Regional ventilation changes in the lung: Treatment response mapping by using hyperpolarized gas MR imaging as a quantitative biomarker

Purpose: To assess the magnitude of regional response to respiratory therapeutics in the lungs using Treatment Response Mapping (TRM) with hyperpolarized gas MRI. TRM is used to quantify regional physiological response in asthmatic adults using a bronchodilator challenge.

Methods: The study was approved by the national research ethics committee and performed with informed consent. Imaging was performed in 20 adult asthmatic patients using hyperpolarized 3He ventilation MRI. Two sets of baseline images were acquired before inhalation of a bronchodilator (Inhaled Salbutamol 400 mcg) and one set was acquired after. All images were registered for voxelwise comparison. Regional treatment response, ΔR(r), is calculated as the difference in regional gas distribution (R(r) = ratio of inhaled gas to total volume of a voxel when normalized for lung inflation volume) before and after intervention. A voxelwise activation threshold from the variability of the baseline images was applied to ΔR(r) maps. The summed global TRM (ΔRnet) was then used as global lung index for comparison with metrics of bronchodilator response measured using spirometry and the global imaging metric, percentage ventilated volume (%VV).

Results: ΔRnet showed significant correlation (p<0.01) with changes in FEV1 (r=0.70), FVC (r=0.84) and %VV (r=0.56). A significant (p<0.01) positive treatment effect was detected by all metrics, however ΔRnet showed a lower inter-subject coefficient of variation (CV=64%) than all of the other tests (CV≥99%).

Conclusions: TRM provides regional quantitative information on changes in inhaled gas ventilation in response to therapy. This method could be used as sensitive regional outcome metric of novel respiratory interventions.

Online supplemental material is available for this article.