Probing lung microstructure with hyperpolarized noble gas diffusion MRI: theoretical models and experimental results

Abstract

The introduction of hyperpolarized gases ( 3 He and 129 Xe) has opened the door to applications for which gaseous agents are uniquely suited-lung MRI. One of the pulmonary applications, diffusion MRI, relies on measuring Brownian motion of inhaled hyperpolarized gas atoms diffusing in lung airspaces. In this article we provide an overview of the theoretical ideas behind hyperpolarized gas diffusion MRI and the results obtained over the decade-long research. We describe a simple technique based on measuring gas apparent diffusion coefficient (ADC) and an advanced technique, in vivo lung morphometry, that quantifies lung microstructure both in terms of Weibel parameters (acinar airways radii and alveolar depth) and standard metrics (mean linear intercept, surface-to-volume ratio, and alveolar density) that are widely used by lung researchers but were previously available only from invasive lung biopsy. This technique has the ability to provide unique three-dimensional tomographic information on lung microstructure from a less than 15 s MRI scan with results that are in good agreement with direct histological measurements. These safe and sensitive diffusion measurements improve our understanding of lung structure and functioning in health and disease, providing a platform for monitoring the efficacy of therapeutic interventions in clinical trials. Approximately 12 million Americans suffer from chronic obstructive pulmonary diseases (COPD) including chronic bronchitis and emphysema as well as asthma. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease caused worldwide, according to a study published by the World Bank/World Health Organization (1). Numerous diagnostic tools have been developed to evaluate the presence and the stage of these diseases. The traditional classification for the severity of COPD is based on measurements of airflow limitation during forced expiration (1). Each stage is characterized by the volume of air that can be forcibly exhaled in 1 s (FEV 1 ) and by the ratio of FEV 1 to the forced vital capacity (FVC). Abnormalities in these tests reflect both the reduction in the force available to drive air out of the lung as a result of emphysematous lung destruction (2) and obstruction to airflow in the smaller conducting airways (3-5). However, the specific pathophysiologic role and contribution of emphysema and small airways abnormalities in expiratory airflow obstruction in COPD has been under debate (6,7). While the role of pathologic changes in small airways has received much attention in recent years (8-10), the early-emphysema component of COPD has not. Conventional pulmonary function tests are insensitive to the onset and initial stages of emphysema (11); the same is valid for conventional chest radiography (12). X-ray CT has substantially greater value for evaluation of emphysema (13); there, enlargement of airspaces and destruction of alveolar walls reduces X-ray attenuation and allows the dete...

Feasibility, tolerability and safety of pediatric hyperpolarized 129Xe magnetic resonance imaging in healthy volunteers and children with cystic fibrosis

“…These hyperpolarized gases displayed approximately 10,000-fold enhanced MRI signal intensities, making it possible to generate MR images in seconds. As a result, hyperpolarized noble gases quickly emerged as promising inhaled contrast agents for pulmonary MRI [1–3], and since then the utility of hyperpolarized-gas MRI to visualize and quantify regional ventilation [4, 5] and assess alveolar airspace microstructural dimensions [6–9] has been demonstrated both in healthy volunteers and in subjects with a range of pulmonary diseases, including chronic obstructive pulmonary disease (COPD) [10, 11], cystic fibrosis (CF) [12, 13] and asthma [14–16]. It is important to note that unlike chest radiographs, scintigraphic ventilation/perfusion scanning and CT, hyperpolarized-gas MRI involves no ionizing radiation, and in stark contrast to lung biopsy (currently the gold standard for assessing alveolar structure), hyperpolarized-gas MRI is noninvasive, making the modality attractive for longitudinally assessing lung pathology.…”

Commentary on “The influence of lung airways branching structure and diffusion time on measurements and models of short-range 3He gas MR diffusion”

“…Our technique has strong theoretical background, it is validated, and it has already produced a number of results related to lung morphology and function that were not previously accessible (see our recent review paper (19) for details).…”

Detection of smoke‐induced pulmonary lesions by hyperpolarized 129Xe diffusion kurtosis imaging in rat models

“…The traditional D app was relevant to the HP gas ( 3 He or 129 Xe) used in the experiment. Due to the heavier atomic weight, the self‐diffusion coefficient of pure xenon gas (0.06 cm 2 /s) was nearly 30 times less than that of pure helium gas (1.80 cm 2 /s) . Therefore, there was no comparability of the D app values obtained by the two different HP gases.…”

“…The MRI protocol was based on gradient‐echo sequence, including an adjustable bipolar diffusion gradient in the frequency‐encoding direction . The b values were given by where γ is the gyromagnetic ratio of 129 Xe, G is the strength of the diffusion gradient, τ is the ramp time of the gradient, δ is the gradient pulse width, and Δ is the diffusion time. In our experiment, δ = 0.8 ms, Δ = 1.2 ms, and τ = 0.123 ms. For Δ = 1.2 ms, the characteristic diffusion length was 120 μm, which is larger than the average alveolar length (70 μm) of healthy rats .…”