Experimental evidence of age-related adaptive changes in human acinar airways

Abstract

The progressive decline of lung function with aging is associated with changes in lung structure at all levels, from conducting airways to acinar airways (alveolar ducts and sacs). While information on conducting airways is becoming available from computed tomography, in vivo information on the acinar airways is not conventionally available, even though acini occupy 95% of lung volume and serve as major gas exchange units of the lung. The objectives of this study are to measure morphometric parameters of lung acinar airways in living adult humans over a broad range of ages by using an innovative MRI-based technique, in vivo lung morphometry with hyperpolarized (3)He gas, and to determine the influence of age-related differences in acinar airway morphometry on lung function. Pulmonary function tests and MRI with hyperpolarized (3)He gas were performed on 24 healthy nonsmokers aged 19-71 years. The most significant age-related difference across this population was a 27% loss of alveolar depth, h, leading to a 46% increased acinar airway lumen radius, hence, decreased resistance to acinar air transport. Importantly, the data show a negative correlation between h and the pulmonary function measures forced expiratory volume in 1 s and forced vital capacity. In vivo lung morphometry provides unique information on age-related changes in lung microstructure and their influence on lung function. We hypothesize that the observed reduction of alveolar depth in subjects with advanced aging represents a remodeling process that might be a compensatory mechanism, without which the pulmonary functional decline due to other biological factors with advancing age would be significantly larger.

Lung morphometry using hyperpolarized 129Xe multi‐b diffusion MRI with compressed sensing in healthy subjects and patients with COPD

“…Table presents the pulmonary function measurements and the global mean values of the morphometric parameters for five healthy subjects and five COPD subjects. The mean values of the morphometric parameters from the healthy subjects were adjusted for aging effects based on the results from previous studies . On average, the COPD subjects were 32 years older than the healthy subjects.…”

“…On average, the COPD subjects were 32 years older than the healthy subjects. Therefore, according to the previously established relationships, the age‐adjusted mean values for the healthy subjects were as follows,where Ra, ra, ha, L m a, and SVRa are the age‐adjusted mean values, R0, r0, h0, L m 0, and SVR0 are the original mean values (as the CS results shown in Table ), and (i.e., 32 years old) is the difference in the ages between the age‐adjusted and original data. The P values of the t ‐test between the morphometric parameters from the healthy and COPD subjects were all less than 0.05, indicating that all the morphometric parameters from the COPD group exhibited significant differences in comparison with those from the healthy group.…”

“…Due to the low SNR of MR images and the long acquisition time of HP 129 Xe multi‐ b diffusion MRI, a low spatial resolution (6 mm × 6 mm) was used in this study. However, because we mainly focused on the lung morphometric parameters, the low spatial resolution still meets the theoretical and experimental requirements . In addition, the centric k‐space acquisition in the phase encoding direction was used to optimize the SNR.…”

“…In previous works, multi‐ b diffusion MRI using HP 3 He was used to study lung microstructure in humans. For example, it was shown to be capable of detecting emphysematous alveolar destruction and discerning changes in lung microstructure caused by different sizes of lung inflation, different diffusion‐sensitizing gradient directions and different ages . However, due to the long scan time required for multi‐ b diffusion MRI, only part of the lung can be imaged in these studies.…”

Multiscale Lung Imaging Provides New Insights into Disease Progression in the Chronic Obstructive Pulmonary Disease Lung

“…Novel new hyperpolarized gas methods for magnetic resonance imaging provide the tools to longitudinally follow indices associated with the terminal bronchioles (10)(11)(12). Dual-energy CT has allowed for the assessment of peripheral distributions of perfused blood volume, a surrogate for parenchymal perfusion, leading to the exploration of vascular dysfunction and its role in smoking-associated emphysema (13).…”