<p>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.<b> </b></p>
<p>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.<b> </b>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
.<b> </b>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 (
). <b></b></p>
Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/12214886 |
Date | 29 April 2020 |
Creators | Daniel R McIlrath (8781065) |
Source Sets | Purdue University |
Detected Language | English |
Type | Text, Thesis |
Rights | CC BY 4.0 |
Relation | https://figshare.com/articles/A_STUDY_OF_RADIATION-INDUCED_PULMONARY_FIBROSIS_RIPF_IN_MOUSE_MODELS_USING_DIAGNOSTIC_IMAGING/12214886 |
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