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

Purpose: Chronic obstructive pulmonary disease (COPD) is an irreversible lung disease characterized by small-airway obstruction and alveolar-airspace destruction. Hyperpolarized ¹²⁹Xe 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) ¹²⁹Xe in explanted lungs to regionally matched morphological measures of airspace size. Methods: Explanted lungs from five COPD patients and two idiopathic pulmonary fibrosis (IPF) patients were imaged using MRI with hyperpolarized ¹²⁹Xe 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 ¹²⁹Xe MRI. Results: 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. Conclusions: Diffusion MRI of HP ¹²⁹Xe quantifies regional airspace enlargement in COPD. ¹²⁹Xe ADC showed much less overlap between groups than quantitative histology, consistent with our past experience with ³He diffusion MRI in COPD. Magn Reson Med 77:265–272, 2017.