wavefield propagation has been established as a high resolution three-dimensional (3D) imaging modality, suitable to reconstruct the intricate structure of soft tissues, and the corresponding pathological alterations. However, for biomedical research, more is needed than 3D visualisation and rendering of the cytoarchitecture in a few selected cases. First, the throughput needs to be increased to cover a statistically relevant number of samples. Second, the cytoarchitecture has to be quantified in terms of morphometric parameters, independent of visual impression. Third, dimensionality reduction and classification are required for identification of effects and interpretation of results. In this work, we present a workflow implemented at a laboratory μCT setup, using semi-automated data acquisition, reconstruction and statistical quantification of lung tissue in an early screen of Covid-19 drug candidates. Different drugs were tested in a hamster model after SARS-CoV-2 infection. To make full use of the recorded high-throughput XPCT data, we then used morphometric parameter determination followed by a dimensionality reduction and classification based on optimal transport. This approach allows efficient discrimination between physiological and pathological lung structure, thereby providing invaluable insights into the pathological progression and partial recovery due to drug treatment.

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Section: Introductionmentioning

confidence: 99%

Cytoarchitecture of SARS-CoV-2 infected hamster lungs by X-ray phase contrast tomography: imaging workflow and classification for drug testing

Reichmann,

Sarrazin,

Schmale

et al. 2024

Preprint

Self Cite

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“…Lung imaging by XPCT has early on been implemented on macro-and microscopic scales (Parsons et al 2008, Leong et al 2014, Stahr et al 2016, Bayat et al 2020, Morgan et al 2020, Borisova et al 2021, Shaker et al 2021, Bayat et al 2022a, 2022b, O'Connell et al 2022, including even live animal models of respiratory diseases. At the histological level, we have recently used multi-scale XPCT to image the parenchymal architecture of unstained FFPE lung tissue of patients who succumbed to COVID-19 (Eckermann et al 2020).…”

Section: Introductionmentioning

confidence: 99%

Human lung virtual histology by multi-scale x-ray phase-contrast computed tomography

et al. 2023

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As the central organ of the respiratory system, the human lung is responsible for supplying oxygen to the blood, which reaches the erythrocytes by diffusion through the alveolar walls and is then distributed throughout the body. By exploiting the difference in electron density detected by a phase shift in soft tissue, high-resolution X-ray phase-contrast computed tomography (XPCT) can resolve biological structures in a sub-μm range, shedding new light on the three-dimensional structure of the lungs, physiological functions and pathological mechanisms.This work presents both synchrotron and laboratory XPCT results of postmortem tissue from autopsies and biopsies embedded with various preparation protocols such as precision-cut lung slices, cryogenically fixed lung tissue, as well as paraffin and alcohol fixed tissue. The selection of pathological abnormalities includes channel of Lambert, bronchus-associated lymphoid tissue, alveolar capillary dysplasia with misalignment of pulmonary veins. Subsequently, quantification and visualization approaches are presented.The overall high image quality even of in-house XPCT scans for the case of FFPE biopsies can be exploited for a wide range of pulmonary pathologies and translated to dedicated and optimized instrumentation which could be operated in clinical setting. By using synchrotron radiation, contrast can be further increased to resolve sub-μm sized features down to the sub-cellular level. The results demonstrate that a wide range of preparation protocols including sample mounting in liquids can be used. With XPCT, poorly understood 3D structures can be identified in larger volume overview and subsequently studied in more detail at higher resolution. With the full 3D structure, the respective physiological functions of airways or vascular networks, and the different pathophysiologic mechanisms can be elucidated or at least underpinned with structural data. Moreover, synchrotron data can be used to validate laboratory protocols and provide ground truth for standardizing the method.

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“…In addition, XPCT can be implemented in multi-scale approach, covering larger tissue scales up to the entire organ level. XPCT has even been implemented for in-vivo imaging of free breathing mice 7 and can quantify morphology and cytoarchitecture of biological tissue. [8][9][10] Different pathologies of the central nervous system (CNS), such as, e.g., Alzheimer 11 or multiple sclerosis, 12 have been addressed by virtual histology based on XPCT.…”

Section: Introductionmentioning

confidence: 99%

Neodymium acetate as a contrast agent for X-ray phase-contrast tomography

Reichmann,

Ruhwedel,

Möbius

et al. 2023

J. Med. Imag.

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.PurposeX-ray phase-contrast tomography (XPCT) is a non-destructive, three-dimensional imaging modality that provides higher contrast in soft tissue than absorption-based CT and allows one to cover the cytoarchitecture from the centi- and millimeter scale down to the nanoscale. To further increase contrast and resolution of XPCT, for example, in view of addressing connectivity issues in the central nervous system (CNS), metal staining is indispensable. However, currently used protocols, for example, based on osmium and/or uranium are less suited for XPCT, due to an excessive β / δ-ratio. In this work, we explore the suitability of different staining agents for XPCT. Particularly, neodymium(III)-acetate (NdAc), which has recently been proposed as a non-toxic, non-radioactive easy to use alternative contrast agent for uranyl acetate (UAc) in electron microscopy, is investigated. Due to its vertical proximity to UAc in the periodic table, similar chemical but better suited optical properties for phase contrast can be expected.ApproachDifferently stained whole eye samples of wild type mouse and tissues of the CNS are embedded into EPON epoxy resin and scanned using synchrotron as well as with laboratory radiation. Phase retrieval is performed on the projection images, followed by tomographic reconstruction, which enables a quantitative analysis based on the reconstructed electron densities. Segmentation techniques and rendering software is used to visualize structures of interest in the sample.ResultsWe show that staining neuronal samples with NdAc enhances contrast, in particular for laboratory scans, allowing high-resolution imaging of biological soft tissue in-house. For the example of murine retina, specifically rods and cones as well as the sclera and the Ganglion cell layer seem to be targeted by the stain. A comparison of electron density by the evaluation of histograms allowed to determine quantitative measures to describe the difference between the examined stains.ConclusionThe results suggest NdAc to be an effective stain for XPCT, with a preferential binding to anionic groups, such as phosphate and carboxyl groups at cell surfaces, targeting certain layers of the retina with a stronger selectivity compared to other staining agents. Due to the advantageous X-ray optical properties, the stain seems particularly well-suited for phase contrast, with a comparably small number density and an overall superior image quality at laboratory sources.

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Phase-contrast X-ray tomography resolves the terminal bronchioles in free-breathing mice

Cited by 11 publications

References 41 publications

Cytoarchitecture of SARS-CoV-2 infected hamster lungs by X-ray phase contrast tomography: imaging workflow and classification for drug testing

Cytoarchitecture of SARS-CoV-2 infected hamster lungs by X-ray phase contrast tomography: imaging workflow and classification for drug testing

Human lung virtual histology by multi-scale x-ray phase-contrast computed tomography

Neodymium acetate as a contrast agent for X-ray phase-contrast tomography

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