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The regional distribution of inflammation during Acute Lung Injury (ALI) is not well known. In an ovine ALI model we studied regional alveolar inflammation, surfactant composition, and CT-derived regional specific volume change (sVol) and specific compliance (sC). 18 ventilated adult sheep received IV lipopolysaccharide (LPS) until severe ALI was achieved. Blood and bronchoalveolar lavage (BAL) samples from apical and basal lung regions were obtained at baseline and injury time points, for analysis of cytokines (IL-6, Il-1 β), BAL protein and surfactant composition. Whole lung CT images were obtained in 4 additional sheep. BAL protein and IL-1 were β significantly higher in injured apical vs. basal regions. No significant regional surfactant composition changes were observed. Baseline sVol and sC were lower in apex vs. base; ALI enhanced this cranio-caudal difference, reaching statistical significance only for sC. This study suggests that apical lung regions show greater inflammation than basal ones during IV LPS-induced ALI which may relate to differences in regional mechanical events.

Computer tomography (CT) imaging techniques permit the noninvasive measurement of regional lung function. Regional specific volume change (sVol), determined from the change in lung density over a tidal breath, should correlate with regional ventilation and regional lung expansion measured with other techniques. sVol was validated against xenon (Xe)-CT-specific ventilation (sV̇) in four anesthetized, intubated, mechanically ventilated sheep. Xe-CT used expiratory gated axial scanning during the washin and washout of 55% Xe. sVol was measured from the tidal changes in tissue density (H, houndsfield units) of lung regions using the relationship sVol = [1,000(Hi − He)]/[He(1,000 + Hi)], where He and Hi are expiratory and inspiratory regional density. Distinct anatomical markings were used to define corresponding lung regions of interest between inspiratory, expiratory, and Xe-CT images, with an average region of interest size of 1.6 ± 0.7 ml. In addition, sVol was compared with regional volume changes measured directly from the positions of implanted metal markers in an additional animal. A linear relationship between sVol and sV̇ was demonstrated over a wide range of regional sV̇ found in the normal supine lung, with an overall correlation coefficient ( R2) of 0.66. There was a tight correlation ( R2 = 0.97) between marker-measured volume changes and sVol. Regional sVol, which involves significantly reduced exposure to radiation and Xe gas compared with the Xe-CT method, represents a safe and efficient surrogate for measuring regional ventilation in experimental studies and patients.

ECG-triggered computed tomography (CT) was used during passage of iodinated contrast to determine regional pulmonary blood flow (PBF) in anesthetized prone/supine dogs. PBF was evaluated as a function of height within the lung (supine and prone) as a function of various normalization methods: raw unit volume data (PBFraw) or PBF normalized to regional fraction air (PBFair), fractional non-air (PBFgm), or relative number of alveoli (PBFalv). The coefficient of variation of PBFraw, PBFair, PBFalv, and PBFgm ranged between 30 and 50% in both lungs and both body postures. The position of maximal flow along the height of the lung (MFP) was calculated for PBFraw, PBFair, PBFalv, and PBFgm. Only PBFgm showed a significantly different MFP height supine vs. prone (whole lung: 2.60 ± 1.08 cm supine vs. 5.08 ± 1.61 cm prone, P < 0.01). Mean slopes (ml/min/gm water content/cm) of PBFgm were steeper supine vs. prone in the right (RL) but not left lung (LL) (RL: −0.65 ± 0.29 supine vs. −0.26 ± 0.25 prone, P < 0.02; LL: −0.47 ± 0.21 supine vs. −0.32 ± 0.26 prone, P > 0.10). Mean slopes of PBFgm vs. vertical lung height were not different prone vs. supine above this vertical height of MFP (VMFP), but PBFgm slopes were steeper in the supine position below the VMFP in the RL. We conclude that PBFgm distribution was posture dependent in RL but not LL. Support of the heart may play a role. We demonstrate that normalization factors can lead to differing attributions of gravitational effects on PBF heterogeneity.

Rationale and Objectives: We seek to establish lung imaging methods which provide for the ability to image the lung under dynamic, non-breath hold conditions while providing “virtual breath hold,” quantifiable volumetric image data sets. We use static, breath hold images as the gold standard for evaluating these virtual breath hold images in both a phantom and sheep. Materials and Methods: We have developed axial methods for gating image acquisition to multiple points in the respiratory cycle interleaved with incremental table stepping during multidetector-row CT (MDCT) scanning. Datasets are generated over multiple breaths, providing volume images representative of multiple points within a respiratory cycle. To determine the reproducibility and accuracy of the methods , 6 anesthetized sheep were studied by MDCT in non-gated and airway-pressure (Pawy)-gated modes where Pawy was 0, 7 and 15 cmH2O. Results: No significant differences were found between the coefficient of variation in air volume measured from repeated static scans (1.74±1.78%), gated scans: Inspiratory gated (1.2±0.44%) or expiratory-gated (1.39±0.98%), or between static (1.74±1.78%) and gated (1.39+/-0.98%) scanning at similar Pawy (p>0.1). Measured air volumes were larger from static vs. gated scans by 5.85±3.77% at 7cmH2O and 4.45±3.6% at 15cmHL2O Pawy (p

Rationale and Objectives. Efforts to establish a quantitative approach to the computed tomography (CT)-based characterization of the lung parenchyma in interstitial lung disease (including emphysema) has been sought. The accuracy of these tools must be site independent. Multi-detector row CT has remained the gold standard for imaging the lung, and it provides the ability to image both lung structure as well as lung function. Material and Methods. Imaging is via multi-detector row CT and protocols include careful control of lung volume during scanning. Characterization includes not only anatomic-based measures but also functional measures including regional parameters derived from measures of pulmonary blood flow and ventilation. Image processing includes the automated detection of the lungs, lobes, and airways. The airways provide the road map to the lung parenchyma. Software automatically detects the airways, the airway centerlines, and the branch points, and then automatically labels the airway tree segments with a standardized set of labels, allowing for intersubject as well intrasubject comparisons across time. By warping all lungs to a common atlas, the atlas provides the range of normality for the various parameters provided by CT imaging. Results. Imaged density and textural changes mark underlying structural changes at the most peripheral regions of the lung. Additionally, texture-based alterations in the parameters of blood flow may provide early evidence of pathologic processes. Imaging of stable xenon gas provides a regional measure of ventilation which, when coupled with measures of flow, provide for a textural analysis regional of ventilation-perfusion matching. Conclusion. With the improved resolution and speed of CT imaging, the patchy nature of regional parenchymal pathology can be imaged as texture of structure and function. With careful control of imaging protocols and the use of objective image analysis methods it is possible to provide site-independent tools for the assessment of interstitial lung disease. There remains a need to validate these methods, which requires interdisciplinary and cross-institutional efforts to gather appropriate data bases of images along with a consensus on appropriate ground truths associated with the images. Furthermore, there is the growing need for scanner manufacturers to focus on not just visually pleasing images, but on quantitatifiably accurate images.

Xenon computed tomography (Xe-CT) is used to estimate regional ventilation by measuring regional attenuation changes over multiple breaths while rebreathing a constant Xe concentration ([Xe]). Xe-CT has potential human applications, although anesthetic properties limit [Xe] to ≤35%. We investigate effects of lower [Xe], including a low [Xe]-krypton (Kr) combination, on time constant (TC) determination. Six anesthetized sheep were scanned prone and supine using multidetector row CT. Lungs were imaged by respiratory gating during washin of a 30%, 40%, 55% Xe, and a 30% Xe/30% Kr mixture. Using Kr avoids unwanted effects of Xe. Mean TCs, coefficients of variation (CV), and half confidence intervals (CI)/mean served as indexes of sensitivity to noise. Mean supine and prone TCs of three [Xe] values were not significantly different. Average CVs of TCs increased from 57% (55% Xe), 58% (40% Xe), and 73% (30% Xe) ( P < 0.05: paired t-tests; 30% Xe vs. higher [Xe]). Monte Carlo simulation indicated a CV based on inherent image noise was 8% for 55% Xe and 17% for 30% Xe ( P < 0.05). Adding 30% Kr to 30% Xe gave a washin signal equivalent to 40% Xe. Half CI/mean using the 30% Xe/30% Kr mixture was not significantly different from 55 and 40% Xe. Although average TCs were not affected by changes in [Xe], the higher CV and half CI/mean suggested reduced signal-to-noise ratio at the 30% [Xe]. The 30% Xe/30% Kr mixture was comparable to that of 40% Xe, providing an important agent for CT-based assessment of regional ventilation in humans.

With the emergence of multidetector-row computed tomography (CT) it is now possible to image both structure and function via use of a single imaging modality. Breath-hold spiral CT provides detail of the airway and vascular trees along with texture reflective of the state of the lung parenchyma. Use of stable xenon gas wash-in and/or wash-out methods using an axial mode of the CT scanner whereby images are acquired through gating to the respiratory cycle provide detailed images of regional ventilation with isotropic voxel dimensions now on the order of 0.4 mm. Axial scanning during a breath hold and gating to the electrocardiogram during the passage of a sharp bolus injection of iodinated contrast agent provide detailed images of regional pulmonary perfusion. These dynamic CT methods for the study of regional lung function are discussed in the context of other methods that have been used to study heterogeneity of lung function.

The study's aim is to establish lung-imaging methods that provide for the ability to image the lung under dynamic non-breath hold conditions while providing "virtual breath hold" quantifiable volumetric image data sets. Static breath hold images are used as the gold standard for evaluating these virtual breath hold images in both a phantom and sheep.Axial methods for gating image acquisition to multiple points in the respiratory cycle interleaved with incremental table stepping during multidetector-row computed tomographic (MDCT) scanning were developed. Data sets are generated over multiple breaths, providing volume images representative of multiple points within a respiratory cycle. To determine the reproducibility and accuracy of the methods, six anesthetized sheep were studied by means of MDCT in nongated and airway-pressure (P(awy))-gated modes in which P(awy) was 0, 7, and 15 cm H2O.No significant differences were found between coefficients of variation in air volume measured from repeated static scans (1.74% +/- 1.78%), gated scans: inspiratory (1.2% +/- 0.44%) or expiratory gated (1.39% +/- 0.98%), or between static (1.74% +/- 1.78%) and gated (1.39% +/- 0.98%) scanning at similar P(awy) (P.1). Measured air volumes were larger from static versus gated scans by 5.85% +/- 3.77% at 7 cm H2O and 4.45% +/- 3.6% at 15 cm H2O of P(awy) (P.05), consistent with hysteresis. Differences between air volumes at 7 and 15 cm H2O measured from either static or gated scans or that delivered by a super syringe were insignificant (P.05). Visual accuracy of three-dimensional anatomic geometry was achieved, and landmark certainty was within 1 mm across respiratory cycles.A method has been shown that provides for accurate gating to respiratory signals during axial scanning. High-resolution volumetric image data sets are achievable while the scanned subject is breathing. Images are quantitatively similar to breath hold images, with differences likely explained by known pressure-volume hysteresis effects.

Xenon-enhanced computed tomography (Xe-CT) has been used to measure regional ventilation by determining the wash-in (WI) and wash-out (WO) rates of stable Xe. We tested the common assumption that WI and WO rates are equal by measuring WO–WI in different anatomic lung regions of six anesthetized, supine sheep scanned using multi-detector-row computed tomography (MDCT). We further investigated the effect of tidal volume, image gating (end-expiratory EE versus end-inspiratory EI), local perfusion, and inspired Xe concentration on this phenomenon. Results: WO time constant was greater than WI in all lung regions, with the greatest differences observed in dependent base regions. WO–WI time constant difference was greater during EE imaging, smaller tidal volumes, and with higher Xe concentrations. Regional perfusion did not correlate with WI–WO. We conclude that Xe-WI rate can be significantly different from the WO rate, and the data suggest that this effect may be due to a combination of anatomic and fluid mechanical factors such as Rayleigh–Taylor instabilities set up at interfaces between two gases of different densities.

Regional lung ventilation can be measured via Xenon-enhanced computed tomography (Xe-CT) by determining washin (WI) and washout (WO) rates of stable Xe. It has been assumed that WI = WO, ignoring Xe solubility in blood and tissue and then other geometric isssues. We test this by measuring WO-WI in lung by Xe-CT. Also, we investigate the effect of tidal volume (TV) and end inspiratory (EI) vs end expiratory (EE) scan gating on WO and WI measurements. 3 anesthetized, supine sheep were scanned using multidetector-row computed tomography (MDCT). Imaging was gated to both EE and EI during a WI (33 breaths) and WO (20 breaths) maneuver using 55% Xe for WI and room air for WO. Time constants (TCs) of Xe WI and WO were obtained by exponential fitting. WO and WI TCs were compared: 1) apex and base 2) dependent, middle, and nondependent 3) EE and EI 4) three TVs. The vertical gradient of WO-WI showed WO > WI in dependent vs non-dependent regions. WO-WI in both dependent and nondependent region at the lung base and apex was larger when measured at EE compared to EI. As TV increases, the global WO-WI difference decreased. TV showed greater influence on WO than WI. Xe WO was longer than WI possibly reflecting Xe solubility in blood and tissue. Higher TVs and gating to EE provided greater effects on WO than WI TCs which may relate to the number of partial volumed conducting airways contributing to the regional voxel-based measures. We conclude that WO mode is more susceptible to errors caused by either xenon solubility or tidal volume than WI mode and EE scanning may more accurately reflect alveolar ventilation.

Efforts to establish a quantitative approach to the computed tomography (CT)-based character ization of the lung parenchyma in interstitial lung disease (including emphysema) has been sought. The accuracy of these tools must be site independent. Multi-detector row CT has remained the gold standard for imaging the lung, and it provides the ability to image both lung structure as well as lung function.Imaging is via multi-detector row CT and protocols include careful control of lung volume during scanning. Characterization includes not only anatomic-based measures but also functional measures including regional parameters derived from measures of pulmonary blood flow and ventilation. Image processing includes the automated detection of the lungs, lobes, and airways. The airways provide the road map to the lung parenchyma. Software automatically detects the airways, the airway centerlines, and the branch points, and then automatically labels the airway tree segments with a standardized set of labels, allowing for intersubject as well intrasubject comparisons across time. By warping all lungs to a common atlas, the atlas provides the range of normality for the various parameters provided by CT imaging.Imaged density and textural changes mark underlying structural changes at the most peripheral regions of the lung. Additionally, texture-based alterations in the parameters of blood flow may provide early evidence of pathologic processes. Imaging of stable xenon gas provides a regional measure of ventilation which, when coupled with measures of flow, provide for a textural analysis regional of ventilation-perfusion matching.With the improved resolution and speed of CT imaging, the patchy nature of regional parenchymal pathology can be imaged as texture of structure and function. With careful control of imaging protocols and the use of objective image analysis methods it is possible to provide site-independent tools for the assessment of interstitial lung disease. There remains a need to validate these methods, which requires interdisciplinary and cross-institutional efforts to gather appropriate data bases of images along with a consensus on appropriate ground truths associated with the images. Furthermore, there is the growing need for scanner manufacturers to focus on not just visually pleasing images, but on quantitatifiably accurate images.

To determine regional pulmonary microvascular mean transit times (MTTs), we used electrocardiogram-gated X-ray computed tomographic imaging to follow bolus radiopaque contrast material through the lungs in anesthetized animals (7 dogs and 1 pig, prone and supine). By deconvolution/reconvolution of regional time-attenuation curves obtained from parenchyma and large lobar arteries, we estimated the microvascular residue function and reconstituted the regional microvascular time-attenuation curves and, thus, regional microvascular MTTs. The mean microvascular MTTs in the supine and prone postures were 3.94 ± 1.0 and 3.40 ± 0.84 (mean ± SD), respectively. The dependent-nondependent vertical gradient of MTT was greater in the supine [slope = 0.25 ± 0.10 (SD), P < 0.001 by t-test] than in the prone (−0.03 ± 0.06 in 6 of 8 animals; 2 outliers had positive slopes) posture. In both postures, there was a trend toward faster transit times in the dorsal-basal lung region in six of the eight animals, suggesting gravity-independent higher vascular conductance dorsocaudally. We conclude that deconvolution methods, in association with electrocardiogram-gated high-speed X-ray computed tomography, can provide insights into regional heterogeneity of pulmonary microvascular MTT in vivo.

Rationale and Objectives To evaluate the adequacy of multibreath and single-breath stable xenon gas techniques to measure regional ventilation during cardiac-gated, high-speed, multisection imaging, the authors carried out a series of studies using electron-beam computed tomography (CT) and a recently introduced subsecond multisection spiral CT scanner. Materials and Methods In four anesthetized pigs, the authors implemented single-breath and/or dynamic multibreath wash-in and washout protocols with respiratory- and cardiac-gated image acquisition. The effects of varying tidal volume and inspiratory flow rate were evaluated independently. Scanning was done at end expiration to avoid artifacts from partial volumed conducting airways, which are filled with inspired gas concentration during inspiration. Results A single breath of 100% xenon provides adequate enhancement in the lung parenchyma (mean, 32 HU ± 1.85 [standard error]) and should not cause unwanted side effects (mean xenon concentration in lung periphery, 21%). The single-breath method is suitable for studies requiring only short periods of apnea. Using the multibreath method, in dependent portions of the lung, there was close agreement between measured changes and predictions based on the xenon calibration data. More than 10 breaths were needed to clear tracer from poorly ventilated areas, and some nondependent regions demonstrated apparently “linear” rather than exponential clearance curves, possibly reflecting longer washout times. Analysis of wash-in and washout curves revealed vertical ventilation gradients and, at higher inspiratory flow rates, redistribution of ventilation to areas of the lung with greater pathway conductance. Conclusion With careful attention to lung volume and use of cardiac gating, it is now possible to correlate lung structure with function to a degree heretofore not possible.