Direct comparison of ¹²⁹ Xe diffusion measurements with quantitative histology in human lungs

Chronic obstructive pulmonary disease (COPD) is an irreversible lung disease characterized by small-airway obstruction and alveolar-airspace destruction. Hyperpolarized ¹²⁹ Xe diffusion MRI of lung is a promising biomarker for assessing airspace enlargement, but has yet to be validated by direct comparison to lung histology. Here we have compared diffusion measurements of hyperpolarized (HP) ¹²⁹ Xe in explanted lungs to regionally matched morphological measures of airspace size.

Explanted lungs from five COPD patients and two idiopathic pulmonary fibrosis (IPF) patients were imaged using MRI with hyperpolarized ¹²⁹ Xe using a two-b-value gradient-echo diffusion sequence, and 34 histological samples were taken from these lungs for quantitative histology. Mean-linear-intercept (L_m ) was compared with spatially matched measures of apparent diffusion coefficient (ADC) from ¹²⁹ Xe MRI.

The mean ADC from COPD lung samples was 0.071 ± 0.011 cm² /s, and for IPF lungs was 0.033 ± 0.001 cm² /s (P < 10^-15 between groups). The mean L_m in COPD samples was 0.076 ± 0.027 cm and 0.041 ± 0.004 cm in IPF (P = 2.7 × 10^-7 between groups). The Pearson-correlation between ADC and L_m measurements was r = 0.59.

Diffusion MRI of HP ¹²⁹ Xe quantifies regional airspace enlargement in COPD. ¹²⁹ Xe ADC showed much less overlap between groups than quantitative histology, consistent with our past experience with ³ He diffusion MRI in COPD. Magn Reson Med 77:265-272, 2017. © 2016 Wiley Periodicals, Inc.