Clinical Radiology 70 (2015) 752e759
Contents lists available at ScienceDirect
Clinical Radiology journal homepage: www.clinicalradiologyonline.net
Pictorial Review
The evolving role of MDCT in the assessment of patients with chronic obstructive pulmonary disease S. Karia a, *, R. Mahadeva b, A. Balan a, J. Babar a a b
Department of Radiology, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, UK Department of Respiratory Medicine, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, UK
article in formation Article history: Received 4 August 2014 Received in revised form 5 January 2015 Accepted 20 February 2015
The purpose of this article is to educate the reader in the value a radiologist can offer in the multidetector (MD) CT assessment of patients with chronic obstructive pulmonary disease (COPD). MDCT can identify patients in whom treatments such as lung volume reduction surgery or newer endobronchial therapies may be of benefit. We will also discuss important and under-recognised associated cardiorespiratory disease, which may be incidentally identified. Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. In the UK approximately 900,000 people have diagnosed COPD, a further 2 million people remain undiagnosed. The radiologist may be the first to suggest the diagnosis in patients imaged for other reasons or with unexplained respiratory symptoms. Between 25,000 and 30,000 deaths are caused by COPD each year, with one in eight emergency admissions to hospital as a direct result of the disease.1,2 COPD is defined as “a disease state characterised by airflow limitation that is not fully reversible”. This airflow limitation is due to small airways remodelling or emphysema but usually a combination of both.3 Pulmonary function tests are essential for the diagnosis of COPD and
* Guarantor and correspondent: S. Karia, Department of Radiology, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, UK. Tel.: þ44 01223 216 320, þ44 07811 325645 (mobile). E-mail address: [email protected] (S. Karia).
assessing response to treatment but provide functional information only. Multidetector (MD) CT provides information about the airways, parenchyma, vascularity, and regional quantity and distribution of emphysema. MDCT is used to differentiate emphysema-predominant and airway-predominant COPD. Needless to say, many patients may have components of both, therefore, forming a mixed phenotype.
Emphysema-predominant COPD Emphysema is defined as a permanent enlargement of the airspace distal to the terminal bronchioles with destruction of the alveolar wall and loss of alveolar attachments. There are three main subcategories of emphysema seen at MDCT. Centrilobular emphysema is the most common type of cigarette smoking-related emphysema (Fig 1). Paraseptal emphysema affects the most distal portion of the acinus, predominantly adjacent to pleura or interlobular septa (Fig 2). Panacinar emphysema uniformly affects the entire secondary lobule, usually associated with severe alpha-1 anti-
http://dx.doi.org/10.1016/j.crad.2015.02.015 0009-9260/Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
S. Karia et al. / Clinical Radiology 70 (2015) 752e759
753
Figure 1 (a) Axial CT image demonstrating moderate centrilobular emphysema (arrow) with (b) coronal MPR image demonstrating upper zonal distribution (arrows).
trypsin deficiency (Pi ZZ mutation) and also with cigarette smoking (Fig 3).
Airway-predominant COPD Chronic exposure to cigarette smoke causes direct damage to the airways with subsequent epithelial cell hyperplasia, smooth muscle hypertrophy, and mucous metaplasia. Fig 4 demonstrates some of the MDCT findings. Decisions regarding treatment of patients with emphysema should be discussed by a multidisciplinary team. The input of COPD physicians, thoracic surgeons, respiratory radiologists, nurses, and physiotherapists are vital to enable optimum assessment and inform an individualised treatment plan. In this review we will discuss the anatomical information the radiologist can provide, which will influence treatment decisions in patients with COPD.
Lung volume reduction Pathological specimens of patients with severe emphysema (physiological features of gas trapping and reduced
Figure 2 (a) Axial CT image demonstrates paraseptal emphysema that commonly abuts pleural surfaces. (b) Coronal MPR image showing severe paraseptal emphysema with a large right upper lobe bulla (arrow) causing compressive atelectasis of the middle lobe (arrowhead).
functional status) show significant loss of normal elastic connective tissue. This results in airway collapse on expiration, resulting in a reduced area for gas exchange with associated dynamic hyperinflation. Lung volume reduction can be achieved by either minimally invasive lung volume reduction surgery (LVRS) or endobronchial volume reduction. Both methods aim to remove (either physically or functionally) a hyperinflated diseased segment or lobe, which results in functional benefit to non-target lobe and diaphragmatic function. The National Emphysema Treatment Trial compared optimal medical treatment with optimal medical treatment combined with bilateral LVRS. In the latter group, patients showed marked improvements in functional capacity and survival in sub-groups of patients with heterogeneous disease4 (i.e., those with predominant upper-zone emphysema compared to lower zones). The initial increased morbidity and mortality associated with LVRS together with the limited patient selection criteria (heterogeneous disease) led to the search for alternative methods of lung volume reduction. The evolution of
Figure 3 (a) Coronal and (b) sagittal MPR images demonstrate diffuse lung parenchymal destruction with lower zone predominance in a patient with severe alpha-1 anti-trypsin deficiency.
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Figure 4 (a) Axial CT image shows decreased vascularity and lung attenuation (arrow) suggestive of air-trapping; this could be confirmed on expiratory imaging. (b) Axial CT image on mediastinal windows shows bronchial wall thickening and mucoid impaction (arrow).
interventional bronchoscopy has led to the development of novel endobronchial therapies such as endobronchial coils, thermal vapour glue, and endobronchial valves. The latter is the most established; these valves reduce the flow of air into the treated lobe during inspiration but allow secretions and air to be expelled from that region during expiration. The aim is isolation of a diseased lobe resulting in shrinkage of the volume of that lobe and eventually collapse5 (Fig 5). The effectiveness of endobronchial valve therapy is dependent on optimal patient selection and correct placement of the valves in the target lobe. As with LVRS, greater heterogeneity is associated with greater improvements in forced expiratory volume in 1 s (FEV1) and exercise capacity. One of the most important factors for successful lobe isolation and atelectasis is the absence of collateral ventilation pathways. The VENT trial (endobronchial valve for emphysema palliation trial) showed that patients with intact lobar fissures at CT had a 17.9% improvement in FEV1 at 12 months compared with 2.8% in patients with incomplete fissures.6
MDCT is a vital tool to evaluate fissure integrity (as a surrogate of interlobar collateral ventilation) and the presence of accessory fissures.7 In our institution, we subjectively assess integrity by using multiplanar reconstruction (MPR) reformatting and categorise fissures into complete or partial defects with subcategories of minor (10%; Fig 6). If the defect is thought to be intact or a minor defect and the patient is otherwise a good candidate for endobronchial valves, we will perform bronchoscopic assessment of collateral ventilation. This is assessed by measurement of flow and resistance following occlusion of the target bronchus by a balloon catheter (Chartis; PulmonX) Endobronchial valves are not without complications; there are increased rates of haemoptysis, exacerbations of COPD, and pneumothoraces6 (Fig 7). Endobronchial valves also may migrate into non-target lobes causing volume loss of potential healthy lung (Fig 8). Plain radiography has a limited role in precisely locating valves, and therefore, MDCT is recommended for full anatomical assessment.
Figure 5 (a) Coronal MPR image pre-endobronchial valve in 2010. (b) Following endobronchial valve placement in the segmental bronchi of the left upper lobe, there is expected left upper lobe atelectasis and elevation of the oblique fissure (arrow). (c) Further follow-up axial CT image shows complete left upper lobe collapse (arrow) with endobronchial valves in the segmental left upper lobe bronchi (asterisk).
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Emphysema quantification
Figure 6 (a) Sagittal MPR image showing a major defect in the right horizontal fissure (arrow) and (b) a different patient showing a minor partial defect in the left oblique fissure (asterisk).
Figure 7 Coronal MPR images showing two endobronchial valves in the left upper lobe segmental bronchi (arrows) with a complicating left pneumothorax (asterisk).
Endobronchial coils are a new therapy that show promising results in patients with heterogeneous disease. The effect seen is independent on collateral ventilation pathways.8 Studies are ongoing in patients with homogeneous disease distribution (Fig 9), an important subgroup of patients who have limited treatment options.9
MDCT can be used in several ways to assess the extent and distribution of emphysema. Subjective assessment relies on the radiologist to score the severity of emphysema in three locations (upper, mid, and lower zones) in each lung but is prone to significant interobserver variation. Quantitative evaluation using MDCT involves assessment of the density of each voxel of lung parenchyma. A threshold value is then set (typically 950 HU), which allows differentiation between areas of emphysema and normal lung parenchyma (Fig 10). Longitudinal evaluation of serial changes in the quantity of emphysema in individuals can be assessed as the lowest 15th percentile (Hounsfield unit point below which 15% of the low-attenuation voxels are distributed [Perc15]). The latest software tools will now often automatically segment out anatomically defined lung lobes so that results can be expressed on a lobar rather than zonal basis providing more anatomical information, which will assist in any lung volume reduction therapy. Heterogeneity between target and adjacent lobes results in better outcomes following lung volume reduction. A variety of definitions of heterogeneity exist in the literature, in our institution we consider >10% difference in the ratio of destruction in the target and adjacent lobes significant (Fig 11). There are sources of variation in the CT measurements of lung density, which require standardisation if such tools are going to be used for treatment planning, patient follow-up, or longitudinal research studies. The attenuation values perceived can be affected by many imaging parameters such as section thickness, radiation dose, volume of inspiration, and use of iterative reconstruction techniques.10 The use of intravenous contrast medium inherently increases the density of the lung parenchyma with a reduction in the amount of quantified emphysema.11
Bullous emphysema As opposed to plain radiography, MDCT is a sensitive technique in the assessment of bullous disease. There are
Figure 8 Coronal MPR MIP images demonstrating endobronchial valves in the left upper lobe and lingular segmental bronchi (white arrows). Follow-up coronal MPR MIP images (b,c) demonstrates the valve originally in the left apico-posterior segmental bronchus (asterisk) now within the right bronchus intermedius (white arrowhead).
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Figure 9 (a) Coronal MPR demonstrates homogeneous distribution of emphysema. (b) Plain radiograph and (c) coronal MIP MPR image showing bilateral lower lobe endobronchial coils in situ.
varying definitions of giant bullae; a large bulla occupying more than one third or a hemithorax, or at least one half or >10 cm in diameter. Irrespective of the definition, these large airspaces do not contribute to gas exchange and exert mass effect by compressing relatively normal adjacent lung (Fig 12). Bullectomy is a form of lung volume reduction surgery and is the treatment of choice for such patients. MDCT has an important role in patient selection, surgical planning, and postoperative follow-up.
Assessment of large airways Variable tracheobronchial anatomy, such as tracheal bronchus is important to recognise, as it may change the approach to endobronchial therapy. If not identified, part of the target lobe may remain hyper-inflated due to ongoing inspiratory air flow. Tracheobronchomalacia (TBM) also known as excessive dynamic airway collapse (EDAC) is characterised by excessive collapsibility (>50%) of the central airways during expiration (Fig 13). It may be present in up to 50% of patients evaluated for COPD. MDCT with dynamic expiratory images
allows quantitative assessment of large airway dimensions. In our institution, routine expiratory sequences are not obtained unless there is clinical or bronchoscopic suspicion of TBM. TBM may itself require treatment, for example, airway stenting or surgical airway stabilisation before any endobronchial lung volume therapy is considered.
Disease associations There are several associated conditions that should be actively sought out on MDCT in patients with COPD. Bronchiectasis is reported to affect up to 50% of patients with moderate to severe COPD (Fig 14). This suggests that there may be a causal relationship in which COPD is a risk factor for bronchiectasis. There is a high prevalence of colonisation by Pseudomonas aeruginosa and higher frequency of hospital admissions due to infective exacerbations.12 Combined pulmonary fibrosis and emphysema (CPFE) is a relatively new entity whereby centrilobular and/or paraseptal emphysema typically in the upper zones with associated lower lobe pulmonary fibrosis.13 Pulmonary hypertension is a common complication during the clinical
Figure 10 (a) Coronal and (b) axial density mask images show areas of predominantly upper zonal emphysema (blue colour code) with a threshold density value of 950 HU. (c) Coronal density mask image with range of densities between 800 and 1000 HU gives an overview of the severity and distribution of emphysema. Images obtained with Pulmo 3D software package of Syngo Via VA11 (Siemens).
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Figure 11 MDCT quantitative package that highlights voxels within a given density range (in this case 950 HU) to quantitate emphysema by defining areas of abnormally low attenuation. This is calculated upper (a) middle (b), and lower zones (c) to identify heterogeneous disease (>10% difference between zones) with an upper zone predominance.
Figure 12 (a) Axial and (a) coronal MPR images demonstrating bilateral upper lobe bullous disease (arrows).
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Figure 13 Axial MDCT showing paired inspiratory (a) and expiratory (b) images that demonstrated excessive collapse of the trachea (arrow).
course of CPFE. Pulmonary artery dilatation with or without right ventricular dilatation may be seen at MDCT. Exacerbations of COPD are characterised by acute deterioration in respiratory symptoms and/or function. These episodes are responsible for considerable morbidity and mortality, particularly in patients with severe COPD. Infective exacerbations are common and mostly related to viral or bacterial infection; the later may result in focal nodular areas of consolidation that may mimic a neoplastic nodule. If the clinical picture is that of infection, in our institution we will sometimes advocate a short-term interval CT in 8 weeks. This avoids unnecessary percutaneous biopsy along with its inherent risks (Fig 15). Chronic airflow obstruction and emphysema are independent risk factors for the development of lung cancer (in addition to cigarette smoking). Ten to 30% of patients assessed with MDCT for consideration of LVRS will have incidental pulmonary nodules.3 Although only 3e5% eventually prove to be malignant, many nodules should be followed up according to the Fleischer society guidelines.14 It is especially important to recognise subsolid nodules as these require longer follow-up than pure solid nodules15 (Fig 16). The prevalence of pulmonary embolism in patients with COPD and suspicion of pulmonary embolism is 6.2%,
Figure 14 Axial CT image of right lower lobe bronchiectasis as evidenced by dilatation and mild thickening of the bronchi (arrow), the so called “signet ring sign”. Background moderate emphysema.
Figure 15 (a) Axial CT image showing nodule in peripheral aspect of middle lobe (arrow) with resolution on follow-up after an interval 8 week CT (b), the so-called “pseudo-tumour” appearance.
Figure 16 (a) Axial CT image showing a ground-glass nodule in the right upper lobe (arrow), which when followed-up at 6 months (b) had increased in both size and density (arrow). This proved to be an adenocarcinoma at biopsy.
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Figure 17 A 50-year-old man admitted with a non-infective exacerbation of COPD. (a) Axial CT image showing bilateral segmental pulmonary emboli (white arrows) on the background of severe centrilobular emphysema (b).
compared with only 1.3% where there was no clinical suspicion of pulmonary embolism. CT pulmonary angiography may, therefore, be required if an acute exacerbation is thought to be due to pulmonary emboli after careful clinical assessment16 (Fig 17). Coronary artery calcification (CAC) is frequently encountered on un-gated MDCT performed for investigation of emphysema and in large lung cancer screening programmes. Studies have shown good correlation of low-dose un-gated MDCT CAC scores with established ECG-gated MDCT (kappa 0.89).17 Furthermore, CAC is a better predictor of cardiovascular events and all-cause mortality than FEV1 and the extent of emphysema.18 Additional investigation of asymptomatic CAD may be triggered for patients with a high CAC score, in particular as part of a preoperative work-up for those patients being considered for LVRS.
Conclusion MDCT forms an important role in the diagnostic work-up of patients with COPD, in particular those with emphysema. Anatomical information can help identify patients whom will benefit from lung volume reduction and aid in the planning of endobronchial intervention. It is important to assess for associated conditions, such as bronchiectasis and neoplasm.
References 1. NICE COPD quality standard QS10 COPD. Available at: http:// publications.nice.org.uk/chronic-obstructive-pulmonary-diseasequality-standard-qs10/introduction-and-overview. [accessed 03.06.14]. 2. HSE Government COPD statistics. Available at: http://www.hse.gov.uk/ STATISTICS/causdis/copd/copd.pdf. [accessed 03.06.14]. 3. Matsuoka S, Yamashiro T, Washko GR, et al. Quantitative CT assessment of chronic obstructive pulmonary disease. RadioGraphics 2010;30:55e66. 4. Washko GR, Hoffman E, Reilly JJ. Radiographic evaluation of the potential lung volume reduction surgery candidate. Proc Am Thorac Soc 2008;5:421e6.
5. Shah PL, Herth FJ. Current status of bronchoscopic lung volume reduction with endobronchial valves. Thorax 2014;69:280e6. 6. Sciurba FC, Ernst A, Herth FJ, et al, VENT Study Research Group. A randomized study of endobronchial valves for advanced emphysema. N Engl J Med 2010;363:1233e44. 7. Koenigkam-Santos M, de Paula WD, Owsijewitsch M, et al. Incomplete pulmonary fissures evaluated by volumetric thin-section CT: semiquantitative evaluation for small fissure gaps identification, description of prevalence and severity of fissural defects. Eur J Radiol 2013;82:2365e70. 8. Slebos DJ, Klooster K, Ernst A, et al. Bronchoscopic lung volume reduction coil treatment of patients with severe heterogeneous emphysema. Chest 2012;142:574e82. 9. Klooster K, Ten Hacken NH, Franz I, et al. Lung volume reduction coil treatment in chronic obstructive pulmonary disease patients with homogeneous emphysema: a prospective feasibility trial. Respiration 2014;88(2):116e25. 10. Coxson HO. Sources of variation in quantitative computed tomography of the lung. J Thorac Imaging 2013;28:272e9. 11. Heussel CP, Kappes J, Hantusch R, et al. Contrast enhanced CT-scans are not comparable to non-enhanced scans in emphysema quantification. Eur J Radiol 2010;74:473e8. Soler-Catalun ~ a JJ, Donat Sanz Y, et al. Factors 12. Martínez-García MA, associated with bronchiectasis in patients with COPD. Chest 2011;140:1130e7. 13. Portillo K, Morera J. Combined pulmonary fibrosis and emphysema syndrome: a new phenotype within the spectrum of smoking-related interstitial lung disease. Pulm Med 2012;2012:867870. 14. MacMahon H, Austin JH, Gamsu G, et al. Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society. Radiology 2005;237:395e400. 15. Naidich DP, Bankier AA, MacMahon H, et al. Recommendations for the management of subsolid pulmonary nodules detected at CT: a statement from the Fleischner Society. Radiology 2013;266:304e17. 16. Rutschmann OT, Cornuz J, Poletti PA, et al. Should pulmonary embolism be suspected in exacerbation of chronic obstructive pulmonary disease? Thorax 2007;62:121e5. 17. Wu MT, Yang P, Huang YL, et al. Coronary arterial calcification on lowdose ungated MDCT for lung cancer screening: concordance study with dedicated cardiac CT. AJR Am J Roentgenol 2008;190:923e8. 18. Sverzellati N, Cademartiri F, Bravi F, et al. Relationship and prognostic value of modified coronary artery calcium score, FEV1, and emphysema in lung cancer screening population: the MILD trial. Radiology 2012;262:460e7.
Contents lists available at ScienceDirect
Clinical Radiology journal homepage: www.clinicalradiologyonline.net
Pictorial Review
The evolving role of MDCT in the assessment of patients with chronic obstructive pulmonary disease S. Karia a, *, R. Mahadeva b, A. Balan a, J. Babar a a b
Department of Radiology, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, UK Department of Respiratory Medicine, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, UK
article in formation Article history: Received 4 August 2014 Received in revised form 5 January 2015 Accepted 20 February 2015
The purpose of this article is to educate the reader in the value a radiologist can offer in the multidetector (MD) CT assessment of patients with chronic obstructive pulmonary disease (COPD). MDCT can identify patients in whom treatments such as lung volume reduction surgery or newer endobronchial therapies may be of benefit. We will also discuss important and under-recognised associated cardiorespiratory disease, which may be incidentally identified. Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. In the UK approximately 900,000 people have diagnosed COPD, a further 2 million people remain undiagnosed. The radiologist may be the first to suggest the diagnosis in patients imaged for other reasons or with unexplained respiratory symptoms. Between 25,000 and 30,000 deaths are caused by COPD each year, with one in eight emergency admissions to hospital as a direct result of the disease.1,2 COPD is defined as “a disease state characterised by airflow limitation that is not fully reversible”. This airflow limitation is due to small airways remodelling or emphysema but usually a combination of both.3 Pulmonary function tests are essential for the diagnosis of COPD and
* Guarantor and correspondent: S. Karia, Department of Radiology, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, UK. Tel.: þ44 01223 216 320, þ44 07811 325645 (mobile). E-mail address: [email protected] (S. Karia).
assessing response to treatment but provide functional information only. Multidetector (MD) CT provides information about the airways, parenchyma, vascularity, and regional quantity and distribution of emphysema. MDCT is used to differentiate emphysema-predominant and airway-predominant COPD. Needless to say, many patients may have components of both, therefore, forming a mixed phenotype.
Emphysema-predominant COPD Emphysema is defined as a permanent enlargement of the airspace distal to the terminal bronchioles with destruction of the alveolar wall and loss of alveolar attachments. There are three main subcategories of emphysema seen at MDCT. Centrilobular emphysema is the most common type of cigarette smoking-related emphysema (Fig 1). Paraseptal emphysema affects the most distal portion of the acinus, predominantly adjacent to pleura or interlobular septa (Fig 2). Panacinar emphysema uniformly affects the entire secondary lobule, usually associated with severe alpha-1 anti-
http://dx.doi.org/10.1016/j.crad.2015.02.015 0009-9260/Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
S. Karia et al. / Clinical Radiology 70 (2015) 752e759
753
Figure 1 (a) Axial CT image demonstrating moderate centrilobular emphysema (arrow) with (b) coronal MPR image demonstrating upper zonal distribution (arrows).
trypsin deficiency (Pi ZZ mutation) and also with cigarette smoking (Fig 3).
Airway-predominant COPD Chronic exposure to cigarette smoke causes direct damage to the airways with subsequent epithelial cell hyperplasia, smooth muscle hypertrophy, and mucous metaplasia. Fig 4 demonstrates some of the MDCT findings. Decisions regarding treatment of patients with emphysema should be discussed by a multidisciplinary team. The input of COPD physicians, thoracic surgeons, respiratory radiologists, nurses, and physiotherapists are vital to enable optimum assessment and inform an individualised treatment plan. In this review we will discuss the anatomical information the radiologist can provide, which will influence treatment decisions in patients with COPD.
Lung volume reduction Pathological specimens of patients with severe emphysema (physiological features of gas trapping and reduced
Figure 2 (a) Axial CT image demonstrates paraseptal emphysema that commonly abuts pleural surfaces. (b) Coronal MPR image showing severe paraseptal emphysema with a large right upper lobe bulla (arrow) causing compressive atelectasis of the middle lobe (arrowhead).
functional status) show significant loss of normal elastic connective tissue. This results in airway collapse on expiration, resulting in a reduced area for gas exchange with associated dynamic hyperinflation. Lung volume reduction can be achieved by either minimally invasive lung volume reduction surgery (LVRS) or endobronchial volume reduction. Both methods aim to remove (either physically or functionally) a hyperinflated diseased segment or lobe, which results in functional benefit to non-target lobe and diaphragmatic function. The National Emphysema Treatment Trial compared optimal medical treatment with optimal medical treatment combined with bilateral LVRS. In the latter group, patients showed marked improvements in functional capacity and survival in sub-groups of patients with heterogeneous disease4 (i.e., those with predominant upper-zone emphysema compared to lower zones). The initial increased morbidity and mortality associated with LVRS together with the limited patient selection criteria (heterogeneous disease) led to the search for alternative methods of lung volume reduction. The evolution of
Figure 3 (a) Coronal and (b) sagittal MPR images demonstrate diffuse lung parenchymal destruction with lower zone predominance in a patient with severe alpha-1 anti-trypsin deficiency.
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Figure 4 (a) Axial CT image shows decreased vascularity and lung attenuation (arrow) suggestive of air-trapping; this could be confirmed on expiratory imaging. (b) Axial CT image on mediastinal windows shows bronchial wall thickening and mucoid impaction (arrow).
interventional bronchoscopy has led to the development of novel endobronchial therapies such as endobronchial coils, thermal vapour glue, and endobronchial valves. The latter is the most established; these valves reduce the flow of air into the treated lobe during inspiration but allow secretions and air to be expelled from that region during expiration. The aim is isolation of a diseased lobe resulting in shrinkage of the volume of that lobe and eventually collapse5 (Fig 5). The effectiveness of endobronchial valve therapy is dependent on optimal patient selection and correct placement of the valves in the target lobe. As with LVRS, greater heterogeneity is associated with greater improvements in forced expiratory volume in 1 s (FEV1) and exercise capacity. One of the most important factors for successful lobe isolation and atelectasis is the absence of collateral ventilation pathways. The VENT trial (endobronchial valve for emphysema palliation trial) showed that patients with intact lobar fissures at CT had a 17.9% improvement in FEV1 at 12 months compared with 2.8% in patients with incomplete fissures.6
MDCT is a vital tool to evaluate fissure integrity (as a surrogate of interlobar collateral ventilation) and the presence of accessory fissures.7 In our institution, we subjectively assess integrity by using multiplanar reconstruction (MPR) reformatting and categorise fissures into complete or partial defects with subcategories of minor (10%; Fig 6). If the defect is thought to be intact or a minor defect and the patient is otherwise a good candidate for endobronchial valves, we will perform bronchoscopic assessment of collateral ventilation. This is assessed by measurement of flow and resistance following occlusion of the target bronchus by a balloon catheter (Chartis; PulmonX) Endobronchial valves are not without complications; there are increased rates of haemoptysis, exacerbations of COPD, and pneumothoraces6 (Fig 7). Endobronchial valves also may migrate into non-target lobes causing volume loss of potential healthy lung (Fig 8). Plain radiography has a limited role in precisely locating valves, and therefore, MDCT is recommended for full anatomical assessment.
Figure 5 (a) Coronal MPR image pre-endobronchial valve in 2010. (b) Following endobronchial valve placement in the segmental bronchi of the left upper lobe, there is expected left upper lobe atelectasis and elevation of the oblique fissure (arrow). (c) Further follow-up axial CT image shows complete left upper lobe collapse (arrow) with endobronchial valves in the segmental left upper lobe bronchi (asterisk).
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Figure 6 (a) Sagittal MPR image showing a major defect in the right horizontal fissure (arrow) and (b) a different patient showing a minor partial defect in the left oblique fissure (asterisk).
Figure 7 Coronal MPR images showing two endobronchial valves in the left upper lobe segmental bronchi (arrows) with a complicating left pneumothorax (asterisk).
Endobronchial coils are a new therapy that show promising results in patients with heterogeneous disease. The effect seen is independent on collateral ventilation pathways.8 Studies are ongoing in patients with homogeneous disease distribution (Fig 9), an important subgroup of patients who have limited treatment options.9
MDCT can be used in several ways to assess the extent and distribution of emphysema. Subjective assessment relies on the radiologist to score the severity of emphysema in three locations (upper, mid, and lower zones) in each lung but is prone to significant interobserver variation. Quantitative evaluation using MDCT involves assessment of the density of each voxel of lung parenchyma. A threshold value is then set (typically 950 HU), which allows differentiation between areas of emphysema and normal lung parenchyma (Fig 10). Longitudinal evaluation of serial changes in the quantity of emphysema in individuals can be assessed as the lowest 15th percentile (Hounsfield unit point below which 15% of the low-attenuation voxels are distributed [Perc15]). The latest software tools will now often automatically segment out anatomically defined lung lobes so that results can be expressed on a lobar rather than zonal basis providing more anatomical information, which will assist in any lung volume reduction therapy. Heterogeneity between target and adjacent lobes results in better outcomes following lung volume reduction. A variety of definitions of heterogeneity exist in the literature, in our institution we consider >10% difference in the ratio of destruction in the target and adjacent lobes significant (Fig 11). There are sources of variation in the CT measurements of lung density, which require standardisation if such tools are going to be used for treatment planning, patient follow-up, or longitudinal research studies. The attenuation values perceived can be affected by many imaging parameters such as section thickness, radiation dose, volume of inspiration, and use of iterative reconstruction techniques.10 The use of intravenous contrast medium inherently increases the density of the lung parenchyma with a reduction in the amount of quantified emphysema.11
Bullous emphysema As opposed to plain radiography, MDCT is a sensitive technique in the assessment of bullous disease. There are
Figure 8 Coronal MPR MIP images demonstrating endobronchial valves in the left upper lobe and lingular segmental bronchi (white arrows). Follow-up coronal MPR MIP images (b,c) demonstrates the valve originally in the left apico-posterior segmental bronchus (asterisk) now within the right bronchus intermedius (white arrowhead).
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Figure 9 (a) Coronal MPR demonstrates homogeneous distribution of emphysema. (b) Plain radiograph and (c) coronal MIP MPR image showing bilateral lower lobe endobronchial coils in situ.
varying definitions of giant bullae; a large bulla occupying more than one third or a hemithorax, or at least one half or >10 cm in diameter. Irrespective of the definition, these large airspaces do not contribute to gas exchange and exert mass effect by compressing relatively normal adjacent lung (Fig 12). Bullectomy is a form of lung volume reduction surgery and is the treatment of choice for such patients. MDCT has an important role in patient selection, surgical planning, and postoperative follow-up.
Assessment of large airways Variable tracheobronchial anatomy, such as tracheal bronchus is important to recognise, as it may change the approach to endobronchial therapy. If not identified, part of the target lobe may remain hyper-inflated due to ongoing inspiratory air flow. Tracheobronchomalacia (TBM) also known as excessive dynamic airway collapse (EDAC) is characterised by excessive collapsibility (>50%) of the central airways during expiration (Fig 13). It may be present in up to 50% of patients evaluated for COPD. MDCT with dynamic expiratory images
allows quantitative assessment of large airway dimensions. In our institution, routine expiratory sequences are not obtained unless there is clinical or bronchoscopic suspicion of TBM. TBM may itself require treatment, for example, airway stenting or surgical airway stabilisation before any endobronchial lung volume therapy is considered.
Disease associations There are several associated conditions that should be actively sought out on MDCT in patients with COPD. Bronchiectasis is reported to affect up to 50% of patients with moderate to severe COPD (Fig 14). This suggests that there may be a causal relationship in which COPD is a risk factor for bronchiectasis. There is a high prevalence of colonisation by Pseudomonas aeruginosa and higher frequency of hospital admissions due to infective exacerbations.12 Combined pulmonary fibrosis and emphysema (CPFE) is a relatively new entity whereby centrilobular and/or paraseptal emphysema typically in the upper zones with associated lower lobe pulmonary fibrosis.13 Pulmonary hypertension is a common complication during the clinical
Figure 10 (a) Coronal and (b) axial density mask images show areas of predominantly upper zonal emphysema (blue colour code) with a threshold density value of 950 HU. (c) Coronal density mask image with range of densities between 800 and 1000 HU gives an overview of the severity and distribution of emphysema. Images obtained with Pulmo 3D software package of Syngo Via VA11 (Siemens).
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Figure 11 MDCT quantitative package that highlights voxels within a given density range (in this case 950 HU) to quantitate emphysema by defining areas of abnormally low attenuation. This is calculated upper (a) middle (b), and lower zones (c) to identify heterogeneous disease (>10% difference between zones) with an upper zone predominance.
Figure 12 (a) Axial and (a) coronal MPR images demonstrating bilateral upper lobe bullous disease (arrows).
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Figure 13 Axial MDCT showing paired inspiratory (a) and expiratory (b) images that demonstrated excessive collapse of the trachea (arrow).
course of CPFE. Pulmonary artery dilatation with or without right ventricular dilatation may be seen at MDCT. Exacerbations of COPD are characterised by acute deterioration in respiratory symptoms and/or function. These episodes are responsible for considerable morbidity and mortality, particularly in patients with severe COPD. Infective exacerbations are common and mostly related to viral or bacterial infection; the later may result in focal nodular areas of consolidation that may mimic a neoplastic nodule. If the clinical picture is that of infection, in our institution we will sometimes advocate a short-term interval CT in 8 weeks. This avoids unnecessary percutaneous biopsy along with its inherent risks (Fig 15). Chronic airflow obstruction and emphysema are independent risk factors for the development of lung cancer (in addition to cigarette smoking). Ten to 30% of patients assessed with MDCT for consideration of LVRS will have incidental pulmonary nodules.3 Although only 3e5% eventually prove to be malignant, many nodules should be followed up according to the Fleischer society guidelines.14 It is especially important to recognise subsolid nodules as these require longer follow-up than pure solid nodules15 (Fig 16). The prevalence of pulmonary embolism in patients with COPD and suspicion of pulmonary embolism is 6.2%,
Figure 14 Axial CT image of right lower lobe bronchiectasis as evidenced by dilatation and mild thickening of the bronchi (arrow), the so called “signet ring sign”. Background moderate emphysema.
Figure 15 (a) Axial CT image showing nodule in peripheral aspect of middle lobe (arrow) with resolution on follow-up after an interval 8 week CT (b), the so-called “pseudo-tumour” appearance.
Figure 16 (a) Axial CT image showing a ground-glass nodule in the right upper lobe (arrow), which when followed-up at 6 months (b) had increased in both size and density (arrow). This proved to be an adenocarcinoma at biopsy.
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Figure 17 A 50-year-old man admitted with a non-infective exacerbation of COPD. (a) Axial CT image showing bilateral segmental pulmonary emboli (white arrows) on the background of severe centrilobular emphysema (b).
compared with only 1.3% where there was no clinical suspicion of pulmonary embolism. CT pulmonary angiography may, therefore, be required if an acute exacerbation is thought to be due to pulmonary emboli after careful clinical assessment16 (Fig 17). Coronary artery calcification (CAC) is frequently encountered on un-gated MDCT performed for investigation of emphysema and in large lung cancer screening programmes. Studies have shown good correlation of low-dose un-gated MDCT CAC scores with established ECG-gated MDCT (kappa 0.89).17 Furthermore, CAC is a better predictor of cardiovascular events and all-cause mortality than FEV1 and the extent of emphysema.18 Additional investigation of asymptomatic CAD may be triggered for patients with a high CAC score, in particular as part of a preoperative work-up for those patients being considered for LVRS.
Conclusion MDCT forms an important role in the diagnostic work-up of patients with COPD, in particular those with emphysema. Anatomical information can help identify patients whom will benefit from lung volume reduction and aid in the planning of endobronchial intervention. It is important to assess for associated conditions, such as bronchiectasis and neoplasm.
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