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使用微型计算机断层扫描对 COVID-19 金色叙利亚仓鼠模型中的肺部病理学特征进行研究

Characterization of Pulmonary Pathology in the Golden Syrian Hamster Model of COVID-19 Using Micro-Computed Tomography.

作者信息

Ramirez Julita A, Dunlap Micah D, Prosnitz Reyna, Watson Anderson, Montgomery Mary K, Gutman Matthew, Coskran Timothy M, Levinson Samantha L, Yang Katharine, Kanevsky Isis, Choudhary Shambhunath

机构信息

Pfizer Inc., Pearl River, New York, USA.

Pfizer Inc., La Jolla, California, USA.

出版信息

Toxicol Pathol. 2025 Apr;53(3):267-277. doi: 10.1177/01926233241300451. Epub 2024 Dec 5.

Abstract

The Golden Syrian hamster is a well-characterized rodent model for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-associated pneumonia. We sought to characterize the pulmonary disease course during SARS-CoV-2 infection (strain USA-WA1/2020) in the hamster model using micro-computed tomography (micro-CT) and compare radiologic observations with histopathologic findings. We observed a range of radiologic abnormalities, including ground glass opacities (GGOs), consolidations, air bronchograms, and pneumomediastinum. The appearance, distribution, and progression of these abnormalities in hamsters were similar to those observed in the lungs of coronavirus disease 2019 (COVID-19) patients by clinical CT and chest X-rays, and correlated with clinical signs and weight loss during the course of disease. Histopathological analysis of infected hamsters revealed lung pathology characteristic of COVID-19 pneumonia, and we observed a strong association between CT and histopathologic scorings. We also analyzed accumulation of air in the thoracic cavity by both manual and automated threshold-based segmentation and found that automated analysis significantly decreases the time needed for data analysis. Data presented here demonstrate that micro-CT imaging can be a major tool in preclinical investigative studies using animal models by providing early and detailed assessment of disease severity and outcomes.

摘要

金黄叙利亚仓鼠是一种特征明确的啮齿动物模型,用于研究严重急性呼吸综合征冠状病毒2(SARS-CoV-2)相关肺炎。我们试图利用微型计算机断层扫描(micro-CT)来描述仓鼠模型在感染SARS-CoV-2(毒株USA-WA1/2020)期间的肺部疾病进程,并将放射学观察结果与组织病理学发现进行比较。我们观察到一系列放射学异常,包括磨玻璃影(GGO)、实变、空气支气管征和气纵隔。仓鼠中这些异常的表现、分布和进展与通过临床CT和胸部X光在2019冠状病毒病(COVID-19)患者肺部观察到的情况相似,并与疾病过程中的临床症状和体重减轻相关。对感染仓鼠的组织病理学分析揭示了COVID-19肺炎的肺部病理特征,并且我们观察到CT评分与组织病理学评分之间存在很强的相关性。我们还通过手动和基于自动阈值的分割分析了胸腔内气体的积聚情况,发现自动分析显著减少了数据分析所需的时间。本文提供的数据表明,micro-CT成像通过对疾病严重程度和结果进行早期和详细评估,可以成为使用动物模型的临床前研究中的一项主要工具。

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