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Romano, M.* ; Bravin, D.A.* ; Wright, D.M.D.* ; Jacques, L.* ; Miettinen, D.A.* ; Hlushchuk, D.R.* ; Dinkel, J.* ; Bartzsch, S. ; Laissue, J.A.* ; Djonov, V.* ; Coan, D.P.*

X-ray Phase Contrast 3D virtual histology: Evaluation of lung alterations after micro-beam irradiation.

Int. J. Radiat. Oncol. Biol. Phys. 112, 818-830 (2022)

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PURPOSE: This study provides the first experimental application of multiscale three-dimensional (3D) X-ray Phase Contrast Imaging Computed Tomography (XPCI-CT) virtual histology for the inspection and quantitative assessment of the late stage effects of radio-induced lesions on lungs in a small animal model. METHODS AND MATERIALS: Healthy male Fischer rats were irradiated with X-ray standard broad beams and Microbeam Radiation Therapy (MRT), a high dose rate (14 kGy/s), FLASH spatially-fractionated X-ray therapy to avoid the beamlets smearing due to cardiosynchronous movements of the organs during the irradiation. After organ dissection, ex-vivo XPCI-CT was applied to all the samples and the results were quantitatively analysed and correlated to histologic data. RESULTS: XPCI-CT enables the 3D visualization of lung tissues with unprecedented contrast and sensitivity allowing alveoli, vessels and bronchi hierarchical visualization. XPCI-CT discriminates in 3D radio-induced lesions such as fibrotic scars, Ca/Fe deposits and, in addition, allows a full-organ accurate quantification of the fibrotic tissue within the irradiated organs. The radiation-induced fibrotic tissue content is less than 10% of the analyzed volume for all the MRT treated organs while it reaches the 34% in the case of irradiations with 50 Gy using a broad beam. CONCLUSIONS: XPCI-CT is an effective imaging technique able to provide detailed 3D information for the assessment of lung pathology and treatment efficacy in a small animal model.

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