Abstract

This work assesses the accuracy of the stretched exponential (SEM) and cylinder models of lung microstructural length scales that can be derived from hyperpolarized gas DWI. This was achieved by simulating 3 He and 129 Xe DWI signals within two micro-CT-derived realistic acinar airspace meshes that represent healthy and idiopathic pulmonary fibrosis lungs. The healthy and idiopathic pulmonary fibrosis acinar airway meshes were derived from segmentations of 3D micro-CT images of excised human lungs and meshed for finite element simulations of the Bloch-Torrey equations. 3 He and 129 Xe multiple b value DWI experiments across a range of diffusion times (3 He Δ = 1.6 ms; 129 Xe Δ = 5 to 20 ms) were simulated in each mesh. Global SEM mean diffusive length scale and cylinder model mean chord length value was derived from each finite element simulation and compared against each mesh's mean linear intercept length, calculated from intercept length measurements within micro-CT segmentation masks. The SEM-derived mean diffusive length scale was within ±10% of the mean linear intercept length for simulations with both 3 He (Δ = 1.6 ms) and 129 Xe (Δ = 7 to 13 ms) in the healthy mesh, and with 129 Xe (Δ = 13 to 20 ms) for the idiopathic pulmonary fibrosis mesh, whereas for the cylinder model-derived mean chord length the closest agreement with mean linear intercept length (11.7% and 22.6% difference) was at 129 Xe Δ = 20 ms for both healthy and IPF meshes, respectively. This work validates the use of the SEM for accurate estimation of acinar dimensions and indicates that the SEM is relatively robust across a range of experimental conditions and acinar length scales.

Highlights

  • The detection of microstructural changes to the acinar airways, the structural units of gas exchange of the lungs that are located distally to the terminal bronchioles, are crucial for the clinical evaluation and longitudinal monitoring of a range of pulmonary diseases

  • We have developed realistic acinar airspace geometrical meshes from 3D micro-CT imaging and utilized them for finite element (FE) simulations of hyperpolarized 3He and 129Xe DWI to validate the stretched exponential model (SEM) and its LmD measurement alongside the cylinder airway model (CM)

  • This work is the first validation of the SEM-derived LmD and the CM Lm with FE simulations of 3He and 129Xe DWI in micro-CT–derived realistic acinar airway geometries representing healthy and idiopathic pulmonary fibrosis (IPF) lungs

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Summary

Introduction

The detection of microstructural changes to the acinar airways, the structural units of gas exchange of the lungs that are located distally to the terminal bronchioles, are crucial for the clinical evaluation and longitudinal monitoring of a range of pulmonary diseases. The derived ADC is a sensitive biomarker of underlying changes in acinar airway microstructure.[10,11] The cylinder airway model (CM)[12,13,14] and stretched exponential model (SEM)[15,16] are theoretical models of hyperpolarized gas DWI signal within the lungs that can derive estimates of in vivo acinar airway dimensions with both 3He and 129Xe gases. These two diffusion models have been used to elucidate quantitative changes in acinar airway microstructure that are additional to basic ADC or mean-square displacement

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