Radiation-induced Hounsfield unit change correlates with dynamic CT perfusion better than 4DCT-based ventilation measures in a novel-swine model

Abstract 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...

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Autores principales:	Antonia E. Wuschner, Eric M. Wallat, Mattison J. Flakus, Dhanansayan Shanmuganayagam, Jennifer Meudt, Gary E. Christensen, Joseph M. Reinhardt, Jessica R. Miller, Michael J. Lawless, Andrew M. Baschnagel, John E. Bayouth
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/07372b9f29ca48a28cc4584233a4001c
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spelling	oai:doaj.org-article:07372b9f29ca48a28cc4584233a4001c2021-12-02T16:07:02ZRadiation-induced Hounsfield unit change correlates with dynamic CT perfusion better than 4DCT-based ventilation measures in a novel-swine model10.1038/s41598-021-92609-x2045-2322https://doaj.org/article/07372b9f29ca48a28cc4584233a4001c2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92609-xhttps://doaj.org/toc/2045-2322Abstract 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. 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. 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 and 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. 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.Antonia E. WuschnerEric M. WallatMattison J. FlakusDhanansayan ShanmuganayagamJennifer MeudtGary E. ChristensenJoseph M. ReinhardtJessica R. MillerMichael J. LawlessAndrew M. BaschnagelJohn E. BayouthNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Antonia E. Wuschner Eric M. Wallat Mattison J. Flakus Dhanansayan Shanmuganayagam Jennifer Meudt Gary E. Christensen Joseph M. Reinhardt Jessica R. Miller Michael J. Lawless Andrew M. Baschnagel John E. Bayouth Radiation-induced Hounsfield unit change correlates with dynamic CT perfusion better than 4DCT-based ventilation measures in a novel-swine model
description	Abstract 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. 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. 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 and 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. 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.
format	article
author	Antonia E. Wuschner Eric M. Wallat Mattison J. Flakus Dhanansayan Shanmuganayagam Jennifer Meudt Gary E. Christensen Joseph M. Reinhardt Jessica R. Miller Michael J. Lawless Andrew M. Baschnagel John E. Bayouth
author_facet	Antonia E. Wuschner Eric M. Wallat Mattison J. Flakus Dhanansayan Shanmuganayagam Jennifer Meudt Gary E. Christensen Joseph M. Reinhardt Jessica R. Miller Michael J. Lawless Andrew M. Baschnagel John E. Bayouth
author_sort	Antonia E. Wuschner
title	Radiation-induced Hounsfield unit change correlates with dynamic CT perfusion better than 4DCT-based ventilation measures in a novel-swine model
title_short	Radiation-induced Hounsfield unit change correlates with dynamic CT perfusion better than 4DCT-based ventilation measures in a novel-swine model
title_full	Radiation-induced Hounsfield unit change correlates with dynamic CT perfusion better than 4DCT-based ventilation measures in a novel-swine model
title_fullStr	Radiation-induced Hounsfield unit change correlates with dynamic CT perfusion better than 4DCT-based ventilation measures in a novel-swine model
title_full_unstemmed	Radiation-induced Hounsfield unit change correlates with dynamic CT perfusion better than 4DCT-based ventilation measures in a novel-swine model
title_sort	radiation-induced hounsfield unit change correlates with dynamic ct perfusion better than 4dct-based ventilation measures in a novel-swine model
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/07372b9f29ca48a28cc4584233a4001c
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Radiation-induced Hounsfield unit change correlates with dynamic CT perfusion better than 4DCT-based ventilation measures in a novel-swine model

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