Establishing a hemoglobin adjustment for Xe-129 gas exchange MRI and MRS

Purpose: Xe-129 MRI and MRS signals from airspaces, membrane tissues (M), and red blood cells (RBCs) provide measurements of pulmonary gas exchange. However, Xe-129 MRI/MRS studies have yet to account for hemoglobin concentration (Hb), which is expected to affect the uptake of Xe-129 in the membrane and RBC compartments. We propose a framework to adjust the membrane and RBC signals for Hb and use this to assess sex-specific differences in RBC/M and establish a Hb-adjusted healthy reference range for the RBC/M ratio. Methods: We combined the 1D model of xenon gas exchange (MOXE) with the principle of TR-flip angle equivalence to establish scaling factors that normalize the dissolved-phase signals with respect to a standard Hb(0) (14 g/dL). Xe-129 MRI/MRS data froma healthy, young cohort (n= 18, age= 25.0 +/- 3.4 years) were used to validate this model and assess the impact of Hb adjustment on M/gas and RBC/gas images and RBC/M. Results: Adjusting for Hb caused RBC/M to change by up to 20% in healthy individualswith normalHb and hadmarked impacts onM/gas and RBC/gas distributions in 3D gas-exchange maps. RBC/M was higher in males than females both before and after Hb adjustment (p< 0.001). After Hb adjustment, the healthy reference value for RBC/M for a consortium-recommended acquisition of TR = 15 ms and flip = 20 degrees was 0.589 +/- 0.083 (mean +/- SD). Conclusion: MOXE provides a useful framework for evaluating the Hb dependence of the membrane and RBC signals. This work indicates that adjusting for Hb is essential for accurately assessing Xe-129 gas-exchange MRI/MRS metrics.