X-ray Computed Tomography

Since its introduction in the early 1970s, CT scanning technology has become so advanced that it is now considered by many as the imaging technology of choice for many diseases. As described above, a limitation of conventional x-ray imaging is that it provides a two-dimensional image of a three-dimensional object. CT overcomes this limitation by acquiring the image in slices thereby providing images of three-dimensional objects. Each slice in a CT image is composed of voxels and each voxel is assigned a CT value or Housfield unit (HU) based on the attenuation coefficient relative to water. Therefore, a voxel that contains water will have a value of 0 HU, while air will have a value of -1000 HU and tissues or structures that have a higher attenuation coefficient than water will have a positive HU value; bone has CT values up to 2000 HU.85

Emphysema is characterized by airspace enlargement,79 and therefore the air-filled emphysematous regions in the lung will appear dark in CT images. Figure 1-13A shows a central slice CT image for a healthy subject and a COPD subject with emphysema. The

Figure 1-12 Chest x-ray of a COPD subject

Posterior-anterior chest x-ray (A) and lateral chest x-ray (B) for a 62-year-old male smoker. Reproduced with permission from Parraga et. al (2007).89

air filled regions, including the trachea as well as the large left apical bullae in the COPD subject with emphysema appear dark in the image. Early pathological correlative studies demonstrated that regions of the lung that visually appeared to be emphysematous on CT images were confirmed as emphysematous in post-mortem evaluations.90 Later, studies that used radiologist CT grading and pathological grading systems demonstrated that there were strong and statistically significant correlations between CT and pathology emphysema scores,91-93 however it was found that CT could not differentiate mild emphysema from normal parenchyma confirmed by pathology in some patients.92

Although CT was demonstrated to be very accurate in the determination of the presence and extent of moderate to severe emphysema, with strong and significant correlations found with both pathology91-93 and measurements of airflow limitation and diffusion capacity,93 these early visual scoring systems were subjective and therefore there was considerable inter-observer and intra-observer variability.93 Because visual assessment was based on the presence of voxels with abnormally low attenuation, the extent of emphysema could be assessed by highlighting voxels within specified ranges of HU called “density masks.”94 Density mask emphysema scores were demonstrated to be comparable to visual emphysema scores and had strong and significant correlations with pathologic scores,94 and importantly, eliminated the inter-observer and intra-observer variability introduced by visual assessment. Figure 1-13B shows the CT density mask with all voxels with attenuation values less than -950 HU highlighted in red. Although there are several thresholds that have been introduced, and some contrasting results on which threshold is most appropriate,94-96 it has been demonstrated that the low attenuating areas quantified on CT are indicative of the lung tissue destruction that accompanies emphysema.

Although strong and significant correlations between CT measurements of emphysema and diffusion capacity measurements have been reported, there have been only moderated correlations with measurements of airflow.93;95 This finding is not surprising given that measurements of airflow limitation (FEV1) are measuring the contributions of the loss of

elastic recoil due emphysematous tissue destruction (emphysema) as well as airway narrowing and obstruction (chronic bronchitis and small airways disease). Therefore, it is

also of great interest to obtain measurements of the airway dimensions from CT. Figure 1-14 shows an airway tree segmentation that was generated in three-dimensions from the CT image. The cross-section of the airway of interest can then be identified and the airway dimensions can be measured. Nakano and colleagues were the first to demonstrate that the percentage of the total airway (airway wall area plus lumen area) that was airway wall (wall area percent, WA%) significantly correlated with airflow limitation, but not DLCO, in COPD smokers independent of emphysema.97 However,

these measurements were based on a large central airway and it is well known, as described above, that the major site of airflow limitation in COPD occurs in the small airways less than 2 mm in diameter.75 Accordingly, more recent studies have demonstrated that the correlation between CT wall area dimensions with airflow limitation was stronger for higher generation airways.98

Figure 1-13 Coronal CT of a healthy smoker and a COPD ex-smoker

The central slice coronal CT image (A) with the corresponding density mask with all voxels with attenuation values less than -950 HU highlighted in red (B) for a healthy subject and a COPD subject with emphysema.

Although thoracic CT is capable of measuring both emphysema and airways disease in COPD, CT is not without its costs and the field of medicine has observed a considerable increase in the number and type of CT scans performed for clinical investigation where now, in the United States, CT accounts for 24% of all radiation exposure and 50% of all medical radiation exposure.99 Importantly, the increase in CT scans was also observed in the paediatric population and a study by Mettler and colleagues100 reported that children aged 0-15 years old accounted for 11.2% of all CT scans performed. This is a concern because the effective dose for a thoracic CT is approximately 8 mSV, which is equivalent to 400 chest x-rays or approximately 4 years of background radiation.85 In COPD, serial imaging is important for evaluating disease progression and response to treatment or intervention, and therefore the increase in radiation exposure from CT has been a major concern because there is an increased risk of radiation-induced cancer from the cumulative dose related to repeated CT investigations.101

Figure 1-14 CT airway analysis of a COPD subject

The airway tree segmentation in three-dimensions is obtained from the original CT image, with the surrounding lung parenchyma removed from view, to identify the airway of interest for measurement of the airway dimensions, as shown in red. The airway tree and airway measurements were performed using the Pulmonary Workstation 2.0 (VIDA Diagnostics, Inc., Coralville, IA).