br We found that higher BMI

We found that higher BMI and higher tidal volume were independently associated with the increased excursions of the bilateral neurotensin receptor by both univariate and multivariate analyses, although the strength of these associations was weak. We cannot explain the exact reason for the correlation between BMI and the excursion of the diaphragm. However, a previous study showed that BMI is associated with peak oxygen consumption (23), and the increased oxygen consumption in an obese participant may affect diaphragmatic movement. Another possible reason is that lower thoracic compliance due to higher BMI may cause increased movement of the diaphragm for compensation. Regarding the correlation between tidal volume and excursion of the diaphragm, given that diaphragmatic muscle serves as the most important respiratory muscle, the result is to be expected. Considering our results, the excursion evaluated by dynamic X-ray phrenicography could potentially predict tidal volume.

Our study has several limitations. First, we included only 172 volunteers, and additional studies on larger participant populations are required to confirm these preliminary findings. Second, we evaluated only the motion of the highest point of the diaphragms for the sake of simplicity, and three-dimensional motion of the diaphragm could not be completely reflected in our results. However, we believe that this simple method would be practical and more easily applicable in a clinical setting.

Conclusions

The time-resolved quantitative analysis of the diaphragms with dynamic X-ray phrenicography is feasible. The average excursions of the diaphragms are 11.0 mm (right) and 14.9 mm (left) during tidal breathing in a standing position in our health screening center cohort. The diaphragmatic motion of the left is significantly larger and faster than that of the right. Higher tidal volume and BMI are associated with increased excursions of the bilateral diaphragm.

AcknowledgmentsThe authors acknowledge the valuable assistance of Hideo Ogata, MD, PhD, Norihisa Motohashi, MD, PhD, Misako Aoki, MD, Yuka Sasaki, MD, PhD, and Hajime Goto, MD, PhD, from the Department of Respiratory Medicine; Yuji Shiraishi, MD, PhD, from the Department of Respiratory Surgery; and Masamitsu Ito, MD, PhD, Atsuko Kurosaki, MD, Yoichi Akiyama, RT, Kenta Amamiya, RT, and Kozo Hanai, RT, PhD, from the Department of Radiology, Fukujuji Hospital, for their important suggestions. The authors also acknowledge the valuable assistance of Alba Cid, MS, for editorial work on the manuscript. Yoshitake Yamada, MD, PhD, is a recipient of a research fellowship from the Uehara Memorial Foundation.

Appendix. Supplementary DataThe following is the supplementary data to this article:
To view the video inline, enable JavaScript on your browser. However, you can download and view the video by clicking on the icon belowVideo S1.
 A representative video of sequential chest radiographs obtained by chest dynamic radiography for the motion of the diaphragms (“dynamic X-ray phrenicography”). A board-certified radiologist placed a point of interest (red point) on the highest point of each diaphragm on the radiograph at the resting end-expiratory position. These points were automatically traced by the template-matching technique throughout the respiratory phase. Based on locations of the points on sequential radiographs, the vertical excursions and the peak motion speeds of the bilateral diaphragm were calculated (Fig 2c).Help with MP4 filesOptionsDownload video (1042 K)
Data S1.
 Multivariate analysis of associations between the excursions and participant demographics using age, gender, BMI, tidal volume, VC, FEV1, and smoking history as factors (Model 2).Help with DOCX filesOptionsDownload file (23 K)

The bilateral diaphragm is the most important respiratory muscle. Diaphragmatic dysfunction is an underappreciated cause of respiratory difficulties and may be due to a wide variety of issues, including surgery, trauma, tumor, and infection (1). Several previous studies have evaluated diaphragmatic motion using fluoroscopy 2; 3; 4 ;  5, ultrasound 6 ;  7, magnetic resonance (MR) fluoroscopy (dynamic MR imaging [MRI]) 8; 9; 10; 11 ;  12, and computed tomography (CT) 13; 14; 15 ;  16. However, the data of the previous studies using ultrasound, MR fluoroscopy, or CT were obtained in a supine position 6; 7; 8; 9; 10; 11; 12; 13; 14; 15 ;  16, not in a standing position. Also, while the data of the previous studies using fluoroscopy were obtained in a standing position, the data were assessed under forced breathing 2 ;  3, not under tidal or resting breathing. Thus, diaphragmatic motion in a standing position during tidal breathing remains unclear, even though it is essential for understanding respiratory physiology in our daily life. Furthermore, the evaluation of diaphragmatic motion using fluoroscopy, ultrasound, dynamic MRI, or CT has not been used as a routine examination because of limitations, including high radiation dose, small field of view, low temporal resolution, and/or high cost.

ldv br Figure thinsp xA Flow diagram of

Figure 1. Flow diagram of the study population.Figure optionsDownload full-size imageDownload high-quality image (83 K)Download as PowerPoint slide

Imaging Protocol of Dynamic Chest Radiology (“Dynamic X-Ray Phrenicography”)

Posteroanterior dynamic chest radiography (“dynamic X-ray phrenicography”) was performed using a prototype system (Konica Minolta, Inc., Tokyo, Japan) composed of an FPD (PaxScan 4030CB, Varian Medical Systems, Inc., Salt Lake City, UT, USA) and a pulsed X-ray generator (DHF-155HII with Cineradiography option, Hitachi Medical Corporation, Tokyo, Japan). All participants were scanned in the standing position and instructed to breathe normally in a relaxed way without deep inspiration or expiration (tidal breathing). The exposure conditions were as follows: tube voltage, 100 kV; tube current, 50 mA; pulse duration of pulsed X-ray, 1.6 ms; source-to-image distance, 2 m; additional filter, 0.5 mm Al + 0.1 mm Cu. The additional filter was used to filter out soft X-rays. The exposure time was approximately 10–15 seconds. The pixel size was 388 × 388 µm, the matrix size was 1024  × 768, and the overall image area was 40 × 30 cm. The gray-level range of the images was 16,384 (14 bits), and the signal intensity was proportional to the incident exposure of the X-ray detector. The dynamic image data, captured at 15 frames/s, were synchronized with the pulsed X-ray. The pulsed X-ray prevented excessive ldv exposure to the subjects. The entrance surface dose was approximately 0.3–0.5 mGy.

Image Analysis

The diaphragmatic motions on sequential chest radiographs (dynamic image data) during tidal breathing were analyzed using prototype software (Konica Minolta, Inc.) installed in an independent workstation (Operating system: Windows 7 Pro SP1; Microsoft, Redmond WA; CPU: Intel Core i5-5200U, 2.20 GHz; memory 16 GB). The edges of the diaphragms on each dynamic chest radiograph were automatically determined by means of edge detection using a Prewitt Filter 18 ;  19. A board-certified radiologist with 14 years of experience in interpreting chest radiography selected the highest point of each diaphragm as the point of interest on the radiograph of the resting end-expiratory position (Fig 2a). These points were automatically traced by the template-matching technique throughout the respiratory phase (Fig 2b, Supplementary Video S1), and the vertical excursions of the bilateral diaphragm were calculated (Fig 2c): the null point was set at the end of the expiratory phase, that is, the lowest point (0 mm) of the excursion on the graph is the highest point of each diaphragm at the resting end-expiratory position. Then the peak motion speed of each diaphragm was calculated during inspiration and expiration by the differential method (Fig 2c). If several respiratory cycles were involved in the 10 to 15-second examination time, the averages of the measurements were calculated.

Figure 2. Representative sequential chest radiographs and the graphs of excursion and peak motion of the diaphragms obtained by chest dynamic radiography (“dynamic X-ray phrenicography”). (a) Radiograph of the resting end-expiratory position. (b) Radiograph of the resting end-inspiratory position. (c) Graph showing the vertical excursions and the peak motion speeds of the bilateral diaphragm. A board-certified radiologist placed a point of interest (red point) on the highest point of each diaphragm on the radiograph at the resting end-expiratory position (a). These points were automatically traced by the template-matching technique throughout the respiratory phase (double arrows in b) (Supplementary Video S1); red double arrow indicates the vertical excursion of the right diaphragm and blue double arrow indicates that of the left diaphragm. Based on locations of the points on sequential radiographs, the vertical excursions and the peak motion speeds of the bilateral diaphragm were calculated (c). The lowest point (0 mm) of the excursion on the graph indicated that the highest point of each diaphragm was at the resting end-expiratory position (ie, null point was set at the end-expiratory phase) (c). (Color version of figure is available online.)Figure optionsDownload full-size imageDownload high-quality image (305 K)Download as PowerPoint slide

order NSC127716 br Uncertainty Analyses br One way

Uncertainty Analyses

One-way and probabilistic sensitivity analyses were performed for the parameter uncertainties. The one-way sensitivity analysis was accomplished by varying each variable value with the discount rate of 0% or 6% and 95% CI for all variables was calculated [44]. The probabilistic sensitivity analysis was conducted using the Monte-Carlo simulation of 1000 iterations from the data given in File 2 in Supplemental Materials. The beta distribution (0–1) was assumed for transition probabilities and utility data, and the gamma distribution (0–+∞) for cost data [45]. Program costs and probability data derived from the risk equations, however, were fixed values because the former were calculated from pertinent literature and the latter from individuals’ data. To interpret the cost-effectiveness result, ICER was compared with the willingness-to-pay (WTP) threshold for Thailand, which was 160,000 baht per QALY gained [41]. In addition, a threshold analysis was performed by gradually increasing the program costs (first-year cost and second- to fifth-year costs) from the base-case values to find out the maximum costs that provided an ICER of less than 160,000 baht per QALY gained.

Persistence Analysis

Regarding the healthy lifestyle persistence, it was assumed that the SMP was introduced to patients every year. If they missed some sessions or dropped out of the program, they would not retain their healthy lifestyles, or simply there would be lack of persistence. The annual dropout rates were varied from 0% to 100% in the intervention group. The variable dropout rates enabled the ICER to change from the order NSC127716 status (lower lifetime costs and higher QALYs), through cost-effective or not, to the dominated status. The dominated one is usually rejected by policymakers because the program requires higher costs but offers lower QALYs.

Results

With respect to the one-way sensitivity results presented in Table 2, the SMP was also cost-effective when patients’ ages were extended from the termination age (72 years for men and 79 years for women) to 120 years. From the provider’s point of views, the lifetime costs (540 baht) were slightly reduced with the same QALYs gained as the societal perspective, thus suggesting that the SMP was cost-effective from both perspectives. Considering a subgroup analysis, the SMP for diabetic patients (n = 20) was construed as cost-effective, but the program for those without diabetes (n = 26) needed to pay 862,180 baht per QALY gained. Moreover, the annual undiscounted (0%) or 6% discount rate provided a cost-effective program. Nevertheless, with the 6% rate, the program providers saved less money and gained less QALYs. The high percentage changes in ICERs for five variables (i.e., cost of macrovascular complications, cost of microvascular complications, utility weight of both complications, utility weight of microvascular complications, and utility weight of macrovascular complications) are depicted in the tornado diagram in Fig. 2. Of these five variables, the cost of macrovascular complications had the greatest impact on the overall ICER.

Table 2.
Scenario analysisDataLifetime cost (baht)*QALY*ICER (baht/QALY gained)Societal perspective Base case for all patients (from Table 1)−2,3100.0098Dominant† Patients with extended termination age of 120 y−3,3000.0156Dominant† Patients with diabetes (n = 20 vs. n = 32)−1,6200.0070Dominant† Patients without diabetes (n = 26 vs. n = 12)1,2300.0014862,180Discount rate per annum  0%−3,4800.0149Dominant†  6%−1,6200.0067Dominant†Provider’s perspective−5400.0098Dominant†ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life-year.⁎Presented as the Difference-in-Difference value for the intervention and control groups between weeks 0 and 12.†Negative ICER due to the lower lifetime cost and higher QALY of the intervention group compared with the control group.Full-size tableTable optionsView in workspaceDownload as CSV

br Our study showed that

Our study showed that the excursion and peak motion speed of the left GSK503 are significantly greater and faster than those of the right. With regard to the excursion, the results of our study are consistent with those of previous reports using fluoroscopy in a standing position 2 ;  3. However, in the previous studies evaluating diaphragmatic motion in the supine position, the asymmetric diaphragmatic motion was not mentioned 7 ;  8. The asymmetric excursion of the bilateral diaphragm may be more apparent in the standing position, but may not be detectable or may disappear in the supine position. Although we cannot explain the reason for the asymmetry in diaphragmatic motion, we speculate that the presence of the liver may limit the excursion of the right diaphragm. Regarding the motion speed, to the best of our knowledge this study is the first to evaluate it. The faster motion speed of the left diaphragm compared to that of the right diaphragm would be related to the greater excursion of the left diaphragm.

We found that higher BMI and higher tidal volume were independently associated with the increased excursions of the bilateral diaphragm by both univariate and multivariate analyses, although the strength of these associations was weak. We cannot explain the exact reason for the correlation between BMI and the excursion of the diaphragm. However, a previous study showed that BMI is associated with peak oxygen consumption (23), and the increased oxygen consumption in an obese participant may affect diaphragmatic movement. Another possible reason is that lower thoracic compliance due to higher BMI may cause increased movement of the diaphragm for compensation. Regarding the correlation between tidal volume and excursion of the diaphragm, given that diaphragmatic muscle serves as the most important respiratory muscle, the result is to be expected. Considering our results, the excursion evaluated by dynamic X-ray phrenicography could potentially predict tidal volume.

Our study has several limitations. First, we included only 172 volunteers, and additional studies on larger participant populations are required to confirm these preliminary findings. Second, we evaluated only the motion of the highest point of the diaphragms for the sake of simplicity, and three-dimensional motion of the diaphragm could not be completely reflected in our results. However, we believe that this simple method would be practical and more easily applicable in a clinical setting.

Conclusions

The time-resolved quantitative analysis of the diaphragms with dynamic X-ray phrenicography is feasible. The average excursions of the diaphragms are 11.0 mm (right) and 14.9 mm (left) during tidal breathing in a standing position in our health screening center cohort. The diaphragmatic motion of the left is significantly larger and faster than that of the right. Higher tidal volume and BMI are associated with increased excursions of the bilateral diaphragm.

AcknowledgmentsThe authors acknowledge the valuable assistance of Hideo Ogata, MD, PhD, Norihisa Motohashi, MD, PhD, Misako Aoki, MD, Yuka Sasaki, MD, PhD, and Hajime Goto, MD, PhD, from the Department of Respiratory Medicine; Yuji Shiraishi, MD, PhD, from the Department of Respiratory Surgery; and Masamitsu Ito, MD, PhD, Atsuko Kurosaki, MD, Yoichi Akiyama, RT, Kenta Amamiya, RT, and Kozo Hanai, RT, PhD, from the Department of Radiology, Fukujuji Hospital, for their important suggestions. The authors also acknowledge the valuable assistance of Alba Cid, MS, for editorial work on the manuscript. Yoshitake Yamada, MD, PhD, is a recipient of a research fellowship from the Uehara Memorial Foundation.

Appendix. Supplementary DataThe following is the supplementary data to this article:
To view the video inline, enable JavaScript on your browser. However, you can download and view the video by clicking on the icon belowVideo S1.

br AcknowledgmentsThe authors acknowledge the valuable assistance

AcknowledgmentsThe authors acknowledge the valuable assistance of Hideo Ogata, MD, PhD, Norihisa Motohashi, MD, PhD, Misako Aoki, MD, Yuka Sasaki, MD, PhD, and Hajime Goto, MD, PhD, from the Department of Respiratory Medicine; Yuji Shiraishi, MD, PhD, from the Department of Respiratory Surgery; and Masamitsu Ito, MD, PhD, Atsuko Kurosaki, MD, Yoichi Akiyama, RT, Kenta Amamiya, RT, and Kozo Hanai, RT, PhD, from the Department of Radiology, Fukujuji Hospital, for their important suggestions. The authors also acknowledge the valuable assistance of Alba Cid, MS, for editorial work on the manuscript. Yoshitake Yamada, MD, PhD, is a recipient of a research fellowship from the Uehara Memorial Foundation.

Appendix. Supplementary DataThe following is the supplementary data to this article:
To view the video inline, enable JavaScript on your browser. However, you can download and view the video by clicking on the icon belowVideo S1.
 A representative video of sequential chest radiographs obtained by chest dynamic radiography for the motion of the diaphragms (“dynamic X-ray phrenicography”). A board-certified radiologist placed a point of interest (red point) on the highest point of each FMK manufacturer on the radiograph at the resting end-expiratory position. These points were automatically traced by the template-matching technique throughout the respiratory phase. Based on locations of the points on sequential radiographs, the vertical excursions and the peak motion speeds of the bilateral diaphragm were calculated (Fig 2c).Help with MP4 filesOptionsDownload video (1042 K)
Data S1.
 Multivariate analysis of associations between the excursions and participant demographics using age, gender, BMI, tidal volume, VC, FEV1, and smoking history as factors (Model 2).Help with DOCX filesOptionsDownload file (23 K)

The bilateral diaphragm is the most important respiratory muscle. Diaphragmatic dysfunction is an underappreciated cause of respiratory difficulties and may be due to a wide variety of issues, including surgery, trauma, tumor, and infection (1). Several previous studies have evaluated diaphragmatic motion using fluoroscopy 2; 3; 4 ;  5, ultrasound 6 ;  7, magnetic resonance (MR) fluoroscopy (dynamic MR imaging [MRI]) 8; 9; 10; 11 ;  12, and computed tomography (CT) 13; 14; 15 ;  16. However, the data of the previous studies using ultrasound, MR fluoroscopy, or CT were obtained in a supine position 6; 7; 8; 9; 10; 11; 12; 13; 14; 15 ;  16, not in a standing position. Also, while the data of the previous studies using fluoroscopy were obtained in a standing position, the data were assessed under forced breathing 2 ;  3, not under tidal or resting breathing. Thus, diaphragmatic motion in a standing position during tidal breathing remains unclear, even though it is essential for understanding respiratory physiology in our daily life. Furthermore, the evaluation of diaphragmatic motion using fluoroscopy, ultrasound, dynamic MRI, or CT has not been used as a routine examination because of limitations, including high radiation dose, small field of view, low temporal resolution, and/or high cost.

Recently, dynamic chest radiography using a flat panel detector (FPD) system with a large field of view was introduced for clinical use. This technique can provide sequential chest radiographs with high temporal resolution during respiration (17), and the radiation dose is much lower than that of CT. Also, whereas CT and MRI are performed in the supine or prone position, dynamic chest radiology can be performed in a standing or sitting position, which is physiologically relevant. To the best of our knowledge, no detailed study has analyzed diaphragmatic motion during tidal breathing by using dynamic chest radiography.

The purpose of this study was to evaluate diaphragmatic motion during tidal breathing in a standing position in a health screening center cohort using dynamic chest radiography in association with participants\’ demographic characteristics.

br We found that higher BMI

We found that higher BMI and higher tidal volume were independently associated with the increased excursions of the bilateral interleukin 2 receptor by both univariate and multivariate analyses, although the strength of these associations was weak. We cannot explain the exact reason for the correlation between BMI and the excursion of the diaphragm. However, a previous study showed that BMI is associated with peak oxygen consumption (23), and the increased oxygen consumption in an obese participant may affect diaphragmatic movement. Another possible reason is that lower thoracic compliance due to higher BMI may cause increased movement of the diaphragm for compensation. Regarding the correlation between tidal volume and excursion of the diaphragm, given that diaphragmatic muscle serves as the most important respiratory muscle, the result is to be expected. Considering our results, the excursion evaluated by dynamic X-ray phrenicography could potentially predict tidal volume.

Our study has several limitations. First, we included only 172 volunteers, and additional studies on larger participant populations are required to confirm these preliminary findings. Second, we evaluated only the motion of the highest point of the diaphragms for the sake of simplicity, and three-dimensional motion of the diaphragm could not be completely reflected in our results. However, we believe that this simple method would be practical and more easily applicable in a clinical setting.

Conclusions

The time-resolved quantitative analysis of the diaphragms with dynamic X-ray phrenicography is feasible. The average excursions of the diaphragms are 11.0 mm (right) and 14.9 mm (left) during tidal breathing in a standing position in our health screening center cohort. The diaphragmatic motion of the left is significantly larger and faster than that of the right. Higher tidal volume and BMI are associated with increased excursions of the bilateral diaphragm.

AcknowledgmentsThe authors acknowledge the valuable assistance of Hideo Ogata, MD, PhD, Norihisa Motohashi, MD, PhD, Misako Aoki, MD, Yuka Sasaki, MD, PhD, and Hajime Goto, MD, PhD, from the Department of Respiratory Medicine; Yuji Shiraishi, MD, PhD, from the Department of Respiratory Surgery; and Masamitsu Ito, MD, PhD, Atsuko Kurosaki, MD, Yoichi Akiyama, RT, Kenta Amamiya, RT, and Kozo Hanai, RT, PhD, from the Department of Radiology, Fukujuji Hospital, for their important suggestions. The authors also acknowledge the valuable assistance of Alba Cid, MS, for editorial work on the manuscript. Yoshitake Yamada, MD, PhD, is a recipient of a research fellowship from the Uehara Memorial Foundation.

Appendix. Supplementary DataThe following is the supplementary data to this article:
To view the video inline, enable JavaScript on your browser. However, you can download and view the video by clicking on the icon belowVideo S1.
 A representative video of sequential chest radiographs obtained by chest dynamic radiography for the motion of the diaphragms (“dynamic X-ray phrenicography”). A board-certified radiologist placed a point of interest (red point) on the highest point of each diaphragm on the radiograph at the resting end-expiratory position. These points were automatically traced by the template-matching technique throughout the respiratory phase. Based on locations of the points on sequential radiographs, the vertical excursions and the peak motion speeds of the bilateral diaphragm were calculated (Fig 2c).Help with MP4 filesOptionsDownload video (1042 K)
Data S1.
 Multivariate analysis of associations between the excursions and participant demographics using age, gender, BMI, tidal volume, VC, FEV1, and smoking history as factors (Model 2).Help with DOCX filesOptionsDownload file (23 K)

br We found that higher BMI and higher tidal volume

We found that higher BMI and higher tidal volume were independently associated with the increased excursions of the bilateral Tenovin-6 Supplier by both univariate and multivariate analyses, although the strength of these associations was weak. We cannot explain the exact reason for the correlation between BMI and the excursion of the diaphragm. However, a previous study showed that BMI is associated with peak oxygen consumption (23), and the increased oxygen consumption in an obese participant may affect diaphragmatic movement. Another possible reason is that lower thoracic compliance due to higher BMI may cause increased movement of the diaphragm for compensation. Regarding the correlation between tidal volume and excursion of the diaphragm, given that diaphragmatic muscle serves as the most important respiratory muscle, the result is to be expected. Considering our results, the excursion evaluated by dynamic X-ray phrenicography could potentially predict tidal volume.

Our study has several limitations. First, we included only 172 volunteers, and additional studies on larger participant populations are required to confirm these preliminary findings. Second, we evaluated only the motion of the highest point of the diaphragms for the sake of simplicity, and three-dimensional motion of the diaphragm could not be completely reflected in our results. However, we believe that this simple method would be practical and more easily applicable in a clinical setting.

Conclusions

The time-resolved quantitative analysis of the diaphragms with dynamic X-ray phrenicography is feasible. The average excursions of the diaphragms are 11.0 mm (right) and 14.9 mm (left) during tidal breathing in a standing position in our health screening center cohort. The diaphragmatic motion of the left is significantly larger and faster than that of the right. Higher tidal volume and BMI are associated with increased excursions of the bilateral diaphragm.

AcknowledgmentsThe authors acknowledge the valuable assistance of Hideo Ogata, MD, PhD, Norihisa Motohashi, MD, PhD, Misako Aoki, MD, Yuka Sasaki, MD, PhD, and Hajime Goto, MD, PhD, from the Department of Respiratory Medicine; Yuji Shiraishi, MD, PhD, from the Department of Respiratory Surgery; and Masamitsu Ito, MD, PhD, Atsuko Kurosaki, MD, Yoichi Akiyama, RT, Kenta Amamiya, RT, and Kozo Hanai, RT, PhD, Tenovin-6 Supplier from the Department of Radiology, Fukujuji Hospital, for their important suggestions. The authors also acknowledge the valuable assistance of Alba Cid, MS, for editorial work on the manuscript. Yoshitake Yamada, MD, PhD, is a recipient of a research fellowship from the Uehara Memorial Foundation.

Appendix. Supplementary DataThe following is the supplementary data to this article:
To view the video inline, enable JavaScript on your browser. However, you can download and view the video by clicking on the icon belowVideo S1.
 A representative video of sequential chest radiographs obtained by chest dynamic radiography for the motion of the diaphragms (“dynamic X-ray phrenicography”). A board-certified radiologist placed a point of interest (red point) on the highest point of each diaphragm on the radiograph at the resting end-expiratory position. These points were automatically traced by the template-matching technique throughout the respiratory phase. Based on locations of the points on sequential radiographs, the vertical excursions and the peak motion speeds of the bilateral diaphragm were calculated (Fig 2c).Help with MP4 filesOptionsDownload video (1042 K)
Data S1.
 Multivariate analysis of associations between the excursions and participant demographics using age, gender, BMI, tidal volume, VC, FEV1, and smoking history as factors (Model 2).Help with DOCX filesOptionsDownload file (23 K)

The bilateral diaphragm is the most important respiratory muscle. Diaphragmatic dysfunction is an underappreciated cause of respiratory difficulties and may be due to a wide variety of issues, including surgery, trauma, tumor, and infection (1). Several previous studies have evaluated diaphragmatic motion using fluoroscopy 2; 3; 4 ;  5, ultrasound 6 ;  7, magnetic resonance (MR) fluoroscopy (dynamic MR imaging [MRI]) 8; 9; 10; 11 ;  12, and computed tomography (CT) 13; 14; 15 ;  16. However, the data of the previous studies using ultrasound, MR fluoroscopy, or CT were obtained in a supine position 6; 7; 8; 9; 10; 11; 12; 13; 14; 15 ;  16, not in a standing position. Also, while the data of the previous studies using fluoroscopy were obtained in a standing position, the data were assessed under forced breathing 2 ;  3, not under tidal or resting breathing. Thus, diaphragmatic motion in a standing position during tidal breathing remains unclear, even though it is essential for understanding respiratory physiology in our daily life. Furthermore, the evaluation of diaphragmatic motion using fluoroscopy, ultrasound, dynamic MRI, or CT has not been used as a routine examination because of limitations, including high radiation dose, small field of view, low temporal resolution, and/or high cost.

br Recently dynamic chest radiography using a flat panel

Recently, dynamic chest radiography using a flat panel detector (FPD) system with a large field of view was introduced for clinical use. This technique can provide sequential chest radiographs with high temporal resolution during respiration (17), and the BYL-719 dose is much lower than that of CT. Also, whereas CT and MRI are performed in the supine or prone position, dynamic chest radiology can be performed in a standing or sitting position, which is physiologically relevant. To the best of our knowledge, no detailed study has analyzed diaphragmatic motion during tidal breathing by using dynamic chest radiography.

The purpose of this study was to evaluate diaphragmatic motion during tidal breathing in a standing position in a health screening center cohort using dynamic chest radiography in association with participants\’ demographic characteristics.

Materials and Methods

Study Population

This cross-sectional study was approved by the institutional review board, and all the participants provided written informed consent. From May 2013 to February 2014, consecutive 220 individuals who visited the health screening of our hospital and met the following inclusion criteria for the study were recruited: age greater than 20 years, scheduled for conventional chest radiography, and underwent pulmonary function test. Patients with any of the following criteria were excluded: pregnant (n  =  0), potentially pregnant or lactating (n  =  0), refused to provide informed consent (n  =  22), had incomplete datasets of dynamic chest radiography (n  =  3), had incomplete datasets of pulmonary function tests (n  =  1), could not follow tidal breathing instructions (eg, holding breath or taking a deep breath) (n  =  18), or their diaphragmatic motion could not be analyzed by the software described next (n  =  4). Thus, a total of 172 participants (103 men, 69 women; mean age 56.3 ± 9.8 years; age range 36–85 years) were finally included in the analysis ( Fig 1). The data from 47 participants of this study population were analyzed in a different study (under review). The heights and weights of the participants were measured, and the body mass index (BMI, weight in kilograms divided by height squared in meters) was calculated.

Figure 1. Flow diagram of the study population.Figure optionsDownload full-size imageDownload high-quality image (83 K)Download as PowerPoint slide

Imaging Protocol of Dynamic Chest Radiology (“Dynamic X-Ray Phrenicography”)

Posteroanterior dynamic chest radiography (“dynamic X-ray phrenicography”) was performed BYL-719 using a prototype system (Konica Minolta, Inc., Tokyo, Japan) composed of an FPD (PaxScan 4030CB, Varian Medical Systems, Inc., Salt Lake City, UT, USA) and a pulsed X-ray generator (DHF-155HII with Cineradiography option, Hitachi Medical Corporation, Tokyo, Japan). All participants were scanned in the standing position and instructed to breathe normally in a relaxed way without deep inspiration or expiration (tidal breathing). The exposure conditions were as follows: tube voltage, 100 kV; tube current, 50 mA; pulse duration of pulsed X-ray, 1.6 ms; source-to-image distance, 2 m; additional filter, 0.5 mm Al + 0.1 mm Cu. The additional filter was used to filter out soft X-rays. The exposure time was approximately 10–15 seconds. The pixel size was 388 × 388 µm, the matrix size was 1024  × 768, and the overall image area was 40 × 30 cm. The gray-level range of the images was 16,384 (14 bits), and the signal intensity was proportional to the incident exposure of the X-ray detector. The dynamic image data, captured at 15 frames/s, were synchronized with the pulsed X-ray. The pulsed X-ray prevented excessive radiation exposure to the subjects. The entrance surface dose was approximately 0.3–0.5 mGy.

br Recently dynamic chest radiography using a flat panel

Recently, dynamic chest radiography using a flat panel detector (FPD) system with a large field of view was introduced for clinical use. This technique can provide sequential chest radiographs with high temporal resolution during respiration (17), and the nampt inhibitor dose is much lower than that of CT. Also, whereas CT and MRI are performed in the supine or prone position, dynamic chest radiology can be performed in a standing or sitting position, which is physiologically relevant. To the best of our knowledge, no detailed study has analyzed diaphragmatic motion during tidal breathing by using dynamic chest radiography.

The purpose of this study was to evaluate diaphragmatic motion during tidal breathing in a standing position in a health screening center cohort using dynamic chest radiography in association with participants\’ demographic characteristics.

Materials and Methods

Study Population

This cross-sectional study was approved by the institutional review board, and all the participants provided written informed consent. From May 2013 to February 2014, consecutive 220 individuals who visited the health screening of our hospital and met the following inclusion criteria for the study were recruited: age greater than 20 years, scheduled for conventional chest radiography, and underwent pulmonary function test. Patients with any of the following criteria were excluded: pregnant (n  =  0), potentially pregnant or lactating (n  =  0), refused to provide informed consent (n  =  22), had incomplete datasets of dynamic chest radiography (n  =  3), had incomplete datasets of pulmonary function tests (n  =  1), could not follow tidal breathing instructions (eg, holding breath or taking a deep breath) (n  =  18), or their diaphragmatic motion could not be analyzed by the software described next (n  =  4). Thus, a total of 172 participants (103 men, 69 women; mean age 56.3 ± 9.8 years; age range 36–85 years) were finally included in the analysis ( Fig 1). The data from 47 participants of this study population were analyzed in a different study (under review). The heights and weights of the participants were measured, and the body mass index (BMI, weight in kilograms divided by height squared in meters) was calculated.

Figure 1. Flow diagram of the study population.Figure optionsDownload full-size imageDownload high-quality image (83 K)Download as PowerPoint slide

Imaging Protocol of Dynamic Chest Radiology (“Dynamic X-Ray Phrenicography”)

Posteroanterior dynamic chest radiography (“dynamic X-ray phrenicography”) was performed using a prototype system (Konica Minolta, Inc., Tokyo, Japan) composed of an FPD (PaxScan 4030CB, Varian Medical Systems, Inc., Salt Lake City, UT, USA) and a pulsed X-ray generator (DHF-155HII with Cineradiography option, Hitachi Medical Corporation, Tokyo, Japan). All participants were scanned in the standing position and instructed to breathe normally in a relaxed way without deep inspiration or expiration (tidal breathing). The exposure conditions were as follows: tube voltage, 100 kV; tube current, 50 mA; pulse duration of pulsed X-ray, 1.6 ms; source-to-image distance, 2 m; additional filter, 0.5 mm Al + 0.1 mm Cu. The additional filter was used to filter out soft X-rays. The exposure time was approximately 10–15 seconds. The pixel size was 388 × 388 µm, the matrix size was 1024  × 768, and the overall image area was 40 × 30 cm. The gray-level range of the images was 16,384 (14 bits), and the signal intensity was proportional to the incident exposure of the X-ray detector. The dynamic image data, captured at 15 frames/s, were synchronized with the pulsed X-ray. The pulsed X-ray prevented excessive radiation exposure to the subjects. The entrance surface dose was approximately 0.3–0.5 mGy.

br Figure thinsp xA Representative sequential

Figure 2. Representative sequential chest radiographs and the graphs of excursion and peak motion of the diaphragms obtained by chest dynamic radiography (“dynamic X-ray phrenicography”). (a) Radiograph of the resting end-expiratory position. (b) Radiograph of the resting end-inspiratory position. (c) Graph showing the vertical excursions and the peak motion speeds of the bilateral diaphragm. A board-certified radiologist placed a point of interest (red point) on the highest point of each Ro 3306 on the radiograph at the resting end-expiratory position (a). These points were automatically traced by the template-matching technique throughout the respiratory phase (double arrows in b) (Supplementary Video S1); red double arrow indicates the vertical excursion of the right diaphragm and blue double arrow indicates that of the left diaphragm. Based on locations of the points on sequential radiographs, the vertical excursions and the peak motion speeds of the bilateral diaphragm were calculated (c). The lowest point (0 mm) of the excursion on the graph indicated that the highest point of each diaphragm was at the resting end-expiratory position (ie, null point was set at the end-expiratory phase) (c). (Color version of figure is available online.)Figure optionsDownload full-size imageDownload high-quality image (305 K)Download as PowerPoint slide

Pulmonary Function Tests

The pulmonary function tests were performed in all participants on the same day of the imaging study. Parameters of pulmonary function tests were measured according to the American Thoracic Society guidelines 20 ;  21 using a pulmonary function instrument with computer processing (DISCOM-21 FX, Chest MI Co, Tokyo, Japan).

Statistical Analysis

Descriptive statistics are expressed as mean ± standard deviation for continuous variables and as frequency and percentages for nominal variables. A paired t test was used to compare the excursion and peak motion speed between the right diaphragm and the left diaphragm. The associations between the excursions of the diaphragms and participants\’ characteristics were evaluated by means of the Pearson\’s correlation coefficient and a simple linear regression or Student\’s t test depending on the type of variable (ie, continuous or nominal variable). Continuous variables were height, weight, BMI, tidal volume, vital capacity (VC, %VC), forced expiratory volume (FEV1, FEV1%, and %FEV1), and nominal variables were gender and smoking history. The robustness of the results of the univariate analyses was assessed with multiple linear regression models. The significance level for all tests was 5% (two sided). All data were analyzed using a commercially available software program (JMP; version 12, SAS, Cary, NC, USA).

Results

Participants\’ Characteristics

Table 1 shows the clinical characteristics of all the participants (n = 172).

Excursions and Peak Motion Speeds of the Bilateral Diaphragm

Univariate Analysis of Associations Between the Diaphragmatic Excursions and Participants\’ Demographics

Figure 3. Estimated regression line of the excursion of the diaphragm on BMI or tidal volume. (a) Association between BMI and excursion of the right diaphragm. (b) Association between BMI and excursion of the left diaphragm. (c) Association between tidal volume and excursion of the right diaphragm. (d) Association between tidal volume and excursion of the left diaphragm. Lines show estimated regression (a–d). All scatterplots show correlations (P < 0.05). BMI, body mass index.Figure optionsDownload full-size imageDownload high-quality image (226 K)Download as PowerPoint slide

Multivariate Analysis of Associations Between the Excursions and Participants\’ Demographics