Measurement and modeling of xenon gas transfer in the human brain with 1H and hyperpolarized 129Xe MRI

• Image contrast in 129Xe brain MRI is influenced by regional perfusion, polarization decay, and gas transfer across the blood-brain barrier. • The study assessed the repeatability of hyperpolarized 129Xe brain MRI and identified the dominant mechanisms of image contrast. • Voxel-wise correlations between 129Xe MRI and proton arterial spin labeling revealed cerebral blood flow as the primary determinant of image contrast. • Combining proton and 129Xe brain MRI provides new quantitative tools for investigating brain pathophysiology and function. The feasibility of imaging hyperpolarized 129 Xe dissolved in brain tissue following inhalation of xenon gas in the lungs has recently been demonstrated in humans. The image contrast in 129 Xe brain MRI represents a combination of factors, including regional perfusion, polarization decay and gas transfer rate across the blood-brain barrier. To investigate the repeatability of hyperpolarized 129 Xe brain MRI in healthy normal individuals and to identify the dominant mechanisms of image contrast by assessing voxel-wise correlation between HP 129 Xe brain MRI and models of 129 Xe brain uptake derived from 1 H arterial spin labeling (ASL) perfusion mapping. To assess repeatability, 3 sets of hyperpolarized 129 Xe brain images were acquired from 5 healthy volunteers. Quantitative maps of the human brain, including cerebral blood flow, volume and predicted xenon uptake, were derived from 1 H arterial spin labeling and T 2 -weighted MRI. These maps were then spatially cross-correlated with hyperpolarized 129 Xe brain MRI. Signal to noise ratios of 8.7–17.7 were observed across volunteers for a voxel size of 8 × 8 × 50 mm 3 with intra-subject repeatability of between 6 and 29 %. Hyperpolarized 129 Xe brain images showed voxel-wise correlations with cerebral blood flow ( R = 0.32 to 0.62), volume ( R = 0.33 to 0.63) and predicted xenon uptake ( R = 0.34 to 0.63), but did not correlate with arterial transit time ( R = 0.05 to 0.26). Voxel-wise cross correlation between 129 Xe and 1 H ASL suggests that the regional quantity of dissolved xenon delivered by cerebral blood flow is the dominant mechanism of image contrast in HP 129 Xe brain MRI, assuming normal blood-brain barrier function. Combining 1 H and 129 Xe brain MRI provides new opportunities to quantitatively investigate brain pathophysiology and function.