Multiple breath washout of hyperpolarized 129 Xe and 3 He in human lungs with three-dimensional balanced steady-state free-precession imaging.

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.

Fundamentals of aerosol therapy in critical care.

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.

Multibreath alveolar oxygen tension imaging.

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.

Regional alveolar partial pressure of oxygen measurement with parallel accelerated hyperpolarized gas MRI.

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.

Combined measurement of pulmonary inert gas washout and regional ventilation heterogeneity by MR of a single dose of hyperpolarized 3He.

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.

Cellular effects of helium in different organs.

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.

Experimental investigation and numerical simulation of 3He gas diffusion in simple geometries: implications for analytical models of 3He MR lung morphometry.

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.

MR imaging of apparent 3He gas transport in narrow pipes and rodent airways.

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.

The role of collateral paths in long-range diffusion of 3He in lungs.

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.

Intrapulmonary 3He gas distribution depending on bolus size and temporal bolus placement.

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.

Efecto del helio sobre los parámetros de los respiradores en ventilación mecánica: estudio in vitro con el respirador Servoi / The effect of helium on ventilator parameters: in vitro study with a Servoi ventilator

Objetivo: Analizar las modificaciones de los parámetros en el respirador Servoi con distintas concentraciones de héliox. Material y métodos: Estudio experimental en el que se utilizó un respirador Servoi (Maquet) en modalidades de volumen control (VC), presión control (PC) y volumen controlado regulado por presión (VCRP) conectado a un pulmón de artificial. El héliox se administró mediante una bombona con el 70 % de helio y el 30 % de oxígeno conectada a la entrada de aire del respirador. Se programó el respirador en VC con volúmenes corrientes de 30, 50, 100, 250 y 500 ml, en PC con presión de 20 y 30 cmH2O, y en VCRP con volumen corriente de 150 ml. En cada modalidad se programó una FiO2 de 21, 30, 40, 50, 60, 70, 80, 90 y 100 % y se comparó el volumen corriente inspirado, el espirado y la presión inspiratoria pico medidas por el respirador y por un espirómetro colocado entre la tubuladura y el pulmón de prueba y conectado a un monitor Datex_S5. Resultados: En modalidad de VC y VCRP el aumento de la concentración de helio produjo una disminución progresiva del pico de presión necesario para administrar el volumen programado y una disminución en el volumen corriente medido por el espirómetro y el volumen espirado medido por el respirador. En modalidad de PC el héliox produjo un aumento progresivo del volumen corriente inspirado con incremento en las diferencias entre el volumen corriente inspirado y el espirado. Conclusiones: La administración de héliox en el respirador Servoi produce una disminución de las presiones inspiratorias en las modalidades de VC y VCRP y un aumento del volumen corriente inspirado en la modalidad de PC. En todas las modalidades produce una falsa disminución en el volumen corriente espirado medido por el respirador y el espirómetro. Es necesario tener en cuenta estas alteraciones si se utiliza héliox con este respirador (AU)

Objective: To analyze the changes in respiratory parameters in a Servoi ventilator with heliox. Material and methods: In vitro study with a Servoi (Maquet) ventilator in volume controlled (VC), pressure controlled (PC) and volume control regulated by pressure (VCPR) modes connected to an artificial lung. A heliox tank with a fixed concentration of helium 70 % and oxygen 30 % was connected to the air inlet of the ventilator. The ventilator was set in VC mode with tidal volumes of 30, 50, 100, 250 and 500 ml; in PC mode with pressure of 20 and 30 cmH2O and in VCPR mode with tidal volume of 150 ml. In each case FiO2 of 21, 30, 40, 50, 60, 70, 80, 90 and 100 % was used. The FiO2, inspired and expired tidal volume and inspiratory pressure measured by the ventilator and a pitot spirometer (Datex_S5) were compared. Results: In VC and VCPR modes the increase in helium produced a progressive decrease in the pressure needed to administrate the set volume. Heliox also produced a decrease in the tidal volume measured by the spirometer and the tidal expired volume measured by the respirator. In PC mode, heliox produced a progressive increase in the inspired tidal volume, increasing the differences between inspired and expired tidal volumes. Conclusions: Heliox used with Servoi ventilator produces a decrease in inspiratory pressures in VC and VCPR modes, and an increase in inspiratory tidal volume in PC mode. In all modes heliox reduced the expired tidal volume measured by the ventilator and the spirometer. These changes should be borne in mind if heliox is used with this ventilator (AU)

Effect of heliox, oxygen and air breathing on helium bubbles after heliox diving.

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.

Functional lung imaging using hyperpolarized gas MRI.

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.

The effect of incomplete acetylene washout on cardiac output measurement using open circuit acetylene uptake.

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 effects of SNR on ADC measurements in diffusion-weighted hyperpolarized He-3 MRI.

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.

Effect of heliox on albuterol delivery by metered-dose inhaler in pediatric in vitro models of mechanical ventilation.

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.

Steady-state free precession with hyperpolarized 3He: experiments and theory.

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.

Acinar structure in symptom-free adults by Helium-3 magnetic resonance.

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.

Alveolar volume determined by single-breath helium dilution correlates with the high-resolution computed tomography-derived nonemphysematous lung volume.

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.

Countercurrent compartmental models describe hind limb skeletal muscle helium kinetics at resting and low blood flows in sheep.

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.