Hyperpolarized 129Xe Ventilation and Gas Exchange Imaging in a Single, Clinically Feasible Breath-Hold

ABSTRACT

Hyperpolarized 129Xe MRI (Xe-MRI) is eliciting increasing interest as an outcome measure in clinical trials, and, with FDA approval expected in 2022, for clinical application. This technique can provide 3D images of pulmonary structure and function non-invasively and with no ionizing radiation. In particular, Xe-MRI can be used to map regional ventilation and gas exchange, both of which have proven effective at identifying structure and function abnormalities in a variety of pulmonary diseases. However, multiple breath-holds are required to collect ventilation and gas exchange images, which increases patient burden and the time/cost of imaging. Building on recent advances to Xe-MRI, namely 3D spiral imaging and flip angle/TR equivalence, we have developed an imaging sequence that can acquire high quality ventilation and gas exchange images within a single, clinically feasible (∼10 s) breath-hold. This sequence uses an interleaved 3D spiral/3D radial 1- point Dixon approach to simultaneously acquire ventilation and gas exchange images. In postprocessing, images are generated of ventilation (voxel size 4 x 4 x 4 mm3) and gas exchange, including xenon dissolved in tissues (“Barrier”) and red blood cells (RBCs) (voxel size 6.25 x 6.25 x 6.25 mm3). This sequence has been used to acquire images in 8 subjects, including 4 healthy volunteers, 1 patient with scleroderma associated ILD (SSc-ILD), and 3 patients experiencing respiratory post-acute sequelae of COVID-19 (PASC). Of these, 7 subjects had a dedicated breath-hold for imaging ventilation, and 5 subjects had a dedicated gas exchange image. In all cases, image signal to noise ratio was equal or superior to dedicated breath-hold images. Qualitative agreement between ventilation/gas exchange images in dedicated breath-holds (Figure A, B) and single-breath images (Figure C) was excellent, and quantitative biomarkers, including ventilation defect percentage (VDP) (ICC = 0.90, p = 0.006), mean barrier signal (ICC = .99, p = 0.001), mean RBC signal (ICC = 0.93, p < 0.001), global RBC oscillation (ICC = 0.984, p = 0.001), percent of the lungs with low barrier (ICC = .98, p = 0.001), and percent with low RBC signal (ICC = 0.92, p = 0.006) were closely correlated. Single-breath imaging was able to identify ventilation defects (Figure C), elevated barrier (in SSc-ILD), and RBC defects (in SSc-ILD, PASC). These data show that hyperpolarized 129Xe ventilation and gas exchange images can effectively be acquired within a single, clinically manageable breath-hold, which may help to pave the way for increased clinical utilization of hyperpolarized 129Xe MRI. (Figure Presented).