
==== Front
Sci Rep
Sci Rep
Scientific Reports
2045-2322
Nature Publishing Group UK London

72786
10.1038/s41598-024-72786-1
Article
Differences in lung attenuation gradients between supine and standing positions in healthy participants on conventional/supine and upright computed tomography
Yagi Fumiko 1
Yamada Yoshitake yamada@rad.med.keio.ac.jp

1
Yamada Minoru 1
Yokoyama Yoichi 1
Kozuka Atsunori 1
Hashimoto Masahiro 1
Otake Yoshito 2
Sato Yoshinobu 2
Chubachi Shotaro 3
Nozaki Taiki 1
Hatabu Hiroto 4
Fukunaga Koichi 3
Jinzaki Masahiro jinzaki@rad.med.keio.ac.jp

1
1 https://ror.org/02kn6nx58 grid.26091.3c 0000 0004 1936 9959 Department of Radiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582 Japan
2 https://ror.org/05bhada84 grid.260493.a 0000 0000 9227 2257 Division of Information Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Nara, Japan
3 https://ror.org/02kn6nx58 grid.26091.3c 0000 0004 1936 9959 Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
4 grid.38142.3c 000000041936754X Center for Pulmonary Functional Imaging, Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA
14 9 2024
14 9 2024
2024
14 2149322 9 2023
10 9 2024
© The Author(s) 2024
2024
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The effect of gravity on the lungs has been evaluated using computed tomography (CT) in the supine and prone positions but not the standing position. However, as humans spend most of the daytime in the standing position, we aimed to compare lung attenuation gradients between the supine and standing positions, and to assess the correlations between the lung attenuation gradients and participant characteristics, including pulmonary function test results. Overall, 100 healthy participants underwent conventional/supine and upright CT, and lung attenuation gradients were measured. Lung attenuation gradients in anteroposterior direction were greater in the supine position than in standing position (all p values < 0.0001) in both upper lobes at the level of the aortic arch (right: standing/supine, -0.02 ± 0.19/0.53 ± 0.21; left: standing/supine, -0.06 ± 0.20/0.51 ± 0.21); in the right middle (standing/supine, -0.26 ± 0.41/0.53 ± 0.39), left upper (standing/supine, -0.35 ± 0.50/0.66 ± 0.54), and lower lobes at the level of the inferior pulmonary vein (right: standing/supine, -0.22 ± 0.30/0.65 ± 0.41; left: standing/supine, -0.16 ± 0.25/0.73 ± 0.54); and in both lower lobes just above the diaphragm (right: standing/supine, -0.13 ± 0.22/0.52 ± 0.32; left: standing/supine, -0.30 ± 0.57/0.55 ± 0.37). Craniocaudal gradients were greater in the standing position (right: standing/supine, 0.41 ± 0.30/0.00 ± 0.16; left: standing/supine, 0.35 ± 0.30/-0.02 ± 0.16, all p values < 0.0001). No moderate to very high correlations were observed between age, sex, height, weight, body index mass, or pulmonary function test results and each lung attenuation gradient. Lung attenuation gradients in anteroposterior direction, which was observed in the supine position, disappeared in the standing position. However, the craniocaudal lung attenuation gradient, which was not present in the supine position, appeared in the standing position.

Subject terms

Respiration
Computed tomography
http://dx.doi.org/10.13039/501100001691 Japan Society for the Promotion of Science JP23K07214 JP21H03799 http://dx.doi.org/10.13039/100007449 Takeda Science Foundation issue-copyright-statement© Springer Nature Limited 2024
==== Body
pmcIntroduction

Humans both sit and stand during the day. However, most three-dimensional imaging techniques, such as magnetic resonance imaging and computed tomography (CT), are performed in the supine position. Consequently, a detailed assessment of the density of the human lung field in the standing position remains unknown. Chest radiography is the most commonly performed imaging examination with patients in the standing position. However, chest radiography is a two-dimensional imaging modality that does not accurately depict changes in lung field density. Previous studies have evaluated the effect of gravity on the lungs using CT in the supine and prone positions1–5, but not in the standing position. Nevertheless, understanding the lung attenuation gradients in the standing position is essential since humans spend most of their time in this posture.

Recently, upright CT was developed based on the conventional/supine 320-detector row CT to clarify the effects of gravity on the human body6. Previous studies have compared lung and lobe volumes, airway volumes, and airway luminal areas in the standing, seated, and supine positions7–10. However, to the best of our knowledge, no clinical study has compared lung attenuation changes in the standing and supine positions. We hypothesised that lung attenuation would increase in the direction of gravity loading and differ between the supine and standing positions.

Therefore, in this study, we aimed to compare lung attenuation gradients in the supine and standing positions in healthy participants and to evaluate the correlation between lung attenuation gradients and participant characteristics, including pulmonary function test (PFT).

Methods

Study population

This prospective study was approved by the Certified Review Board of Keio (#N20160384) and has been registered in the UMIN Clinical Trials Registry (UMIN-CTR) (UMIN000026586) (date of first trial registration, 17/03/2017). All the participants provided written informed consent. All methods were performed in accordance with relevant guidelines and regulations.

Healthy men and women who understood the purpose of the study were recruited by a volunteer recruitment company. To assess the normal anatomy of the entire body, participants with a history of smoking, diabetes, hypertension, dyslipidaemia, as well as those who reported experiencing dysuria were excluded. Additionally, individuals displaying any symptoms including respiratory symptoms, those who were pregnant or potentially pregnant, and those currently undergoing treatment or who had undergone surgery were excluded from the study8,10–12. Between June 2017 and August 2018, 100 healthy participants participated in the study.

CT imaging protocol

All participants prospectively underwent conventional/supine CT320-detector row CT (supine CT) (Aquilion ONE, Canon Medical Systems Corporation, Otawara, Japan) in the supine position and upright CT (prototype TSX-401R; Canon Medical Systems Corporation)6–10 in the standing position within 2 h. Upright CT is capable of up-and-down movements of a transverse 320 row-detector gantry (isotropic 0.5 mm in detector size), with a 0.275-second gantry rotation speed, maximum vertical speed of 100 mm/s, and a 1200 view, at optimal performance. Noise characteristics examined by analyzing the noise power spectrum (NPS), spatial resolution examined by analyzing the modulation transfer function (MTF), and CT numbers of upright CT using the Catphan 504 phantom (The Phantom Laboratory, Salem, NY) were comparable to those of conventional/supine 320-detector row CT.

Data from 97 of the 100 cases had been previously used to evaluate lung and lobe volumes8 and airway luminal areas/volume10; however, this was the first time they were used to assess lung attenuation gradients.

CT scans were obtained in the standing and supine positions. All CT examinations were unenhanced and performed at 100 kVp with a gantry rotation speed of 0.5 s in the helical scan mode (80-row detector), noise index of 24, and helical pitch of 0.8 for the body trunk7–10. A series of contiguous 0.5-mm-thick images were reconstructed using Adaptive Iterative Dose Reduction 3D (Canon Medical Systems)13.

Pulmonary function test (PFT)

All participants underwent PFT within 2 h of CT examination10,14,15. PFT was performed with the participants in a stable condition and sitting position using a chest spirometer (Chestac-8900, Chest M.I., Tokyo, Japan) in accordance with the ATS/European Respiratory Society recommendations16,17. The predicted values of the spirometric measurements were derived from the guidelines of Japanese Respiratory Society10,14,15. We measured Vital Capacity (VC), Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 s (FEV1), Tidal Volume (TV), Residual Volume (RV), Functional Residual Capacity (FRC) and Total Lung Capacity (TLC). We also calculated VC (% predicted), FEV1 (% predicted) and FEV1/FVC (%).

Measurement of the lung attenuation gradients using CT

Lung field reconstruction and measurements of lung attenuation gradients were performed by a radiologist with 6 years of experience using a commercially available workstation (Synapse Vincent, Fuji Film Co., Ltd., Tokyo, Japan). The workstation incorporates a computer-assisted system that automatically extracts the lung field, airways, bronchi7–10,14,15, pulmonary arteries, and pulmonary veins. Using this system, proximal large pulmonary arteries and veins, trachea, bilateral bronchi, and proximal airways were removed. Then, we reconstructed lung field CT images without the trachea, bilateral bronchi, proximal airways, or proximal pulmonary arteries and veins for the analyses.

The lung attenuation gradients were calculated by drawing a straight line in the lung field at each measurement point in the anteroposterior or craniocaudal direction18, measuring lung attenuation at 0.5 mm intervals, and calculating the slope of the line (Fig. 1). The direction of the measurement was the direction of gravity loading, that is, from front to back for the anteroposterior direction and from head to tail for the craniocaudal direction.

Fig. 1 Reconstructed lung field computed tomography (CT) images and representative measurements in a healthy participant. These images have been obtained from a 57-year-old man. The figure panels show axial images at the level of the aortic arch (A), right inferior pulmonary vein (B), and just above the diaphragm on both sides (C), and sagittal images (D) acquired in the supine and standing positions. The attenuation gradient of the lungs was calculated by drawing a straight line (yellow line) in the lung field at each measurement point. The major or minor fissures are indicated by a white dotted line in the lung field. A graph of the lung attenuation gradient is shown on the right. The upper and lower sides represent the raw and filtered data, respectively.

For the anteroposterior direction, measurements were taken at the level of the aortic arch (Fig. 1A), right inferior pulmonary vein (Fig. 1B), and just above the diaphragm on both sides (Fig. 1C) at sites where each lung lobe was at its maximum cross-section. For the craniocaudal direction, measurements were taken at the dorsal level of the lower lobe (2 cm ventral to the posterior margin of the thorax) at the site where the right and left lungs were at their maximum cross-sectional areas (Fig. 1D). For each measurement point, the average value of the lung attenuation gradients was calculated for three lines and used for the analysis. The distance between lines was set to 1 mm. In addition to calculating the overall lung attenuation gradients, we calculated each lung attenuation gradient by dividing it into two sections in the anteroposterior or craniocaudal directions.

During the analysis, a 7-mm-thick median filter was used on the reconstructed lung fields to exclude the effects of the trachea, bronchus, pulmonary arteries, and pulmonary veins, which could not be removed using the automatic software. This was because the remaining thin pulmonary arteries and veins and remaining walls of the airways that could not be removed by the automatic software were all less than 7 mm.

To assess the intra-observer agreement, the same radiologist performed a second measurement 2 months after the first assessment. To assess the inter-observer agreement, another radiologist with 2 years of experience performed the measurements. All measurements were performed in a randomised, blinded manner. We randomized the order of the measurements using the RAND function. During all measurements, the radiologists were not informed about the characteristics of the participants such as age, years, sex, body weight, height, body mass index (BMI), or the PFT results.

Statistical analysis

Data are presented as mean ± standard deviation (SD) and assessed for normality using the Shapiro–Wilk test. The mean differences in the attenuation gradients between the standing and supine positions were compared using a paired t-test. In order to analyze the discrepancies between CT-based lung volume and TLC (at PFT), the ratio of TLC and CT-based lung volume was calculated. Then, the correlations between the lung attenuation gradients and the ratio of TLC/CT-based lung volume were evaluated using Spearman’s correlation analyses. When assessing the correlation between the lung attenuation gradients in the supine or standing position and the ratio of TLC/CT-based lung volume, we used the value of CT-based lung volume in the supine or standing position, respectively. Correlations between the lung attenuation gradients and age, BMI, height, body weight, and PFT results were assessed using Spearman’s correlation coefficients analyses. The strength of the correlations was defined as follows: negligible; 0 ≤ |ρ| < 0.3; low, 0.3 ≤ |ρ| < 0.5; moderate, 0.5 ≤ |ρ| < 0.7; high, 0.7 ≤ |ρ| ≤ 0.9; very high, 0.9 ≤ |ρ| ≤ 1.019. The inter-observer and intra-observer agreements were evaluated by calculating the intra-class correlation coefficients. The significance level for all tests was set at 5% (two-sided). All data were analysed using a commercially available software program (JMP version 17; SAS Institute Inc., Cary, NC, USA).

Results

Participant characteristics

The participant characteristics are presented in Table 1. The median age of the participants was 47.2 years, with an age range of 30 to 79 years; 50.7% of the participants were women.

Table 1 Characteristics of the study population.

Variables	Overall (n = 100)
Mean ± SD or n	Range	
Age, years	47.2 ± 11.2	30–79	
Sex, Male/Female	33/67		
Body weight, kg	57.9 ± 12.0	37.8–106.8	
Height, centimetres	161.3 ± 9.0	141.4–187.5	
BMI, kg/m2	22.2 ± 3.6	15.7–33.7	
Pulmonary function test			
VC (L)	3.63 ± 0.91	1.79–6.13	
FVC (L)	3.57 ± 0.91	1.79–5.98	
VC (% predicted)	105.4 ± 10.1	81.6–138.9	
FEV1 (L)	2.87 ± 0.73	1.37–4.61	
FEV1 (% predicted)	101.7 ± 12.1	71.1–133.5	
FEV1/FVC (%)	80.6 ± 7.6	55.5–96.0	
TV (L)	0.58 ± 0.17	0.29–1.06	
RV (L)	1.52 ± 0.39	0.80–2.92	
FRC (L)	2.92 ± 0.71	1.36–4.86	
TLC (L)	5.15 ± 1.67	2.65–8.22	
SD: Standard Deviation, BMI: Body Mass Index, VC: Vital Capacity, FVC: Forced Vital Capacity, FEV: Forced Expiratory Volume in 1 s, TV: Tidal Volume, RV: Residual Volume, FRC: Functional Residual Capacity, TLC: Total Lung Capacity.

Lung attenuation gradients in the anteroposterior direction and the craniocaudal direction

The mean lung attenuation gradients in the anteroposterior direction at each level (aortic arch, inferior pulmonary vein, and just above the diaphragm) and the craniocaudal direction, and mean differences between the standing and supine positions are shown in Table 2. The lung attenuation gradients in the anteroposterior direction were significantly greater in the supine position than in the standing position (all p values < 0.0001) in both upper lobes of the lungs at the level of the aortic arch (right: standing/supine, -0.02 ± 0.19/0.53 ± 0.21; left: standing/supine, -0.06 ± 0.20/0.51 ± 0.21); in the right middle (standing/supine, -0.26 ± 0.41/0.53 ± 0.39), left upper (standing/supine, -0.35 ± 0.50/0.66 ± 0.54), and lower lobes of the lungs at the level of the right inferior pulmonary vein (right: standing/supine, -0.22 ± 0.30/0.65 ± 0.41; left: standing/supine, -0.16 ± 0.25/0.73 ± 0.54); and in both lower lobes of the lungs just above the diaphragm (right: standing/supine, -0.13 ± 0.22/0.52 ± 0.32; left: standing/supine, -0.30 ± 0.57/0.55 ± 0.37). Furthermore, the lung attenuation gradients in the craniocaudal direction were greater in the standing position than in the supine position (right: standing/supine, 0.41 ± 0.30/0.00 ± 0.16; left: standing/supine, 0.35 ± 0.30/-0.02 ± 0.16, all p values < 0.0001).

Table 2 Lung attenuation gradients following computed tomography in the standing and supine positions (100 participants).

Attenuation gradient	Mean ± SD	
Standing	Supine	Mean difference (95% CI)	p-value	
Anteroposterior direction					
Level of the aortic arch					
Right upper lobe	-0.02 ± 0.19	0.53 ± 0.21	0.55 (0.49–0.61)	< 0.0001	
Left upper lobe	-0.06 ± 0.20	0.51 ± 0.21	0.57 (0.51–0.63)	< 0.0001	
Level of the inferior pulmonary vein					
Right middle lobe	-0.26 ± 0.41	0.53 ± 0.39	0.80 (0.70–0.90)	< 0.0001	
Right lower lobe	-0.22 ± 0.30	0.65 ± 0.41	0.87 (0.77–0.97)	< 0.0001	
Left upper lobe	-0.35 ± 0.50	0.66 ± 0.54	1.01 (0.87–1.15)	< 0.0001	
Left lower lobe	-0.16 ± 0.25	0.73 ± 0.54	0.89 (0.77–1.01)	< 0.0001	
Level just above the diaphragm					
Right lower lobe	-0.13 ± 0.22	0.52 ± 0.32	0.65 (0.57–0.73)	< 0.0001	
Left lower lobe	-0.30 ± 0.57	0.55 ± 0.37	0.86 (0.71–1.00)	< 0.0001	
Craniocaudal direction					
Right lower lobe	0.41 ± 0.30	0.00 ± 0.16	-0.40 (-0.46–-0.35)	< 0.0001	
Left lower lobe	0.35 ± 0.30	-0.02 ± 0.16	-0.37 (-0.43–-0.31)	< 0.0001	
SD: Standard Deviation.

Significant values are in bolditalic.

The mean lung attenuation gradients of the two divisions in the anteroposterior direction at each level (aortic arch, inferior pulmonary vein, and just above the diaphragm) and the craniocaudal direction, and mean differences between the standing and supine positions are presented in Table 3. At the level of the aortic arch, the lung attenuation gradients were significantly greater in the posterior portion than in the anterior portion on both the left and right sides in the supine position (right: anterior/posterior, 0.38 ± 0.37/0.83 ± 0.58; left: anterior/posterior, 0.34 ± 0.42/0.75 ± 0.55, p < 0.0001) but there was no significant difference in the standing position (right: anterior/posterior, -0.05 ± 0.38/-0.05 ± 0.37; left: anterior/posterior, -0.05 ± 0.39/-0.05 ± 0.61). At the level of the inferior pulmonary vein, the two divided attenuation gradients were significantly different between the anterior and posterior portions in the supine position, except for the left upper lobe, but not in the standing position, except for the right lower lobe. At the level just above the diaphragm, no significant difference was observed in the anteroposterior direction between the standing and supine positions. In the craniocaudal direction, the two divided lung attenuation gradients were significantly greater in the inferior portion on both the left and right sides in the standing position (right: superior/inferior, 0.02 ± 0.23/0.64 ± 0.45; left: superior/inferior, 0.08 ± 0.26/0.71 ± 0.48, p < 0.0001) but not significantly different in the lower lobe of the left lung in the supine position (right: anterior/posterior, -0.15 ± 0.29/0.20 ± 0.35; left: anterior/posterior, -0.02 ± 0.31/0.05 ± 0.51). In the anteroposterior direction, upon comparing the two divided anterior lung attenuation gradients with the posterior lung attenuation gradients, the posterior lung attenuation gradients were significantly greater in the supine position than those in the standing position for both upper lobes of the lungs at the level of the aortic arch and for both lower lobes at the level of the inferior pulmonary veins (p < 0.0001). In the craniocaudal direction, upon comparing the two divided superior lung attenuation gradients with the inferior lung attenuation gradients, the inferior lung attenuation gradients were significantly greater in both lungs in the standing position than those in the supine position (p < 0.0001).

Table 3 Lung attenuation gradients when the lung field was divided into two parts on computed tomography in the standing and supine positions (100 participants).

		Mean ± SD	
Anterior or Superior	Posterior or Inferior	Mean difference (95% CI)	p-value	
Supine	Anteroposterior direction					
Level of the aortic arch					
Right upper lobe	0.38 ± 0.37	0.83 ± 0.58	0.44 (0.31–0.68)	< 0.0001	
Left upper lobe	0.34 ± 0.42	0.75 ± 0.55	042 (0.28–0.56)	< 0.0001	
Level of the inferior pulmonary vein					
Right middle lobe	0.01 ± 0.84	0.53 ± 1.18	0.58 (0.17–1.00)	0.0045	
Right lower lobe	0.30 ± 0.59	1.19 ± 0.97	1.01 (0.14–1.28)	< 0.0001	
Left upper lobe	0.32 ± 0.79	0.44 ± 1.14	0.09 (-0.17–0.36)	0.4745	
Left lower lobe	0.30 ± 0.89	1.40 ± 1.24	1.14 (0.83–1.45)	< 0.0001	
Level just above the diaphragm					
Right lower lobe	0.45 ± 0.59	0.58 ± 0.80	0.16 (-0.05–0.38)	0.1358	
Left lower lobe	0.64 ± 0.76	0.57 ± 0.72	-0.08 (-0.26–0.09)	0.3333	
Craniocaudal direction					
Right lower lobe	-0.15 ± 0.29	0.20 ± 0.35	0.35 (0.25–0.44)	< 0.0001	
Left lower lobe	-0.02 ± 0.31	0.05 ± 0.51	0.05 (-0.05–0.15)	0.3498	
Standing	Anteroposterior direction					
Level of the aortic arch					
Right upper lobe	-0.05 ± 0.38	-0.05 ± 0.37	-0.003 (-0.11–0.10)	0.9496	
Left upper lobe	-0.05 ± 0.39	-0.05 ± 0.61	-0.04 (-0.16–0.09)	0.5517	
Level of the inferior pulmonary vein					
Right middle lobe	-0.61 ± 1.27	-0.33 ± 1.27	0.28 (-0.13–0.70)	0.1849	
Right lower lobe	-0.34 ± 0.64	0.01 ± 0.55	0.36 (0.18–0.86)	< 0.0001	
Left upper lobe	-0.36 ± 1.16	-0.58 ± 0.89	-0.26 (-0.57–0.54)	0.1044	
Left lower lobe	-0.12 ± 0.79	0.08 ± 0.70	0.19 (-0.02–0.40)	0.0802	
Level just above the diaphragm					
Right lower lobe	-0.15 ± 0.62	-0.18 ± 0.42	-0.03 (-0.19–0.13)	0.7302	
Left lower lobe	-0.25 ± 1.34	-0.14 ± 0.52	-0.04 (-0.16–0.87)	0.4343	
Craniocaudal direction					
Right lower lobe	0.02 ± 0.23	0.64 ± 0.45	0.62 (0.54–0.70)	0.0001	
Left lower lobe	0.08 ± 0.26	0.71 ± 0.48	0.64 (0.56–0.72)	< 0.0001	
CI: Confidence Interval, SD: Standard Deviation.

Significant values are in Italic and bolditalic.

Correlations between the lung attenuation gradients and the ratio of TLC/CT-based lung volume

Spearman’s correlation coefficients (ρ) between the lung attenuation gradients and the ratio of TLC/CT-based lung volume are shown in Table 4. No moderate to very high correlations were observed between the lung attenuation gradients and the ratio of TLC/CT-based lung volume except the lung attenuation gradients of the right lower lobe at the level just above the diaphragm in the supine position.

Table 4 Spearman’s correlation coefficients (ρ) between the lung attenuation gradients and the ratio of TLC/CT-based lung volume (100 participants).

		ρ between the lung attenuation gradients and the ratio of TLC/CT-based lung volume (supine)	
Supine	Anteroposterior direction		
Level of the aortic arch		
Right upper lobe	0.2531	
Left upper lobe	0.3861	
Level of the inferior pulmonary vein		
Right middle lobe	0.1491	
Right lower lobe	0.3823	
Left upper lobe	0.2827	
Left lower lobe	0.4700	
Level just above the diaphragm		
Right lower lobe	0.5311	
Left lower lobe	0.4470	
Craniocaudal direction		
Right lower lobe	0.2836	
Left lower lobe	0.1716	
		ρ between the lung attenuation gradients and the ratio of TLC/CT-based lung volume (standing)	
Standing	Anteroposterior direction		
Level of the aortic arch		
Right upper lobe	-0.1430	
Left upper lobe	-0.0675	
Level of the inferior pulmonary vein		
Right middle lobe	-0.3204	
Right lower lobe	0.1349	
Left upper lobe	-0.1473	
Left lower lobe	-0.0746	
Level just above the diaphragm		
Right lower lobe	-0.2180	
Left lower lobe	-0.1191	
Craniocaudal direction		
Right lower lobe	0.1592	
Left lower lobe	0.2150	
IQR: interquartile range.

Correlations between the lung attenuation gradients and participant characteristics (including PFT)

Spearman’s correlation coefficients (ρ) between the lung attenuation gradients and participant characteristics (including PFT) are shown in Table 5. No moderate to very high correlations were observed between age, sex, height, weight, BMI, or PFT results and each lung attenuation gradient.

Table 5 Spearman’s correlation coefficients (ρ) between the lung attenuation gradients and participant characteristics (including PFT) (100 participants).

	Spearman’s correlation coefficients (ρ)	
Age	Sex	Height	Weight	BMI	VC (L)	FVC (L)	VC (% predicted)	FEV1 (L)	FEV1 (% predicted)	FEV1/FVC (%)	TV (L)	RV (L)	FRC (L)	TLC (L)	
Supine	Anteroposterior direction																
Level of the aortic arch																
Right upper lobe	-0.2103	0.1632	-0.0500	-0.1993	-0.2465	-0.1389	-0.1344	-0.1711	-0.0818	0.2573	-0.0423	-0.0987	-0.1594	-0.0993	-0.1644	
Left upper lobe	-0.0060	0.0836	-0.0513	-0.0429	-0.1156	-0.0427	-0.0453	-0.0083	-0.0482	0.0348	-0.0417	-0.1559	-0.1390	-0.0690	-0.0855	
Level of the inferior pulmonary vein																
Right middle lobe	0.0274	0.0269	-0.1613	0.0522	0.1240	-0.1297	-0.1294	-0.0999	-0.1158	0.0378	-0.0506	-0.0748	-0.0399	-0.1268	-0.1239	
Right lower lobe	-0.0545	0.0549	-0.1311	-0.0110	0.0441	-0.0862	-0.0845	-0.0547	-0.0696	0.0518	0.0328	0.0034	-0.1242	-0.0774	-0.1277	
Left upper lobe	0.0474	0.2560	-0.2786	-0.1138	0.0075	-0.3006	-0.3217	-0.0953	-0.3318	-0.1511	-0.1705	-0.1606	-0.2160	-0.2644	-0.3037	
Left lower lobe	-0.1240	0.2523	-0.1577	-0.0561	-0.0087	-0.1651	-0.1809	-0.0822	-0.1336	0.1431	0.0648	-0.1815	-0.1985	-0.1476	-0.2049	
Level just above the diaphragm																
Right lower lobe	-0.0989	0.1919	-0.2013	-0.1895	-0.1135	-0.1665	-0.1783	-0.0543	-0.1556	0.0055	0.0347	-0.1205	-0.1448	-0.0748	-0.1975	
Left lower lobe	-0.1698	0.1212	-0.1301	-0.0599	-0.0393	-0.1056	-0.1087	-0.1330	-0.0881	0.0857	-0.0405	-0.1170	-0.1942	-0.1924	-0.1634	
Craniocaudal direction																
Right lower lobe	0.1048	-0.0799	-0.0833	0.0484	0.1005	-0.0255	-0.0456	0.0182	-0.0083	0.0556	0.0543	-0.0923	-0.0636	-0.0658	-0.0242	
Left lower lobe	0.1037	-0.2067	0.1213	0.1024	0.0609	0.2088	0.1973	0.2308	0.2126	0.0350	0.2569	0.1562	0.1173	0.2127	0.1950	
Standing	Anteroposterior direction																
Level of the aortic arch																
Right upper lobe	0.1022	-0.0888	0.0187	0.0041	0.0127	0.0624	0.0739	0.1065	0.0836	-0.0128	0.1017	0.0933	0.1497	0.1070	0.1049	
Left upper lobe	0.0945	-0.1352	0.2214	0.0796	-0.0795	0.2092	0.1950	0.1868	0.1525	-0.0682	0.0882	0.1475	0.2313	0.2619	0.2422	
Level of the inferior pulmonary vein																
Right middle lobe	0.2498	0.1241	-0.2575	-0.0714	0.0972	-0.2860	-0.2872	-0.1410	-0.2875	-0.0541	-0.0378	-0.0916	-0.1346	-0.2531	-0.2609	
Right lower lobe	-0.0882	-0.0858	0.0647	0.0133	-0.0252	0.1248	0.1291	0.0071	0.1432	0.0602	0.0515	0.1060	0.0488	0.0953	0.1046	
Left upper lobe	-0.0197	0.0204	0.0232	-0.0384	-0.0959	-0.0263	-0.0196	-0.0526	0.0079	0.0417	0.0198	0.0184	-0.0787	-0.0475	-0.0353	
Left lower lobe	0.0022	-0.0284	0.1053	0.2335	0.1994	0.0727	0.0582	0.0250	0.0379	-0.1084	-0.0543	0.0082	0.0217	-0.0323	0.0641	
Level just above the diaphragm																
Right lower lobe	0.1367	-0.0785	0.0297	-0.0192	-0.0365	-0.0392	-0.0424	-0.0579	-0.0276	-0.0653	-0.0035	0.0104	0.3165	0.0786	0.0320	
Left lower lobe	-0.2468	-0.1131	0.0662	0.0471	0.0265	0.1782	0.1655	0.0015	0.1678	-0.0218	-0.0377	-0.0655	0.0153	0.0843	0.1322	
Craniocaudal direction																
Right lower lobe	0.3165	0.0682	-0.2758	0.1436	0.3238	-0.2312	-0.2493	0.0487	-0.2440	-0.0465	0.1161	-0.1500	-0.2764	-0.3083	-0.2767	
Left lower lobe	0.2422	-0.0181	-0.1727	0.1689	0.3072	-0.1614	-0.1659	0.0125	-0.1564	-0.0427	0.0709	-0.0352	-0.1849	-0.2464	-0.1866	

Inter- and intra-observer correlation coefficients

The inter- and intra-observer correlation coefficients were between 0.85 and 0.90 and between 0.98 and 0.99, respectively, for all quantitative measurements.

Discussion

To the best of our knowledge, this is the first study to assess gravity effects in the lung field using CT in the standing position. Previous studies have evaluated the effect of gravity on the lungs using CT in the supine and prone positions and shown that the most significant changes in lung density occurred in the dependent regions in the supine and prone positions2. Lee et al. have reported that the degree of dependent opacity correlated with the diameter of a segmental arterial branch and the CT attenuation of a dependent region correlated with the arterial diameter1. It has been also reported that the lung attenuation gradients may imply lung compliance, distribution of mechanical stress, or distensibility of vessels18,20,21. In addition, previous several studies have reported that pulmonary lung blood flow increases in the caudal regions of the vertical lung in the standing position, suggesting a greater influence of gravity in this position22–30. Furthermore, previous studies have shown that regional ventilation was greater in the dependent part of the lung31 due to differences between the shape of the lung tissue and the surrounding pleural space32. It has also been reported that spontaneous changes in respiratory movement33 and diaphragmatic activity34 affect regional ventilation more clearly than the gravity effect, reducing differences between the lung regions. Petersson et al. reported the effects of standing positions on regional pulmonary blood flow and ventilation using SPECT35. They clarified that in comparison with supine positions, both blood flow and ventilation were greater in the caudal regions when upright, and that the redistribution was greater for blood flow than for ventilation, resulting in decreasing ventilation-to-perfusion ratios in the caudal regions of the lung in the standing position35.

In this prospective study, we demonstrated that the lung attenuation gradients of the lung fields in the anteroposterior direction disappeared (decreased) in the standing position, and the craniocaudal lung attenuation gradient appeared in the craniocaudal direction in the standing position, which was not observed in the supine position. CT values in the lung field are believed to be a mixture of lung tissue, air, and blood CT values. A previous study using SPECT35 showed that the ventilation/blood flow ratio decreases in the caudal regions, which supports our finding of increased lung attenuation gradients in the standing position, i.e., relatively higher lung field CT values in caudal regions. We believe our findings would be important because our study involved asymptomatic participants, and we determined normal reference values for lung measurements in the standing position using upright CT. A previous study has shown that the total access time in upright CT is significantly shorter than those in conventional/supine CT6. Therefore, it may be useful when a large number of images of healthy individuals need to be acquired in a short period of time, such as in lung cancer screening examinations.

No moderate to very high correlations were observed between the lung attenuation gradients and the ratio of TLC/CT-based lung volume in almost any measurements. If the participant did not inhale well during the CT, it can be expected that the lung field is collapsed, and thus the lung attenuation would increase. Considering our results, we speculate that even if participants did not inhale well during CT, the lung attenuation gradients would not have changed, because the lung attenuation would have increased uniformly.

In this study, as mentioned in Table 2, the lung attenuation gradients in the anteroposterior direction were all negative in the standing position compared with in the supine position. These results mean that in the standing position, the lung attenuation was lower in the posterior side than in the anterior side. In the standing position, compared with the anterior portion of the diaphragm, the posterior portion of the diaphragm appears to be pulled more toward the ground by gravity, which would cause the posterior lung fields to be more stretched than the anterior lung fields. Since the stretched posterior lung fields are less concentrated than the anterior ones, the lung attenuation gradients in the anteroposterior direction in the standing position are expected to show a negative value.

In this study, when the lung field was divided into two parts in the supine position at the level of the aortic arch, the lung attenuation gradient was more elevated in the posterior portion, that is, the gravity loading direction. In contrast, in the standing position at the level of the aortic arch, no significant difference was observed in the lung attenuation gradient between the anterior and posterior portions. When the lung field was divided into two sections at the level of the inferior pulmonary vein, the lung attenuation gradient was significantly greater in the posterior portion than in the anterior portion of both lower lobes compared with those in the right middle and left upper lobes in the supine position. Both lower lobes of the lungs are more dorsally located in the supine position compared with the middle lobe of the right lung and the upper lobe of the left lung. In other words, both lower lobes of the lungs are located more in the direction of gravity loading. Therefore, gravity is stronger in the lower lobes of both lungs, resulting in a more pronounced lung collapse. As a result, the CT values of both lower lobes of the lungs are higher, which is thought to increase the lung attenuation gradients of both lower lobes. At a level just above the diaphragm, when the lung field was divided into two sections, there was no significant difference between the anterior and posterior lung attenuation gradients in either standing or supine positions. This finding may suggest that the diaphragm’s effect on attenuation was not completely eliminated. There are several factors that may contribute to the effect of the diaphragm. For example, the diaphragm may not have a clean dome shape and may have some bulges. In addition, the liver is located just below the diaphragm on the right side and the gastric bubble and spleen are located just below the diaphragm on the left side, and the shape of the diaphragm may be changed by the movement of these organs during positional changes between in standing and supine positions. The combination of these factors may have resulted in no significant difference between the anterior and posterior lung attenuation gradients in the lung field when the lung field was divided into two parts. When the lung field was divided into two sections in the standing position, the lung attenuation gradient was more elevated in the caudal portion, that is, in the direction of gravity loading. Contrastingly, in the supine position, the lung attenuation gradient was more elevated in the caudal portion than in the superior portion on the right side. However, no significant difference was observed on the left side. This could be because the liver is generally located on the right side, which makes attenuation more likely to increase in the caudal portion.

The causes of interstitial pneumonia (especially idiopathic pulmonary fibrosis) have been assessed, including genetic predisposition, smoking, viral infection, environmental contaminants, chronic microaspiration, and drug use; however, no clear cause has been established36,37. In addition, interstitial pneumonia tends to originate in the peripheral lung fields, predominantly in the dorsal and caudal areas, in the early stages of the disease; however, the reasons for this have not been clearly elucidated, although anatomic factors and the involvement of blood and lymphatic flow have been speculated. In the present study, the lung attenuation gradient in the craniocaudal direction was significantly greater in the standing position than in the supine position. This may be because, in the standing position, gravity squashes the lung parenchyma in the caudal areas, and in the standing position, more blood or lymphatic flow is present in the caudal areas35,38,39. Gravity’s influence on the caudal side of the lung parenchyma in the standing position may be related to the fact that interstitial pneumonia lesions are more common in the caudal region. Future evaluations of the distribution and location of lesions in patients with early-stage interstitial pneumonia using CT in multiple body positions, including upright CT, may provide insights into the pathogenesis of interstitial pneumonia, especially anatomic factors.

This study had some limitations. Firstly, our sample size was small, and the study was restricted to a single center in Japan. Therefore, further studies involving other ethnicities and larger patient populations are required. Secondly, although the observers independently evaluated the images in a blinded, randomised manner, they could only recognise the positions of the participants to some extent because of the presence or absence of a CT table. However, the inter-observer and intra-observer agreements were relatively high in this study. Thirdly, we measured lung attenuation gradients in the lung field, but this assessment was limited because the lung attenuation gradient is measured by drawing a straight line through the lung field, and we did not measure whole lung attenuation in the entire lung field.

In conclusion, in our study involving healthy asymptomatic participants, the lung attenuation gradient in the anteroposterior direction disappeared (decreased) in the standing position. Moreover, the craniocaudal lung attenuation gradient, which was initially absent in the supine position, appeared in the standing position.

Acknowledgements

This work was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant Numbers JP23K07214, JP21H03799, and JP20K08056) and the Takeda Science Foundation. The authors acknowledge all the participants for their willingness to participate in this study. The authors thank Drs. Keiichi Narita, Takehiro Nakahara, Naomi Tamaki, Yoko Tauchi, and Kyoko Komatsu for their assistance with the study.

Author contributions

F.Y. participated in data analysis and wrote the manuscript. Y. Yamada and M.Y. participated in protocol development, data collection and interpretation and edited the manuscript. Y. Yokoyama participated in data collection and interpretation and edited the manuscript. A.K. participated in the data collection. M.H. participated in the data analysis. Y.O., Y.S., S.C., H.H., T.N., and K.F. participated in data interpretation. M.J. developed the project and helped write and edit the manuscript. All authors approved the final version to be published and agreed to be accountable for all aspects of the work to ensure that questions related to the accuracy or integrity of any part were appropriately investigated and resolved.

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests

Masahiro Jinzaki received a grant from Canon Medical Systems, which loaned an upright CT device to Keio University. The funder was not involved in the design of the study; collection, analysis, interpretation of data; or writing of the manuscript. The remaining authors have no conflicts of interest to declare.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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