Childhood to adulthood: Accounting for age dependence in healthy-reference distributions in 129 Xe gas-exchange MRI

Abstract

Purpose: Xenon-129 (¹²⁹ Xe) gas-exchange MRI is a pulmonary-imaging technique that provides quantitative metrics for lung structure and function and is often compared to pulmonary-function tests. Unlike such tests, it does not normalize to predictive values based on demographic variables such as age. Many sites have alluded to an age dependence in gas-exchange metrics; however, a procedure for normalizing metrics has not yet been introduced.

Theory: We model healthy reference values for ¹²⁹ Xe gas-exchange MRI against age using generalized additive models for location, scale, and shape (GAMLSS). GAMLSS takes signal data from an aggregated heathy-reference cohort and fits a distribution with flexible median, variation, skewness, and kurtosis to predict age-dependent centiles. This approach mirrors methods by the Global Lung Function Initiative for modeling pulmonary-function test data and applies it to binning methods widely used by the ¹²⁹ Xe MRI community to interpret and quantify gas-exchange data.

Methods: Ventilation, membrane-uptake, red blood cell transfer, and red blood cell:membrane gas-exchange metrics were collected on 30 healthy subjects over an age range of 5 to 68 years. A GAMLSS model was fit against age and compared against widely used linear and generalized-linear binning ¹²⁹ Xe MRI analysis schemes.

Results: All 4 gas-exchange metrics had significant skewness, and membrane-uptake had significant kurtosis compared to a normal distribution. Age has significant impact on distribution parameters. GAMLSS-binning produced narrower bins compared to the linear and generalized-linear binning schemes and distributed signal data closer to a normal distribution.

Conclusion: The proposed "proof-of-concept" GAMLSS-binning approach can improve diagnostic accuracy of ¹²⁹ Xe gas-exchange MRI by providing a means of modeling voxel distribution data against age.

Keywords: 129Xe MRI; GAMLSS; age dependence; gas exchange; healthy-reference distributions; pulmonary imaging.