Daniel McIlrath's Thesis_Final.pdf (2.39 MB)

A STUDY OF RADIATION-INDUCED PULMONARY FIBROSIS (RIPF) IN MOUSE MODELS USING DIAGNOSTIC IMAGING

Download (2.39 MB)
thesis
posted on 29.04.2020, 18:25 by Daniel R McIlrath

Radiation-induced lung injury (RILI) is a common condition 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 and quantifying pathology on histological sections.

With this study, we used a longitudinal microCT and a 7T MRI to characterize male C57Bl/6 mice irradiated with a single dose of 20 Gy to the whole thoracic area delivered by an X-Rad cabinent irradiator. CT was performed with a respiratory gating sequence at 2 week timepoints to construct an RIPF model. The fraction of RIPF to total lung volume was calculated at each time point from images, and the data was anaylzed using one-way ANOVA Welch and Dunnett’s T3 multiple comparisons tests. Tidal lung volumes were also calculated and anlyazed in a simlar manner. Mice were then imaged using MRI and CT at 0, 5, and 8 week timepoints to compare results. These results were analyzed for comparison (ANOVA and Dunnett’s T3) and correlation (Pearson’s r) with each other. Histology was later performed using H&E and Trichrome stains to provide ex-vivo verification of pathology. At the 10-12 week time point ( ) significant RIPF formed. Weeks proceeding showed increased significance until the 22+ week timepoint, which showed less statistical significance ( ) due to increased variance at this timepoint. Dunnett’s T3 test showed no significant differences between tidal lung volumes over time. Tests also showed no significant differences between CT and MRI results with a correlation coefficient of . Early in the study, problems arose when pre-marture mortality was occurring to a significant portion of our subjects. Analysis later showed issues during irradiation that resulted in significant dose being absorbed by the stomach. Adjusting our shiedling lead to increased early survival of our subjects enabling us to contine our study. Significant RIPF development was not significant until 10-12 weeks post-irradiation, then RIPF became more severe at proceeding timepoints. Tidal lung volume showed no significant deviation over the development of RIPF. This result is most likely affected by the variation of results at later timepoints, since several mice with severe RIPF were significantly hindered in their ability to breathe during the study. MRI results showed close correlation with CT results and prodcued similar values at early timepoints. However, noticeable differences were seen at later timepoints when significant RIPF developed ( ).

History

Degree Type

Doctor of Philosophy

Department

Health Science

Campus location

West Lafayette

Advisor/Supervisor/Committee Chair

Dr. Carlos Perez-Torres

Additional Committee Member 2

Dr. Ulrike Dydak

Additional Committee Member 3

Dr. Craig Goergen

Additional Committee Member 4

Dr. Jonathan Shannahan

Licence

Exports