In Vivo Characterization of the Swine Airway Morphometry and Motion Based on Computed Tomographic Imaging During Respiration

Abstract

Swine are a commonly used model in translational pulmonary research. However, in vivo airway morphometry during respiration has not been studied in extensive detail using modern imaging tools. Chest computed tomographic was performed in swine (n = 3) at multiple stages of respiration. Morphometric parameters of each airway segment at end-expiration and end-inspiration were compared as well as among matched anatomical regions (proximal and distal; ventral, lateral, and dorsal). Analysis included segment diameter, length, ellipticity, and the bifurcation angle between daughter branches. Deformation of the airway during respiration was qualitatively visualized using a point-to-point deformation map. Comparison of airway generation showed airway diameter and length were larger at end-inspiration in the fourth and seventh generations compared to end-expiration. Bifurcation angle was larger at end-inspiration compared to end-expiration. Analysis by anatomical region showed that length and bifurcation angle were larger at inspiration in the distal airway regions only. Regardless of respiratory phase, the lateral regions had larger diameters and lengths compared to the ventral and dorsal regions at similar generations and proximal regions had larger bifurcation angles. The findings that morphological changes were more prevalent in distal airways during respiration was confirmed by analysis of a deformation map. Compared to human airway models, the relative diameter may be smaller and length may be greater in swine in similar airway generations. This morphometric description of the swine airways during respiration may guide conduct of preclinical translational studies, revealing advantages and limitations of swine models for specific evaluations. Such morphometric parameters may directly determine the suitability of the swine model for the study of lung interventions, in terms of recapitulation of human morphometry dynamics.

Introduction

Swine are a commonly used model for translational research [1–3]. Similarities between human and swine lung include a comparable number of bronchial generations, the general decrease in diameter and length with distal generations, and the highly lobulated lung with well-defined lobes [4–7]. Despite the value of swine as a translational model for pulmonary studies, the airway morphometry during respiration has not been well studied.

An understanding of swine airway and lung deformation during respiration may inform the planning and design of preclinical and translational studies. Previous work has assisted in device sizing and analysis [3], tumor tracking for radiotherapy planning [8], aerosol delivery [9,10], and in lung navigation for biopsy or therapy [11–14]. Preclinical studies provide a model to evaluate the safety and potential effectiveness of diagnostics and therapies for pulmonary disease. The provision of predictive data may support applications for regulatory approval of devices. Additionally, a clear understanding of the limitations of the model, gained through a comparative analysis of swine and human lung morphometry during respiration, may inform translational research in the swine model.

Prior postmortem studies have described and measured swine airway morphometry by analyzing casts after silicone rubber or celluloid solution injection into the airways in situ after thoracotomy or in excised lungs [5,7,15]. Such methods can measure up to the 24th generation but have potential shortcomings including material shrinkage, the inability to examine respiratory dynamics, and possible error from manual measurements. For in vivo measurements of the airways, anatomical optical coherence tomography has been proposed and has shown promise in an excised swine airway [16], and micro-computed tomographic (CT) has been shown to be able to capture distal airways in anesthetized piglets [6]. However, morphometry of the swine lung in vivo and during respiration has yet to be described in detail.

The purpose of this study was to characterize the morphometry of the airways in domestic swine and the changes that occurred during normal respiration. This study analyzed in vivo CT images of swine lungs over the respiratory cycle. The airways and lungs were segmented and morphological parameters were extracted and analyzed. Airway morphometry was studied during respiration at different bronchial generations, and in different anatomical regions of the lungs. Lastly, a preliminary relationship between swine and human airways was made by comparing this data to commonly accepted human airway models. These results defined dynamic changes in airway morphometry during respiration as well as significant similarity to human airway morphometry, especially in the distal airways.

Methods

Imaging Data.

Pre-existing chest CT scans of domestic swine (n = 3, 70–90 kg) were analyzed. The studies had been conducted under protocols approved by the Institutional Animal Care and Use Committee and with the animals under general anesthesia and mechanically ventilated. CT scans were performed on a Toshiba Aquilion ONE CT scanner at 120 kVp. Image reconstruction was performed with 0.5 mm slice thickness and pixel size of 0.509 × 0.509, 0.557 × 0.557, and 0.592 × 0.592 mm for swine A, B, and C, respectively. For each animal, a series of scans were acquired with fixed airway pressures from 0 to 35 cm H₂O, with stepwise increments of 5 cm H₂O for each scan. To analyze the respiratory cycle, two scans were compared: a scan at passive end-expiration (0 cm H₂O) and a scan closest to the physiologic lung volume at peak or end-inspiration (15 cm H₂O). Scans with higher pressures were not analyzed because they were higher than physiologic lung volume at end-inspiration.

Model Creation and Airway Segmentation.

Airways were segmented and analyzed in the Mimics Pulmonary Module (Materialise, Leuven, Belgium). Surface meshes, centerlines, and morphologic parameters were extracted (Fig. 1). During segmentation, each branch was manually edited to eliminate erroneous segments or obvious spurious features, or to connect gaps in branches where the segmentation failed. The manual edits were done while comparing the segmentation to the raw CT images. Nomenclature for the swine lung segments was adopted from Bauer et al. [6] and Nakakuki et al. [5] with each bronchial tree analyzed based on bronchial segments or anatomical region. The numbering of the order of each airway began at the carina with the mainstem bronchi as generation 1 and subsequent branches manually labeled as higher generations. Uniformity between the inspiration and expiration segmented geometries was assured by segmenting to the same airway generation. This resulted in the same number of segments and bifurcations in each geometry allowing for comparison. The anatomical regions of the lung were separated into ventral, lateral, and dorsal regions as well as proximal (airway generations 1 and 2) and distal regions (airway generations 3 and higher). The right cranial lobe that arises directly from the trachea was not included in the comparison of ventral, lateral, and dorsal regions, since this lobar origin is not present in humans.

Fig. 1.

Representative segmentation of swine lung, lobes, and airways. The airway centerlines and bifurcation points are shown in red: (a) right cranial lobe, (b) right medial lobe, (c) right caudal, (d) left cranial/bilobed middle lobe, and (e) left caudal lobe.

Morphological Analysis of the Airways.

To analyze the deformation that occurs over the respiratory cycle, morphological parameters from the paired expiration and inspiration scans for each animal were compared. Parameters analyzed included diameter, D, the average diameter of the best fit circle along the centerline of the segment; length of the segment, L, the length of the centerline of the segment; the bifurcation angle, θ, the angle between the parent and daughter segments calculated from the center point of the parent to the daughter segments; and ellipticity, E, the difference between the long and short semi-axes of the airway divided by the long semiaxis. In addition, the deformation of the airways was calculated and visualized using the open-source software CloudCompare.3 The segmented airways were imported and registered using a built-in iterative closest point algorithm then manually adjusted to reflect the assumption that there was no deformation at the trachea and the carina. Normal vectors were projected from the center of each surface element of the baseline airway model (expiration) until it intersected with the surface of the deformed model (inspiration). The magnitude of the vector was calculated and defined as the deformation. To visually represent this deformation, a color map was projected onto the baseline airway model with red representing the largest magnitude or the largest deformation.

Statistical Analysis.

Comparison of morphological parameters, expiration, and inspiration scans, between swine was done using a two-way anova with repeated measures test. For comparison between three groups (specifically, dorsal, ventral, and lateral regions), a post hoc two-way ANOVA with repeated measures test was done to determine the difference between individual groups. Differences were considered statistically significant if p < 0.05.

Comparison to Human Airway Models.

A preliminary comparison to human airway models was accomplished by quantitatively comparing the diameter and length of airway segments observed at similar bronchial generations in the swine [4,17–19]. The combined human results are shown as the mean of the three models with error bars indicating the minimum and maximum values. These results are shown together with the analysis of the three swine models for comparison.

Results

Morphometry Versus Airway Generation.

Table 1 summarizes the swine lung morphometry relative to airway generation. Averages and standard deviations are shown but significance tests were not performed on the first airway generation because of the low degrees-of-freedom (df). Figure 2 shows the average diameter, length, ellipticity, and bifurcation angle of the airway generation for all three swine combined. The error bars represent the standard deviation. The diameter and length tend to decrease with increasing bronchial generations (Figs. 2(a) and 2(b)). When inspiration and expiration scans were compared, the diameters at expiration were smaller than at inspiration in the fourth generation only (D_exp = 4.0 ± 0.7 mm, D_insp = 4.6 ± 0.8 mm, p = 0.02). The segment lengths at expiration were smaller than at inspiration in the second generation (L_exp = 129 ± 15 mm, L_insp = 160 ± 7.6 mm, p = 0.003) and in the seventh generation (L_exp = 18 ± 12 mm, L_insp = 38 ± 11 mm, p = 0.02).

Table 1.

Swine lung morphometry versus airway generation

Diameter (mm)				Comparison between
Airway generation	Expiration	Inspiration		Respiratory phase	Swine
	Average ± SD	Average ± SD	% Change	p-Value	p-Value	df
1	13 ± 9.0	9.5 ± 3.0	2%	—	—	5
2	7.2 ± 1.3	7.1 ± 1.1	−2%	0.88	0.47	11
3	4.9 ± 1.1	5.5 ± 1.4	11%	0.11	0.07	47
4	4.0 ± 0.7	4.6 ± 0.8	12%	0.02*	0.04	35
5	3.8 ± 0.6	4.1 ± 0.8	8%	0.21	0.71	35
6	3.8 ± 0.6	4.0 ± 0.5	3%	0.66	0.82	17
7	3.6 ± 0.4	3.9 ± 0.3	7%	0.16	0.14	11
Length (mm)
Airway generation	Expiration	Inspiration		Respiratory phase	Swine
	Average ± SD	Average ± SD	% Change	p-Value	p-Value	df
1	66 ± 55	26 ± 18	−46%	—	—	5
2	129 ± 15	160 ± 7.6	−2%	0.003*	0.29	11
3	52 ± 33	52 ± 24	11%	0.95	0.61	47
4	47 ± 24	52 ± 25	12%	0.53	0.72	35
5	33 ± 21	40 ± 24	8%	0.42	0.96	35
6	31 ± 13	44 ± 18	3%	0.14	0.68	17
7	18 ± 12	38 ± 11	7%	0.02*	0.78	11
Bifurcation angle (deg)
Daughter Generation	Expiration	Inspiration		Respiratory phase	Swine
	Average ± SD	Average ± SD	% Change	p-Value	p-Value	df
2	53 ± 2	49 ± 3	−7%	-	-	5
3	46 ± 12	44 ± 13	−6%	0.52	0.93	47
4	57 ± 11	54 ± 15	−6%	0.55	0.42	29
5	32 ± 16	57 ± 18	44%	0.003*	0.96	23
6	25 ± 3.3	56 ± 16	55%	0.004*	0.72	11
7	25 ± 1.5	33 ± 23	12%	0.45	0.44	11
Ellipticity
Airway generation	Expiration	Inspiration		Respiratory phase	Swine
	Average ± SD	Average ± SD	% Change	p-Value	p-Value	df
1	0.57 ± 0.18	0.55 ± 0.17	3%	—	—	5
2	0.42 ± 0.02	0.48 ± 0.08	−13%	0.12	0.32	11
3	0.47 ± 0.06	0.45 ± 0.04	4%	0.23	0.96	47
4	0.45 ± 0.04	0.44 ± 0.04	1%	0.61	0.86	35
5	0.45 ± 0.03	0.43 ± 0.06	4%	0.26	0.59	35
6	0.43 ± 0.04	0.42 ± 0.04	2%	0.55	0.91	17
7	0.41 ± 0.04	0.43 ± 0.04	−5%	0.19	0.008*	11

^*p < 0.05.

Fig. 2.

Changes in swine airway diameter (a), length (b), bifurcation angle (c), and ellipticity (d) with respect to airway generation at expiration (blue) and inspiration (pink). Trend lines are shown and statistically significant differences between expiration and inspiration are indicated with brackets for the airway generations with sufficient degrees-of-freedom. A preliminary comparison to common human airway models is shown (gray).

After an initial increase between the third and fourth daughter airway generations, the bifurcation angle tended to decrease with increasing daughter airway generations (Fig. 2(c)). The bifurcation angles at expiration were smaller than during inspiration in the fifth generation (θ_exp = 32 ± 16 deg, θ_insp = 57 ± 18 deg, p = 0.003) and the sixth generation (θ_exp = 25 ± 3.3 deg, θ_insp = 56 ± 16 deg, p = 0.004).

There was no overall trend in ellipticity observed relative to bronchial generation (Fig. 2(d)) and there were no differences in ellipticity between expiration and inspiration. Across all measured parameters, there was no difference between swine except for the ellipticity in the seventh generation (p = 0.008), indicated that there was a difference in ellipticity between swine in only one instance.

Morphometry Versus Anatomical Lung Regions.

Table 2 summarizes the comparison of swine airway morphometry between different anatomical locations and between expiration and inspiration scans. A comparison between the anatomical regions, regardless of the respiratory phase, showed several differences. Figure 3 shows the average diameter, length, ellipticity, and bifurcation angle of the airways based on anatomical regions for all three swine combined. The error bars represent the standard deviation. The diameter (Fig. 3(a)) was found to be different between the lateral (D_lat = 5.0 ± 0.8 mm), dorsal (D_dor = 4.0 ± 0.9 mm), and ventral regions (D_vent = 4.0 ± 1.3 mm, overall p < 0.001). Post hoc tests showed that the lateral region had a larger diameter than the dorsal (p < 0.001) and ventral regions (p < 0.001), but there was no difference between the dorsal and ventral regions (p = 0.89). Likewise, the length (Fig. 3(b)) was different between the lateral (L_lat = 71 ± 20 mm), dorsal (L_dor = 26 ± 10 mm), and the ventral regions (L_vent = 29 ± 14 mm, overall p < 0.001). Post hoc tests showed that the lateral region had longer segment lengths compared to the dorsal (p < 0.001) and ventral regions (p < 0.001), but no difference between the dorsal and ventral regions (p = 0.26).

Table 2.

Swine lung morphometry versus anatomical region

Diameter (mm)			Comparison between
	Expiration	Inspiration	Anatomical region	Respiratory phase	Swine
	Average ± SD	Average ± SD	p-Value	p-Value	p-Value	df
Dorsal	3.8 ± 0.6	4.2 ± 1.1	<0.001a	0.11	0.94
Lateral	4.9 ± 0.8	5.2 ± 0.8		0.20
Ventral	3.8 ± 1.2	4.1 ± 1.5		0.44
Proximal	4.5 ± 1.1	5.0 ± 1.4	<0.001	0.13	0.51	135
Distal	3.7 ± 0.6	4.0 ± 0.6		0.11
Total	4.2 ± 1.0	4.5 ± 1.2	—	0.05	—	113
Length (mm)
	Expiration	Inspiration	Anatomical region	Respiratory phase	Swine
	Average ± SD	Average ± SD	p-Value	p-Value	p-Value	df
Dorsal	23 ± 9.7	28 ± 11	<0.001b	0.20	0.97	119
Lateral	68 ± 26	74 ± 13		0.41
Ventral	26 ± 12	32 ± 15		0.17
Proximal	47 ± 30	50 ± 25	<0.001	0.70	0.40	135
Distal	29 ± 18	39 ± 21		0.04
Total	39 ± 27	44 ± 25	—	0.07	—	113
Bifurcation angle (degrees)
	Expiration	Inspiration	Anatomical region	Respiratory phase	Swine
	Average ± SD	Average ± SD	p-Value	p-Value	p-Value	df
Dorsal	46 ± 20	56 ± 18	0.79	0.10	0.44	119
Lateral	50 ± 17	51 ± 16		0.86
Ventral	44 ± 17	53 ± 17		0.10
Proximal	54 ± 13	55 ± 15	<0.001	0.71	0.02	127
Distal	34 ± 18	49 ± 21		0.003
Total	46 ± 18	53 ± 17	—	0.04	—	113
Ellipticity
	Expiration	Inspiration	Anatomical region	Respiratory phase	Swine
	Average ± SD	Average ± SD	p-Value	p-Value	p-Value	df
Dorsal	0.43 ± 0.07	0.45 ± 0.05	0.13	0.25	0.59	119
Lateral	0.46 ± 0.03	0.46 ± 0.05		0.99
Ventral	0.43 ± 0.04	0.45 ± 0.05		0.25
Proximal	0.45 ± 0.03	0.46 ± 0.06	0.05	0.27	0.95	135
Distal	0.43 ± 0.06	0.44 ± 0.04		0.27
Total	0.44 ± 0.05	0.45 ± 0.05	—	0.16	—	113

^aPost hoc comparison tests: D_dor versus D_lat, p < 0.001; D_lat versus D_vent p < 0.001, D_dor versus D_vent, p = 0.89.

^bPost hoc comparison tests: L_dor versus L_lat, p < 0.001; L_lat versus L_vent, p < 0.001, L_dor versus L_vent, p = 0.26.

Fig. 3.

Summary of changes in swine airway diameter (a), length (b), bifurcation angle (c), and ellipticity (d) based on anatomical regions at expiration and inspiration. Statistically significant differences between anatomical regions are indicated with brackets.

When the airways were separated into proximal and distal regions, regardless of the respiratory phase, the diameter was found to be larger in the proximal airways (D_prox = 4.7 ± 1.3 mm) compared to the distal airways (D_dist = 3.9 ± 0.6 mm, p < 0.001). The length was found to be larger in the proximal airways (L_prox = 48 ± 27 mm) compared to the distal airways (L_dist = 34 ± 20 mm, p < 0.001). The bifurcation angles (Fig. 3(c)) were found to be larger in the proximal airways (θ_prox = 55 ± 13 deg) compared to the distal airways (θ_dist = 41 ± 17 deg, p < 0.001). No differences in ellipticity were found between any anatomical regions (Fig. 3(d)).

When analyzing the differences between expiration and inspiration scans in different anatomical regions (Fig. 3), the length of segments was found to be smaller at expiration (L_exp/dist = 29 ± 18 mm) compared to inspiration (L_insp/dist = 39 ± 21 mm) in the distal airways only (p = 0.04). Likewise, the bifurcation angles were found to be smaller at expiration (θ_dist = 34 ± 18 deg) compared to inspiration (θ_dist = 49 ± 21 deg) in the distal airways only (p = 0.003). No differences were found between respiratory phases when the airways were examined by the dorsal, lateral, and ventral regions.

Overall Deformation.

When examining the difference in morphologic features during respiration without dividing the airways into anatomical regions or generations, the bifurcation angle was found to be smaller at expiration (θ_exp = 46 ± 18 deg) compared to inspiration (θ_insp = 53 ± 17 deg, p = 0.04). Globally, there was no difference in diameter (p = 0.05), length (p = 0.07), or ellipticity (p = 0.16); therefore, justifying the examination based on generation or region.

Visualizations of the deformation of the airway at different respiratory scans show, consistent with the quantitative findings in the present study, the largest deformation occurs at the distal airways as illustrated qualitatively on the heat map of local deformation (Fig. 4). The heat map analysis shows the mean deformation of the geometry was 6.0 ± 7.8 mm, 5.6 ± 6.3 mm, and 5.4 ± 7.1 mm for swine A, B, and C, respectively; with the distal airways showing a maximum of 20 mm or above of deformation.

Fig. 4.

Airway segmentations with illustrative heat maps of local deformation from n = 3 swine. Three views are shown for each case. Red indicates high amounts of deformation and blue represents no deformation. Qualitative observations suggest that most deformation during respiration occurs in the distal airways. Abbreviations: A, anterior; P, posterior; R, right; L, left.

Comparison to Human Models.

A comparison of the swine respiratory morphometry to common human airway models [4,17–19] shows some similarities (Fig. 2). Both human and swine data showed a decrease in length with increasing airway generations. Additionally, our data suggest that, at similar airway generations, swine airways tend to have smaller diameters, and larger lengths regardless of the respiratory phase. However, the swine and the human data tend to have more similar diameters and segment lengths at distal generations. Conversely, the bifurcation angle was consistently smaller in the human models when qualitatively compared to the swine data.

Discussion

Swine airway morphometry has been previously described [6,7,15,16,20]. However, the dynamics of morphometry of the swine airway during respiration has not been described. Previous studies have used casted airways and physical measurements or ex vivo scans of static airways to perform their analyses [7,15]. Limitations such as material shrinkage, poor filling, the application of static pressures, and human error could hamper the accuracy of these prior models. In the present study, in vivo CT-based imaging data were used for airway measurements in addition to the evaluation of morphometric change during controlled respiration. We showed differences in airway morphometry occur more prominently in distal airway segments and thus at higher airway generations including an increase in diameter, length, and bifurcation angles with ventilator-assisted inspiration.

Interestingly, we found no change in ellipticity during the respiratory cycle or with increasing airway generations, although for higher generation airways that evaluation may be limited by the spatial resolution of the imaging relative to the lumen size. This finding indicates that there is relatively little change in the cross-sectional shape of the airway during respiration, rather only a change in size via diameter and length. This may be an important consideration when designing and evaluating implanted devices as it could impact the distribution of forces.

Consistent with previous studies, comparing human airway models to swine and other mammalian species [21,22], we found that the swine airway geometry generally mimics human airways [1,15]. Both have bronchial segments that decrease in diameter and length with increasing bronchial generations [15,23]. However, our analysis suggests that the swine airway diameter is smaller, the length is greater, and the bifurcation angles are greater when compared to the common human airway models in the same proximal airway generation. At distal generations, the general morphometries tend to converge as illustrated in Fig. 2. This trend persists regardless of the respiratory phase. However, a direct comparison between the swine used in this study and the available human models cannot be extrapolated to all swine respiratory models. Additionally, Fig. 2(b) shows rapid tapering in swine to a consistent length, which represents species-specific geometry that may be relevant for navigational interventional modeling, given the differences from human. Further analysis of the morphological parameters in swine of different sizes could elucidate further similarities or differences between human airways.

The bifurcation pattern, however, is notably different between human and swine airways. Swine airways show a monopodial bifurcation pattern where the mainstem bronchi extend for several generations [4], whereas human airways have a bipodial branching pattern [1,24]. To compare swine and human airways, previously established nomenclature was adopted that defined swine airway segments, or tiers, similar to human airway generations [6]. In addition, swine have a longer trachea [3] and the right upper lobe bronchus arises proximal to the carina, directly from the trachea [6]. This may have implications when analyzing and designing studies that examine device performance in a swine model. Navigation equipment may not be exactly tested in swine lung in terms of angles of bifurcations to be navigated, and the effects of inspiration may be more pronounced in swine than in humans. The monopodial branching pattern of swine airways may result in differences in endobronchial navigation. The mainstem bronchi traverse nearly the full extent of the lungs. The daughter branches arise from the mainstem bronchi and extend caudally in the same general direction as the mainstem bronchi. A similar pattern is observed in higher-order airways. In contrast, in the bipodial branching pattern of humans, the parent airway divides into two or more daughter airways. Therefore, endobronchial navigation times and challenges may be different between species. Likewise, implantable devices designed to traverse from a parent to a daughter branch could behave differently in swine and human. The additional dynamics of adjacent airways in a “y” formation may need to be considered. Whether the differences in respiratory dynamics between swine and human airways are due to geometries or biology such as different elastin content in airways, the changes in angles observed during breathing in swine may be important to integrate during translational device modeling.

Limitations.

The sample number in this study is small, however, a sufficient number of data points were available to perform statistical analyses given the high number of airway segments in each swine. While we have analyzed three healthy swine of the same breed and with weights similar to the average human, future studies may consider improving study power and control for subject size or gender, which has been suggested to correlate to airway size in human subjects [25]. Additionally, the accuracy of measurements is dependent on the segmentation method and, primarily, image resolution. Although this study shows airway segmentation up to the seventh generation, limitations in image resolution did not allow for a greater number of generations to be segmented. Studies with smaller slice thicknesses and higher pixel resolutions would allow for more distal branches to be segmented. Further, the visualization of the deformation by the color map is not guaranteed to be a point-to-point comparison between the baseline and deformed geometries. Differences between the two geometries were minimized by uniformly segmenting the same number of generations, segments, and bifurcation points. Future studies could register the images before segmentation by matching additional static landmarks such as bones.

While normal inspiration occurs due to the motion of the diaphragm and chest wall to increase thoracic volume and decrease intrathoracic pressure, these studies were performed on a ventilator with forced inflation where the inflation of the lungs also drives the expansion of the thoracic cavity. It is unknown whether there would be a difference in airway geometry between the two. Our measurements were also performed on static images where positive pressure was being held for inhalation and exhalation was passive. Therefore, our analysis does not fully capture the dynamics of the airway deformation that could be expected during respiration. In addition, we have only examined two pressures, 0 and 15 cm H₂O, to represent end-expiration and peak-inspiration. The analysis of intermediate pressures, although still static, could be illuminating. Similarly, the swine were in a supine position and the effect of gravity was not taken into consideration. Future studies could implement the same imaging protocol with the subject in a prone and lateral decubitus position.

Although the present data suggest that distal airway segments may have more geometric similarities to human airways, this analysis should be replicated using similar in vivo human imaging. The human airway models' morphometry measurements used in this preliminary comparative analysis were using a different measurement technique, taken from physical casts. Ideally, a comparison to human morphometry would be better performed using the same temporal in vivo imaging data, as described in this study, and using a large cohort of human subjects. This data analysis is also performed on healthy swine lungs and can therefore not be readily translated to disease states such as restrictive fibrosis or COPD.

Conclusions

The morphometric description of the swine airways during respiration may have translational implications. There is greater deformation occurring in distal airways during respiration compared to larger, more proximal airways. Comparison to human airway models showed that the relative diameter may be smaller and length may be larger in swine in similar airway generations. This information elucidates the advantages and limitations of the swine model and provides guidance to researchers for the design and conduct of preclinical studies including device evaluation.

Funding Data

• Center for Interventional Oncology in the Intramural Research Program of the National Institutes of Health (Grant Nos. NIH Z01 1ZID BC011242 and CL040015; Funder ID: 10.13039/100000054).

• Cooperative Research and Development Agreement between the National Institutes of Health Clinical Center and Philips (Funder IDs: 10.13039/100000098 and 10.13039/100004320).

Nomenclature

D =

airway diameter

E =

airway ellipticity

kVp =

kilovolt potential

L =

segment length

θ =

airway bifurcation angle