Abstract
BACKGROUND: Without aggressive treatment, pulmonary arterial hypertension (PAH) has a 5-year mortality of approximately 40%. A patient's response to vasodilators at diagnosis impacts the therapeutic options and prognosis. We hypothesized that analyzing perfusion images acquired before and during vasodilation could identify characteristic differences between PAH and control subjects. METHODS: We studied 5 controls and 4 subjects with PAH using HRCT and (13)NN PET imaging of pulmonary perfusion and ventilation. The total spatial heterogeneity of perfusion (CV(2)(Qtotal)) and its components in the vertical (CV(2)(Qvgrad)) and cranio-caudal (CV(2)(Qzgrad)) directions, and the residual heterogeneity (CV(2)(Qr)), were assessed at baseline and while breathing oxygen and nitric oxide (O(2) + iNO). The length scale spectrum of CV(2)(Qr) was determined from 10 to 110 mm, and the response of regional perfusion to O(2) + iNO was calculated as the mean of absolute differences. Vertical gradients in perfusion (Q(vgrad)) were derived from perfusion images, and ventilation-perfusion distributions from images of (13)NN washout kinetics. RESULTS: O(2) + iNO significantly enhanced perfusion distribution differences between PAH and controls, allowing differentiation of PAH subjects from controls. During O(2) + iNO, CV(2)(Qvgrad) was significantly higher in controls than in PAH (0.08 (0.055-0.10) vs. 6.7 × 10(-3) (2 × 10(-4)-0.02), p < 0.001) with a considerable gap between groups. Q(vgrad) and CV(2)(Qtotal) showed smaller differences: - 7.3 vs. - 2.5, p = 0.002, and 0.12 vs. 0.06, p = 0.01. CV(2)(Qvgrad) had the largest effect size among the primary parameters during O(2) + iNO. CV(2)(Qr), and its length scale spectrum were similar in PAH and controls. Ventilation-perfusion distributions showed a trend towards a difference between PAH and controls at baseline, but it was not statistically significant. CONCLUSIONS: Perfusion imaging during O2 + iNO showed a significant difference in the heterogeneity associated with the vertical gradient in perfusion, distinguishing in this small cohort study PAH subjects from controls.