Correlation of Regional Lung Ventilation and Gas Transfer to Red Blood Cells: Implications for Functional-Avoidance Radiation Therapy Planning

Purpose To investigate the degree to which lung ventilation and gas exchange are regionally correlated, using the emerging technology of hyperpolarized (HP)- 129 Xe magnetic resonance imaging (MRI). Methods and Materials Hyperpolarized- 129 Xe MRI studies were performed on 17 institutional review board–approved human subjects, including 13 healthy volunteers, 1 emphysema patient, and 3 non-small cell lung cancer patients imaged before and approximately 11 weeks after radiation therapy (RT). Subjects inhaled 1 L of HP- 129 Xe mixture, followed by the acquisition of interleaved ventilation and gas exchange images, from which maps were obtained of the relative HP- 129 Xe distribution in three states: (1) gaseous, in lung airspaces; (2) dissolved interstitially, in alveolar barrier tissue; and (3) transferred to red blood cells (RBCs), in the capillary vasculature. The relative spatial distributions of HP- 129 Xe in airspaces (regional ventilation) and RBCs (regional gas transfer) were compared. Further, we investigated the degree to which ventilation and RBC transfer images identified similar functional regions of interest (ROIs) suitable for functionally guided RT. For the RT patients, both ventilation and RBC functional images were used to calculate differences in the lung dose–function histogram and functional effective uniform dose. Results The correlation of ventilation and RBC transfer was ρ  = 0.39 ± 0.15 in healthy volunteers. For the RT patients, this correlation was ρ  = 0.53 ± 0.02 before treatment and ρ  = 0.39 ± 0.07 after treatment; for the emphysema patient it was ρ  = 0.24. Comparing functional ROIs, ventilation and RBC transfer demonstrated poor spatial agreement: Dice similarity coefficient = 0.50 ± 0.07 and 0.26 ± 0.12 for the highest-33%- and highest-10%-function ROIs in healthy volunteers, and in RT patients (before treatment) these were 0.58 ± 0.04 and 0.40 ± 0.04. The average magnitude of the differences between RBC- and ventilation-derived functional effective uniform dose, fV20Gy, fV10Gy, and fV5Gy were 1.5 ± 1.4 Gy, 4.1% ± 3.8%, 5.0% ± 3.8%, and 5.3% ± 3.9%, respectively. Conclusion Ventilation may not be an effective surrogate for true regional lung function for all patients.