Four-dimensional computed tomography-based biomechanical measurements of pulmonary function and their correlation with clinical outcome for lung stereotactic body radiation therapy patients.

BACKGROUND: Functional image guided radiotherapy allows for the delivery of an equivalent dose to tumor targets while sparing high ventilation lung tissues. In this study, we investigate whether radiation dose to functional lung is associated with clinical outcome for stereotactic body radiation therapy (SBRT) patients. METHODS: Four-dimensional computed tomography (4DCT) images were used to assess lung function. Deformable image registration (DIR) was performed from the end-inhale phase to the end-exhale phase with resultant displacement vectors used to calculate ventilation maps. In addition to the Jacobian-based ventilation we introduce a volumetric variation method (Rv) based on a biomechanical finite element method (FEM), to assess lung ventilation. Thirty NSCLC patients, treated with SBRT, were evaluated in this study. 4DCT images were used to calculate both Jacobian and Rv-based ventilation images. Areas under the receiver operating characteristic curve (AUC) were used to assess the predictive power of functional metrics. Metrics were calculated over the whole lung as well as high and low ventilated regions. RESULTS: Ventilation in dose regions between 1 and 5 Gy had higher AUC values compared to other dose regions. Rv based ventilation imaging method also showed to be less spatially variant and less heterogeneous, and the resultant Rv metrics had higher AUC values for predicting grade 2+ dyspnea. CONCLUSIONS: Low dose delivered to high ventilation areas may also increase the risk of compromised pulmonary function. Rv based ventilation images could be useful for the prediction of clinical toxicity for lung SBRT patients.

4-Dimensional computed tomography-based ventilation and compliance images for quantification of radiation-induced changes in pulmonary function.

INTRODUCTION: 4-Dimensional computed tomography (4DCT)-based ventilation imaging is a promising technique for evaluating pulmonary function, but lung elasticity and mechanics are usually not part of the ventilation image analysis. In this study we demonstrate a 4DCT-based imaging technique that can be used to calculate regional lung compliance changes after radiotherapy (RT). METHODS: Six lung cancer patients were included in this study. Four of the patients had 4DCT images acquired pre-RT, 3 and 9 months post-RT. Ventilation and compliance were calculated from the deformable image registration (DIR) of 4DCTs, performed from the end-inhale to the end-exhale breathing phase. Regional compliance was defined as the ratio of volumetric variation and associated stress in each voxel, representing lung elasticity and computed using a FEM-based framework. Ventilation, compliance and CT density were calculated for all pre-RT and post-RT 4DCTs and evaluation metrics were computed. RESULTS: Average CT density changes were 13.6 ± 11.4HU after 3 months and 26.9 ± 15.8HU after 9 months. Ventilation was reduced at 3 months, but improved at 9 months in regions with dose ≥ 35 Gy, encompassing about 10% of the lung volume; compliance was reduced at both time-points. Radiation dose ≥ 35 Gy caused major change in lung density and ventilation, which was higher than that previously reported in the literature (i.e. 24 Gy). CONCLUSION: Lung tissue response is diverse with respect to CT density, ventilation and compliance. Combination of ventilation and compliance with CT density could be beneficial for understanding radiation-induced lung damage and consequently could help develop improved treatment protocols for lung cancer patients.