Purpose: To analyze radiation induced changes in Hounsfield units and determine their correlation with changes in perfusion and ventilation. Additionally, to compare the post-RT changes in human subjects to those measured in a swine model used to quantify perfusion changes, and validate their use as a preclinical model.
Methods: A cohort of 5 Wisconsin Miniature Swine (WMS™) were studied. Additionally, 19 human subjects were recruited as part of an IRB approved clinical trial studying functional avoidance radiation therapy for lung cancer and were treated with SBRT. Imaging (a contrast enhanced dynamic perfusion CT in the swine and 4DCT in the humans) was performed prior to and post-RT. Jacobian elasticity maps were calculated on all 4DCT images. Contours were created from the isodose lines to discretize analysis into 10 Gy dose bins. B-spline deformable image registration allowed for voxel-by-voxel comparative analysis in these contours between timepoints. The WMS™ underwent a research course of 60 Gy in 5 fractions delivered locally to a target in the lung using an MRI-LINAC system. In the WMS™ subjects, the dose-bin contours were copied onto the contralateral lung, which received < 5 Gy for comparison. Changes in HU and changes in Jacobian were analyzed in these contours.
Results: Statistically significant (p < 0.05) changes in the mean HU value post-RT compared to pre-RT were observed in both the human and WMS™ groups at all timepoints analyzed. The HU increased linearly with dose for both groups. Strong linear correlation was observed between the changes seen in the swine and humans (Pearson coefficient > 0.97, p< 0.05) at all timepoints. Changes seen in the swine closely modeled the changes seen in the humans at 12 months post RT (slope=0.95). Jacobian analysis showed between 30-60% of voxels were damaged post-RT. Perfusion analysis in the swine showed a statistically significant (p < 0.05) reduction in contrast inside the vasculature 3 months post-RT compared to pre-RT. The increases in contrast outside the vasculature was strongly correlated (Pearson Correlation 0.88) with the reduction in HU inside the vasculature but were not correlated with the changes in Jacobians.
Conclusions: Radiation induces changes in pulmonary anatomy at 3 months post-RT, with a strong linear correlation with dose. The change in HU seen in the non-vessel lung parenchyma suggests this metric is a potential biomarker for change in perfusion. Finally, this work suggests that the WMS™ swine model is a promising pre-clinical model for analyzing radiation-induced changes in humans and poses several benefits over conventional swine models.