Imaging Regional Lung Structure and Function in Small Animals Using Synchrotron Radiation Phase-Contrast and K-Edge Subtraction Computed Tomography

Bayat, Sam; Fardin, Luca; Cercos-Pita, Jose Luis; Perchiazzi, Gaetano; Bravin, Alberto

doi:10.3389/fphys.2022.825433

Cited by 9 publications

(9 citation statements)

References 26 publications

(43 reference statements)

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“…Advances in imaging methodology including tracking X-ray tomography ( Chang et al, 2015 ) and synchrotron-based, phase-contrast micro computed tomography ( Bayat et al, 2022 ) now allow study of dynamic processes within the acinus. Chang and co-workers tracked profiles of alveoli in different lung regions of mice during spontaneous breathing by X-ray tomography.…”

Section: Respiration Related Deformation Of the Lung Parenchyma: Visu...mentioning

confidence: 99%

Acinar micromechanics in health and lung injury: what we have learned from quantitative morphology

et al. 2023

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Within the pulmonary acini ventilation and blood perfusion are brought together on a huge surface area separated by a very thin blood-gas barrier of tissue components to allow efficient gas exchange. During ventilation pulmonary acini are cyclically subjected to deformations which become manifest in changes of the dimensions of both alveolar and ductal airspaces as well as the interalveolar septa, composed of a dense capillary network and the delicate tissue layer forming the blood-gas barrier. These ventilation-related changes are referred to as micromechanics. In lung diseases, abnormalities in acinar micromechanics can be linked with injurious stresses and strains acting on the blood-gas barrier. The mechanisms by which interalveolar septa and the blood-gas barrier adapt to an increase in alveolar volume have been suggested to include unfolding, stretching, or changes in shape other than stretching and unfolding. Folding results in the formation of pleats in which alveolar epithelium is not exposed to air and parts of the blood-gas barrier are folded on each other. The opening of a collapsed alveolus (recruitment) can be considered as an extreme variant of septal wall unfolding. Alveolar recruitment can be detected with imaging techniques which achieve light microscopic resolution. Unfolding of pleats and stretching of the blood-gas barrier, however, require electron microscopic resolution to identify the basement membrane. While stretching results in an increase of the area of the basement membrane, unfolding of pleats and shape changes do not. Real time visualization of these processes, however, is currently not possible. In this review we provide an overview of septal wall micromechanics with focus on unfolding/folding as well as stretching. At the same time we provide a state-of-the-art design-based stereology methodology to quantify microarchitecture of alveoli and interalveolar septa based on different imaging techniques and design-based stereology.

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Section: Respiration Related Deformation Of the Lung Parenchyma: Visu...mentioning

confidence: 99%

Acinar micromechanics in health and lung injury: what we have learned from quantitative morphology

et al. 2023

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“…The continuous search for finding new imaging-based techniques to obtain regional lung function and biomechanics data led to employing synchrotron radiation sources to produce highly coherent, high flux x-rays that are required for phase contrast x-ray imaging (PCXI) [see ( Bayat et al, 2001 ), ( Bayat et al, 2009 ), ( Porra et al, 2004 ), ( Monfraix et al, 2004 ), ( Bayat et al, 2022a ), ( Cercos-Pita et al, 2022 ), ( Bayat et al, 2022b )]. PCXI is a high-resolution imaging technique, capable of differentiating between soft tissues by enhancing the contrast of biological interfaces and also providing dynamic motions of lung tissue.…”

Section: The Role Of Pulmonary Function Tests In Preclinical Lung Res...mentioning

confidence: 99%

Lung function measurements in preclinical research: What has been done and where is it headed?

2023

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Due to the close interaction of lung morphology and functions, repeatable measurements of pulmonary function during longitudinal studies on lung pathophysiology and treatment efficacy have been a great area of interest for lung researchers. Spirometry, as a simple and quick procedure that depends on the maximal inspiration of the patient, is the most common lung function test in clinics that measures lung volumes against time. Similarly, in the preclinical area, plethysmography techniques offer lung functional parameters related to lung volumes. In the past few decades, many innovative techniques have been introduced for in vivo lung function measurements, while each one of these techniques has their own advantages and disadvantages. Before each experiment, depending on the sensitivity of the required pulmonary functional parameters, it should be decided whether an invasive or non-invasive approach is desired. On one hand, invasive techniques offer sensitive and specific readouts related to lung mechanics in anesthetized and tracheotomized animals at endpoints. On the other hand, non-invasive techniques allow repeatable lung function measurements in conscious, free-breathing animals with readouts related to the lung volumes. The biggest disadvantage of these standard techniques for lung function measurements is considering the lung as a single unit and providing only global readouts. However, recent advances in lung imaging modalities such as x-ray computed tomography and magnetic resonance imaging opened new doors toward obtaining both anatomical and functional information from the same scan session, without the requirement for any extra pulmonary functional measurements, in more regional and non-invasive manners. Consequently, a new field of study called pulmonary functional imaging was born which focuses on introducing new techniques for regional quantification of lung function non-invasively using imaging-based techniques. This narrative review provides first an overview of both invasive and non-invasive conventional methods for lung function measurements, mostly focused on small animals for preclinical research, including discussions about their advantages and disadvantages. Then, we focus on those newly developed, non-invasive, imaging-based techniques that can provide either global or regional lung functional readouts at multiple time-points.

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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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Imaging Regional Lung Structure and Function in Small Animals Using Synchrotron Radiation Phase-Contrast and K-Edge Subtraction Computed Tomography

Cited by 9 publications

References 26 publications

Acinar micromechanics in health and lung injury: what we have learned from quantitative morphology

Acinar micromechanics in health and lung injury: what we have learned from quantitative morphology

Lung function measurements in preclinical research: What has been done and where is it headed?

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

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