A Comparison of Two Hyperpolarized 129Xe MRI Ventilation Quantification Pipelines: The Effect of Signal to Noise Ratio

Rationale: Hyperpolarized Xe-129 MRI enables quantitative evaluation of regional ventilation. To this end, multiple classifiers have been proposed to determine ventilation defect percentage (VDP) as well as other cluster populations. However, consensus has not yet been reached regarding which of these methods to deploy for multicenter clinical trials. Here, we compare two published classification techniques linear-binning and adaptive K-means to establish their limits of agreement and their robustness against reduced signal-to-noise ratio (SNR). Methods: A total of 29 subjects (age: 38.4 +/- 19.0 years) were retrospectively identified for inter-method comparison. For each Xe-129 ventilation image, 7 images with reduced SNR were generated with equal decrements relative to the native SNR. All 8 sets of images were then analyzed using both methods independently to classify all lung voxels into four clusters: VDP, low-, medium-, and high-ventilation-percentage (LVP, MVP and HVP). For each cluster, the percentage of the lung it comprised was compared between the two methods, as well as how these values persisted as SNR was degraded. Results: The limits of agreement for calculating VDP were [+0.2%, +4.0%] with a +1.5% bias for binning relative to K-means. However, the inter-method agreement for the other clusters was moderate, with biases of -5.7%, -8.1%, and -4.0% for LVP, MVP, and HVP, respectively. As SNR decreased below similar to 4, both methods began reporting values that deviated substantially from the native image. By requiring VDP to remain within <= 1.8% of that calculated from the native image, the minimum tolerable SNR values were 2.4 +/- 1.0 for the linear-binning, and 3.5 +/- 1.5 for the K-means. Conclusions: Both methods agree well in quantifying VDP, but agreement for LVP and MVP remains variable. We suggest a required SNR threshold be two standard deviations above the minimum value of 3.5 +/- 1.5 for robust determination of VDP, suggesting a minimum SNR of 6.6. However, robust quantification of the ventilated clusters required an SNR of 13.4.