Alveolar duct expansion greatly enhances aerosol deposition: a three-dimensional computational fluid dynamics study

Obtaining in vivo data of particle transport in the human lung is often difficult, if not impossible. Computational fluid dynamics (CFD) can provide detailed information on aerosol transport in realistic airway geometries. This paper provides a review of the key CFD studies of aerosol transport in the acinar region of the human lung. It also describes the first ever three-dimensional model of a single fully alveolated duct with moving boundaries allowing for the cyclic expansion and contraction that occurs during breathing. Studies of intra-acinar aerosol transport performed in models with stationary walls (SWs) showed that flow patterns were influenced by the geometric characteristics of the alveolar aperture, the presence of the alveolar septa contributed to the penetration of the particles into the lung periphery and there were large inhomogeneities in deposition patterns within the acinar structure. Recent studies have now used acinar models with moving walls. In these cases, particles penetrate the alveolar cavities not only as a result of sedimentation and diffusion but also as a result of convective transport, resulting in a much higher deposition prediction than that in SW models. Thus, models that fail to incorporate alveolar wall motions probably underestimate aerosol deposition in the acinar region of the lung

Regional Ventilation Is the Main Determinant of Alveolar Deposition of Coarse Particles in the Supine Healthy Human Lung during Tidal Breathing

Background: To quantify the relationship between regional lung ventilation and coarse aerosol deposition in the supine healthy human lung, we used oxygen-enhanced magnetic resonance imaging and planar gamma scintigraphy in seven subjects. Methods: Regional ventilation was measured in the supine posture in a 15 mm sagittal slice of the right lung. Deposition was measured by using planar gamma scintigraphy (coronal scans, 40 cm FOV) immediately postdeposition, 1 hour 30 minutes and 22 hours after deposition of 99mTc-labeled particles (4.9 μm MMAD, GSD 2.5), inhaled in the supine posture (flow 0.5 L/s, 15 breaths/min). The distribution of retained particles at different times was used to infer deposition in different airway regions, with 22 hours representing alveolar deposition. The fraction of total slice ventilation per quartile of lung height from the lung apex to the dome of the diaphragm at functional residual capacity was computed, and co-registered with deposition data - apices aligned - using a transmission scan as reference. The ratio of fractional alveolar deposition to fractional ventilation of each quartile (r) was used to evaluate ventilation and deposition matching (r > 1, regional aerosol deposition fraction larger than regional ventilation fraction). Results: r was not significantly different from 1 for all regions (1.04 ± 0.25, 1.08 ± 0.22, 1.03 ± 0.17, 0.92 ± 0.13, apex to diaphragm, p > 0.40) at the alveolar level (r22h). For retention times r0h and r1h30, only the diaphragmatic region at r1h30 differed significantly from 1. Conclusions: These results support the hypothesis that alveolar deposition is directly proportional to ventilation for ∼5 μm particles that are inhaled in the supine posture and are consistent with previous simulation predictions that show that convective flow is the main determinant of aerosol transport to the lung periphery

Comparison of quantitative multiple breath specific ventilation imaging using co-localized 2D oxygen enhanced MRI and hyperpolarized 3He MRI

Two magnetic resonance specific ventilation imaging (SVI) techniques namely, oxygen enhanced proton (OE-1H) and hyperpolarized 3He (HP-3He) were compared in eight healthy supine subjects (age 32(6) yr). An in-house radio-frequency coil array for 1H configured with the 3He transmit-receive coil in-situ enabled acquisition of SVI data from two nuclei from the same slice without repositioning the subjects. Following 3×3 voxel-down-sampling to account for spatial registration errors between the two SV images, the voxel-by-voxel correlation coefficient of two SV maps ranged from 0.11 to 0.63 (0.46 mean (0.17 SD), (p < 0.05). Several indices were analysed and compared from the tidal volume matched SV maps; the mean of SV log-normal distribution (SVmean), standard deviation of the distribution as a measure of SV heterogeneity (SVwidth) and the gravitational gradient (SVslope). There were no significant differences in SVmean: OE-1H: 0.28(0.08) and HP-3He: 0.32(0.14), SVwidths: OE-1H: 0.28(0.08) and HP-3He: 0.27(0.10) and SVslopes: OE-1H: -0.016(0.006) cm-1 and HP-3He: -0.013(0.007) cm-1. Despite the statistical similarities of the population averages, Bland-Altman analysis demonstrated large individual inter-technique variability. Standard deviations of differences in these indices were SVmean: 42%, SVwidths: 46%, and SVslopes: 62% of their corresponding overall mean values. The present study showed that two independent, spatially co-registered, SVI techniques presented a moderate positive voxel-by-voxel correlation. Population averages of SVmean, SVwidth and SVslope were in close agreement. However, the lack of agreement when the data sets were analysed individually might indicate some fundamental mechanistic differences between the techniques

A Large Human Centrifuge for Exploration and Exploitation Research

This paper addresses concepts regarding the development of an Altered Gravity Platform (AGP) that will serve as a research platform for human space exploration. Space flight causes a multitude of physiological problems, many of which are due to gravity level transitions. Going from Earth’s gravity to microgravity generates fluid shifts, space motion sickness, cardiovascular deconditioning among other changes, and returning to a gravity environment again puts the astronauts under similar stressors. A prolonged stay in microgravity provokes additional deleterious changes such as bone loss, muscle atrophy and loss of coordination or specific psychological stresses. To prepare for future manned space exploration missions, a ground-based research test bed for validating countermeasures against the deleterious effects of g-level transitions is needed. The proposed AGP is a large rotating facility (diameter > 150 m), where gravity levels ranging from 1.1 to 1.5g are generated, covering short episodes or during prolonged stays of weeks or even months. On this platform, facilities are built where a crew of 6 to 8 humans can live autonomously. Adaptation from 1g to higher g levels can be studied extensively and monitored continuously. Similarly, re-adaptation back to 1g, after a prolonged period of altered g can also be investigated. Study of the physiological and psychological adaptation to changing g-levels will provide instrumental and predictive knowledge to better define the ultimate countermeasures that are needed for future successful manned space exploration missions to the Moon, Mars and elsewhere. The AGP initiative will allow scientific experts in Europe and worldwide to investigate the necessary scientific, operational, and engineering inputs required for such space missions. Because so many different physiological systems are involved in adaptation to gravity levels, a multidisciplinary approach is crucial. One of the final and crucial steps is to verify the AGP concept through a large scientific community through feedback from various scientific societies. This facility will also serve clinical research on Earth, because a multitude of health problems such as osteoporosis, frailty of the elderly, inactivity, sarcopenia, obesity, insulin resistance and diabetes, cardiovascular problems, connective tissue ageing and immune deficiency, among others stand to benefit from the fundamental insights into the effects of our ever-present terrestrial gravity gained with such a novel research platform