In vivo radioactive tracer and microsphere studies have differing conclusions as to the magnitude of the gravitational effect on the distribution of pulmonary blood flow. We hypothesized that some of the apparent vertical perfusion gradient in vivo is due to compression of dependent lung increasing local lung density and therefore perfusion/volume. To test this, six normal subjects underwent functional magnetic resonance imaging with arterial spin labeling during breath holding at functional residual capacity, and perfusion quantified in nonoverlapping 15 mm sagittal slices covering most of the right lung. Lung proton density was measured in the same slices using a short echo 2D-Fast Low-Angle SHot (FLASH) sequence. Mean perfusion was 1.7 +/- 0.6 ml x min(-1) x cm(-3) and was related to vertical height above the dependent lung (slope = -3%/cm, P < 0.0001). Lung density averaged 0.34 +/- 0.08 g/cm3 and was also related to vertical height (slope = -4.9%/cm, P < 0.0001). By contrast, when perfusion was normalized for regional lung density, the slope of the height-perfusion relationship was not significantly different from zero (P = 0.2). This suggests that in vivo variations in regional lung density affect the interpretation of vertical gradients in pulmonary blood flow and is consistent with a simple conceptual model: the lung behaves like a Slinky (Slinky is a registered trademark of Poof-Slinky Incorporated), a deformable spring distorting under its own weight. The greater density of lung tissue in the dependent regions of the lung is analogous to a greater number of coils in the dependent portion of the vertically oriented spring. This implies that measurements of perfusion in vivo will be influenced by density distributions and will differ from excised lungs where density gradients are reduced by processing.

Henderson AC, Sá RC, Theilmann RJ, Buxton RB, Prisk GK, Hopkins SR. The gravitational distribution of ventilation-perfusion ratio is more uniform in prone than supine posture in the normal human lung. J Appl Physiol 115: 313-324, 2013. First published April 25, 2013 doi:10.1152/japplphysiol.01531.2012.-The gravitational gradient of intrapleural pressure is suggested to be less in prone posture than supine. Thus the gravitational distribution of ventilation is expected to be more uniform prone, potentially affecting regional ventilation-perfusion (V A/Q ) ratio. Using a novel functional lung magnetic resonance imaging technique to measure regional V A/Q ratio, the gravitational gradients in proton density, ventilation, perfusion, and V A/Q ratio were measured in prone and supine posture. Data were acquired in seven healthy subjects in a single sagittal slice of the right lung at functional residual capacity. Regional specific ventilation images quantified using specific ventilation imaging and proton density images obtained using a fast gradient-echo sequence were registered and smoothed to calculate regional alveolar ventilation. Perfusion was measured using arterial spin labeling. Ventilation (ml·min Ϫ1 ·ml Ϫ1 ) images were combined on a voxel-by-voxel basis with smoothed perfusion (ml·min Ϫ1 ·ml Ϫ1 ) images to obtain regional V A/Q ratio. Data were averaged for voxels within 1-cm gravitational planes, starting from the most gravitationally dependent lung. The slope of the relationship between alveolar ventilation and vertical height was less prone than supine (Ϫ0.17 Ϯ 0.10 ml·min, P ϭ 0.02) as was the slope of the perfusion-height relationship (Ϫ0.14 Ϯ 0.05 ml·min, P ϭ 0.02). There was a significant gravitational gradient in V A/Q ratio in both postures (P Ͻ 0.05) that was less in prone (0.09 Ϯ 0.08 cm Ϫ1 supine, 0.04 Ϯ 0.03 cm Ϫ1 prone, P ϭ 0.04). The gravitational gradients in ventilation, perfusion, and regional V A/Q ratio were greater supine than prone, suggesting an interplay between thoracic cavity configuration, airway and vascular tree anatomy, and the effects of gravity on V A/Q matching. magnetic resonance imaging; arterial spin labeling; specific ventilation imaging; ventilation-perfusion ratio; gravity WHILE THE LUNG HAS A NUMBER of functions, it is primarily a gas exchange organ. 1 Ventilation-perfusion (V A/Q ) matching, such that regions of the lung that receive fresh gas also receive deoxygenated capillary blood, is the most important mechanism determining gas exchange efficiency (53). Although several mechanisms are thought to accomplish V A/Q matching in the healthy lung (see Ref. 18 for review), it is thought that passive mechanisms dominate under normal conditions. Such passive mechanisms include vascular branching structure and the effect of gravity on ventilation and perfusion (53).Modeling studies suggest that, because of the shape of the lungs within the thorax, the gradient of intrapleural pressures is more uniform in prone posture compared with supine (48). This predicts that the g...

Specific ventilation (SV) is the ratio of fresh gas entering a lung region divided by its end-expiratory volume. To quantify the vertical (gravitationally dependent) gradient of SV in eight healthy supine subjects, we implemented a novel proton magnetic resonance imaging (MRI) method. Oxygen is used as a contrast agent, which in solution changes the longitudinal relaxation time (T1) in lung tissue. Thus alterations in the MR signal resulting from the regional rise in O(2) concentration following a sudden change in inspired O(2) reflect SV-lung units with higher SV reach a new equilibrium faster than those with lower SV. We acquired T1-weighted inversion recovery images of a sagittal slice of the supine right lung with a 1.5-T MRI system. Images were voluntarily respiratory gated at functional residual capacity; 20 images were acquired with the subject breathing air and 20 breathing 100% O(2), and this cycle was repeated five times. Expired tidal volume was measured simultaneously. The SV maps presented an average spatial fractal dimension of 1.13 ± 0.03. There was a vertical gradient in SV of 0.029 ± 0.012 cm(-1), with SV being highest in the dependent lung. Dividing the lung vertically into thirds showed a statistically significant difference in SV, with SV of 0.42 ± 0.14 (mean ± SD), 0.29 ± 0.10, and 0.24 ± 0.08 in the dependent, intermediate, and nondependent regions, respectively (all differences, P < 0.05). This vertical gradient in SV is consistent with the known gravitationally induced deformation of the lung resulting in greater lung expansion in the dependent lung with inspiration. This SV imaging technique can be used to quantify regional SV in the lung with proton MRI.

The arterial spin labeling (ASL) method provides images in which, ideally, the signal intensity of each image voxel is proportional to the local perfusion. For studies of pulmonary perfusion, the relative dispersion (RD, standard deviation/mean) of the ASL signal across a lung section is used as a reliable measure of flow heterogeneity. However, the RD of the ASL signals within the lung may systematically differ from the true RD of perfusion because the ASL image also includes signals from larger vessels, which can reflect the blood volume rather than blood flow if the vessels are filled with tagged blood during the imaging time. Theoretical studies suggest that the pulmonary vasculature exhibits a lognormal distribution for blood flow and thus an appropriate measure of heterogeneity is the geometric standard deviation (GSD). To test whether the ASL signal exhibits a lognormal distribution for pulmonary blood flow, determine whether larger vessels play an important role in the distribution, and extract physiologically relevant measures of heterogeneity from the ASL signal, we quantified the ASL signal before and after an intervention (head-down tilt) in six subjects. The distribution of ASL signal was better characterized by a lognormal distribution than a normal distribution, reducing the mean squared error by 72% (p < 0.005). Head-down tilt significantly reduced the lognormal scale parameter (p = 0.01) but not the shape parameter or GSD. The RD increased post-tilt and remained significantly elevated (by 17%, p < 0.05). Test case results and mathematical simulations suggest that RD is more sensitive than the GSD to ASL signal from tagged blood in larger vessels, a probable explanation of the change in RD without a statistically significant change in GSD. This suggests that the GSD is a useful measure of pulmonary blood flow heterogeneity with the advantage of being less affected by the ASL signal from tagged blood in larger vessels.

Based on the tenets of role congruity theory, the current study examined the unequal representation of men and women in athletic administration positions. A total of 158 female and 118 male (n = 276) athletic administrators evaluated a male or female candidate for an athletic director, compliance director, or life skills director position within athletics. Participants indicated no significant differences in masculine ratings of male or female candidates and significant differences in feminine ratings for female candidates in the life skills position. Male and female candidates were perceived as similar in potential and likely success in all positions. Finally, the female candidate was evaluated as significantly less likely to be offered the athletic director position when compared with the male candidate.

Bronchoscopic lung volume reduction (BLVR), a minimally invasivewas based on the simple concept that collapse of target reprocedure based on tissue engineering principles, was performed in gions could be initiated using a washout solution to disrupt six sheep with papain-induced experimental emphysema (EMPH).surfactant function, and be maintained with a biocompatible Physiologic measurements, at baseline, after generation of EMPH, "tissue sealant" to prevent re-expansion. The concept was and at 3 and 9 weeks after BLVR, included lung volumes, diffusing tested using a sheep model of EMPH, in which lung zones capacity (DL CO ), pressure-volume relationships for the lung and chest supplied by 5 to 7 mm airways were blocked, collapsed, and wall , pleural pressures generated during active respiratory muscle filled with a fibrin hydrogel sealant. This "mechanical" apcontraction, lung resistance and dynamic elastance. The animal proach to bronchoscopic volume reduction produced atelecmodel displayed hyperinflation (change in total lung capacity ϩ8%; tasis with subsequent scarring in 55% of the treated sites, change in residual volume ϩ66%), reduced DL CO (Ϫ21%), and eleconfirming the feasibility of BLVR. However, the procedure vated airway resistance (ϩ76%) that resembled advanced human was associated with a 15% incidence of sterile abscess forma-EMPH. BLVR was well tolerated without complications, and it retion (10). Although physiologic benefits in successfully duced lung volumes (change in total lung capacity Ϫ16%; change treated sheep were comparable with those of a 20 to 25% in residual volume Ϫ55%) in a pattern that resulted in significant surgical volume reduction, the high failure rate, and unac- though the ultimate objective of the remodeling process is emphysema; tissue engineering to produce a mechanical response, this can only happen if an appropriate biologic response is first generated. Thus, we Lung volume reduction therapy refers to elimination of emhypothesized that redesigning BLVR to improve its safety physematous hyperinflated lung, which allows the remaining and effectiveness would require a method that mimics scar pulmonary parenchyma and the respiratory muscles to function more effectively (1). Observational studies, and randomformation similar to what occurs during normal healing. ized clinical trials, provide convincing evidence that the proSuch responses in the lung are usually initiated by an cedure improves respiratory function, exercise capacity, and injury that causes loss of epithelial integrity, followed by symptoms of dyspnea in selected patients with advanced eminflammation leading to scar formation (12). The BLVR sysphysema (EMPH) to a greater extent than optimal medical tem has been designed to replicate key aspects of this healing therapy (1-7). To date, lung volume reduction in humans process without producing inflammation. This second generahas been accomplished exclusively through surgical means tion system uses an enzymatic primer solution to remove (lung volume reduction surge...

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.

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.