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Thoracic Radiation Injury Murine Model for Pulmonary Fibrosis

D McIlrath1*, C Perez-Torres2 , (1) Purdue Univ, West Lafayette, IN, (2) Purdue University, West Lafayette, IN


(Sunday, 7/14/2019)  

Room: ePoster Forums

Purpose: Radiation-induced lung injury (RILI) is a common sequelae in the setting of lung and breast cancer. Often, patients who suffer from RILI experience pneumonitis and pulmonary fibrosis months after treatment. These pathologies have commonly been modeled using mice and observing their deterioration until mortality, then quantifying pathology on histological sections.

Methods: With this study, we attempt to use longitudinal microCT to characterize male C57Bl/6 mice irradiated with a single dose of 20 Gy to the whole thoracic area delivered by an X-Rad cabinet irradiator. CT was performed with a 4 minute respiratory gating sequence at 2 to 4 week timepoints to construct a timeline of pathology leading up to fibrosis and, additionally, to quantify severity of fibrosis afterwards. Images were analyzed on ITK-SNAP to segment anatomy and pathology using their machine learning algorithm. Histology was later performed using H&E and Trichrome stains to provide ex-vivo verification of pathology.

Results: At the 4-6 week timepoint, observable physical pathology occurred – most notably alopecia and erythemea. CT images showed little lung pathology at that time, but later timepoints – closer to 12 weeks – showed areas within the lung of hyperintense nodules, expanding over time. Figure 1 shows CT images of a mouse who exhibited this pathology 18 weeks post-irradiation.

Conclusion: The hyperintense nodules were believed to be fibrotic tissue, and histology confirmed collagen production localized to tissue near the bronchi – correlated with the hyperintense areas on the CT images. Mice that survived to later timepoints showed exponential deterioration of their health and exponential progression of pulmonary fibrosis. Mice eventually exhibited extreme lethargy as a precursor to death if not euthanized before mortality.


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