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Purpose: To compare quantitative fractional ventilation measurements from multiple breath washout imaging (MBW-I) using hyperpolarized 3 He with both spoiled gradient echo (SPGR) and balanced steady-state free precession (bSSFP) three-dimensional (3D) pulse sequences and to evaluate the feasibility of MBW-I with hyperpolarized 129 Xe., Methods: Seven healthy subjects were scanned using 3 He MBW-I with 3D SPGR and bSSFP sequences. Five also underwent MBW-I with 129 Xe. A dual-tuned coil was used to acquire MBW-I data from both nuclei in the same subject position, enabling direct comparison of regional information., Results: High-quality MBW images were obtained with bSSFP sequences using a reduced dose (100 mL) of inhaled hyperpolarized 3 He. 3D MBW-I with 129 Xe was also successfully demonstrated with a bSSFP sequence. Regional quantitative ventilation measures derived from 3 He and 129 Xe MBW-I correlated well in all subjects (P < 0.001) with mean Pearson's correlation coefficients of r = 0.61 and r = 0.52 for 3 He SPGR-bSSFP and 129 Xe- 3 He (bSSFP) comparisons. The average intersubject mean difference (and standard deviation) in fractional ventilation in SPGR-bSSFP and 129 Xe- 3 He comparisons was 15% (28%) and 9% (38%), respectively., Conclusions: Improved sensitivity in MBW-I can be achieved with polarization-efficient bSSFP sequences. Same scan-session 3D MBW-I with 3 He and 129 Xe has been demonstrated using a dual-tuned coil. Magn Reson Med 77:2288-2295, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., (© 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Drug dosing in critically ill patients is challenging due to the altered drug pharmacokinetics-pharmacodynamics associated with systemic therapies. For many drug therapies, there is potential to use the respiratory system as an alternative route for drug delivery. Aerosol drug delivery can provide many advantages over conventional therapy. Given that respiratory diseases are the commonest causes of critical illness, use of aerosol therapy to provide high local drug concentrations with minimal systemic side effects makes this route an attractive option. To date, limited evidence has restricted its wider application. The efficacy of aerosol drug therapy depends on drug-related factors (particle size, molecular weight), device factors, patient-related factors (airway anatomy, inhalation patterns) and mechanical ventilation-related factors (humidification, airway). This review identifies the relevant factors which require attention for optimization of aerosol drug delivery that can achieve better drug concentrations at the target sites and potentially improve clinical outcomes.

Purpose: This study tested the ability of a multibreath hyperpolarized HP (3) He MRI protocol to increase the accuracy of regional alveolar oxygen tension (PA O2 ) measurements by lessening the influence of gas-flow artifacts. Conventional single-breath PA O2 measurement has been susceptible to error induced by intervoxel gas flow, particularly when used to study subjects with moderate-to-severe chronic obstructive pulmonary disease (COPD)., Methods: Both single-breath and multibreath PA O2 imaging schemes were implemented in seven human subjects (one healthy, three asymptomatic smokers, and three COPD). The number and location of voxels with nonphysiologic PA O2 values generated by intervoxel gas flow were compared between the two protocols., Results: The multibreath scheme resulted in a significantly lower total percentage of nonphysiologic PA O2 values (6.0%) than the single-breath scheme (13.7%) (P = 0.006). PA O2 maps showed several patterns of gas-flow artifacts that were present in the single-breath protocol but mitigated by the multibreath approach. Multibreath imaging also allowed for the analysis of slow-filling areas that presented no signal after a single breath., Conclusion: A multibreath approach enhances the accuracy and completeness of noninvasive PA O2 measurement by significantly lessening the proportion of nonphysiologic values generated by intervoxel gas flow. Magn Reson Med 76:1092-1101, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Rationale and Objectives: Alveolar oxygen tension (Pao2) is sensitive to the interplay between local ventilation, perfusion, and alveolar-capillary membrane permeability, and thus reflects physiologic heterogeneity of healthy and diseased lung function. Several hyperpolarized helium ((3)He) magnetic resonance imaging (MRI)-based Pao2 mapping techniques have been reported, and considerable effort has gone toward reducing Pao2 measurement error. We present a new Pao2 imaging scheme, using parallel accelerated MRI, which significantly reduces measurement error., Materials and Methods: The proposed Pao2 mapping scheme was computer-simulated and was tested on both phantoms and five human subjects. Where possible, correspondence between actual local oxygen concentration and derived values was assessed for both bias (deviation from the true mean) and imaging artifact (deviation from the true spatial distribution)., Results: Phantom experiments demonstrated a significantly reduced coefficient of variation using the accelerated scheme. Simulation results support this observation and predict that correspondence between the true spatial distribution and the derived map is always superior using the accelerated scheme, although the improvement becomes less significant as the signal-to-noise ratio increases. Paired measurements in the human subjects, comparing accelerated and fully sampled schemes, show a reduced Pao2 distribution width for 41 of 46 slices., Conclusion: In contrast to proton MRI, acceleration of hyperpolarized imaging has no signal-to-noise penalty; its use in Pao2 measurement is therefore always beneficial. Comparison of multiple schemes shows that the benefit arises from a longer time-base during which oxygen-induced depolarization modifies the signal strength. Demonstration of the accelerated technique in human studies shows the feasibility of the method and suggests that measurement error is reduced here as well, particularly at low signal-to-noise levels., (Copyright © 2013 AUR. Published by Elsevier Inc. All rights reserved.)

Washout of inert gases is a measure of pulmonary function well-known in lung physiology. This work presents a method combining inert gas washout and spatially resolved imaging using hyperpolarized (3) He, thus providing complementary information on lung function and physiology. The nuclear magnetic resonance signal of intrapulmonary hyperpolarized (3) He is used to track the total amount of gas present within the lungs during multiple-breath washout via tidal breathing. Before the washout phase, 3D ventilation images are acquired using (3) He magnetic resonance imaging from the same dose of inhaled gas. The measured washout signal is corrected for T(1) relaxation and radiofrequency depletion, converting it into a quantity proportional to the apparent amount of gas within the lungs. The use of a pneumotachograph for acquisition of breathing volumes during washout, together with lung volumes derived from the magnetic resonance imaging data, permits assessment of the washout curves against physiological model predictions for healthy lungs. The shape of the resulting washout curves obtained from healthy volunteers matches the predictions, demonstrating the utility of the technique for the quantitative assessment of lung function. The proposed method can be readily integrated with a standard breath-hold (3) He ventilation imaging sequence, thus providing additional information from a single dose of gas., (Copyright © 2010 Wiley-Liss, Inc.)

Models of lung acinar geometry have been proposed to analytically describe the diffusion of (3)He in the lung (as measured with pulsed gradient spin echo (PGSE) methods) as a possible means of characterizing lung microstructure from measurement of the (3)He ADC. In this work, major limitations in these analytical models are highlighted in simple diffusion weighted experiments with (3)He in cylindrical models of known geometry. The findings are substantiated with numerical simulations based on the same geometry using finite difference representation of the Bloch-Torrey equation. The validity of the existing "cylinder model" is discussed in terms of the physical diffusion regimes experienced and the basic reliance of the cylinder model and other ADC-based approaches on a Gaussian diffusion behaviour is highlighted. The results presented here demonstrate that physical assumptions of the cylinder model are not valid for large diffusion gradient strengths (above approximately 15 mT/m), which are commonly used for (3)He ADC measurements in human lungs., ((c) 2010 Elsevier Inc. All rights reserved.)

Experimental research in cardiac and neuronal tissue has shown that besides volatile anesthetics and xenon, the nonanesthetic noble gas helium also reduces ischemia-reperfusion damage. Even though the distinct mechanisms of helium-induced organ protection are not completely unraveled, several signaling pathways have been identified. Beside the protective effects on heart and brain that are mainly obtained by different pre- and postconditioning protocols, helium also exerts effects in the lungs, the immune system, and the blood vessels. Obviously, this noble gas is biochemically not inert and exerts biologic effects, although until today the question remains open on how these changes are mediated. Because of its favorable characteristics and the lack of hemodynamic side effects, helium is suitable for use also in critically ill patients. This review covers the cellular effects of helium, which may lead to new clinical strategies of tissue salvage in ischemia-reperfusion situations, both within and outside the perioperative setting.

High sensitivity makes hyperpolarized (3)He an attractive signal source for visualizing gas flow with magnetic resonance (MR) imaging. Its rapid Brownian motion, however, can blur observed flow lamina and alter measured diffusion rates when excited nuclei traverse shear-induced velocity gradients during data acquisition. Here, both effects are described analytically, and predicted values for measured transport during laminar flow through a straight, 3.2-mm diameter pipe are validated using two-dimensional (2D) constant-time images of different binary gas mixtures. Results show explicitly how measured transport in narrow conduits is characterized by apparent values that depend on underlying gas dynamics and imaging time. In ventilated rats, this is found to obscure acquired airflow images. Nevertheless, flow splitting at airway branches is still evident and use of 3D vector flow mapping is shown to reveal surprising detail that highlights the correlation between gas dynamics and lung structure.

Rationale and Objectives: The hyperpolarized (3)He long-range diffusion coefficient (LRDC) in lungs is sensitive to changes in lung structure due to emphysema, reflecting the increase in collateral paths resulting from tissue destruction. However, no clear understanding of LRDC in healthy lungs has emerged. Here we compare LRDC measured in healthy lungs with computer simulations of diffusion along the airway tree with no collateral connections., Materials and Methods: Computer simulations of diffusion of spatially modulated spin magnetization were performed in computer-generated, symmetric-branching models of lungs and compared with existing LRDC measurements in canine and human lungs., Results: The simulations predict LRDC values of order 0.001 cm(2)/sec, approximately 20 times smaller than the measured LRDC. We consider and rule out possible mechanisms for LRDC not included in the simulations: incomplete breath hold, cardiac motion, and passage of dissolved (3)He through airway walls. However, a very low density of small (micron) holes in the airways is shown to account for the observed LRDC., Conclusion: It is proposed that LRDC in healthy lungs is determined by small collateral pathways.

Objective: Dynamic ventilation (3)He-MRI is a new method to assess pulmonary gas inflow. As differing airway diameters throughout the ventilatory cycle can influence gas inflow this study intends to investigate the influence of volume and timing of a He gas bolus with respect to the beginning of the tidal volume on inspiratory gas distribution., Materials and Methods: An ultrafast 2-dimensional spoiled gradient echo sequence (temporal resolution 100 milliseconds) was used for dynamic ventilation (3)He-MRI of 11 anesthetized and mechanically ventilated pigs. The applied (3)He gas bolus was varied in volume between 100 and 200 mL. A 150-mL bolus was varied in its application time after the beginning of the tidal volume between 0 and 1200 milliseconds. Signal kinetics were evaluated using an in-house developed software after definition of parameters for the quantitative description of (3)He gas inflow., Results: The signal rise time (time interval between signal in the parenchyma reaches 10% and 90% of its maximum) was prolonged with increasing bolus volume. The parameter was shortened with increasing delay of (3)He application after the beginning of the tidal volume. Timing variation as well as volume variation showed no clear interrelation to the signal delay time 10 (time interval between signal in the trachea reaches 50% of its maximum and signal in the parenchyma reaches 10% of its maximum)., Conclusions: Dynamic ventilation (3)He-MRI is able to detect differences in bolus geometry performed by volume variation. Pulmonary gas inflow as investigated by dynamic ventilation (3)He-MRI tends to be accelerated by an increasing application delay of a (3)He gas bolus after the beginning of the tidal volume.

The noninvasive assessment of lung function using imaging is increasingly of interest for the study of lung diseases, including chronic obstructive pulmonary disease (COPD) and asthma. Hyperpolarized gas MRI (HP MRI) has demonstrated the ability to detect changes in ventilation, perfusion, and lung microstructure that appear to be associated with both normal lung development and disease progression. The physical characteristics of HP gases and their application to MRI are presented with an emphasis on current applications. Clinical investigations using HP MRI to study asthma, COPD, cystic fibrosis, pediatric chronic lung disease, and lung transplant are reviewed. Recent advances in polarization, pulse sequence development for imaging with Xe-129, and prototype low magnetic field systems dedicated to lung imaging are highlighted as areas of future development for this rapidly evolving technology., ((c) 2007 Wiley-Liss, Inc.)

The theoretical dependence of the mean and standard deviation of ADC values on signal-to-noise ratio (SNR) was derived and compared to measured values in porous phantoms and the lungs of human subjects using diffusion-weighted hyperpolarized helium-3 MRI. For SNR values below 15, mean ADC values were highly SNR-dependent due to a combination of noise and choice of noise thresholding. Above SNR values of 15 and for mean ADC values within ranges relevant for evaluating lung disease (<0.6 cm2/s), the mean ADC was largely independent of SNR. The standard deviation, by contrast, was highly dependent on SNR over a much larger range, but this dependence was well predicted by theory, suggesting the histogram of ADC values might be corrected for these stochastic processes to more accurately evaluate disease using restricted diffusion measures in the lungs.

In helium saturated rat abdominal adipose tissue, helium bubbles were studied at 101.3 kPa during breathing of either heliox(80:20), 100% oxygen or air after decompression from an exposure to heliox at 405 kPa for one hour. While breathing heliox bubbles initially grew for 15-115 minutes then shrank slowly; three out of 10 bubbles disappeared in the observation period. During oxygen breathing all bubbles initially grew for 10-80 minutes then shrank until they disappeared from view; in the growing phase, oxygen caused faster growth than heliox breathing, but bubbles disappeared sooner with oxygen breathing than with heliox or air breathing. In the shrinking phase, shrinkage is faster with heliox and oxygen breathing than with air breathing. Air breathing caused consistent growth of all bubbles. With heliox and oxygen breathing, most animals survived during the observation period but with air breathing, most animals died of decompression sickness regardless of whether the surrounding atmosphere was helium or air. If recompression beyond the maximum treatment pressure of oxygen is required, these results indicate that a breathing mixture of heliox may be better than air during the treatment of decompression sickness following heliox diving.

The open circuit acetylene uptake method is a useful non-invasive means of measuring cardiac output. However, because of accumulation of inhaled acetylene in tissues, the cardiac output uptake is underestimated, if residual acetylene is not allowed to wash out completely in between measurements. We determined the effect of applying a correction factor that estimates mixed venous acetylene concentration from endtidal values to the calculation of cardiac output. This accounts for mixed venous acetylene present during measurements made before complete washout. Six healthy subjects performed steady-state exercise at approximately 30% and 60% of V(O2 max). Cardiac output measurements were made at each exercise intensity using the open circuit acetylene uptake method (inspired [acetylene] approximately 1%), with the first and last measurements having no detectible levels of acetylene in expired gas (reference measurement). Data were also obtained with immediate pre-measurement endtidal concentrations ranging from 3% to 15% of the inspired [acetylene], in random order in between. Oxygen consumption, carbon dioxide production and heart rate did not change significantly during testing at each exercise intensity. Reference cardiac output also did not change significantly and averaged 11.1+/-0.8 L/min at 30% of V(O2 max) and 16.5+/-2.0 L/min at 60% of V(O2 max). Uncorrected cardiac output measurements progressively underestimated cardiac output by 15% at the 3% of inspired endtidal [acetylene] and by over 50% at 15% [acetylene] (p<0.0001). However, when corrected for residual endtidal [acetylene], cardiac outputs were not significantly different from the reference measurements. The results of this study suggest that by accounting for residual endtidal acetylene in mixed venous blood, cardiac output can be accurately measured even when washout of acetylene is incomplete, allowing measurements as often as every 10-15 s.

The magnetization response of hyperpolarized 3He gas to a steady-state free precession (SSFP) sequence was simulated using matrix product operators. The simulations included the effects of flip angle (alpha), sequence timings, resonant frequency, gas diffusion coefficient, imaging gradients, T1 and T2. Experiments performed at 1.5 T, on gas phantoms and with healthy human subjects, confirm the predicted theory, and indicate increased SNR with SSFP through use of higher flip angles when compared to optimized spoiled gradient echo (SPGR). Simulations and experiments show some compromise to the SNR and some point spread function broadening at high alpha due to the incomplete refocusing of transverse magnetization, caused by diffusion dephasing from the readout gradient. Mixing of gas polarization levels by diffusion between slices is also identified as a source of signal loss in SSFP at higher alpha through incomplete refocusing. Nevertheless, in the sample experiments, a SSFP sequence with an optimized flip angle of alpha=20 degrees, and 128 sequential phase encoding views, showed a higher SNR when compared to SPGR (alpha=7.2 degrees) with the same bandwidth. Some of the gas sample experiments demonstrated a transient signal response that deviates from theory in the initial phase. This was identified as being caused by radiation damping interactions between the large initial transverse magnetization and the high quality factor (Q=250) birdcage resonator. In 3He NMR experiments, performed without imaging gradients, diffusion dephasing can be mitigated, and the effective T2 is relatively long (1 s). Under these circumstances the SSFP sequence behaves like a CPMG sequence with sinalpha/2 weighting of SNR. Experiments and simulations were also performed to characterize the off-resonance behaviour of the SSFP HP 3He signal. Characteristic banding artifacts due to off-resonance harmonic beating were observed in some of the in vivo SSFP images, for instance in axial slices close to the diaphragm where B0 inhomogeneity is highest. Despite these artifacts, a higher SNR was observed with SSFP in vivo when compared to the SPGR sequence. The trends predicted by theory of increasing SSFP SNR with increasing flip angle were observed in the range alpha=10-20 degrees without compromise to image quality through blurring caused by excessive k-space filtering.

Study Objective: To determine the effect of varying concentrations of heliox, a mixture of helium and oxygen, on albuterol delivery administered by metered-dose inhaler (MDI) in pediatric mechanically ventilated models., Design: Prospective in vitro laboratory study., Setting: University-affiliated research laboratory., Models: The lungs of a 10-kg infant and 30-kg child receiving humidified pressure-regulated volume-controlled ventilation were simulated. The infant settings were an endotracheal tube (ETT) of 4.0 mm, tidal volume of 150 ml, positive end-expiratory pressure of 2 cm H(2)O, rate of 20 breaths/minute, inspiratory time of 0.7 second; the child settings were an ETT of 6.0 mm, tidal volume of 450 ml, positive end-expiratory pressure of 2 cm H(2)O, rate of 16 breaths/minute, and inspiratory time of 0.8 second., Measurements and Main Results: Ten albuterol MDI canisters with chlorofluorocarbon propellants were each actuated once sequentially (total dose 1000 mug) with a commercially available aerosol holding chamber. Albuterol was collected onto a filter proximal to a lung simulator. The filter was rinsed, and concentrations were determined by high-performance liquid chromatography. In the infant model, heliox mixtures of 70:30, 60:40, and 50:50 were compared with nitrogen:oxygen (N(2):O(2)) mixtures in the same ratios. The effect of the 70:30 mixtures was also explored in a child model. Each gas mixture was tested 5 times. At all three ratios, albuterol delivery to the end of the ETT was improved with heliox compared with N(2):O(2) (approximately 7% vs 3-4%, p<0.0001, one-way analysis of variance [ANOVA] with a Bonferroni correction for multiple comparisons). No significant difference was noted in mean percentage albuterol delivery among the varying ratios of heliox studied. By two-way ANOVA, significantly greater albuterol delivery was noted with 70:30 heliox compared with 70:30 N(2):O(2) (7-8% vs 3%, p<0.0001), with no significant difference between the infant and child model (p=0.21). The gas mixture, model, and interaction of the two explained 88% of the variability in mean percentage albuterol delivery., Conclusion: Heliox increased albuterol delivery administered by MDI to the end of the ETT in these in vitro pediatric models of mechanical ventilation. Further studies are needed to determine if the improved albuterol delivery with heliox enhances clinical response in infants and children needing mechanical ventilation.

Rationale: The apparent diffusion coefficient of hyperpolarized (3)He in the lungs has been shown to correlate directly in animal models with the peripheral airspace size and can detect changes in lung microstructure., Objectives: To study in vivo the (3)He apparent diffusion coefficient and to demonstrate its sensitivity to changes in lung morphometry as a result of aging, exposure to cigarette smoke, and lung inflation., Methods: We assessed the variation in the diffusion of hyperpolarized (3)He gas in the lungs by magnetic resonance techniques. Spirometric lung volumes were recorded., Measurements: We measured the dependence of (3)He diffusion on age and on reported cigarette smoke exposure in 32 symptom-free adults. We also measured the dependence of the apparent diffusion coefficient on the degree of lung inflation., Results: In healthy never-smokers, the apparent diffusion coefficient increased with age from 0.115 to 0.155 cm(2) . s(-1) at 20 and 70 yr, respectively, increased linearly with lung inflation and was independent of individual's lung size after correcting for age. For active and passive smokers, the apparent diffusion coefficient increased by up to 40% compared with never-smokers with mean values significantly higher (p=0.016 and p=0.0007, respectively)., Conclusions: Peripheral airspace size increases with age and after exposure to smoke in healthy adults in agreement with previous histologic studies. We have confirmed in vivo that peripheral airspace size is independent of intersubject lung size.

Background: The alveolar volume (V(A)), determined by single-breath helium dilution, is a measure for the total lung capacity (TLC) that is very sensitive to ventilatory disturbances. In chronic obstructive pulmonary disease (COPD), the emphysematous lung parts are less accessible to test gas; therefore, the V(A) is smaller than TLC measured by multiple-breath helium dilution (TLC(He))., Objectives: The aim of this study was to investigate whether the V(A) represents the nonemphysematous lung parts., Methods: We measured V(A) as part of the diffusing capacity for carbon monoxide (DL(CO)), TLC(He) and spirometry in 50 patients with COPD. High-resolution computed tomography (HRCT) scans of all subjects were analyzed with the density mask method, where parts with an attenuation of less than -950 Hounsfield units were considered as emphysematous., Results: A strong correlation was observed between the V(A) (mean 5.2 liters) and nonemphysematous HRCT lung volume (mean 5.2 liters, r(2) = 0.9) and between the TLC(He) (mean 6.6 liters) and total HRCT lung volume (mean 6.4 liters, r(2) = 0.9). Bland-Altman plots showed considerable disagreement between the V(A) and the nonemphysematous HRCT lung volume. A weak correlation between the forced expiratory volume in 1 s (mean 46% predicted) and DL(CO) (mean 46% predicted) versus the HRCT emphysema ratio (nonemphysematous/total HRCT lung volume) was observed (r(2) = 0.3 and 0.3, respectively)., Conclusion: We concluded that the V(A) correlates with the nonemphysematous HRCT lung volume, although the two measurements are not equivalent, possibly due to technical factors.

Aims: This study evaluated the relative importance of perfusion and diffusion mechanisms in compartmental models of blood : tissue helium exchange in a predominantly skeletal muscle tissue bed in the sheep hind limb. Helium has different physiochemical properties from previously studied gases and is a common diluent gas in underwater diving where decompression schedules are based on theoretical models of inert gas kinetics., Methods: Helium kinetics across skeletal muscle were determined during and after 20 min of helium inhalation, at separate resting and low steady-states of femoral vein blood flow in six sheep under isoflurane anaesthesia. Helium concentrations in arterial and femoral vein blood were determined using gas chromatographic analysis and femoral vein blood flow was monitored continuously. Parameters and model selection criteria of various perfusion-limited or perfusion-diffusion compartmental models of skeletal muscle were estimated by simultaneous fitting of the models to the femoral vein helium concentrations for both blood flow states., Results: A model comprising two parallel perfusion-limited compartment models fitted the data well but required a 51-fold difference in relative compartment perfusion that did not seem physiologically plausible. Models that allowed a countercurrent diffusion exchange of helium between arterial and venous vessels outside of the tissue compartments provided better overall fit of the data and credible parameter estimates., Conclusions: These results suggest a role of arterial-venous diffusion in blood : tissue helium equilibration in skeletal muscle.

Recent single breath washout (SBW) studies in microgravity and on the ground have suggested an important effect of airway closure on gas mixing in the human lung, reflected particularly in the phase III slope of vital capacity SBW and bolus tests. In order to explore this effect, we designed a SBW in which subjects inspired 2-l from residual volume (RV) starting with a 150 ml bolus of He and SF6. In an attempt to vary the pattern of airways closure configuration before the test, the experiments were conducted in 1G and in microgravity during parabolic flight allowing the pre-test expiration to RV to be either in microgravity or at 1.8 G, with the actual test gas inhalation performed entirely in microgravity. Contrary to our expectations, the measured phase III slope and phase IV height and volume obtained from seven subjects in microgravity were essentially identical irrespective of the gravity level during the pre-test expiration to RV. The results suggest that airway closure configuration at RV before the test inspiration has no apparent impact on phases III and IV generation.

In healthy lung tissue, pulsed-gradient-spin-echo (PGSE) methods reveal apparent diffusion coefficients (ADC) of the order 0.20 cm2 s(-1); for diffusion times of approximately 2 ms. For these short diffusion times the ADC is only sensitive to structures approximately (2Dt)1/2 approximately 0.6mm in size. Recent work, using magnetic tagging of the longitudinal magnetization has revealed much smaller ADC values for longer length scales. In this work, the in vivo ADC from within the air-spaces, was measured using a new technique. The signal from a series of images was analyzed from a slice that was repeatedly imaged. Diffusion tends to "top-up" the non-renewable polarization within the slice, which leads to a non-exponential decay in image signal. Image data were compared to 1D finite-difference simulations of diffusion to calculate a long range ADC value. The results yield values of the order 0.034 cm2 s(-1), which are nearly an order of magnitude smaller than those reported by PGSE measurements at shorter diffusion times.

Purpose: During recent years, magnetic resonance imaging (MRI) using hyperpolarised (HP) 3He gas has emerged as a promising new method for the imaging of lung ventilation. However, systematic comparisons with nuclear medicine techniques have not yet been performed. The aim of this study was to compare ventilation imaging methods in 26 patients with chronic obstructive pulmonary disease (COPD) and nine lung healthy volunteers., Methods: HP 3He MRI, 81mKr single-photon emission computed tomography (SPECT), high-resolution computed tomography (HRCT) and pulmonary function tests were performed. The three scans were scored visually as percentage of non-ventilated/diseased lung, and a computer-based objective measure of the ventilated volume in HP 3He MRI and 81mKr SPECT and an emphysema index in HRCT were calculated., Results: We found a good correlation between HP 3He MRI and 81mKr SPECT for both visual defect score (r=0.80, p<0.0001) and objective estimate of ventilation (r=0.45, p=0.0157). In addition, both scans were well correlated with reference methods for the diagnosis of emphysema (pulmonary function test and HRCT). The defect scores were largest on 81mKr SPECT (the score on HP 3He MRI was one-third less than that on 81mKr SPECT), but the difference was reduced after normalisation for different breathing depths (HP 3He MRI at total lung capacity; 81mKr SPECT at tidal breathing at functional residual capacity)., Conclusion: HP 3He MRI provides detailed ventilation distribution images and defect scores are comparable on HP 3He MRI and 81mKr SPECT. Additionally, new insights into the regional pulmonary microstructure via the apparent diffusion coefficient measurements are provided by HP 3He MRI. HP 3He MRI is a promising new diagnostic tool for the assessment of ventilation distribution.

This study evaluated the relative importance of perfusion and diffusion mechanisms in compartmental models of blood:tissue helium exchange in the brain. Helium has different physiochemical properties from previously studied gases, and is a common diluent gas in underwater diving where decompression schedules are based on theoretical models of inert gas kinetics. Helium kinetics across the cerebrum were determined during and after 15 min of helium inhalation, at separate low and high steady states of cerebral blood flow in seven sheep under isoflurane anaesthesia. Helium concentrations in arterial and sagittal sinus venous blood were determined using gas chromatographic analysis, and sagittal sinus blood flow was monitored continuously. Parameters and model selection criteria of various perfusion-limited or perfusion-diffusion compartmental models of the brain were estimated by simultaneous fitting of the models to the sagittal sinus helium concentrations for both blood flow states. Purely perfusion-limited models fitted the data poorly. Models that allowed a diffusion-limited exchange of helium between a perfusion-limited tissue compartment and an unperfused deep compartment provided better overall fit of the data and credible parameter estimates. Fit to the data was also improved by allowing countercurrent diffusion shunt of helium between arterial and venous blood. These results suggest a role of diffusion in blood:tissue helium equilibration in brain.

Time-dependent measurements of 3He diffusion in the lung could provide an accurate method to quantify alveolar length scales and the progression of diseases such as emphysema. However, the apparent diffusion coefficient (ADC) presents a complex problem to model and solve analytically. Here, finite-difference methods were used to simulate diffusion in 3D alveolar ducts. The results were compared to the only available analytical model--the "cylinder model"--from which it is possible to estimate the average radii of the alveolar ducts from in vivo data. The trend in data observed from simulations was found to agree well with the cylinder model. However, the cylinder model always overestimated the average radii of the simulated alveolar ducts. The simulations also demonstrated that the measurement of the longitudinal ADC (along the alveolar ducts) should be sensitive to early emphysematous changes, whereas the measured radii should be far less sensitive.

Finite difference simulations have been used to model (3)He gas diffusion in simulated lung tissue. The technique has the advantage that a wide range of structural models and diffusion-sensitizing gradient waveforms can be investigated, for which analytical methods would otherwise be virtually impossible. Results from simulations and in vivo pulsed-gradient-spin-echo (PGSE) experiments show that the apparent diffusion coefficient (ADC) is a function of diffusion time and gradient strength, and suggests diffusion is locally anisotropic. The simulations have been compared to recent work on an analytical model that characterizes lung tissue as a series of independent cylinders. The results presented may have clinical implications for (3)He ADC measurements in assessing lung diseases such as chronic-obstructive-pulmonary-disease.

During a series of dry chamber dives using compressed heliox, five attendants and one wet diver experienced eight episodes of hand discomfort, the character of which was atypical of limb pain during decompression sickness. Although immersed for most of the dive, during the compression and decompression phases, the wet diver's hands were out of the water and hence exposed to the helium-containing chamber atmosphere. In all cases, symptoms resolved within a maximum of 48 h. There was no response to hyperbaric oxygen therapy in the three cases that presented before spontaneous resolution. While the attendants wore dry suits to minimize skin absorption of helium, their hands, were exposed to the heliox atmosphere. After the first six cases of hand symptoms, a dry glove assembly was added to prevent helium absorption through the exposed hand. Two cases of hand discomfort occurred following the addition of the dry glove assembly to the dry suit. In both cases, the symptoms were less severe and resolved over a significantly shorter time period. Adoption of the dry gloves resulted in the incidence of hand discomfort among attendants falling from 25% (5/20) to 2.4% (2/84) (p = 0.005). Possible mechanisms of causation of this hand discomfort, thought to be the result of local tissue absorption of helium, are discussed.

The aim of the study was to assess how deep into the acinar region the airway response to cold dry-air hyperventilation challenge (CACh) reaches in subjects with asthma of different severity. Peripheral airway function was measured using a single-breath sulphur hexafluoride (SF6) and helium (He) washout test and overall airway function by forced expiratory volume in one second (FEV1) at rest, after CACh and beta2-therapy in 55 adults with a history of asthma. The normalised phase-III slopes (SnIII) for SF6 and He were used to assess peripheral airway obstruction and the (SF6-He) SnIII difference to indicate where obstruction occurred. While a greater He versus SF6 slope increase indicates a response close to the acinar entrance, the reverse indicates a response deeper into the acinar airspaces. Twelve subjects had a major fall in FEV1 (> or = 20%) after CACh, 16 a minor fall (10-19%), and 27 did not react. Resting He and SF6 SnIII were significantly greater in major responders with respect to minor and nonresponders, while resting FEV1 did not differ between the three groups. The major responders showed marked increases of He and SF6 SnIII after CACh, with greater increase for He resulting in a negative (SF6-He) SnIII difference. To conclude, airways close to the acinar entrance participate in the overall airway response to cold-air challenge in asthmatic adults with marked airway hyperresponsiveness to cold, dry air.

Hyperpolarized noble gas MRI shows promise in the functional imaging of the pulmonary air spaces. The production of hyperpolarized (HP) gas requires specialized laser optical pumping apparatus, which is not likely to be home built in the majority of clinical MRI radiology centres. There are two routes through which HP gas will be made available to hospitals for clinical use: either the apparatus will be installed locally at a considerable expense to the centre, or a central facility will produce the gas and then deliver it to remote MRI sites as and when required. In this study, the feasibility of transporting large quantities of HP gas for in vivo MR imaging from a remote production facility in Mainz, Germany, by airfreight to Sheffield, UK, was successfully demonstrated.

Three-dimensional (3D) perfusion imaging allows the assessment of pulmonary blood flow in parenchyma and main pulmonary arteries simultaneously. MRI using laser-polarized (3)He gas clearly shows the ventilation distribution with high signal-to-noise ratio (SNR). In this report, the feasibility of combined lung MR angiography, perfusion, and ventilation imaging is demonstrated in a porcine model. Ultrafast gradient-echo sequences have been used for 3D perfusion and angiographic imaging, in conjunction with the use of contrast agent injections. 2D multiple-section (3)He imaging was performed subsequently by inhalation of 450 ml of hyperpolarized (3)He gas. The MR techniques were examined in a series of porcine models with externally delivered pulmonary emboli and/or airway occlusions. With emboli, perfusion deficits without ventilation defects were observed; airway occlusion resulted in matched deficits in perfusion and ventilation. High-resolution MR angiography can unambiguously reveal the location and size of the blood emboli. The combination of the three imaging methods may provide complementary information on abnormal lung anatomy and function., (Copyright 2002 Wiley-Liss, Inc.)

In this work, the use of a new carrier agent for intravascular laser-polarized 3He imaging is reported. Lipid-based helium microbubbles were investigated. Their average diameter of 3 microm, which is smaller than that of the capillaries, makes it possible to conduct in vivo studies. The NMR relaxation parameters T1, T2, and T2* of a microbubble suspension were measured as 90 s, 300 ms, and 4.5 ms, respectively, and in vivo images of encapsulated 3He with signal-to-noise ratios (SNRs) larger than 30 were acquired. Dynamic cardiac images and vascular images of encapsulated 3He were obtained in rats using intravenous injections of microbubble suspensions. Excellent preservation of 3He polarization through the lung capillaries and heart cavities was observed. The first images of 3He microbubble distributions in the lungs were obtained. Additionally, the potential of this technique for lung perfusion assessment was validated through an experimental embolism model with the visualization of perfusion defects., (Copyright 2001 Wiley-Liss, Inc.)

Helium dilution maneuver is used to determine the functional residual capacity (FRC) 14 newborns ages 1-5 mo. The model equation describes the changing alveolar fractions of He and the ventilation promoted by a rebreathing procedure that does not exceed 40 s. The model does not involve the volume of the rebreathing bag usually needed when applying rebreathing technique and which is a source of error. The equation is discretized and solved for recorded data obtained with equipment adapted to newborns. Results show a strong relationship between FRC and the biometrical indexes, and confirm those found in the literature featuring that the measurement duration of FRC can be considerably shortened.

The fate of bubbles formed in tissues during the ascent from a real or simulated air dive and subjected to therapeutic recompression has only been indirectly inferred from theoretical modeling and clinical observations. We visually followed the resolution of micro air bubbles injected into adipose tissue, spinal white matter, muscle, and tendon of anesthetized rats recompressed to and held at 284 kPa while rats breathed air, oxygen, heliox 80:20, or heliox 50:50. The rats underwent a prolonged hyperbaric air exposure before bubble injection and recompression. In all tissues, bubbles disappeared faster during breathing of oxygen or heliox mixtures than during air breathing. In some of the experiments, oxygen breathing caused a transient growth of the bubbles. In spinal white matter, heliox 50:50 or oxygen breathing resulted in significantly faster bubble resolution than did heliox 80:20 breathing. In conclusion, air bubbles in lipid and aqueous tissues shrink and disappear faster during recompression during breathing of heliox mixtures or oxygen compared with air breathing. The clinical implication of these findings might be that heliox 50:50 is the mixture of choice for the treatment of decompression sickness.

A measuring method of the emission rate of an atmospheric pollutant source, based on the use of a tracer gas (helium) and developed in the case of a gaseous source, was tested for an aerosol source. The influence of both particle sedimentation and wall depositions was studied. The transport coefficients of the tracer gas and of alumina particles of various particle sizes (MMAD from 8 to 36 microns) were measured on a vertical axis close to the source, in a 71 m3 room swept by a piston flow. The measurements clearly demonstrated the predominant influence of sedimentation in the case of particles with aerodynamic diameters greater than 10 microns. Particle wall deposition was determined by measuring the gas and particle concentration decay in the ventilated room. To do this, a new tracing method using a fluorescent aerosol was developed. The measured aerosol deposition rates are much higher than those calculated from the formula of Corner for a cubical volume. Aerosol sedimentation and wall deposition are two phenomena limiting the use of a tracer gas to measure the aerosol emission rate. The chemical substances and materials used in work premises are likely to be released into the atmosphere and lead to the formation of pollutants. These emissions stem from either physical or chemical processes (evaporation of a solvent) or from mechanical processes (dispersion of oil droplets at the source of mists).

We simulated the intra-acinar contribution to phase III slope (S(acin)) for gases of differing diffusivities (He and SF(6)) by solving equations of diffusive and convective gas transport in multi-branch-point models (MBPM) of the human acinus. We first conducted a sensitivity study of S(acin) to asymmetry and its variability in successive generations. S(acin) increases were greatest when asymmetry and variability of asymmetry were increased at the level of the respiratory bronchioles (generations 17-18) for He and at the level of the alveolar ducts (generations 20-21) for SF(6), corresponding to the location of their respective diffusion fronts. On the basis of this sensitivity study and in keeping with reported acinar morphometry, we built a MBPM that actually reproduced experimental S(acin) values obtained in normal subjects for He, N(2), and SF(6). Ten variants of such a MBPM were constructed to estimate intrinsic S(acin) variability owing to peripheral lung structure. The realistic simulation of S(acin) in the normal lung and the understanding of how asymmetry affects S(acin) for different diffusivity gases make S(acin) a powerful tool to detect structural alterations at different depths in the lung periphery.

Magnetic resonance imaging (MRI) using laser-polarized noble gases, such as (129)Xe and (3)He, allows unparalleled noninvasive information on gas distribution in lung airways and distal spaces. In addition to pulmonary ventilation, lung perfusion assessment is crucial for proper diagnosis of pathological conditions, such as pulmonary embolism. Magnetic resonance perfusion imaging usually can be performed using techniques based on the detection of water protons in tissues. However, lung proton imaging is extremely difficult due to the low proton density and the magnetically inhomogeneous structure of the lung parenchyma. Here we show that laser-polarized (3)He can be used as a noninvasive probe to image, in a single MRI experiment, not only the ventilation but also the perfusion state of the lungs. Blood volume maps of the lungs were generated based on the (3)He signal depletion during the first pass of a superparamagnetic contrast agent bolus. The combined and simultaneous lung ventilation and perfusion assessments are demonstrated in normal rat lungs and are applied to an experimental animal model of pulmonary embolism. Magn Reson Med 44:1-4, 2000., (Copyright 2000 Wiley-Liss, Inc.)

We applied the rapid imaging capability of echo planar MR pulse sequences and hyperpolarized (3)He ventilation imaging to observe the dynamic distribution of gas in the lungs during breathing. Findings in five normal volunteers (age 19-53 years) and four patients with severe smoking-related emphysema (age 56-71 years) were compared. All studies were performed on a 1.5 T whole body scanner using a 30 cm Helmholtz surface coil and 0.5 l of 20-40% polarized (3)He mixed with 1-2 l nitrogen. Our echo planar imaging pulse sequence allowed acquisition of each image in 0.04 s, with a pixel size of 7 mm(2) (TR = 40.5 ms, TE = 12.1 ms, flip angle = 22 degrees, echo train length = 32, matrix = 32 x 64, field of view = 225 x 450 mm, slice thickness = 10 mm). Imaging was performed in the transaxial plane repeatedly at 3, 10 or 20 evenly spaced levels, immediately before and during breathing of the gas mixture. In normal subjects during the first breath, (3)He appeared throughout each slice first in the mid lungs, then in the lower lungs, then in the upper lungs, with slightly greater signal in the dependent posterior regions. In patients with emphysema, sequential filling of different lung regions was seen during the first breath, with delayed filling of other regions observed during rebreathing and room air washout. We conclude that subsecond dynamic (3)He MR ventilation imaging can reveal normal and abnormal ventilation phenomena not seen with conventional scintigraphic methods, and offers another approach to the study of ventilation physiology and pathophysiology., (Copyright 2000 John Wiley & Sons, Ltd.)

The use of spiral scan techniques is investigated for (3)He lung imaging on small animals. Dynamic series of up to 40 high temporal resolution (3)He ventilation images are obtained using a single bolus of gas. General properties of the spiral technique are discussed and compared to those of standard imaging techniques in relation to the specific case of rare gas imaging. To improve temporal resolution of the image series, the efficiency of a sliding window technique, combining data from two consecutive spiral images, is demonstrated. An example of the typical global (3)He signal variation during the (3)He breathing of the animal is shown. Pixel-by-pixel measurements of the (3)He signal derivative during the gas inspiration are performed. A corresponding lung map of the magnetization per time unit entering the lung during gas inflow is presented., (Copyright 2000 John Wiley & Sons, Ltd.)

MRI with hyperpolarized helium-3 ((3)He) provides high-resolution imaging of ventilated airspaces. The first aim of this (3)He-study was to compare observations of localized signal defects in healthy smokers and non-smokers. A second aim was to describe relationships between parameters of lung function, volume of inspired (3)He and signal-to-noise ratio. With Ethics Committee approval and informed consent, 12 healthy volunteers (seven smokers and five non-smokers) were studied. Imaging was performed in a 1.5 T scanner using a two-dimensional FLASH sequence at 30V transmitter amplitude (TR/TE/alpha = 11 ms/4.2 ms/<10 degrees ). Known amounts of (3)He were inhaled from a microprocessor-controlled delivery device and imaged during single breath-holds. Images were evaluated visually, and scored using a prospectively defined 'defect-index'. Signal-to-noise ratio of the images were correlated with localization, (3)He volumes and static lung volumes. Due to poor image quality studies of two smokers were not eligible for the evaluation. Smokers differed from non-smokers in total number and size of defects: the 'defect-index' of smokers ranged between 0.8 and 6.0 (median = 1.1), that of non-smokers between 0.1 and 0.8 (median = 0.4). Intraindividually, an anteroposterior gradient of signal-to-noise ratio was apparent. Signal-to-noise ratio correlated with the estimated amount of hyperpolarization administered (r = 0. 77), but not with static lung volumes. We conclude that (3)He MRI is a sensitive measure to detect regional abnormalities in the distribution of ventilation in clinically healthy persons with normal pulmonary function tests., (Copyright 2000 John Wiley & Sons, Ltd.)

The exchange rates of CO2 and He across the tympanic membrane were estimated in 5 monkeys. For these experiments, the monkey was anesthetized and one arm of a polyethylene "T" tube was introduced into the external canal of the test ear and sealed to the ambient environment with wax. One arm of the T tube was attached to a pressure transducer and the other to an argon gas source via a valve. Silica tubing sealed within the probe provided periodic gas samples for composition analysis by an online mass spectrometer. Prior to each experiment, the probe was washed with Argon. In 5 experiments the probe was sealed within the external canal of animals with physiological middle ear gas compositions, and in 5 experiments the probe was sealed within the external canal of animals whose middle ears were partially washed with He. The gas in the probe was sampled and analyzed at 10-min intervals for up to 4 h. The results documented a significant increase in the percentage composition of CO2 but not He in the experiments conducted with physiological middle ear gas compositions, and increases in both He and CO2 in the experiments conducted after the middle ear was washed with He. Estimated, average exchange constants for He and CO2 were 0.0005 microl/min/mmHg and 0.0103 microl/min/mmHg, respectively. Using data from previous experiments, the relative trans-mucosal to trans-tympanic membrane gas exchange rates in monkeys are estimated to be in the order of 10:1 for inert gases and 180:1 for chemically active gases.

Magnetic resonance imaging using the MR signal from hyperpolarized noble gases 129Xe and 3He may become an important new diagnostic technique. Alex Pines (adapting the hyperpolarization technique pioneered by William Happer) presented MR spectroscopy studies using hyperpolarized 129Xe. The current authors recognized that the enormous enhancement in the delectability of 129Xe, promised by hyperpolarization, would solve the daunting SNR problems impeding their attempts to use 129Xe as an in vivo MR probe, especially in order to study the action of general anesthetics. It was hoped that hyperpolarized 129Xe MRI would yield resolutions equivalent to that achievable with conventional 1H2O MRI, and that xenon's solubility in lipids would facilitate investigations of lipid-rich tissues that had as yet been hard to image. The publication of hyperpolarized 129Xe images of excised mouse lungs heralded the emergence of hyperpolarized noble-gas MRI. Using hyperpolarized 3He, researchers have obtained images of the lung gas space of guinea pigs and of humans. Lung gas images from patients with pulmonary disease have recently been reported. 3He is easier to hyperpolarize than 129Xe, and it yields a stronger MR signal, but its extremely low solubility in blood precludes its use for the imaging of tissue. Xenon, however, readily dissolves in blood, and the T1, of dissolved 129Xe is long enough for sufficient polarization to be carried by the circulation to distal tissues. Hyperpolarized 129Xe dissolved-phase tissue spectra from the thorax and head of rodents and humans have been obtained, as have chemical shift 129 Xe images from the head of rats. Lung gas 129Xe images of rodents, and more recently of humans, have been reported. Hyperpolarized 129Xe MRI (HypX-MRI) may elucidate the link between the structure of the lung and its function. The technique may also be useful in identifying ventilation-perfusion mismatch in patients with pulmonary embolism, in staging and tracking the success of therapeutic approaches in patients with chronic obstructive airway diseases, and in identifying candidates for lung transplantation or reduction surgery. The high lipophilicity of xenon may allow MR investigations of the integrity and function of excitable lipid membranes. Eventually, HypX-MRI may permit better imaging of the lipid-rich structures of the brain. Cortical brain function is one perfusion-dependent phenomena that may be explored with hyperpolarized 129Xe MR. This leads to the exciting possibility of conducting hyperpolarized 129Xe functional MRI (HypX-fMRI) studies.

Hyperpolarized noble gas MRI is a new technique for imaging of gas spaces and tissues that have been hitherto difficult to image, making it a promising diagnostic tool. The unique properties of hyperpolarized species, particularly the non-renewability of the large non-equilibrium spin polarization, raises questions about the feasibility of hyperpolarized noble gas MRI methods. In this paper, the critical issue of T1 relaxation is discussed and it is shown that a substantial amount of polarization should reach the targets of interest for imaging. We analyse various pulse sequence designs, and point out that total scan times can be decreased so that they are comparable or shorter than tissue T1 values. Pulse sequences can be optimized to effectively utilize the non-renewable hyperpolarization, to enhance the SNR, and to eliminate image artifacts. Hyperpolarized noble gas MRI is concluded to be quite feasible.

To study the consequences of diving with gas mixtures, we simulated growth of decompression bubbles using an equation system that accounts for major determinants of bubble behavior. When breathing a mixture, bubbles are smaller than expected from linear interpolation between bubbles with either of the unmixed component gases because of disproportionate diffusion effects: a) When few bubbles form, the inert gas that permeates fastest becomes over-represented, relative to the breathing gas, inside bubbles during growth; this slows further entrance of the fast gas and enhances entrance of the slower gas. b) With N2-He mixtures and few bubbles, the over-represented gas is He in aqueous tissue, but is N2 in lipid tissue. c) When many bubbles form, the over-represented gas is the one with higher tissue solubility. Our simulations indicate that the smallest bubbles always occur with breathing of one of the component gases, but which gas that is depends on whether the tissue is lipid or aqueous and whether few or many bubbles form.

The influence of gas composition on convective and diffusive gas transport in the lungs was assessed by studying the dispersion of combined particle and argon (Ar) boluses induced by the passage through the lungs filled with three different gas mixtures. Particles, as a "nondiffusing gas," served as a tracer for convective gas transport, while the significance of diffusive gas transport was inferred from the difference in the behavior of Ar and particles. The lungs of six anesthetized and mechanically ventilated beagle dogs were equilibrated with air or either of the test atmospheres, He-O2 or SF6-O2, where nitrogen was replaced by helium (He) or sulfur hexafluoride (SF6). Due to differences in gas density and gas viscosity Reynolds numbers varied by a factor of twelve and Ar diffusivity by a factor of four between He-O2 and SF6-O2, suggesting that both kinds of intrapulmonary gas transport, convection and diffusion, should be affected. Combined particle and Ar boluses were inhaled into various lung depths and the extent of gas transport was inferred from changes in bolus shape induced by the passage through the lungs. In air, convective bulk gas transport generally followed the symmetric first-in, last-out principle and acted at all tested lung depths. Within the conducting airways, gas transport to the lung periphery was primarily due to convection but beyond these airways diffusion became rapidly significant. Breathing test atmospheres affects intrapulmonary gas transport only slightly. The extent of convective mixing was increased by 4% in SF6-O2 (p < .01) and reduced by 5% in He-O2 (p < .01) as compared to air. The symmetry of convective lung filling and emptying was slightly disturbed. In SF6-O2 the mean of the exhaled bolus was shifted by 8% toward the lung periphery. In He-O2 it was shifted by 4% toward the airway opening. In both test atmospheres exhaled Ar boluses were similar, suggesting that diffusive gas transport overwhelms the small changes in convective gas transport. Hence, factors other than gas composition-related flow characteristics, e.g., nonreversibility of in- and expiratory flow profiles or features of lung geometry, are the major determinants of gas transport in the lungs.

The method of maximum likelihood was used to calibrate a probabilistic bubble evolution model against data of bubbles detected in divers. These data were obtained from a diverse set of 2,064 chamber man-dives involving air and heliox with and without oxygen decompression. Bubbles were measured with Doppler ultrasound and graded according to the Kisman-Masurel code from which a single maximum bubble grade (BG) per diver was compared to the maximum bubble radius (Rmax) predicted by the model. This comparison was accomplished using multinomial statistics by relating BG to Rmax through a series of probability functions. The model predicted the formation of the bubble according to the critical radius concept and its evolution was predicted by assuming a linear rate of inert gas exchange across the bubble boundary. Gas exchange between the model compartment and blood was assumed to be perfusion-limited. The most successful calibration of the model was found using a trinomial grouping of BG according to no bubbles, low, and high bubble activity, and by assuming a single tissue compartment. Parameter estimations converge to a tissue volume of 0.00036 cm3, a surface tension of 5.0 dyne.cm-1, respective time constants of 27.9 and 9.3 min for nitrogen and helium, and respective Ostwald tissue solubilities of 0.0438 and 0.0096. Although not part of the calibration algorithm, the predicted evolution of bubble size compares reasonably well with the temporal recordings of BGs.

Carbon dioxide is the most commonly used gas for abdominal insufflation in laparoscopy today. Due to the solubility of carbon dioxide large volumes are absorbed into the circulation causing a high PCO2 and a low pH (respiratory acidosis). Carbon dioxide is also stored in several sites in the body and is released at the conclusion of the procedure prolonging the respiratory acidosis when the patient is least able to cope with this additional burden. Cardiac effects of CO2 consist of a lowering of the arrhythmia threshold, increased blood pressure, pulse and cardiac output. At a sustained high level this can lead to cardiac depression and death. These effects are particularly prone to occur in cardiac and respiratory cripples. Other gases that have been used include air, oxygen, nitrous oxide and nitrogen. Their use has been discontinued because of the danger of embolism. Air, oxygen and nitrous oxide are also not safe to use in the presence of electrosurgical instruments thereby limiting their usefulness even further. Helium has been proposed as a very promising alternative to CO2. In the laboratory and in a clinical trial, helium has not produced the respiratory acidosis associated with CO2 insufflation. This is further evidence that the acidosis is not primarily due to elevation of the diaphragm and consequent increased dead space, but to the large amount of CO2 that is absorbed directly from the peritoneal cavity. Helium would seem to be the gas of choice at this time as it comes close to fitting the criteria for an ideal insufflating gas. Helium is clear and colorless, allowing unimpeded vision to the operator. It is non toxic, not flammable or explosive and can be safely used with electrocautery and laser. Helium is easy to handle and not very soluble which decreases the amount absorbed from the peritoneal cavity and consequently the amount used. That which is absorbed is quickly cleared by the lungs. Helium is metabolically inactive (in contrast to CO2) and does not interfere with normal metabolic processes. In view of this promising initial work, further studies are indicated.

A catheter for intra-airway sampling of gas concentrations was constructed from concentric polyethylene tubes. The internal tube (0.58 mm ID, 0.91 mm OD) was connected to a gas analyzer while the external tube (1.20 mm ID, 1.75 mm OD) was constantly flushed by air or a calibration gas, except during sampling. Injection and sampling dead spaces were 0.35 and 0.28 ml, respectively. Delay at 4-ml/min sampling rate was 4.0 +/- 0.2 s. The 0-90% step response to a sudden change in gas composition was 0.24 s when connected to a mass spectrometer. This catheter was used to assess tracer gas dispersion during oscillatory flow (1-20 Hz) in a straight long tube. Local concentrations measured through the catheter, after a small bolus of tracer gas was injected through the external tube, compared favorably with direct measurements through needles inserted via the tube wall and with theoretical predictions. The catheter was also used to measure intra-airway gas concentrations in dog airways during spontaneous breathing, conventional mechanical ventilation, high-frequency ventilation, high-frequency vibration ventilation, and constant-flow ventilation. It ws placed by a fiber-optic bronchoscope and used to measure local quasi-steady concentrations of CO2 and local dispersion with the bolus method. The occurrence of catheter clogging with secretions was substantially reduced with flow through the external tube. Transmitting a calibration gas through the external tube facilitated in situ recalibration of the gas analyzer without removing the catheter. The use of this catheter improved the efficiency and accuracy of measurements of gas concentrations inside lung airways.

The underlying hypothesis of this study is that collateral ventilation by diffusion of occluded air spaces in the lungs of patients with chronic obstructive pulmonary disease (COPD) may play a substantial role in the pulmonary gas exchange of these patients. Using a related lung model we have simulated: a) the multiple-breath washout of helium (He) and sulphur hexafluoride (SF6) from the alveolar space, and b) the washout of inert tracer gases with different blood-gas partition coefficients, range 0.01-330, from mixed venous blood. These computations were carried out for different values of the collateral diffusion capacity (CDC). Next, the results obtained at each individual value of CDC were used to compute the breath number (NCR) at the crossing-over of the He-SF6 washout curves and the inert gas shunt fraction QS/QC. NCR and QS/QC range up to about 100 and 0.04, respectively, when CDCSF6 ranges down to about 0.1 ml.min-1.mmHg-1. These ranges for NCR and QS/QC, and the typical finding of relatively large values for NCR in combination with small values for QS/QC, are also reported in the literature for patients with COPD. These agreements thus support our hypothesis. In line with the small values for QS/QC, our results further indicate that even large, well-perfused, occluded air spaces in the lung will hardly affect the recovered ventilation/perfusion distribution obtained from inert gas data when CDCSF6 exceeds 0.1 ml.min-1.mmHg-1.

Investigation of superficial counterdiffusion of nitrogen against helium has been carried out to evaluate a possibility of its progress in divers (107 tests) under pressures equivalent to 32-450 m of sea water when breathing trimix being saturated in heliox at a constant ambient pressure without changing chamber environment. Breathing gas mixture contained 248-800 kPa of nitrogen, while chamber heliox media contained some additions of nitrogen (6-108 kPa). Clinical manifestations of breathing trimix (itching and gas bubble formation) were studied in divers. The development of counterdiffusion depends on the partial pressure of nitrogen not only in the breathing gas mixture but also in the chamber media. The breathing nitrogen level being increased and (or) decreased in the chamber media, the counterdiffusion symptoms grow relative to the number (%) of cases. Minimal critical values of nitrogen partial pressure gradients in the mixture which induce counterdiffusion skin lesions are 260-320 kPa on the average for the nitrogen concentration in the chamber mixture to 30 kPa. Isobaric supersaturation due to inert gases countertransport in body tissues as a result of gas-switching from heliox to trimix is responsible for the syndrome development.

Because tracer techniques are gaining an increasing importance for imaging flow (and metabolism) in the heart, experimental evidence is needed on the role of convection and diffusion in the transcoronary transport of solutes. In the present work, the transport of four different inert gases through the coronary system is studied in five closed-chest dog experiments and is compared with a digital multicapillary convection-diffusion model. Transport may be defined as flow dependent, as judged by the gross similarity of shape of the time-normalized dilution curves. However, the results show that the transcoronary transport of helium and xenon is more dispersed than that of argon and krypton, probably because of differences in diffusibility and solubility. A comparison of the animal and model experiments emphasizes the importance of diffusive transport of the gases. It is suggested that there is a diffusion shunt that is mainly located within the capillary network itself rather than between conduit vessels. Only for helium (which has the highest diffusivity) was a small arteriovenous shunt fraction seen that is thought to bypass the capillary exchange region. The conclusion is that although there is evidence of diffusional shunting at a capillary level, the inert gas kinetics in the heart are compatible with a basically flow-limited transport.