Vertical gradients in regional alveolar oxygen tension in supine human lung imaged by hyperpolarized 3He MRI

The purpose of this study was to evaluate whether regional alveolar oxygen tension (P(A)O2) vertical gradients imaged with hyperpolarized (3)He can identify smoking-induced pulmonary alterations. These gradients are compared with common clinical measurements including pulmonary function tests (PFTs), the six minute walk test, and the St. George's Respiratory Questionnaire. 8 healthy non-smokers, 12 asymptomatic smokers, and 7 symptomatic subjects with chronic obstructive pulmonary disease (COPD) underwent two sets of back-to-back P(A)O2 imaging acquisitions in the supine position in two opposite directions (top to bottom and bottom to top), followed by clinically standard pulmonary tests. The whole-lung mean, standard deviation (DP(A)O2) and vertical gradients of P(A)O2 along the slices were extracted, and the results were compared with clinically derived metrics. Statistical tests were performed to analyze the differences between cohorts. The anterior-posterior vertical gradients and DP(A)O2 effectively differentiated all three cohorts (p < 0.05). The average vertical gradient P(A)O2 in healthy subjects was -1.03 ± 0.51 Torr/cm toward lower values in the posterior/dependent regions. The directional gradient was absent in smokers (0.36 ± 1.22 Torr/cm) and was in the opposite direction in COPD subjects (2.18 ± 1.54 Torr/cm). The vertical gradients correlated with smoking history (p = 0.004); body mass index (p = 0.037), PFT metrics (forced expiratory volume in 1 s, p = 0.025; residual volume/total lung capacity percent predicted, p = 0.033) and with distance walked in 6 min (p = 0.009). Regional P(A)O2 data indicate that cigarette smoke induces physiological alterations that are not being detected by the most widely used physiological tests.