The sensitivity of in vivo low-dose high-resolution micro-computed tomography imaging enables monitoring the lung damage caused by tuberculosis. Here, we propose a radiological score integrated in the experimental workflow that enables longitudinal monitoring for prospective efficacy studies in drug development programs. The score is based on an automatic measurement of total unaffected lung volume in vivo normalized for inter-subject comparison. It was validated on well-characterized progression of chronic tuberculosis in Erdman and H37Rv strains in C3HeB/FeJ-based models. We demonstrated that a decrease in the score value indicates increasing adverse effects and vice versa. The colony-forming units count confirmed the variability in the host response suggested by the score values. The correlation between changes in the mice's weight and the score is consistent with disease progression. The classification of disease extent by k-means clustering of the score values provided the definition of the lung damage severity according to the bacillus strain. The proposed score will reduce sources of bias and improve the statistical robustness of studies by the attrition of non-infected subjects or subjects with a weak immune response. Readily available quantifications allow for a fast assessment of the therapeutic potential in drug-resistant tuberculosis strains.

中文翻译：

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用于评估结核病进展的放射学评分：在小鼠模型中的验证

体内低剂量高分辨率微型计算机断层扫描成像的灵敏度能够监测结核病引起的肺损伤。在这里，我们提出了一个集成在实验工作流程中的放射学评分，可以对药物开发计划中的前瞻性疗效研究进行纵向监测。该分数基于自动测量的总未受影响的 体内 肺体积，归一化用于受试者间比较。它在基于 C3HeB/FeJ 的模型中 Erdman 和 H37Rv 菌株的慢性结核病的充分表征的进展中得到验证。我们证明，评分值的降低表明不良反应增加，反之亦然。菌落形成单位计数证实了评分值建议的宿主反应的可变性。小鼠变化之间的相关性 s 体重和评分与疾病进展一致。通过对评分值进行 k 均值聚类对疾病程度进行分类，根据芽孢杆菌菌株提供了肺损伤严重程度的定义。提议的分数将通过减少未感染的受试者或免疫反应较弱的受试者来减少偏见的来源并提高研究的统计稳健性。随时可用的量化允许快速评估耐药结核病菌株的治疗潜力。提议的分数将通过减少未感染的受试者或免疫反应较弱的受试者来减少偏见的来源并提高研究的统计稳健性。随时可用的量化允许快速评估耐药结核病菌株的治疗潜力。提议的分数将通过减少未感染的受试者或免疫反应较弱的受试者来减少偏见的来源并提高研究的统计稳健性。随时可用的量化允许快速评估耐药结核病菌株的治疗潜力。