help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Published ahead of print on February 14, 2008, doi:10.1164/rccm.200709-1322OC
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Online Supplement
Right arrow All Versions of this Article:
200709-1322OCv1
177/10/1095    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ohno, Y.
Right arrow Articles by Sugimura, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ohno, Y.
Right arrow Articles by Sugimura, K.
American Journal of Respiratory and Critical Care Medicine Vol 177. pp. 1095-1102, (2008)
© 2008 American Thoracic Society
doi: 10.1164/rccm.200709-1322OC

Original Article

Oxygen-enhanced Magnetic Resonance Imaging versus Computed Tomography

Multicenter Study for Clinical Stage Classification of Smoking-related Chronic Obstructive Pulmonary Disease

Yoshiharu Ohno1, Tae Iwasawa2, Joom Beom Seo3, Hisanobu Koyama1, Hiroshi Takahashi4, Yeon-Mok Oh5, Yoshihiro Nishimura6 and Kazuro Sugimura1

1 Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Japan; 2 Department of Radiology, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan; 3 Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 4 Pulmonary Division, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan; 5 Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea; and 6 Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan

Correspondence and requests for reprints should be addressed to Yoshiharu Ohno, M.D., Ph.D., Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan. E-mail: yosirad{at}kobe-u.ac.jp


   ABSTRACT
TOP
 ABSTRACT
AT A GLANCE COMMENTARY
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Rationale: Oxygen-enhanced magnetic resonance imaging (MRI) has been proposed as a useful tool for assessing regional morphological and functional changes in chronic obstructive pulmonary disease (COPD).

Objectives: To prospectively and directly compare the efficacy of O2-enhanced MRI and quantitative computed tomography (CT) for smoking-related pulmonary functional loss assessment and clinical stage classification of smoking-related COPD.

Methods: One hundred sixty smokers were classified into four age- and gender-matched groups by using the GOLD criteria for smokers: Smokers without COPD (n = 40), Mild COPD (n = 40), Moderate COPD (n = 40), and Severe or Very Severe COPD (n = 40). All smokers underwent O2-enhanced MRI, multidetector-row CT, and pulmonary function test. Mean relative enhancement ratio on O2-enhanced MRI and CT-based functional lung volume (FLV) on quantitative CT were calculated. To compare the efficacy of O2-enhanced MRI and quantitative CT for pulmonary functional loss assessment, both indexes were correlated with pulmonary functional parameters. To determine the efficacy of two methods for clinical stage classification, the four clinical groups' mean relative enhancement ratio and CT-based FLV were statistically compared.

Measurements and Main Results: Correlations of both indexes with pulmonary functional parameters were significant (P < 0.0001). Pulmonary functional parameters and mean relative enhancement ratio for the four clinical groups showed significant differences (P < 0.05). CT-based FLVs of smokers without COPD and mild COPD were significantly different from those for moderate COPD and severe or very severe COPD (P < 0.05).

Conclusions: O2-enhanced MRI is effective for pulmonary functional loss assessment and clinical stage classification of smoking-related COPD and quantitative CT.

Key Words: lung • magnetic resonance • oxygen • lung ventilation • diffusing capacity



   AT A GLANCE COMMENTARY
TOP
 ABSTRACT
 AT A GLANCE COMMENTARY
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Scientific Knowledge on the Subject
Oxygen-enhanced magnetic resonance imaging (MRI) has been proposed as a useful tool for assessing regional morphological and functional changes in chronic obstructive pulmonary disease (COPD) but there is limited information comparing oxygen-enhanced MRI and quantitative computed tomography (CT).

What This Study Adds to the Field
Oxygen-enhanced MRI has the potential for pulmonary functional loss assessment and clinical stage classification in smoking-related COPD. It can evaluate COPD as well as pulmonary function testing and quantitatively assessed thin-section CT.

 
Chronic obstructive pulmonary disease (COPD) is a slowly progressive disease characterized by airflow limitation, cough, sputum production, and, at later stages, dyspnea (1). COPD is the fourth leading cause of mortality and the 12th leading cause of disability, and by the year 2020 it is expected to be the third leading cause of death and the fifth leading cause of disability worldwide (2, 3). The diagnosis of COPD largely relies on a history of exposure to noxious stimuli and abnormal lung function test results. Because the pathology of COPD varies and the molecular mechanisms are only slightly understood, the diagnosis of COPD has relied on the presence of persistent airflow obstruction in cigarette smokers (1) because smoking is by far the most important risk factor, accounting for more than 80% of all cases in Western societies (1). Approximately 15% to 20% of smokers will develop COPD, although Lundbäck and colleagues argue in a recent study that this figure may be as high as 50% (4–7).

Staging of COPD uses guidelines that are mainly based on the results of the pulmonary function test (1, 8–11). In addition, it has been suggested that chest radiography, computed tomography (CT), and ventilation and/or perfusion scans are useful for the evaluation of morphological changes or regional pulmonary functional changes. CT is the most widely used for these purposes, and several commercially available and many proprietary software and visual scoring systems, such as the national emphysema treatment trial score, have been adapted for CT-based assessment of pulmonary emphysema in clinical and academic practice (12–19).

Recently, oxygen-enhanced magnetic resonance imaging (MRI) and hyperpolarized noble gas MRI have been proposed as useful procedures for assessing regional morphological and functional changes (20–31). It has been reported that oxygen-enhanced MRI could be used for the detection of regional ventilation and alveolocapillary gas transfer (25–31). However, the literature shows no publications dealing with prospective and direct comparison of the capability of quantitatively assessed thin-section CT using the density-masked CT technique (quantitative CT) and of O2-enhanced MRI for smoking-related functional loss assessment and clinical stage classification of smoking-related COPD in a large prospective cohort, such as multicenter trials in various countries.

We hypothesized that a multicenter trial could demonstrate that, in addition to quantitative CT, O2-enhanced MRI may be used for pulmonary functional loss assessment and clinical stage classification of smoking-related COPD. The purpose of the multicenter trial was to prospectively and directly compare the efficacy of O2-enhanced MRI and quantitative CT for smoking-related pulmonary functional loss assessment and clinical stage classification of smoking-related COPD. Some of the results of this study have been previously reported in an abstract (32).


   METHODS
TOP
 ABSTRACT
 AT A GLANCE COMMENTARY
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
A total of 250 consecutive smokers (180 men and 70 women; age range, 40–85 yr; mean age, 63 yr) prospectively underwent pulmonary function test, 16-detector row CT, and O2-enhanced magnetic resonance (MR) examinations at two university hospitals and at one medical center. Lifetime smoking exposures of all subjects were quantified by using pack-years (range, 8–250 pack-years; mean 61 pack-years) (33). According to age, gender, the results of the pulmonary function test, and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline (10), 160 smokers (120 men and 40 women; age range, 40–80 yr; mean age, 62 yr) were prospectively selected and classified into the following four age- and gender-matched groups: smokers without COPD (n = 40), mild COPD (n = 40), moderate COPD (n = 40), and severe or very severe COPD (n = 40).

Oxygen-enhanced MR images were obtained with inhaled oxygen as the T1 contrast agent. The T1-weighted images were continually collected by means of a respiratory synchronized, half-Fourier acquisition, centrically reordered, inversion recovery, single-shot turbo spin-echo pulse sequence and three 1.5-T scanners. The following paradigm for oxygen inhalation using a nonrebreathing ventilation mask was used to obtain all coronal sections: Subjects first breathed 21% oxygen (room air) for 10 dynamic series, 100% oxygen (15 L/min) for 10 dynamic series, and room air for 10 dynamic series. The details of the O2-enhanced MRI procedure have been reported elsewhere (25–31).

For a quantitative estimate of the CT-based functional lung volume (FLV), all multidetector-row CT data were computationally analyzed by using proprietary software with the density-masked CT technique (31, 34, 35). To visualize the relative enhancement map of oxygen-enhanced MRI, oxygen-enhanced MR images were expressed as the percentage change between the oxygen-enhanced and baseline images by using commercially available software. Each pixel in the percentage change map was then calculated as described elsewhere (28, 30, 31), and the mean relative enhancement ratio (MRER) for every subject was determined as the average of the relative enhancement ratio measured from regions of interest drawn over both lungs on the coronal section.

Adverse events related to 100% oxygen inhalation were monitored and evaluated as mild, moderate, or severe. Monitoring was performed from the start of 100% oxygen inhalation until completion of the examination.

To compare the efficacy of the two methods for pulmonary functional loss assessment, both indexes were correlated with lifetime smoking exposure and each pulmonary functional parameter in all groups.

To demonstrate the efficacy of the two methods for early detection of smoking-related pulmonary functional loss, both indexes were correlated with lifetime smoking exposure and each pulmonary functional parameter in smokers without COPD and mild COPD groups.

To determine the efficacy of the two methods for clinical stage classification, MRER and CT-based FLV of subjects at all COPD stages were compared by using analysis of variance followed by Fisher's protected least significant difference test. A P value of less than 0.05 was considered significant for all statistical analyses.


   RESULTS
TOP
 ABSTRACT
 AT A GLANCE COMMENTARY
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
All 160 oxygen-enhanced MR examinations were completed successfully without any adverse effects. A representative case of each group is shown in Figures 1, 2, 3, and 4.


Figure 1
Figure 1
View larger version (85K):
[in this window]
[in a new window]

  		Figure 1. A 59-year-old male patient in the smokers without COPD group (lifetime smoking exposure, 20 pack-years; FEV1/FVC%, 77%; %FEV1, 111%; %DLCO/VA, 103%). (A) Quantitative computed tomography (CT) in axial and coronal planes show normal lung as gray scale and small emphysemas as red; the calculated CT-based functional lung volume is 0.68. (B) Relative enhancement maps from O2-enhanced magnetic resonance data demonstrate heterogeneous and high oxygen enhancement within the lung; the calculated mean relative enhancement ratio is 0.28. On each relative enhancement map, the relative enhancement in each pixel was expressed as a color-coded map showing pixels with 0 to 50% enhancement progressing from dark blue to red.

 

Figure 2
Figure 2
View larger version (82K):
[in this window]
[in a new window]

  		Figure 2. A 65-year-old male patient in the mild COPD group (lifetime smoking exposure, 31 pack-years; FEV1/FVC%, 51.3%; %FEV1, 92.3%; %DLCO/VA, 56.0%). (A) Quantitative computed tomography (CT) in axial and coronal planes show normal lung as gray scale and various-sized emphysemas as red; the calculated CT-based functional lung volume is 0.63. (B) Relative enhancement maps from O2-enhanced magnetic resonance data demonstrate heterogeneous and moderate or high oxygen enhancements within the lung; the calculated mean relative enhancement ratio is 0.18. On each relative enhancement map, the relative enhancement in each pixel was expressed as a color-coded map showing pixels with 0 to 50% enhancement progressing from dark blue to red.

 

Figure 3
Figure 3
View larger version (90K):
[in this window]
[in a new window]

  		Figure 3. A 63-year-old male patient in the moderate COPD group (lifetime smoking exposure, 50 pack-years; FEV1/FVC%, 44.8%; %FEV1, 70.6%; %DLCO/VA, 44.7%). (A) Quantitative computed tomography (CT) in axial and coronal planes show normal lung as gray scale and heterogeneously located emphysemas as red; the calculated CT-based functional lung volume is 0.50. (B) Relative enhancement maps from O2-enhanced magnetic resonance data demonstrate heterogeneous and fair oxygen enhancement within the lung; the calculated mean relative enhancement ratio is 0.14. On each relative enhancement map, the relative enhancement in each pixel was expressed as a color-coded map showing pixels with 0 to 50% enhancement progressing from dark blue to red.

 

Figure 4
Figure 4
View larger version (110K):
[in this window]
[in a new window]

  		Figure 4. A 69-year-old male patient in the severe or very severe COPD group (lifetime smoking exposure, 50 pack-years; FEV1/FVC%, 31.0%; %FEV1, 47.7%; %DLCO/VA, 58.5%). (A) Quantitative computed tomography (CT) images in axial and coronal planes show remained normal lung as gray and various-sized emphysemas as red; calculated CT-based functional lung volume is 0.41. (B) Relative enhancement maps from O2-enhanced magnetic resonance data demonstrate heterogeneous and markedly decreased oxygen enhancement within the lung; the calculated mean relative enhancement ratio is 0.09. On each relative enhancement map, the relative enhancement in each pixel was expressed as a color-coded map showing pixels with 0 to 50% enhancement progressing from dark blue to red.

 
Correlations among lifetime smoking exposure and pulmonary functional parameters, such as FEV1/FVC%, FEV1%, %DLCO/VA, MRER, and CT-based FLV, in all groups are shown in Table 1. Scattergrams among lifetime smoking exposure, FEV1/FVC%, FEV1%, %DLCO/VA, MRER, and CT-based FLV in all subjects are shown in Figures E1, E2, E3, and E4 in the online supplement.


View this table:
[in this window]
[in a new window]

  		TABLE 1. CORRELATIONS AMONG LIFETIME SMOKING EXPOSURE, PULMONARY FUNCTIONAL PARAMETERS, OXYGEN-ENHANCED MAGNETIC RESONANCE IMAGING, AND QUANTITATIVE COMPUTED TOMOGRAPHY IN ALL GROUPS

 
Correlations of MRER or CT-based FLV with lifetime smoking exposure and pulmonary functional parameters were significant (P < 0.0001). In addition, correlation coefficients of MRER with the lifetime smoking exposure or pulmonary functional parameters were slightly better than those of CT-based FLV.

Correlations among lifetime smoking exposure, FEV1/FVC%, %FEV1, %DLCO/VA, MRER, and CT-based FLV in smokers without COPD and mild COPD groups are shown in Table 2.


View this table:
[in this window]
[in a new window]

  		TABLE 2. CORRELATIONS AMONG LIFETIME SMOKING EXPOSURE, PULMONARY FUNCTIONAL PARAMETERS, OXYGEN-ENHANCED MAGNETIC RESONANCE IMAGING, AND QUANTITATIVE COMPUTED TOMOGRAPHY IN THE "SMOKERS WITHOUT COPD" AND "MILD COPD" GROUPS

 

View this table:
[in this window]
[in a new window]

  		TABLE 3. CHARACTERISTICS AND STATISTICAL RESULTS OF OXYGEN-ENHANCED MAGNETIC RESONANCE IMAGING AND QUANTITATIVE COMPUTED TOMOGRAPHY FOR ALL GROUPS

 
FEV1/FVC% and %FEV1 had significant correlation with MRER or CT-based FLV (P < 0.05). In addition, lifetime smoking exposure and %DLCO/VA had significant correlation with MRER (P < 0.001).

Detailed characteristics of the four clinical stage groups and the results of the statistical comparison of MRER and CT-based FLV for clinical stage classification are shown in Table 3. All pulmonary functional parameters and MRER for each clinical group showed significant differences among each other (P < 0.05). Lifetime cigarette smoking exposure and CT-based FLVs of the smokers without COPD and mild COPD groups showed significant differences with those of the moderate COPD and severe or very severe COPD groups (P < 0.05).


   DISCUSSION
TOP
 ABSTRACT
 AT A GLANCE COMMENTARY
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Several classifications for patients with COPD have been adopted in clinical and academic practice to assess the severity of COPD (1–12). In addition, clinicians want to assess the physiological, physiopathological, and pharmacokinetical changes in the lung and in lung regions for the management of patients with COPD at various stages. The pulmonary function test, which includes spirometry, is the gold standard for classification of patients with COPD and for assessing changes in the entire lung of patients with COPD at various disease stages. Our results demonstrated that oxygen-enhanced MRI had slightly better correlations with lifetime smoking exposure and parameters derived from the pulmonary function test than did quantitatively assessed thin-section CT in all subjects and in the smokers without COPD and mild COPD groups. In addition, O2-enhanced MRI showed the potential for more accurate clinical stage classification. To the best of our knowledge, this is the first published study in which O2-enhanced MRI was used in a large prospective cohort for assessment of smoking-related pulmonary functional loss and clinical stage classification of subjects with smoking-related COPD and for a direct comparison with quantitatively assessed thin-section CT.

For the epidemiological and clinical assessment of the effect of cigarette smoke on humans, lifetime smoking exposure has been commonly used in clinical and academic research. Expiratory airflow limitation, on the other hand, is the hallmark physiologic change in COPD and is the key diagnosing the disease. According to the past literature (1–12, 36, 37), cigarette smoking affects the lung at multiple levels: at the bronchi, the bronchioles, and the pulmonary parenchyma. In the bronchi or large airways, smoking has a prominent effect on the structure and function of the mucus-secreting apparatus (i.e., the bronchial mucous glands). In the small airways (i.e., bronchioles less than approximately 2 mm in diameter), smoking induces bronchiolar narrowing, inflammation, and fibrosis, resulting in airflow obstruction. These changes in the bronchioles are believed to be responsible for much of the airflow obstruction seen in patients with smoking-related COPD, especially those assessed as mild COPD. In the case of lung parenchyma, cigarette smoke induces destruction of the connective tissue matrix of the alveolar walls, which reduces gas exchange proportional to the remaining surface area, but there is no change in the thickness of the barrier unless there is an associated infection, inflammation, fibrosis, or scar tissue from previous infections. These changes are believed to be responsible for airflow limitation and for the oxygen transfer abnormalities of the smoking-related pulmonary emphysema seen in patients with smoking-related COPD, especially those assessed as moderate COPD or severe or very severe COPD. In line with these physiopathological findings, regional oxygen enhancement observed on O2-enhanced MRI in our study might produce a more sensitive assessment of the influence of cigarette smoke exposure, pulmonary functional abnormalities, and significant differences among patients with COPD at all clinical stages than did the morphological changes observed on quantitatively assessed thin-section CT. Our results are compatible with the underlying physiopathology of smokers and suggest that, in addition to the pulmonary function test, O2-enhanced MRI may have the potential to play a complementary role in the management of subjects with smoking-related COPD.

There are several limitations to this study. First, the administration of oxygen to patients with pulmonary diseases may alter or modify the existing pulmonary pathophysiological parameters in subjects with non-smoking–related and smoking-related COPD, especially patients with advanced COPD (37, 38). Second, we obtained all thin-section CT images at the end of inspiration and did not use respiratory gating. Even with breathing practice, breath-holding volumes vary by up to 20%, and the level of inspiration affects the appropriate cutoff value on density-masked CT for quantitative assessment of smoking-related COPD as well as X-ray tube drift (39–43). Therefore, each CT-based FLV may be affected by the level of inspiration of the subject and by the CT scanner. Third, although our results demonstrated that O2-enhanced MRI featured superior correlation with smoking-related pulmonary functional loss and more accurate classification of clinical stages of patients with smoking-related COPD, CT is much more widely used in routine clinical practice. In addition, O2-enhanced MR indexes used in our study were compared only with CT-based FLV assessed with our software based on density-masked CT and could not be compared with that assessed with other software based on other methodologies (13–19). Fourth, although the O2-enhanced MR index had better correlations with smoking-related pulmonary functional loss than the CT index, these results are not surprising. CT-based FLV assessed only pulmonary emphysema. However, MRER assessed pulmonary emphysema and airway obstruction. In addition, we could not compare the capability of expiratory CT that might have better correlation with measures of obstructive physiology than inspiratory CT with that of O2-enhanced MRI for pulmonary functional loss assessment and clinical stage classification in a patient with smoking-related COPD. Moreover, we could not measure wash-in or wash-out parameters of O2-enhanced MRI in this study, although a few studies suggested that they are useful evaluating pulmonary function (27, 44). Therefore, further investigations may be warranted to confirm the significant advantages (beside the fact that no radiation exposure is involved) of O2-enhanced MRI over thin-section CT. Fifth, although we sometimes find regional discrepancies between regional morphological changes and relative enhancement ratio, we could not compare them in this study. We also found some discrepancies between MRER and CT-based FLV. However, we could not explain the reasons because we compared the O2-enhanced MR parameter with quantitatively assessed morphologically changes of COPD in this study and could not compare them with functional information derived from other functional imaging techniques, such as nuclear medicine study, hyperpolarized noble gas MRI, and perfusion MRI (45–50). Therefore, we will plan new comparative studies between O2-enhanced MRI and other functional imaging techniques, including quantitatively assessed thin-section multidetector-row CT for further investigation of O2-enhanced MR indexes and the demonstration of the real significance of O2-enhanced MRI for management of patients with smoking-related COPD in the near future.

In conclusion, O2-enhanced MRI was found to be as effective as quantitative thin-section CT for smoking-related pulmonary functional loss assessment and clinical stage classification of smoking-related COPD. Detailed correlation analysis of O2-enhanced MR parameters and pulmonary function test results and power analysis of O2-enhanced MR parameters for patients with smoking-related COPD at all clinical stages demonstrated that assessment of the regional signal intensity changes due to inhalation of 100% oxygen on O2-enhanced MRI yielded maps that show correlation with not only airflow limitation in the lungs, but also with diffusing capacity.


   Acknowledgments
 
The authors thank Yoshiyuki Ohno, M.D., Ph.D., M.P.H., Professor Emeritus, Nagoya University (Department of Preventive Medicine, Graduate School of Medicine) for his valuable advice concerning the statistical aspects of this study. The authors also thank Munenobu Nogami, M.D., Ph.D. (Department of Image-based Medicine, Institute of Biomedical Research and Innovation, Kobe), Daisuke Takenaka, M.D. (Department of Radiology, Kobe University Graduate School of Medicine), Yoshikazu Kotani, M.D. (Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine), and Sang Do Lee, M.D. (Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine) for their contribution to this work.


   FOOTNOTES
 
Supported by Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science, and Technology (JSTS.KAKEN; No. 18591346); the Knowledge Cluster Initiative of the Ministry of Education, Culture, Sports, Science and Technology, Japan; the Cancer Research Fund of Kanagawa Prefectural Hospitals; the Yokohama Foundation for Advancement of Medical Science; and the Korean Health 21 R and D Project, Ministry of Health and Welfare, Republic of Korea (0412-CR03-0704-0001).

This article has an online supplement, which is accessible from this issue's table of contents at www.atsjournals.org

Originally Published in Press as DOI: 10.1164/rccm.200709-1322OC on February 14, 2008

Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

Received in original form September 6, 2007; accepted in final form February 8, 2008


   REFERENCES
TOP
 ABSTRACT
 AT A GLANCE COMMENTARY
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Pauwels RA, Buist AS, Calverley PM, Jenkins CR, Hurd SS; GOLD Scientific Committee. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) workshop summary. Am J Respir Crit Care Med 2001;163:1256–1276.[Free Full Text]
  2. Michaud CM, Murray CJ, Bloom BR. Burden of disease–implications for future research. JAMA 2001;285:535–539.[Abstract/Free Full Text]
  3. Sullivan SD, Ramsey SD, Lee TA. The economic burden of COPD. Chest 2000;117:5S–9S.[CrossRef][Medline]
  4. Fletcher C, Peto R. The natural history of chronic airflow obstruction. BMJ 1977;1:1645–1648.[Abstract/Free Full Text]
  5. Tashkin DP, Clark VA, Coulson AH, Bourque LB, Simmons M, Reems C, Detels R, Rokaw S. Comparison of lung function in young nonsmokers and smokers before and after initiation of the smoking habit: a prospective study. Am Rev Respir Dis 1983;128:12–16.[Medline]
  6. Bjornsson E, Plaschke P, Norrman E, Janson C, Lundbäck B, Rosenhall A, Lindholm N, Rosenhall L, Berglund E, Boman G. Symptoms related to asthma and chronic bronchitis in three areas of Sweden. Eur Respir J 1994;7:2146–2153.[Abstract]
  7. Lundback B, Lindberg A, Lindstrom M, Rönmark E, Jonsson AC, Jönsson E, Larsson LG, Andersson S, Sandström T, Larsson K; Obstructive Lung Disease in Northern Sweden Studies. Not 15 but 50% of smokers develop COPD? Report from the Obstructive Lung Disease in Northern Sweden Studies. Respir Med 2003;97:115–122.[CrossRef][Medline]
  8. Petty T. Chronic obstructive pulmonary disease. In: Hanley M, Welsh C, editors. Current diagnosis and treatment in pulmonary medicine. San Francisco, CA: McGraw-Hill; 2003. pp. 82–90.
  9. Celli BR, MacNee W, ATS/ERS Task Force. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J 2004;23:932–946.[Free Full Text]
  10. Global Initiative for Chronic Obstructive Lung Disease. 2006 Global strategy for diagnosis, management, and prevention of COPD [Internet] [accessed 2007 May 30]. Available from: http://www.goldcopd.com/
  11. Halpin D. NICE guidance for COPD. Thorax 2004;59:181–182.[Free Full Text]
  12. Naunheim KS, Wood DE, Krasna MJ, DeCamp MM Jr, Ginsburg ME, McKenna RJ Jr, Criner GJ, Hoffman EA, Sternberg AL, Deschamps C; National Emphysema Treatment Trial Research Group. Predictors of operative mortality and cardiopulmonary morbidity in the National Emphysema Treatment Trial. J Thorac Cardiovasc Surg 2006;131:43–53.[Abstract/Free Full Text]
  13. Mishima M, Oku Y, Kawakami K, Sakai N, Fukui M, Hirai T, Chin K, Ohi M, Nishimura K, Itoh H, et al. Quantitative assessment of the spatial distribution of low attenuation areas on X-ray CT using texture analysis in patients with chronic pulmonary emphysema. Front Med Biol Eng 1997;8:19–34.[Medline]
  14. Hoffman EA, McLennan G. Assessment of the pulmonary structure-function relationship and clinical outcomes measures: quantitative volumetric CT of the lung. Acad Radiol 1997;4:758–776.[CrossRef][Medline]
  15. Madani A, Keyzer C, Gevenois PA. Quantitative computed tomography assessment of lung structure and function in pulmonary emphysema. Eur Respir J 2001;18:720–730.[Abstract/Free Full Text]
  16. Nakano Y, Muller NL, King GG, Niimi A, Kalloger SE, Mishima M, Paré PD. Quantitative assessment of airway remodeling using high-resolution CT. Chest 2002;122:271S–275S.[CrossRef]
  17. Goldin JG. Quantitative CT of emphysema and the airways. J Thorac Imaging 2004;19:235–240.[CrossRef][Medline]
  18. Coxson HO, Rogers RM. Quantitative computed tomography of chronic obstructive pulmonary disease. Acad Radiol 2005;12:1457–1463.[CrossRef][Medline]
  19. Hoffman EA, Simon BA, McLennan G. State of the art: a structural and functional assessment of the lung via multidetector-row computed tomography: phenotyping chronic obstructive pulmonary disease. Proc Am Thorac Soc 2006;3:519–532.[Abstract/Free Full Text]
  20. Saam BT, Yablonskiy DA, Kodibagkar VD, Leawoods JC, Gierada DS, Cooper JD, Lefrak SS, Conradi MS. MR imaging of diffusion of (3)He gas in healthy and diseased lungs. Magn Reson Med 2000;44:174–179.[CrossRef][Medline]
  21. Salerno M, de Lange EE, Altes TA, Truwit JD, Brookeman JR, Mugler JP III. Emphysema: hyperpolarized helium 3 diffusion MR imaging of the lungs compared with spirometric indexes–initial experience. Radiology 2002;222:252–260.[Abstract/Free Full Text]
  22. Salerno M, Altes TA, Brookeman JR, de Lange EE, Mugler JP III. Rapid hyperpolarized 3He diffusion MRI of healthy and emphysematous human lungs using an optimized interleaved-spiral pulse sequence. J Magn Reson Imaging 2003;17:581–588.[CrossRef][Medline]
  23. Swift AJ, Wild JM, Fichele S, Woodhouse N, Fleming S, Waterhouse J, Lawson RA, Paley MN, Van Beek EJ. Emphysematous changes and normal variation in smokers and COPD patients using diffusion 3He MRI. Eur J Radiol 2005;54:352–358.[CrossRef][Medline]
  24. Fain SB, Panth SR, Evans MD, Wentland AL, Holmes JH, Korosec FR, O'Brien MJ, Fountaine H, Grist TM. Early emphysematous changes in asymptomatic smokers: detection with 3He MR imaging. Radiology 2006;239:875–883.[Abstract/Free Full Text]
  25. Edelman RR, Hatabu H, Tadamura E, Li W, Prasad PV. Noninvasive assessment of regional ventilation in the human lung using oxygen-enhanced magnetic resonance imaging. Nat Med 1996;2:1236–1239.[CrossRef][Medline]
  26. Loffler R, Muller CJ, Peller M, Penzkofer H, Deimling M, Schwaiblmair M, Scheidler J, Reiser M. Optimization and evaluation of the signal intensity change in multisection oxygen-enhanced MR lung imaging. Magn Reson Med 2000;43:860–866.[CrossRef][Medline]
  27. Hatabu H, Tadamura E, Chen Q, Stock KW, Li W, Prasad PV, Edelman RR. Pulmonary ventilation: dynamic MRI with inhalation of molecular oxygen. Eur J Radiol 2001;37:172–178.[CrossRef][Medline]
  28. Ohno Y, Hatabu H, Takenaka D, Adachi S, Van Cauteren M, Sugimura K. Oxygen-enhanced MR ventilation imaging of the lung: preliminary clinical experience in 25 subjects. AJR Am J Roentgenol 2001;177:185–194.[Abstract/Free Full Text]
  29. Muller CJ, Schwaiblmair M, Scheidler J, Deimling M, Weber J, Löffler RB, Reiser MF. Pulmonary diffusing capacity: assessment with oxygen-enhanced lung MR imaging preliminary findings. Radiology 2002;222:499–506.[Abstract/Free Full Text]
  30. Ohno Y, Hatabu H, Takenaka D, Van Cauteren M, Fujii M, Sugimura K. Dynamic oxygen-enhanced MRI reflects diffusing capacity of the lung. Magn Reson Med 2002;47:1139–1144.[CrossRef][Medline]
  31. Ohno Y, Hatabu H, Higashino T, Nogami M, Takenaka D, Watanabe H, Van Cauteren M, Yoshimura M, Satouchi M, Nishimura Y, et al. Oxygen-enhanced MR imaging: correlation with postsurgical lung function in patients with lung cancer. Radiology 2005;236:704–711.[Abstract/Free Full Text]
  32. Ohno Y, Iwasawa T, Seo JB, Koyama H, Takahashi H, Oh YM, Nishimura Y, Sugimura K. Oxygen-enhanced MRI versus quantitative CT: multicenter trial for pulmonary functional loss assessment and clinical stage classification of smoking-related COPD in Asia [abstract]. Radiology 2007;245:A279.
  33. Prignot J. Quantification and chemical markers of tobacco-exposure. Eur J Respir Dis 1987;70:1–7.[Medline]
  34. Zaporozhan J, Ley S, Eberhardt R, Weinheimer O, Iliyushenko S, Herth F, Kauczor HU. Paired inspiratory/expiratory volumetric thin-slice CT scan for emphysema analysis: comparison of different quantitative evaluations and pulmonary function test. Chest 2005;128:3212–3220.[CrossRef][Medline]
  35. Matsuoka S, Kurihara Y, Yagihashi K, Nakajima Y. Morphological progression of emphysema on thin-section CT: analysis of longitudinal change in the number and size of low-attenuation clusters. J Comput Assist Tomogr 2006;30:669–674.[CrossRef][Medline]
  36. Weinberger SE. Chronic obstructive pulmonary disease. In: Weinberger SE, editor. Principles of pulmonary medicine, 3rd ed. Philadelphia: W.B. Saunders; 1998. pp. 91–111.
  37. West JB. Obstructive disease. In: West JB, editor. Pulmonary pathophysiology, 5th ed. Philadelphia: Lippincott, Williams & Wilkins; 1997. pp. 49–76.
  38. West JB, Wanger PD. Ventilation-perfusion relationships. In: Grystal RG, West JB, Weibel ER, Barnes PJ, editors. The lung: scientific foundations, 2nd ed. Philadelphia: Lippincott-Raven; 1997. pp. 1693–1710.
  39. Gierada DS, Yusen RD, Pilgram TK, Crouch L, Slone RM, Bae KT, Lefrak SS, Cooper JD. Repeatability of quantitative CT indexes of emphysema in patients evaluated for lung volume reduction surgery. Radiology 2001;220:448–454.[Abstract/Free Full Text]
  40. Kauczor HU, Hast J, Heussel CP, Schlegel J, Mildenberger P, Thelen M. CT attenuation of paired HRCT scans obtained at full inspiratory/expiratory position: comparison with pulmonary function tests. Eur Radiol 2002;12:2757–2763.[Medline]
  41. Parr DG, Stockley RA. Standardization of CT densitometry. Radiology 2004;230:887.[Free Full Text]
  42. Parr DG, Stoel BC, Stolk J, Nightingale PG, Stockley RA. Influence of calibration on densitometric studies of emphysema progression using computed tomography. Am J Respir Crit Care Med 2004;170:883–890.[Abstract/Free Full Text]
  43. Bakker ME, Stolk J, Putter H, Shaker SB, Parr DG, Piitulainen E, Russi EW, Dirksen A, Stockley RA, Reiber JH, et al. Variability in densitometric assessment of pulmonary emphysema with computed tomography. Invest Radiol 2005;40:777–783.[CrossRef][Medline]
  44. Ohno Y, Koyama H, Nogami M, Takenaka D, Matsumoto S, Obara M, Sugimura K. Dynamic oxygen-enhanced MRI versus quantitative CT: pulmonary functional loss assessment and clinical stage classification of smoking-related COPD. AJR Am J Roentgenol 2008;190:W93–W99.[Abstract/Free Full Text]
  45. Amundsen T, Torheim G, Waage A, Bjermer L, Steen PA, Haraldseth O. Perfusion magnetic resonance imaging of the lung: characterization of pneumonia and chronic obstructive pulmonary disease: a feasibility study. J Magn Reson Imaging 2000;12:224–231.[CrossRef][Medline]
  46. Ohno Y, Hatabu H, Murase K, Higashino T, Kawamitsu H, Watanabe H, Takenaka D, Fujii M, Sugimura K. Quantitative assessment of regional pulmonary perfusion in the entire lung using three-dimensional ultrafast dynamic contrast-enhanced magnetic resonance imaging: preliminary experience in 40 subjects. J Magn Reson Imaging 2004;20:353–365.[CrossRef][Medline]
  47. Ogasawara N, Suga K, Zaki M, Okada M, Kawakami Y, Matsunaga N. Assessment of lung perfusion impairment in patients with pulmonary artery-occlusive and chronic obstructive pulmonary diseases with noncontrast electrocardiogram-gated fast-spin-echo perfusion MR imaging. J Magn Reson Imaging 2004;20:601–611.[CrossRef][Medline]
  48. Yilmaz E, Akkoclu A, Degirmenci B, Cooper RA, Sengun B, Gulcu A, Osma E, Ucan ES. Accuracy and feasibility of dynamic contrast-enhanced 3D MR imaging in the assessment of lung perfusion: comparison with Tc-99 MAA perfusion scintigraphy. Clin Radiol 2005;60:905–913.[CrossRef][Medline]
  49. Ley-Zaporozhan J, Ley S, Eberhardt R, Weinheimer O, Fink C, Puderbach M, Eichinger M, Herth F, Kauczor HU. Assessment of the relationship between lung parenchymal destruction and impaired pulmonary perfusion on a lobar level in patients with emphysema. Eur J Radiol 2007;63:76–83.[CrossRef][Medline]
  50. Ohno Y, Koyama H, Nogami M, Takenaka D, Matsumoto S, Yoshimura M, Kotani Y, Sugimura K. Postoperative lung function in lung cancer patients: comparative analysis of predictive capability of MRI, CT, and SPECT. AJR Am J Roentgenol 2007;189:400–408.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 Proc Am Thorac SocHome page
K. Emami, M. Stephen, S. Kadlecek, R. V. Cadman, M. Ishii, and R. R. Rizi
Quantitative Assessment of Lung Using Hyperpolarized Magnetic Resonance Imaging
Proceedings of the ATS, August 15, 2009; 6(5): 431 - 438.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
J. D Maclay, R. A Rabinovich, and W. MacNee
Update in Chronic Obstructive Pulmonary Disease 2008
Am. J. Respir. Crit. Care Med., April 1, 2009; 179(7): 533 - 541.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Online Supplement
Right arrow All Versions of this Article:
200709-1322OCv1
177/10/1095    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ohno, Y.
Right arrow Articles by Sugimura, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ohno, Y.
Right arrow Articles by Sugimura, K.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2008 American Thoracic Society