Regional and organ-level responses to local lung irradiation in sheep.

摘要: Lung is a dose-limiting organ in radiotherapy. This may limit tumour control when effort made planning to the likelihood of radiation-induced lung injury (RILI). Understanding factors that dictate susceptibility pulmonary fibrosis will aid prevention and management RILI, lead more effective personalized radiotherapy treatment. As interaction regional organ-level responses shape chronic consequences we sought characterise both aspects response an ovine model. A defined volume left parenchyma was prescribed 5 fractions 6 Gy within 14 days while contralateral dose constrained. Radiographic changes via computed tomography (CT) were documented define differences radio-exposed relative non-exposed at d21, d63 d171 (n = 2), d147 d227 (n = 2). Gross histologic evaluated samples derived necropsy examination radiation. Irradiated demonstrated reduced radio-density increased homogeneity as evidenced from texture based radiomic feature analysis, lung. At necropsy, radiation field readily by pallor on pleural surface, which also evident cut surface fixed specimens. The degree reflected sparse presence erythrocytes alveolar septal capillaries radiation-exposed These contrasted with dilated congested microvasculature Referencing data measurements volumes sheep experiencing acute RILI indicated interstitial collagen continues deposit field. Overall vascularity during response, expression endothelial cell marker (CD31); however, consistently decreased irradiated negatively correlated collagen. Other included alpha smooth muscle actin (ASMA), numbers proliferating cells (Ki67 positive), expressing dendritic cell-lysosomal associated membrane protein (DC-LAMP) antigen. this model effected whole local level. Whilst long-term exposure involved continued deposition field, vascularization ASMA, Ki67 DC-LAMP. Interrupting interplay between these influence after We advocate for importance large animal systems pursuing opportunities target local, systemic mechanisms parallel same subject over time.