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Updated: Sep 10, 2025

Author Spotlight: Using Hyperpolarized Xenon-129 MRI to Study Lung Diseases
Published on: January 5, 2024
Optimizing reliability of RBC signal oscillation measures from hyperpolarized 129Xe MRI
Ivina Mali1, Bradie Frizzell1, Steven Haworth1
1Division of Pulmonary, Critical Care, and Sleep Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States of America.
Abstract:
Recent advances to gas exchange hyperpolarized 129Xe MRI (Xe-MRI) have demonstrated that cardiogenic oscillations within the xenon red blood cell (RBC) signal are sensitive to pulmonary disease. Moreover, by implementing keyhole image reconstruction with gas exchange images collected using standard methodology, maps of regional oscillation amplitude can be generated. While such mapping has been demonstrated on a limited basis, validating these maps remains challenging due to the absence of easily measured biomarkers of pulmonary microvascular health. Moreover, as this is a very new technique, each of the previous implementations has used different methodology; it is unclear which of these methods provides optimal measures of regional oscillation amplitude. In this study, we evaluated oscillation mapping using the different published methods to determine which has the best same-day reliability. Because there are no easily obtainable measures of pulmonary vascular health, reliability serves as a valuable endpoint for validating that these maps are sensitive to real pulmonary physiology. We evaluated the same-day reliability of RBC oscillation measures in patients with systemic sclerosis (N = 6) and pulmonary arterial hypertension (PAH; N = 10), using single-time-point data from healthy volunteers (N = 9) to demonstrate "healthy" oscillation amplitude maps. Global measures of RBC oscillation amplitude (intraclass correlation coefficient; ICC = 0.88) had comparable reliability to standard xenon MRI measures (ICC ≥ 0.82). When examining oscillation mapping, some regional features showed disagreement across scans, but reliability of overall means was strong (ICC ≥ 0.86). Moreover, we show that recent advances in oscillation amplitude mapping for generating both amplitude and phase can provide equivalent maps to those methods that only provide amplitude. Overall, our findings demonstrate that Xe-MRI oscillation mapping has strong reliability when using optimized methods, even in participants with pulmonary disease.
Insights
Hyperpolarized 129Xe MRI (Xe-MRI) oscillation mapping shows reliable results for assessing pulmonary microvascular health. Optimized methods ensure strong reliability, even in patients with lung disease.
Area of Science:
- Pulmonary Medicine
- Medical Imaging
- Cardiovascular Research
Background:
- Gas exchange hyperpolarized 129Xe MRI (Xe-MRI) detects cardiogenic oscillations in red blood cell (RBC) signals, indicating sensitivity to pulmonary disease.
- Generating regional oscillation amplitude maps via keyhole image reconstruction is possible but validation is hindered by a lack of pulmonary microvascular health biomarkers.
- Varied methodologies in previous Xe-MRI implementations obscure optimal techniques for measuring regional oscillation amplitude.
Purpose of the Study:
- To evaluate and compare different published methods for Xe-MRI oscillation mapping to determine which offers the best same-day reliability.
- To establish reliability as a surrogate endpoint for validating Xe-MRI oscillation maps' sensitivity to pulmonary physiology, given the absence of direct microvascular health biomarkers.
- To demonstrate "healthy" oscillation amplitude maps using data from healthy volunteers.
Main Methods:
- Assessed same-day reliability of RBC oscillation measures in patients with systemic sclerosis (N=6) and pulmonary arterial hypertension (PAH, N=10).
- Utilized single-time-point data from healthy volunteers (N=9) to generate reference "healthy" oscillation amplitude maps.
- Compared reliability across different published oscillation mapping methodologies, including those generating both amplitude and phase information.
Main Results:
- Global RBC oscillation amplitude measures demonstrated strong reliability (Intraclass Correlation Coefficient, ICC=0.88), comparable to standard Xe-MRI measures (ICC≥0.82).
- Overall means for regional oscillation mapping showed strong reliability (ICC≥0.86), despite some inter-scan disagreement in regional features.
- Advanced oscillation amplitude mapping techniques providing both amplitude and phase yielded maps equivalent to amplitude-only methods.
Conclusions:
- Optimized Xe-MRI oscillation mapping exhibits robust reliability, even in individuals with pulmonary disease.
- The findings support the use of Xe-MRI oscillation mapping as a reliable tool for assessing pulmonary microvascular function.
- Methodological standardization is crucial for maximizing the reliability and clinical utility of Xe-MRI oscillation mapping.

