HRCT features noted in individual COPD patients
Chronic obstructive pulmonary disease (COPD) is a preventable and treatable respiratory disease with some significant extrapulmonary effects that may contribute to the severity in individual patients. Its pulmonary components are characterized by airflow limitation that is not fully reversible. COPD is a leading cause of morbidity and mortality worldwide. The economic and social burdens due to it are substantial and anticipated to increase in the coming decades due to continued exposure to COPD risk factors and the changing age profile of the world’s population. COPD mortality trends generally track several decades behind smoking trends. In US in 2000, more women than men died of COPD or its related complications.
COPD comprise of a heterogeneous group of disorders conventionally including emphysema, chronic bronchitis, peripheral airways disease and pulmonary vascular disease. It is a disease state that has seen significant changes in defining and excluding criteria over past 50 years. Spirometry, the most frequently used tool to diagnose COPD and to assess response to treatment in these patients, can provide only functional assessment. In contrast to spirometry, radiological imaging allows for regional assessment of the various compartments involved i.e. airways, parenchyma and vasculature. High-resolution computed tomography (HRCT) is recommended for the non-invasive and sensitive assessment of morphological changes in emphysema and has been shown to correlate well with pathology. With the advent of new imaging techniques like multi-detector row CT (MDCT), contrast-enhanced CT methods, spirometric controlled MDCT, use of Xenon gas to assess regional ventilation of the lungs, magnetic resonance imaging (MRI) of the lung developing its own arsenal like hyperpolarized He-3 MRI – new avenues are being opened up which are now increasingly supplemented with advanced and dedicated softwares.
2. Advantages of high resolution computed tomography
At present the diagnostic criteria recommended by the Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Lung Disease (GOLD guidelines) do not consider CT findings during initial diagnostic assessment (Pauwels & Buist 2001) and principally rely on spirometry. However, enough scientific literature suggests that HRCT is an important and indispensable tool for evaluation of COPD. Some of the uses of HRCT are described below in next sections.
2.1. Identifying causes of airway obstruction other than COPD
Chronic airflow obstruction may be caused by a wide variety of diseases like bronchiectasis, upper airway lesions, bronchiolar diseases, interstitial lung diseases etc that may often produce clinical symptoms inseparable those due to COPD. HRCT can clearly identify different causes of airflow obstruction. Kurashima et al (2005) showed in 516 consecutive patients whose postbronchodilator FEV1/FVC was less than 70%, HRCT was able to identify 12.7% of patients with pulmonary diseases other than COPD including sarcoidosis, diffuse panbronchiolitis and pneumoconiosis. The exact diagnosis of underlying pathology leading to air flow obstruction is essential in management and to predict response to treatment in these patients.
2.2. Identification of emphysema before appearance of clinical symptoms
HRCT can detect pulmonary emphysema even in asymptomatic smokers with normal lung functions. Recent GOLD guidelines have abolished stage 0 that included asymptomatic patients who were smokers and had normal lung functions; however, Sverzellati et al (2007) observed that 13/18 subjects with stage 0 had emphysema detected over HRCT scan. It reflects that HRCT is a sensitive tool to detect emphysema before it is manifesting clinically or with deranged pulmonary functions. Detection of early emphysema may be of enormous value to prevent its progression by smoking cessation and medical intervention (Morgan 1992).
2.3. Identifying and quantifying emphysema in patients with COPD
Emphysema, characterised by a parenchymal-predominant pathology in COPD and chronic bronchitis with an airway-predominant one are distinct phenotypes and might have evolved due to different responses to and pathogenesis related to smoking (Patel et al 2006). The emphysematous phenotype is conventionally associated with a more severe form of disease (Boschetto et al 2003, 2006). COPD patients with emphysema on HRCT have been observed to have higher BODE index (body mass index, airflow obstruction, dyspnoea, exercise performance) and a lower inspiratory capacity to total lung capacity ratio (IC/TLC) than those without emphysema. This suggests emphysematous patients have more extensive systemic involvements (Boschetto et al 2006). The ability to separate airway-predominant from parenchymal-predominant pathology in COPD may prove useful in applying specific therapies designed to prevent airway remodelling and parenchymal destruction (Grenier 2005).
HRCT often makes it possible to distinguish between different phenotypes of emphysema: smoking related phenotype, the centriacinar emphysema; and phenotype associated with α1-antitrypsin deficiency, panacinar emphysema. Moreover, HRCT can detect the coexistence of both panacinar and centriacinar emphysema in the same individual, as some patients with α1-antitrypsin deficiency may also be smokers (Copley et al 2002).
2.4. Detection of co-existing bronchiectasis
Presence of bronchiectasis in COPD patients on functional evaluation using spirometry is often not detected; this fact become appreciable when HRCT studies are done. One study observed that 29% of COPD patients who were having frequent exacerbations had bronchiectatic changes detected on HRCT (O’Brien et al 2000). Patel et al (2004) found that the extent of lower lobes bronchiectasis in these patients was related to colonization by the potential pathogens, increased inflammatory markers, and a longer time to symptom recovery after exacerbation. The likely pathogenesis for typical structural abnormalities seen on HRCT include damaged muco-ciliary transport, localized or diffuse peripheral obliteration of the bronchial tree and lung tissue scarring – all these may be acting in concert in COPD.
2.5. Evaluation of large airways
Airway predominant pathology in COPD is significant and it is diagnosed conventionally based on clinical symptomatology of chronic or recurrent excess of mucus secretion in the bronchial tree (chronic was defined as occurring on most days of three months of a year, for at least two successive years), in whom other causes of chronic cough have been excluded (American thoracic society, 1995). With the development of multidetector-row computed tomography (MDCT) understanding of the larger airway diseases has been improved dramatically. Volumetric thin-section CT scans are able to detect small pits or diverticulae along the inner surfaces of the large bronchi (Zompatori et al 2006). These pits are supposed to correspond to dilated bronchial gland ducts opening into the large airway lumen (Grenier et al 2004; Zompatori et al 2006).
2.6. Assessment of regional distribution of emphysema
HRCT scan can also provide details regarding regional distribution of emphysema. The role of distribution of emphysema on HRCT as a predictor of mortality is a hot topic. One study reported a greater proportion of emphysema in the lower lung versus the upper lung to be predictive of mortality; the authors speculated that lower-lobe emphysema may be either a marker of increased disease severity or, alternatively, a phenotypic or pathobiologic variant (Martinez et al 2006). Other studies explored the influence of the distribution pattern of emphysema on different lung function parameters. A higher percentage of emphysema in the core was associated with a more reduction in diffusion capacity (Aziz et al 2005). The contribution of emphysema at core to pulmonary dysfunction (with FEV1/ FVC %) may be larger than at periphery (Nakano et al 1999).
2.7. Essential for surgical interventions in COPD
Two surgical therapies, bullectomy and lung volume reduction surgery (LVRS), are sometimes recommended in COPD patients. A chest radiograph may suggest the presence of bullae, but accurate existence and extent of such lesions can only be assessed with chest CT scans (Martinez & Chang 2005). Similarly, the presence, extent, and distribution of emphysema can precisely be determined with a chest CT scan. The work over lung volume reduction surgery (LVRS) suggests more benefits in patients with upper lobe emphysema (Cooper et al 1995).
A chest CT scan is an important tool to determine patients who should not undergo LVRS (Group NETTR 2001). In NETT, LVRS was associated with a high risk of death (16% with LVRS compared with 0% in subjects treated medically) at 30 days in two types of subjects with emphysema: (1) those with FEV1 of less than or equal to 20% of predicted and non–upper lobe–predominant disease, and (2) subjects with FEV1 of less than or equal to 20% of predicted and a diffusing capacity less than or equal to 20% of predicted.
3. High resolution computed tomography: evolution with the time
During the last couple of decades, HRCT has been widely used to evaluate emphysematous and chronic bronchitis components of COPD. The initial work by Edinburg group was to use computed tomography to diagnose emphysema in living patients (Gould et al 1988). Since then, HRCT has been widely established to detect and quantify COPD and its subtypes. Several workers have studied the correlation of semi-quantitative scoring of COPD by HRCT, pathology, clinical features and pulmonary function tests (Sanders et al 1988; Gupta et al 2008, 2009). HRCT indices of emphysema reflect lung anatomy and represent the best way to assess emphysema severity in life (Newell et al 2004). The introduction of multidetector-row CT (MDCT) scanners has provided powerful tools to evaluate changes in both small and large airways. In addition, dynamic imaging via MDCT allows the assessment of perfusion and ventilation in the lung parenchyma. Therefore, CT is able to precisely define the pathological process by providing accurate anatomic informations as well as functional data from the area of interest.
The parameters that have been extensively used by different workers to detect and differentiate various diseases grouped under COPD, and to quantify these diseases are described in following sections.
4. Measurements of lung density
The digital data provided by HRCT can be analyzed to detect the presence and severity of emphysema by several means. The measurement of lung density for quantifying emphysema may be done by
The extent of emphysema can be determined by using a
Another objective way to measure emphysema on HRCT is assessment of
The softwares available in addtion with MDCT scanners make it possible to recognize and quantify emphysema faster than human evaluation; and it is now possible to apply techniques measuring lung density to volumetric data. The resolution achieved in thoracic HRCT allows the application of
A density-masking approach alone is not sufficient to accurately distinguish between normal and diseased lung, especially in the case of early or mixed pathologic processes (Uppaluri et al 1997, 1999; Hoffman et al 2006). Further, CT densitometry is known to be influenced by several factors (eg, age, weight, beam hardening from adjacent ribs etc.) and calibration must be performed in order to obtain reliable densitometry. Neither visual nor pure densitometric approaches to CT quantification of emphysema are, therefore, perfect.
In addition to assessment of percentage of voxels below a certain threshold, more sophisticated analytic softwares may analyse the CT scan data, contiguous emphysematous lesions can be clustered to obtain the volumes for small-sized, medium-sized, and large-sized emphysematous areas (
5. Mosaic attenuation pattern and air trapping
Abnormalities on HRCT that reflect small airways disease can be broadly categorized into indirect and direct signs: widespread scarring and obliteration of the bronchioles results in the indirect sign of patchy density differences of the lung parenchyma, representing areas of under-ventilated and under-perfused lung (
In our studies (Gupta et al 2008, 2009) including 40 COPD patients who were diagnosed based on GOLD criteria and who were evaluted for HRCT characteristics, 16/40 patients had classic mosaic attenuation pattern; the HRCT scans were undertaken during full inspiration. Some of these are shown in figure 1 (A to F).
6. Directly visible small airways
Several pathological studies have shown that the major site of airway obstruction in COPD is in airways with internal diameter lesser than 2 mm. The 2 mm airways are located between the fourth and the 14th generation of the tracheobronchial tree. These airways are not visible on HRCT scan in normal subjects. However, considerable thickening of the bronchiolar walls by inflammatory infiltrate and/or luminal and surrounding exudates render them directly visible (Hansell 2001). These diseased airways are visible on HRCT as dilated, air-filled, branching, tubular or ring-like structures in the lung periphery by wall thickening and dilation. When the airways are obliterated by submucosal or peribronchial fibrosis, nodular, linear, or branching peripheral opacities may be seen (Teel et al 1996). In our study, 36 out of 40 COPD patients showed directly visible small airways (figure 2).
7. Measurements of airway wall thickness
It has been observed that the size of the large and intermediate airways reflect airway dimensions in the smaller airways (Nakano et al 2005). Due to the interobserver disagreement in the visual interpretation of bronchial wall thickness on CT scans (Muller and Coxson 2002), there has been considerable interest in the development of objective measurements of airway wall dimensions. The most frequently reported method for measuring the airway lumen and wall areas relies on the “
In 42 COPD patients, bronchi with external diameter of greater than 2 mm and maximum to minimum diameter ratio less than 1.5 were selected (Orlandi et al 2005). Thickness to diameter ratio (TDR) and the percentage wall area (PWA) of these bronchi were computed. For each patient, mean TDR and mean PWA were calculated. The combination of PWA, TDR and PWA normalized to body weight correlated significantly (P < 0.05) with FEV1/SVC ratio and DLco in patients with chronic bronchitis but not in patients without chronic bronchitis.
In another study, thickness to diameter ratio (TDR), and percentage of wall area (WA%) were calculated on HRCT in 4 groups of patients : group O - healthy non smokers, group I - healthy current smokers, group II - patients with moderate COPD and group III - those with severe COPD as per GOLD classification (Deveci et al 2004). Both groups II and III had higher T/D ratio and WA% than group I and group I had higher values than group O. Airway wall thickening was found to be inversely correlated with FEV1 and positively related to the quantum of smoking.
8. Low attenuation areas of emphysema
HRCT is a reliable tool for demonstrating even subtle changes in secondary pulmonary lobules. Low attenuation areas of emphysema are distinctly visible on HRCT scan. These focal areas of decreased attenuation present differently in different types of emphysema (Nowell 2002).
to zonal differences in respiratory kinetics and lymph flow. HRCT in early centriacinar emphysema shows evenly distributed centrilobular tiny areas of low attenuation with ill-defined borders; with enlargement of the dilated airspace, the surrounding lung parenchyma is compressed and a clear border may be observed between the emphysematous area and normal lung.
Fig. 4. (A-B): Panacinar emphysema: HRCT scans showing diffuse low attenuation lung parenchyma – typical of panacinar emphysema
The subtypes of emphysema can usually be determined in mild or moderate cases, but classification into anatomic subtypes becomes more difficult by HRCT and pathological examinations as emphysema becomes more severe, with even highly trained and experienced pathologists sometimes disagreeing on the classification. Centriacinar and panacinar emphysema may coexist in the same patient; for example, with centriacinar emphysema in the upper lobe and panacinar emphysema in the lower lobe.
Studies have been done to assess the accuracy of CT in diagnosis of emphysema by visual scoring of low attenuation areas. In a study, CT thorax was performed on 32 patients scheduled for elective thoracotomies for suspected lung tumours (Bergin et al 1986). Each slice was assessed and graded depending upon the percentage area showing emphysematous areas. Similarly, emphysema was graded on the resected lung specimens. It was found that compared to pulmonary function tests, CT was a better predictor of assessing the presence and severity of emphysema.
A retrospective study used HRCT scans for scoring the severity of emphysema (Klein et al 1992). Each of the six lung sections was evaluated and extent of emphysema multiplied by the severity was summed for the six sections. Concomitant chest radiographs and pulmonary function tests were reviewed. The severity of emphysema on HRCT correlated inversely with single breath carbon monoxide diffusion capacity.
9. Vascular attenuation and vascular distortion
On HRCT of emphysema patients, low attenuation areas are frequently accompanied with vascular attenuation and distortion (Nowell 2002).
In a study, two radiologists and one chest physician assessed for destructive changes of emphysema manifested by low attenuation areas and disruption of vascular pattern (Kuwano et al 1990). Each slice was individually assessed using a modification of the
10. Saber-sheath trachea and tracheal index
In cross-section, the resting trachea is roughly horse-shoe shaped, with the open end of the cartilage rings closed by a compliant posterior sheath. In COPD patients, the coronal diameter is reduced and the saggital diameter correspondingly increased, a condition called
In a study, it was found that patients with COPD had a reduced tracheal index. Saber-sheath trachea (tracheal index < 2/3) was observed to be a specific radiographic diagnostic parameter for the diagnosis of COPD (specificity, 92.9%), although sensitivity (39.1%) was low (Tsao et al 1994).
In another study (Trigaux et al 1994), 20 patients with saber-sheath trachea were compared with 20 controls without saber-sheath trachea by measuring standard HRCT indices of COPD and functional tests including FEV1, DLco and FRC. Tracheal index was significantly correlated with the FRC values and it was concluded that saber-sheath trachea is basically a sign of hyperinflation in COPD pateints. Similarly, in a different study ( Arakawa 1998 ), reduced tracheal index and other signs of hyperinflation of thoracic cage on CT were found to correlate significantly with pulmonary functions of chronic airway obstruction.
11. Sterno-aortic distance and mediastinal anterior junctional line
In retrosternal region, right and left lung with their corresponding pleural layers approach each other so closely that the area of contrast form a linear density. When present, the line is 1 to 2 mm wide and formed by two pleural layers on each side of a narrow zone of mediastinal connective tissue. This line is called
In a study, AJL and sterno-aortic distance (distance between sternum and ascending aorta) were measured in CT sections at carinal level in 22 patients with emphysema and 22 control subjects (Hagen & Kolebenstvedt 1993). The AJL could be measured in all emphysema patients. In the control group the line was non-existent in 11 of the 22 patients. The AJL was 3 cm or more in 10 of the emphysema patients, but in none of the controls. The sterno-aortic distance was 4 cm or more in 16 of the emphysema patients, but in none among control group.
In another study, significant correlation was found between FEV1 / FVC and sterno-aortic distance (measured at tracheal carina on CT) in 74 patients who underwent thoracic surgery for lung cancer (Arakawa et al 1998).
12. Thoracic cage ratio and barrel chest
Arakawa et al (1998) measured thoracic cage ratios (anteroposterior/ transverse diameters) at carina and 5 cm below carina on CT in 74 patients. Other measurements of hyperinflation were also calculated and it was found that increased thoracic cage ratio correlated most significantly with a pulmonary functions of chronic airway obstruction.
In another study, normal thoracic cage ratio was 0.70 to 0.75 in adults. The thoracic cage ratio was found high in COPD patients and may reach upto > 0.9 which was called as barrel chest (Pierce et al 1958). Figure 10 (A-B) shows HRCT scans with barrel chest feature found in our studies (Gupta et al 2008, 2009).
13. Thoracic cross-sectional area (TCSA) index
The assessment of thoracic cross-sectional area (TCSA) is an important measure of thoracic cage hyperinflation commonly seen in advance COPD with air trapping and increased total lung capacity. TCSA is the area surrounded by the rib cage measured on CT scan made 1 cm below the top of the aortic arch. In a study (Kasai et al 2003) TCSA and pulmonary functions and dyspnea grade were measured in 24 COPD patients. In the group with grade IV dyspnea, the TCSA/ht2 ratios were significantly greater than those in the groups with grade II and III dyspnea, combined. Analysis of data showed a good correlation between TCSA and total lung capacity, as well as functional residual capacity and residual volume.
14. HRCT characteristics observed in our studies
Our studies included 40 male patients with COPD. Their mean age was 58.55 years (range: 50-69 years). Total duration of illness due to COPD was in range from 2 to 25 years with a mean of 12.63 years. All subjects were significant smoker with mean smoking history of 33.25 pack years (range 20-74 pack years). They were evaluated for HRCT features including vascular attenuation and distortion, mosaic attenuation pattern, directly visible small airways, low attenuation areas of emphysema and measures of hyperinflation of lungs: tracheal index, sterno-aortic distance, thoracic cage ratio and thoracic cross-sectional area. Individual COPD patients having characteristics HRCT findings were as shown in table-1.
In our studies, tracheal index was observed to have significant inverse correlations with duration of illness, smoking pack years, and dyspnea scale; and had direct correlations with FEV1, PEFR, FEV1/FVC ratio, and FEV1/SVC ratio. Thoracic cage ratio at carina as well as thoracic cage ratio at 5 cm below carina had direct correlations with duration of illness, smoking pack years and dyspnea scale; and had inverse correlations with FEV1, FEV1/FVC ratio and FEV1/SVC ratio. Sterno-aortic distance and thoracic cross sectional area had correlations with duration of illness, smoking pack years and dyspnea scale; and they had inverse correlations with FEV1, FEV1/FVC ratio, and FEV1/SVC ratio.
|Saber sheath trachea with tracheal index less than 0.67||14||35|
|Thoracic cage ratio over 0.75 at the level of carina||5||12.5|
|Thoracic cage ratio over 0.75 at the level 5 cm below carina||11||27.5|
|Sterno-aortic distance more than 4 cm||5||12.5|
|Thoracic cross-sectional area/ht2 more than 80.00 cm2/m2||28||70|
|Mosaic attenuation pattern||16||40|
|Directly visible small airways||36||90|
|Any type of emphysema||25||62.5|
Vascular attenuation had significant correlations with duration of illness, dyspnoea scale, smoking pack years, FEV1, FEV1/FVC ratio, and FEV1/SVC ratio. Vascular distortion had no significant correlation with any of the observed parameter. The mosaic attenuation pattern correlated significantly with duration of illness, dyspnea scale, smoking pack years, FEV1, FEV1/FVC ratio, and FEV1/SVC ratio. Correlation of presence of directly visible small airways was significant only with dyspnea scale. Centriacinar emphysema had significant correlations with PEFR, FEV1, FVC, FEV1/FVC ratio and FEV1/SVC ratio. Correlations of presence of any type of emphysema with age, duration, dyspnea scale, pack-years, PEFR, FEV1, FVC, FEV1/FVC ratio and FEV1/SVC ratio were statistically significant.
15. Recent advances
COPD is a heterogeneous group of disorders and needs to be evaluated by a combination of morphological and functional assessment. Recently, newer HRCT techniques as well as MRI have provided new insights to characterisation of various pulmonary components of COPD in term of morphology as well as functionality. Three-dimensional HRCT has been described as the technique of choice for morphological imaging. Inspiratory and expiratory 3D-HRCT with volumetric and texture analysis allows for deeper insights to regional hyperinflation and expiratory obstruction. Three-dimensional HRCT has also been described as the “gold standard” for non-invasive quantitative evaluation of airway dimensions. Newer generations of MRI allow for better visual assessment of the lung morphology as well as comprehensive functional imaging. The major advantage of MRI is the assessment of regional lung function including perfusion, respiratory dynamics and ventilation. The comprehensive diagnostic possibilities of CT complemented by MRI will allow for a more sensitive detection, phenotype-driven characterization and dedicated therapy monitoring of COPD.
While all this description appears voluminous, many things have not been discussed in detail due to want of space. The imaging techniques we are applying in day to day practice at present have opened new avenues for morphological and functional characterisation of various diseases incorporated under the heterogeneous group of COPD and helped in phenotyping as well as assessment of the progression of COPD. And, this is just beginning! In future we are definitely going to get more powerful equipments, supplemented with dedicated and advanced softwares that will provide deeper insight into the various diseases grouped under the umbrella of COPD.
The author wish to express his profound gratitude to Prof. Rohtas Yadav, Senior Professor, Radiodiagnosis; Dr Manish Verma, Ex-Resident, Respiratory Medicine; Prof. K B Gupta, Senior Professor, Respiratory Medicine; Dr Dipti Agarwal, Assistant Professor, Physiology; and Dr Manoj Kumar, Expert, Biostatistics – all from Postgraduate Institute of Medical Sciences, University of Health Sciences, Rohtak, India for their kind help, necessary inputs and critical review of the literature.