Detection of local lung air content by electrical impedance tomography compared with electron beam CT.

The aim of the study was to validate the ability of electrical impedance tomography (EIT) to detect local changes in air content, resulting from modified ventilator settings, by comparing EIT findings with electron beam computed tomography (EBCT) scans obtained under identical steady-state conditions. The experiments were carried out on six anesthetized supine pigs ventilated with five tidal volumes (VT) at three positive end-expiratory pressure (PEEP) levels. The lung air content changes were determined both by EIT (Goe-MF1 system) and EBCT (Imatron C-150XP scanner) in six regions of interest, located in the ventral, middle, and dorsal areas of each lung, with respect to the reference air content at the lowest VT and PEEP, as a change in either local electrical impedance or lung tissue density. An increase in local air content with VT and PEEP was identified by both methods at all regions studied. A good correlation between the changes in lung air content determined by EIT and EBCT was revealed. Mean correlation coefficients in the ventral, middle, and dorsal regions were 0.81, 0.87, and 0.93, respectively. The study confirms that EIT is a suitable, noninvasive method for detecting regional changes in air content and monitoring local effects of artificial ventilation.     

Physiological evaluation of a new quantitative SPECT method measuring regional ventilation and perfusion.

We have developed a new quantitative single-photon-emission computed tomography (SPECT) method that uses (113m)In-labeled albumin macroaggregates and Technegas ((99m)Tc) to estimate the distributions of regional ventilation and perfusion for the whole lung. The multiple inert-gas elimination technique (MIGET) and whole lung respiratory gas exchange were used as physiological evaluations of the SPECT method. Regional ventilation and perfusion were estimated by SPECT in nine healthy volunteers during awake, spontaneous breathing. Radiotracers were administered with subjects sitting upright, and SPECT images were acquired with subjects supine. Whole lung gas exchange of MIGET gases and arterial Po(2) and Pco(2) gases was predicted from estimates of regional ventilation and perfusion. We found a good agreement between measured and SPECT-predicted exchange of MIGET and respiratory gases. Correlations (r(2)) between SPECT-predicted and measured inert-gas excretions and retentions were 0.99. The method offers a new tool for measuring regional ventilation and perfusion in humans.     

Physiological imaging of the lung: single-photon-emission computed tomography (SPECT).

Emission tomography provides three-dimensional, quantitative images of the distribution of radiotracers used to mark physiological, metabolic, or pathological processes. Quantitative single photon emission computed tomography (SPECT) requires correction for the image-degrading effects due to photon attenuation and scatter. Phantom experiments have shown that radioactive concentrations can be assessed within some percentage of the true value when relevant corrections are applied. SPECT is widely spread, and radiotracers are available that are easy to use and comparably inexpensive. Compared with other methods, SPECT suffers from a lower spatial resolution, and the time required for image acquisition is longer than for some alternative methods. In contrast to some other methods, SPECT allows simultaneous imaging of more than one process, e.g., both regional blood flow and ventilation, for the whole lung. SPECT has been used to explore the influence of posture and clinical interventions on the spatial distribution of lung blood flow and ventilation. Lung blood flow is typically imaged using macroaggregates of albumin. Both radioactive gases and particulate aerosols labeled with radioactivity have been used for imaging of regional ventilation. However, all radiotracers are not equally suited for quantitative measurements; all have specific advantages and limitations. With SPECT, both blood flow and ventilation can be marked with radiotracers that remain fixed in the lung tissue, which allows tracer administration during conditions different from those at image registration. All SPECT methods have specific features that result from the used radiotracer, the manner in which it is administered, and how images are registered and analyzed.     

Imaging lung perfusion

From the first measurements of the distribution of pulmonary blood flow using radioactive tracers by West and colleagues (J Clin Invest 40: 1-12, 1961) allowing gravitational differences in pulmonary blood flow to be described, the imaging of pulmonary blood flow has made considerable progress. The researcher employing modern imaging techniques now has the choice of several techniques, including magnetic resonance imaging (MRI), computerized tomography (CT), positron emission tomography (PET), and single photon emission computed tomography (SPECT). These techniques differ in several important ways: the resolution of the measurement, the type of contrast or tag used to image flow, and the amount of ionizing radiation associated with each measurement. In addition, the techniques vary in what is actually measured, whether it is capillary perfusion such as with PET and SPECT, or larger vessel information in addition to capillary perfusion such as with MRI and CT. Combined, these issues affect quantification and interpretation of data as well as the type of experiments possible using different techniques. The goal of this review is to give an overview of the techniques most commonly in use for physiological experiments along with the issues unique to each technique.     

Paradoxical redistribution of pulmonary blood flow in prone and supine humans exposed to hypergravity.

We hypothesized that exposure to hypergravity in the supine and prone postures causes a redistribution of pulmonary blood flow to dependent lung regions. Four normal subjects were exposed to hypergravity by use of a human centrifuge. Regional lung perfusion was estimated by single-photon-emission computed tomography (SPECT) after administration of (99m)Tc-labeled albumin macroaggregates during normal and three times normal gravity conditions in the supine and prone postures. All images were obtained during normal gravity. Exposure to hypergravity caused a redistribution of blood flow from dependent to nondependent lung regions in all subjects in both postures. We speculate that this unexpected and paradoxical redistribution is a consequence of airway closure in dependent lung regions causing alveolar hypoxia and hypoxic vasoconstriction. Alternatively, increased vascular resistance in dependent lung regions is caused by distortion of lung parenchyma. The redistribution of blood flow is likely to attenuate rather than contribute to the arterial desaturation caused by hypergravity.     

Gravity effects on regional lung ventilation determined by functional EIT during parabolic flights.

Gravity-dependent changes of regional lung function were studied during normogravity, hypergravity, and microgravity induced by parabolic flights. Seven healthy subjects were followed in the right lateral and supine postures during tidal breathing, forced vital capacity, and slow expiratory vital capacity maneuvers. Regional 1) lung ventilation, 2) lung volumes, and 3) lung emptying behavior were studied in a transverse thoracic plane by functional electrical impedance tomography (EIT). The results showed gravity-dependent changes of regional lung ventilation parameters. A significant effect of gravity on regional functional residual capacity with a rapid lung volume redistribution during the gravity transition phases was established. The most homogeneous functional residual capacity distribution was found at microgravity. During vital capacity and forced vital capacity in the right lateral posture, the decrease in lung volume on expiration was larger in the right lung region at all gravity phases. During tidal breathing, the differences in ventilation magnitudes between the right and left lung regions were not significant in either posture or gravity phase. A significant nonlinearity of lung emptying was determined at normogravity and hypergravity. The pattern of lung emptying was homogeneous during microgravity.     

Tracer kinetic model of regional pulmonary function using positron emission tomography.

To determine the spatial distributions of pulmonary perfusion, shunt, and ventilation, we developed a compartmental model of regional (13)N-labeled molecular nitrogen ((13)NN) kinetics measured from positron emission tomography (PET) images. The model features a compartment for right heart and pulmonary vasculature and two compartments for each region of interest: 1) aerated alveolar units and 2) alveolar units with no gas content (shunting). The model was tested on PET data from normal animals (dogs and sheep) and from animals with experimentally injured lungs simulating acute respiratory distress syndrome. The analysis yielded estimates of regional perfusion, shunt fraction, and specific ventilation with excellent goodness-of-fit to the data (R(2) > 0.99). Model parameters were estimated to within 10% accuracy in the presence of exaggerated levels of experimental noise by using a Monte Carlo sensitivity analysis. Main advantages of the present model are that 1) it separates intraregional blood flow to aerated alveolar units from that shunting across nonaerated units and 2) it accounts and corrects for intraregional tracer removal by shunting blood when estimating ventilation from subsequent washout of tracer. The model was thus found to provide estimates of regional parameters of pulmonary function in sizes of lung regions that could potentially approach the intrinsic resolution for PET images of (13)NN in lung (approximately 7.0 mm for a multiring PET camera).     

Les examens cardiaques en tomographie par émission de positons

Cardiac positron emission tomography (PET) is yet considered as a reference imaging technique but remains poorly used in clinical practice. At the present time, the advantages of cardiac PET investigations are far to be evident, when compared with conventional tomoscintigraphy (SPECT), except for perfusion imaging in the obese and for viability assessment in case of very severe cardiac dysfunction. However, this situation might quickly move because of an enhanced availability of PET imaging, dramatic technical progresses and promising new tracers. In particular, the last-generation PET-cameras allow reaching spatial resolutions and detection sensitivities, which are now spectacularly higher than those from conventional SPECT imaging. In addition, the list mode recording allows the subsequent images reconstruction to be synchronized to cardiac cycle but also to respiratory cycle; and the quantifications of myocardial perfusion flow and of coronary flow reserve are now available in clinical routine. Furthermore, new tracers labelled with fluorine-18 are under development, especially for perfusion investigations, and kinetics properties of these new tracers are dramatically enhanced when compared with current perfusion SPECT tracers.     

Ventilation distribution in rats: Part I - The effect of gas composition as measured with electrical impedance tomography

ABSTRACT: The measurement of ventilation distribution is currently performed using inhaled tracer gases for multiple breath inhalation studies or imaging techniques to quantify spatial gas distribution. Most tracer gases used for these studies have properties different from that of air. The effect of gas density on regional ventilation distribution has not been studied. This study aimed to measure the effect of gas density on regional ventilation distribution. METHODS: Ventilation distribution was measured in seven rats using electrical impedance tomography (EIT) in supine, prone, left and right lateral positions while being mechanically ventilated with either air, heliox (30% oxygen, 70% helium) or sulfur hexafluoride (20% SF6, 20% oxygen, 60% air). The effect of gas density on regional ventilation distribution was assessed. RESULTS: Gas density did not impact on regional ventilation distribution. The non-dependent lung was better ventilated in all four body positions. Gas density had no further impact on regional filling characteristics. The filling characteristics followed an anatomical pattern with the anterior and left lung showing a greater impedance change during the initial phase of the inspiration. CONCLUSION: It was shown that gas density did not impact on convection dependent ventilation distribution in rats measured with EIT.     

Ventilation distribution in rats: Part 2 -- A comparison of electrical impedance tomography and hyperpolarised helium magnetic resonance imaging

ABSTRACT: BACKGROUND: Hyperpolarised helium MRI (He3 MRI) is a new technique that enables imaging of the air distribution within the lungs. This allows accurate determination of the ventilation distribution in vivo. The technique has the disadvantages of requiring an expensive helium isotope, complex apparatus and moving the patient to a compatible MRI scanner. Electrical impedance tomography (EIT) a non-invasive bedside technique that allows constant monitoring of lung impedance, which is dependent on changes in air space capacity in the lung. We have used He3MRI measurements of ventilation distribution as the gold standard for assessment of EIT. METHODS: Seven rats were ventilated in supine, prone, left and right lateral position with 70% helium/30% oxygen for EIT measurements and pure helium for He3 MRI. The same ventilator and settings were used for both measurements. Image dimensions, geometric centre and global in homogeneity index were calculated. RESULTS: EIT images were smaller and of lower resolution and contained less anatomical detail than those from He3 MRI. However, both methods could measure positional induced changes in lung ventilation, as assessed by the geometric centre. The global in homogeneity index were comparable between the techniques. CONCLUSION: EIT is a suitable technique for monitoring ventilation distribution and inhomgeneity as assessed by comparison with He3 MRI.     

Assessment of Regional Ventilation Distribution: Comparison of Vibration Response Imaging (VRI) with Electrical Impedance Tomography (EIT)

Background

Vibration response imaging (VRI) is a bedside technology to monitor ventilation by detecting lung sound vibrations. It is currently unknown whether VRI is able to accurately monitor the local distribution of ventilation within the lungs. We therefore compared VRI to electrical impedance tomography (EIT), an established technique used for the assessment of regional ventilation.

Methodology/Principal Findings

Simultaneous EIT and VRI measurements were performed in the healthy and injured lungs (ALI; induced by saline lavage) at different PEEP levels (0, 5, 10, 15 mbar) in nine piglets. Vibration energy amplitude (VEA) by VRI, and amplitudes of relative impedance changes (rel.ΔZ) by EIT, were evaluated in seven regions of interest (ROIs). To assess the distribution of tidal volume (V_T) by VRI and EIT, absolute values were normalized to the V_T obtained by simultaneous spirometry measurements. Redistribution of ventilation by ALI and PEEP was detected by VRI and EIT. The linear correlation between pooled V_T by VEA and rel.ΔZ was R² = 0.96. Bland-Altman analysis showed a bias of −1.07±24.71 ml and limits of agreement of −49.05 to +47.36 ml. Within the different ROIs, correlations of V_T-distribution by EIT and VRI ranged between R² values of 0.29 and 0.96. ALI and PEEP did not alter the agreement of V_T between VRI and EIT.

Conclusions/Significance

Measurements of regional ventilation distribution by VRI are comparable to those obtained by EIT.     

Regional trapping of microspheres in the lung compares well with regional blood flow

Microspheres (MS) are often used to measure the distribution of pulmonary blood flow in the assumption that the number of MS trapped in a region is proportional to blood flow. However, regional distribution of trapped MS has not been directly compared with regional blood flow in the lung. Regional trapping of MS was compared with regional flow of erythrocytes (RBC's) in isolated, perfused left lungs of dogs. Radioactivity from labeled MS and RBC's was measured by external detection using a gamma camera. We defined six regions of interest in the image of the left lateral surface of the lung: a dorsocaudal, a caudal, two ventral, an apical, and a central region. In each lung, regional trapping of MS was measured from the image of radioactivity obtained after slow injection of a suspension of MS into the arterial perfusion tubing. A radioactive bolus of labeled RBC's was injected during rapid imaging of the lung to obtain radioactivity vs. time curves from each region. The peaks of the regional radioactivity vs. time curves were used to estimate regional flows, though compensation had to be made for overlap of the washout and washin phases of the bolus of labeled RBC's. The results indicated that there were no differences in the regional distribution of MS compared with the regional distribution of RBC flow in isolated, perfused dog lungs.     

Monitoring changes in lung air and liquid volumes with electrical impedance tomography

Adler, A., R. Amyot, R. Guardo, J. H. T. Bates, and Y. Berthiaume. Monitoring changes in lung air and liquid volumes withelectrical impedance tomography. J. Appl.Physiol. 83(5): 1762-1767, 1997.Electricalimpedance tomography (EIT) uses electrical measurements at electrodesplaced around the thorax to image changes in the conductivitydistribution within the thorax. This technique is well suited tostudying pulmonary function because the movement of air, blood, andextravascular fluid induces significant conductivity changes within thethorax. We conducted three experimental protocols in a total of 19 dogsto assess the accuracy with which EIT can quantify changes in thevolumes of both gas and fluid in the lungs. In the first protocol, lungvolume increments from 50 to 1,000 ml were applied with a largesyringe. EIT measured these volume changes with an average error of 27 ± 6 ml. In the second protocol, EIT measurements were made at endexpiration and end inspiration during regular ventilation with tidalvolume ranging from 100 to 1,000 ml. The average error in the EITestimates of tidal volume was 90 ± 43 ml. In the third protocol,lung liquid volume was measured by instilling 5% albumin solution intoa lung lobe in increments ranging from 10 to 100 ml. EIT measured thesevolume changes with an average error of 10 ± 10 ml and was alsoable to detect into which lobe the fluid had been instilled. These results indicate that EIT can noninvasively measure changes in thevolumes of both gas and fluid in the lungs with clinically usefulaccuracy.

     

Imaging regional PAO2 and gas exchange

Several methods allow regional gas exchange to be inferred from imaging of regional ventilation and perfusion (V/Q) ratios. Each method measures slightly different aspects of gas exchange and has inherent advantages and drawbacks that are reviewed. Single photon emission computed tomography can provide regional measure of ventilation and perfusion from which regional V/Q ratios can be derived. PET methods using inhaled or intravenously administered nitrogen-13 provide imaging of both regional blood flow, shunt, and ventilation. Electric impedance tomography has recently been refined to allow simultaneous measurements of both regional ventilation and blood flow. MRI methods utilizing hyperpolarized helium-3 or xenon-129 are currently being refined and have been used to estimate local PaO(2) in both humans and animals. Microsphere methods are included in this review as they provide measurements of regional ventilation and perfusion in animals. One of their advantages is their greater spatial resolution than most imaging methods and the ability to use them as gold standards against which new imaging methods can be tested. In general, the reviewed methods differ in characteristics such as spatial resolution, possibility of repeated measurements, radiation exposure, availability, expensiveness, and their current stage of development.     

Mechanical strain promotes osteoblast ECM formation and improves its osteoinductive potential

Background

Hyperpolarised helium MRI (He3 MRI) is a new technique that enables imaging of the air distribution within the lungs. This allows accurate determination of the ventilation distribution in vivo. The technique has the disadvantages of requiring an expensive helium isotope, complex apparatus and moving the patient to a compatible MRI scanner. Electrical impedance tomography (EIT) a non-invasive bedside technique that allows constant monitoring of lung impedance, which is dependent on changes in air space capacity in the lung. We have used He3MRI measurements of ventilation distribution as the gold standard for assessment of EIT.

Methods

Seven rats were ventilated in supine, prone, left and right lateral position with 70% helium/30% oxygen for EIT measurements and pure helium for He3 MRI. The same ventilator and settings were used for both measurements. Image dimensions, geometric centre and global in homogeneity index were calculated.

Results

EIT images were smaller and of lower resolution and contained less anatomical detail than those from He3 MRI. However, both methods could measure positional induced changes in lung ventilation, as assessed by the geometric centre. The global in homogeneity index were comparable between the techniques.

Conclusion

EIT is a suitable technique for monitoring ventilation distribution and inhomgeneity as assessed by comparison with He3 MRI.     

Vertical gradients in regional lung density and perfusion in the supine human lung: the Slinky effect.

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

Eicosanoid balance and perfusion redistribution of oleic acid-induced acute lung injury.

We have proposed that endogenous prostacyclin opposes the vasoconstriction responsible for redistribution of regional pulmonary blood flow (rPBF) away from areas of increased regional lung water concentration (rLWC) in canine oleic acid- (OA) induced acute lung injury (D. P. Schuster and J. Haller. J. Appl. Physiol. 69: 353-361, 1990). To test this hypothesis, we related regional lung tissue concentrations of 6-ketoprostaglandin (PG) F1 alpha and thromboxane (Tx) B2 in tissue samples obtained 2.5 h after administration of OA (0.08 ml/kg iv) to rPBF and rLWC measured by positron emission tomography. After OA only (n = 16), rLWC increased in dependent lung regions. Some animals responded to increased rLWC by redistribution of rPBF away from the most edematous regions (OA-R, n = 6), whereas others did not (OA-NR, n = 10). In another six animals, meclofenamate was administered after OA (OA-meclo). After OA, tissue concentrations of 6-keto-PGF1 alpha were greater than TxB2 in all groups, but concentrations of 6-keto-PGF1 alpha were not different between OA-R and OA-NR animals. TxB2 was increased in the dependent regions of animals in both OA-R and OA-NR groups compared with controls (no OA, n = 4, P < 0.05). The tissue TxB2/6-keto-PGF1 alpha ratio was smaller in controls and OA-NR in which no perfusion redistribution occurred than in OA-R and OA-meclo in which it did occur. This TxB2/6-keto-PGF1 alpha ratio correlated significantly with the magnitude of perfusion redistribution.(ABSTRACT TRUNCATED AT 250 WORDS)     

Marked differences between prone and supine sheep in effect of PEEP on perfusion distribution in zone II lung.

The classic four-zone model of lung blood flow distribution has been questioned. We asked whether the effect of positive end-expiratory pressure (PEEP) is different between the prone and supine position for lung tissue in the same zonal condition. Anesthetized and mechanically ventilated prone (n = 6) and supine (n = 5) sheep were studied at 0, 10, and 20 cm H2O PEEP. Perfusion was measured with intravenous infusion of radiolabeled 15-microm microspheres. The right lung was dried at total lung capacity and diced into pieces (approximately 1.5 cm3), keeping track of the spatial location of each piece. Radioactivity per unit weight was determined and normalized to the mean value for each condition and animal. In the supine posture, perfusion to nondependent lung regions decreased with little relative perfusion in nondependent horizontal lung planes at 10 and 20 cm H2O PEEP. In the prone position, the effect of PEEP was markedly different with substantial perfusion remaining in nondependent lung regions and even increasing in these regions with 20 cm H2O PEEP. Vertical blood flow gradients in zone II lung were large in supine, but surprisingly absent in prone, animals. Isogravitational perfusion heterogeneity was smaller in prone than in supine animals at all PEEP levels. Redistribution of pulmonary perfusion by PEEP ventilation in supine was largely as predicted by the zonal model in marked contrast to the findings in prone. The differences between postures in blood flow distribution within zone II strongly indicate that factors in addition to pulmonary arterial, venous, and alveolar pressure play important roles in determining perfusion distribution in the in situ lung. We suggest that regional variation in lung volume through the effect on vascular resistance is one such factor and that chest wall conformation and thoracic contents determine regional lung volume.     

Pulmonary blood flow affects recovery from constriction in dog lung periphery

The influence of blood flow through the pulmonary circulation on the time course of recovery of the lung periphery from challenge with three bronchoconstrictive agents was studied in dogs. The rate of perfusion of the left lower lobe was varied between 0 and 300 ml/min. A fiber-optic bronchoscope (OD = 5.5 mm) was wedged in a small airway in the same lobe, and resistance to airflow through the collateral system was continuously monitored. The lung was challenged with histamine aerosol for 1 min, or with intravenous boluses of histamine, acetylcholine, or methacholine. The time constant (tau) of recovery from each of the challenges was measured under the various pulmonary blood flow conditions. The mean tau of the recoveries from histamine was inversely related to the rate of blood flow. However, pulmonary blood flow had no effect on recovery from challenge with acetylcholine or methacholine, two agents metabolized by cholinesterase in lung tissue. From this study we conclude that recovery of the lung periphery from histamine is perfusion dependent, whereas recovery from acetylcholine or methacholine is perfusion independent. This suggests that the rate of blood flow through the pulmonary circulation could play an important role in recovery of the peripheral airways from certain mediators of bronchoconstriction.     

Regional VA, Q, and VA/Q during PLV: effects of nitroprusside and inhaled nitric oxide.

Partial liquid ventilation (PLV) with high-specific-weight perfluorocarbon liquids has been shown to improve oxygenation in acute lung injury, possibly by redistributing perfusion from dependent, injured regions to nondependent, less injured regions of the lung. Our hypothesis was that during PLV in normal lungs, a shift in perfusion away from dependent lung zones might, in part, be due to vasoconstriction that could be reversed by infusing sodium nitroprusside (NTP). In addition, delivering inhaled NO during PLV should improve gas exchange by further redistributing blood flow to well-ventilated lung regions. To examine this, we used a single transverse-slice positron emission tomography camera to image regional ventilation and perfusion at the level of the heart apex in six supine mechanically ventilated sheep during five conditions: control, PLV, PLV + NTP, and PLV + NO at 10 and 80 ppm. We found that PLV shifted perfusion from dependent to middle regions, and the dependent region demonstrated marked hypoventilation. The vertical distribution of perfusion changed little when high-dose intravenous NTP was added during PLV, and inhaled NO tended to shift perfusion toward better ventilated middle regions. We conclude that PLV shifts perfusion to the middle regions of the lung because of the high specific weight of perflubron rather than vasoconstriction.