Standardized Spectral Mapping With 129 Xe Chemical Shift Imaging: Investigating Red Blood Cell Shift Heterogeneity in Pulmonary Hypertension

Hyperpolarized 129 Xe chemical shift imaging (CSI) is emerging as an alternative approach to Dixon‐based methods for assessing pulmonary gas exchange. CSI additionally permits mapping spectral parameters like linewidths, enabling more accurate, regional estimation of . Moreover, regionally mapping the 129 Xe chemical shift in red blood cells (RBCs) offers a novel means to assess arteriolar pathology through local measurements of blood oxygenation. However, such CSI‐based mapping requires standardized acquisition and processing workflows along with well‐defined healthy reference distributions to enable robust quantification of patterns reflecting normal physiology. To this end, we implemented a fast, elliptically sampled Cartesian 129 Xe CSI acquisition at 3 T, exciting the dissolved resonances at 208 ppm. We used simulations to determine the optimal k‐space filter and minimum SNR for reliable spectral fitting. This approach was applied in a cohort of healthy 18–30‐year‐olds ( N = 11) to establish healthy reference distributions for quantitative mapping of RBC and membrane , RBC chemical shift, and the RBC:Membrane signal ratio. CSI reference mean values ( standard deviation after Box–Cox transform) for membrane and RBC were 1.07 ms (0.97–1.17 ms) and 1.13 ms (1.05–1.22 ms), respectively, with an RBC shift of 217.9 ppm (217.2–218.5 ppm), and RBC:Membrane of 0.44 (0.37–0.54). CSI‐derived mean values were all significantly different from those measured by whole‐lung spectroscopy ( p 0.02). Notably, RBC:Membrane and membrane increased significantly from the gravitationally non‐dependent to dependent lung regions, while isogravitational heterogeneity of RBC and RBC shift decreased. Conversely, in a preliminary cohort of pulmonary hypertension (PH) patients ( N = 4), RBC shift heterogeneity was elevated, even in gravitationally dependent lung, although significance was not reached in this small sample ( p = 0.07). These results demonstrate how standardized quantitative 129 Xe CSI facilitates rigorous characterization of cardiopulmonary disease signatures and, specifically, highlight RBC shift heterogeneity as a promising marker of PH.