G. K. Prisk

Hypoxic pulmonary vasoconstriction does not contribute to pulmonary blood flow heterogeneity in normoxia in normal supine humans

We hypothesized that some of the heterogeneity of pulmonary blood flow present in the normal human lung in normoxia is due to hypoxic pulmonary vasoconstriction (HPV). If so, mild hyperoxia would decrease the heterogeneity of pulmonary perfusion, whereas it would be increased by mild hypoxia. To test this, six healthy nonsmoking subjects underwent magnetic resonance imaging (MRI) during 20 min of breathing different oxygen concentrations through a face mask [normoxia, inspired O(2) fraction (Fi(O(2))) = 0.21; hypoxia, Fi(O(2)) = 0.125; hyperoxia, Fi(O(2)) = 0.30] in balanced order. Data were acquired on a 1.5-T MRI scanner during a breath hold at functional residual capacity from both coronal and sagittal slices in the right lung. Arterial spin labeling was used to quantify the spatial distribution of pulmonary blood flow in milliliters per minute per cubic centimeter and fast low-angle shot to quantify the regional proton density, allowing perfusion to be expressed as density-normalized perfusion in milliliters per minute per gram. Neither mean proton density [hypoxia, 0.46(0.18) g water/cm(3); normoxia, 0.47(0.18) g water/cm(3); hyperoxia, 0.48(0.17) g water/cm(3); P = 0.28] nor mean density-normalized perfusion [hypoxia, 4.89(2.13) ml x min(-1) x g(-1); normoxia, 4.94(1.88) ml x min(-1) x g(-1); hyperoxia, 5.32(1.83) ml x min(-1) x g(-1); P = 0.72] were significantly different between conditions in either imaging plane. Similarly, perfusion heterogeneity as measured by relative dispersion [hypoxia, 0.74(0.16); normoxia, 0.74(0.10); hyperoxia, 0.76(0.18); P = 0.97], fractal dimension [hypoxia, 1.21(0.04); normoxia, 1.19(0.03); hyperoxia, 1.20(0.04); P = 0.07], log normal shape parameter [hypoxia, 0.62(0.11); normoxia, 0.72(0.11); hyperoxia, 0.70(0.13); P = 0.07], and geometric standard deviation [hypoxia, 1.88(0.20); normoxia, 2.07(0.24); hyperoxia, 2.02(0.28); P = 0.11] was also not different. We conclude that HPV does not affect pulmonary perfusion heterogeneity in normoxia in the normal supine human lung.

Pulmonary perfusion heterogeneity is increased by sustained, heavy exercise in humans

Exercise presents a considerable stress to the pulmonary system and ventilation-perfusion (Va/Q) heterogeneity increases with exercise, affecting the efficiency of gas exchange. In particular, prolonged heavy exercise and maximal exercise are known to increase Va/Q heterogeneity and these changes persist into recovery. We hypothesized that the spatial heterogeneity of pulmonary perfusion would be similarly elevated after prolonged exercise. To test this, athletic subjects (n = 6, Vo(2max) = 61 ml. kg(-1).min(-1)) with exercising Va/Q heterogeneity previously characterized by the multiple inert gas elimination technique (MIGET), performed 45 min of cycle exercise at approximately 70% Vo(2max). MRI arterial spin labeling measures of pulmonary perfusion were acquired pre- and postexercise (at 20, 40, 60 min post) to quantify the spatial distribution in isogravitational (coronal) and gravitationally dependent (sagittal) planes. Regional proton density measurements allowed perfusion to be normalized for density and quantified in milliliters per minute per gram. Mean lung density did not change significantly in either plane after exercise (P = 0.19). Density-normalized perfusion increased in the sagittal plane postexercise (P =or <0.01) but heterogeneity did not (all P >or= 0.18), likely because of perfusion redistribution and vascular recruitment. Density-normalized perfusion was unchanged in the coronal plane postexercise (P = 0.66), however, perfusion heterogeneity was significantly increased as measured by the relative dispersion [RD, pre 0.62(0.07), post 0.82(0.21), P < 0.0001] and geometric standard deviation [GSD, pre 1.74(0.14), post 2.30(0.56), P < 0.005]. These changes in heterogeneity were related to the exercise-induced changes of the log standard deviation of the ventilation distribution, an MIGET index of Va/Q heterogeneity (RD R(2) = 0.68, P < 0.05, GSD, R(2) = 0.55, P = 0.09). These data are consistent with but not proof of interstitial pulmonary edema as the mechanism underlying exercise-induced increases in both spatial perfusion heterogeneity and Va/Q heterogeneity.

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.

Convective flow dominates aerosol delivery to the lung segments

Most previous computational studies on aerosol transport in models of the central airways of the human lung have focused on deposition, rather than transport of particles through these airways to the subtended lung regions. Using a model of the bronchial tree extending from the trachea to the segmental bronchi (J Appl Physiol 98: 970-980, 2005), we predicted aerosol delivery to the lung segments. Transport of 0.5- to 10-μm-diameter particles was computed at various gravity levels (0-1.6 G) during steady inspiration (100-500 ml/s). For each condition, the normalized aerosol distribution among the lung segments was compared with the normalized flow distribution by calculating the ratio (R(i)) of the number of particles exiting each segmental bronchus i to the flow. When R(i) = 1, particle transport was directly proportional to segmental flow. Flow and particle characteristics were represented by the Stokes number (Stk) in the trachea. For Stk < 0.01, R(i) values were close to 1 and were unaffected by gravity. For Stk > 0.01, R(i) varied greatly among the different outlets (R(i) = 0.30-1.93 in normal gravity for 10-μm particles at 500 ml/s) and was affected by gravity and inertia. These data suggest that, for Stk < 0.01, ventilation defines the delivery of aerosol to lung segments and that the use of aerosol tracers is a valid technique to visualize ventilation in different parts of the lung. At higher Stokes numbers, inertia, but not gravitational sedimentation, is the second major factor affecting the transport of large particles in the lung.

Assessing potential errors of MRI-based measurements of pulmonary blood flow using a detailed network flow model

MRI images of pulmonary blood flow using arterial spin labeling (ASL) measure the delivery of magnetically tagged blood to an image plane during one systolic ejection period. However, the method potentially suffers from two problems, each of which may depend on the imaging plane location: 1) the inversion plane is thicker than the imaging plane, resulting in a gap that blood must cross to be detected in the image; and 2) ASL includes signal contributions from tagged blood in conduit vessels (arterial and venous). By using an in silico model of the pulmonary circulation we found the gap reduced the ASL signal to 64-74% of that in the absence of a gap in the sagittal plane and 53-84% in the coronal. The contribution of the conduit vessels varied markedly as a function of image plane ranging from ∼90% of the overall signal in image planes that encompass the central hilar vessels to <20% in peripheral image planes. A threshold cutoff removing voxels with intensities >35% of maximum reduced the conduit vessel contribution to the total ASL signal to ∼20% on average; however, planes with large contributions from conduit vessels underestimate acinar flow due to a high proportion of in-plane flow, making ASL measurements of perfusion impractical. In other image planes, perfusion dominated the resulting ASL images with good agreement between ASL and acinar flow. Similarly, heterogeneity of the ASL signal as measured by relative dispersion is a reliable measure of heterogeneity of the acinar flow distribution in the same image planes.

A Method for the Analysis of Respiratory Sinus Arrhythmia Using Continuous Wavelet Transforms

A continuous wavelet transform-based method is presented to study the nonstationary strength and phase delay of the respiratory sinus arrhythmia (RSA). The RSA is the cyclic variation of instantaneous heart rate at the breathing frequency. In studies of cardio-respiratory interaction during sleep, paced breathing or postural changes, low respiratory frequencies, and fast changes can occur. Comparison on synthetic data presented here shows that the proposed method outperforms traditional short-time Fourier-transform analysis in these conditions. On the one hand, wavelet analysis presents a sufficient frequency-resolution to handle low respiratory frequencies, for which time frames should be long in Fourier-based analysis. On the other hand, it is able to track fast variations of the signals in both amplitude and phase for which time frames should be short in Fourier-based analysis.

Particulate deposition in the human lung under lunar habitat conditions.

INTRODUCTION Lunar dust may be a toxic challenge to astronauts. While deposition in reduced gravity is less than in normal gravity (1 G), reduced gravitational sedimentation causes particles to penetrate deeper in the lung, potentially causing more harm. The likely design of the lunar habitat has a reduced pressure environment and low-density gas has been shown to reduce upper airway deposition and increase peripheral deposition. METHODS Breathing air and a reduced-density gas approximating the density of the proposed lunar habitat atmosphere, five healthy subjects inhaled 1 -microm diameter aerosol boluses at penetration volumes (V(p)) of 200 ml (central airways), 500 ml, and 1000 ml (lung periphery) in microgravity during parabolic flight, and in 1 G. RESULTS Deposition in the lunar habitat was significantly less than for Earth conditions (and less than in 1 G with the low-density gas) with a relative decrease in deposition of -59.1 +/- 14.0% (-46.9 +/- 11.7%), -50.7 +/- 9.2% (-45.8 +/- 11.2%), and -46.0 +/- 8.3% (-45.3 +/- 11.1%) at V(p) = 200, 500, and 1000 ml, respectively. There was no significant effect of reduced density on deposition in 1 G. DISCUSSION While minimally affected by gas density, deposition was significantly less in microgravity than in 1 G for both gases, with a larger portion of particles depositing in the lung periphery under lunar conditions than Earth conditions. Thus, gravity, and not gas properties, mainly affects deposition in the peripheral lung, suggesting that studies of aerosol transport in the lunar habitat need not be performed at the low density proposed for the atmosphere in that environment.

Three dimensional Ballistocardiogram and Seismocardiogram: What do they have in common?

3D-body accelerations, i.e. Ballistocardiograms (BCG) and Seismocardiograms (SCG), ECG and Impedance-cardiograms (ICG) were recorded on healthy volunteers participating to the European Space Agency (ESA) 59th parabolic flight campaign. In the present paper we document the similarities and differences that can be seen in the seismo-and ballisto-cardiogram signals in different positions (standing and supine) under normal gravity condition as well as during the weightlessness phases (0G) of a parabolic flight. Our results demonstrate that SCG and BCG both present a similar three dimensional (3D) nature, with components of the BCG having lower frequency content than the SCG. The recordings performed in the 0G environment are the one with the smoothest shape and largest maximum magnitude of the Force vector. The differences seen between SCG and BCG stress further the importance for the need of using different nomenclature for the identification of peaks in both signals.

A statistical clustering approach to discriminating perfusion from conduit vessel signal contributions in a pulmonary ASL MR image

The measurement of pulmonary perfusion (blood delivered to the capillary bed within a voxel) using arterial spin labeling (ASL) magnetic resonance imaging is often complicated by signal artifacts from conduit vessels that carry blood destined for voxels at a distant location in the lung. One approach to dealing with conduit vessel contributions involves the application of an absolute threshold on the ASL signal. While useful for identifying a subset of the most dominant high signal conduit image features, signal thresholding cannot discriminate between perfusion and conduit vessel contributions at intermediate and low signal. As an alternative, this article discusses a data‐driven statistical approach based on statistical clustering for characterizing and discriminating between capillary perfusion and conduit vessel contributions over the full signal spectrum. An ASL flow image is constructed from the difference between a pair of tagged magnetic resonance images. However, when viewed as a bivariate projection that treats the image pair as independent measures (rather than the univariate quantity that results from the subtraction of the two images), the signal associated with capillary perfusion contributions is observed to cluster independently of the signal associated with conduit vessel contributions. Analyzing the observed clusters using a Gaussian mixture model makes it possible to discriminate between conduit vessel and capillary‐perfusion‐dominated signal contributions over the full signal spectrum of the ASL image. As a demonstration of feasibility, this study compares the proposed clustering approach with the standard absolute signal threshold strategy in a small number of test images. Copyright

Pulmonary function in microgravity: Spacelab 4 and beyond☆

This paper refers principally to the composition gradient of gases within the lung in various conditions of gravity, as revealed by exhaled breath. A rapid gas analyzer-based system has been developed for tests in Spacelab 4. The test sequence and expected results are presented.