Introduction

Radiation induced lung injury (RILI) is a major side effect in patients undergoing thoracic irradiation for lung or breast cancer [1]. The injury typically manifests as pneumonitis before progressing to irreversible pulmonary fibrosis. Unfortunately, the conventional rat models are not ideal for studying this phenomenon, due to their relative insensitivity to RILI at dosages comparable to those used for radiation therapy (RT) in humans [2]. In this study, we developed a two-hit RILI model that better simulates the etiology of the disease in humans, and characterized it via a multibreath hyperpolarized (HP) 129Xe imaging technique to assess lung function and structure one month post-radiation.

Methods

The two-hit RILI model consists of priming the lungs with an intratracheal instillation of LPS (10mg/mL) followed by right hemi-thorax radiation (25Gy) after 24 hours, in Fisher rats (n=8). Animals were imaged one month post-radiation, when early fibrosis can typically be detected. Gated micro-computed tomography (uCT) (current = 60mA, voltage = 40kV, reconstructed isotropically at 200 um) was used to detect structural changes. A 1.5T MRI system (Seimens MAGNETOM) with a custom-built quadrature volume coil was used to to perform a hybrid multibreath hyperpolarized 129Xe imaging sequence that was used to derive the following functional parameters: fractional ventilation (FV), alveolar oxygen tension (PAO2), apparent diffusion coefficient (ADC), and oxygen uptake (R) [3]. The fractional ventilation image series consisted of 10 wash-in breaths followed by a final long breath-hold for T1 and flip angle correction, as previously presented [3]. Two 10mm sagittal slices with a 2D multi-slice GRE sequence were acquired with a matrix size of 48x36 (3mm x 3mm in-plane resolution), flip-angle = 6^o, and TR/TE=9.0/4.1ms.

Results and Discussion

The preliminary findings show that the PAO2 in the radiated lungs significantly increased to 145±41 Torr, compared to 124±40 Torr in the contralateral lungs, and 125±39 Torr in the healthy cohort (both lungs). On the other hand, the radiated lungs had an R of 6.3±6.1 Torr/s, compared to 9.8±7.3 Torr/s in the contralateral lungs. The control cohort had a R of 7.0±10.3 Torr/s, which suggests that the lowered oxygen uptake in the radiated lungs may have been compensated by an increased uptake in the contralateral lung. Physiologically, these observed changes in R are most likely due to the increased alveolar wall thickness with the onset of fibrosis. Although no significant differences were observed for FV and ADC between the radiated lungs and the other cohorts, the heterogeneity in their measurements may serve as a potential biomarker as well.

Conclusions

Conclusions: This study demonstrates that HP 129Xe-derived functional parameters, particularly changes in the alveolar oxygen tension and oxygen uptake can serve as biomarkers during the early fibrotic stage of RILI. The next goal of this study is to quantify these changes at earlier timepoints (pneumonitis stage) of the disease in order to determine the sensitivity of the imaging technique and its feasibility for early detection of RILI.

Acknowledgements

No acknowledgement found.