Mapping the Chemical Shift of 129Xe in Red Blood Cells as a Biomarker for Pulmonary Hypertension

Rationale: Inhaled hyperpolarized 129Xe exhibits a distinct resonance in the red blood cells (RBCs) of the pulmonary capillaries, allowing MR imaging and spectroscopy (MRI/MRS) of the distal pulmonary vasculature. Recent work has shown that MRI/MRS of 129Xe dissolved in RBCs offers indirect sensitivity to elevated pulmonary vascular resistance (PVR). Elevated PVR driven by localized occlusion of the pulmonary arterioles reduces blood flow through distal capillaries, increasing transit time and paradoxically enhancing capillary blood oxygenation. Since cardiac output is conserved, blood flow through unobstructed vascular branches increases, shortening transit times and reducing capillary blood oxygenation. This variation in blood oxygenation shifts the frequency of the 129Xe RBC resonance. Thus, mapping the RBC chemical shift regionally may offer direct sensitivity to pre-capillary pulmonary hypertension (PH) pathology (Figure 1A.) Here, we use hyperpolarized 129Xe lung chemical shift imaging (CSI) to generate and compare RBC frequency shift maps in healthy volunteers and pre-capillary PH patients. Methods: Healthy volunteers (n=4) and pre-capillary PH patients (n=6) underwent 129Xe gas exchange imaging, whole-lung spectroscopy, and CSI. Spectra in all CSI voxels were fit with Lorentzian RBC and gas-phase profiles, and a Voigt membrane profile. RBC frequency shift maps were calculated as the voxel-wise difference between the center frequency fit parameters of the gas-phase and RBC peaks. Maps were interpolated to the resolution of each subject's gas exchange image, then registered to it and masked by the corresponding segmentation, to identify lung boundaries. Heterogeneity of the RBC shift distributions was quantified using the interquartile range (IQR). Results: RBC shift maps in healthy subjects were relatively homogeneous, with narrow distributions about well-defined central peaks (Figure 1B). However, PH subjects exhibited regions of very high shift, with reduced values across the remaining lung (Figure 1C). Their shift distributions were broader, with larger concentrations of extreme values, at both ends. Accordingly, all healthy subjects had a shift distribution IQR<1ppm, while all but one PH subject had IQR>1ppm (Figure 1D). Conclusions: Regional mapping of 129Xe RBC chemical shift values in the lungs yields distinct regions of paradoxically high values in pre-capillary PH. These are hypothesized to reflect capillary blood oxygenation distal to pre-capillary occlusions. Further improving the accuracy of such shift maps will necessitate optimizing the balance between CSI artifact reduction and image resolution. Once optimized, these results suggest that RBC chemical shift mapping via 129Xe CSI may permit non-invasive PH detection with localization, which will be particularly valuable in CTEPH.

Duke Scholars

Author Bastiaan Driehuys Radiology