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

• Published in: Magnetic resonance in medicine Vol. 89; no. 3; pp. 1117 - 1133
• Main Authors: Plummer, Joseph W, Willmering, Matthew M, Cleveland, Zackary I, Towe, Christopher, Woods, Jason C, Walkup, Laura L
• Format: Journal Article
• Language: English
• Published: United States 01.03.2023
• Subjects: Adolescent; Adult; Aged; Child; Child, Preschool; Erythrocytes; Humans; Lung - diagnostic imaging; Magnetic Resonance Imaging - methods; Middle Aged; Respiration; Respiratory Function Tests; Xenon Isotopes; Young Adult; 129Xe MRI; GAMLSS; healthy-reference distributions; pulmonary imaging; age dependence; gas exchange
• ISSN: 0740-3194; 1522-2594; 1522-2594
• DOI: 10.1002/mrm.29501

Xenon-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. We model healthy reference values for 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 Xe MRI community to interpret and quantify gas-exchange data. 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 Xe MRI analysis schemes. 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. The proposed "proof-of-concept" GAMLSS-binning approach can improve diagnostic accuracy of Xe gas-exchange MRI by providing a means of modeling voxel distribution data against age.