Conclusión final

Conventional x-ray imaging is inherently limited to providing two-dimensional (2D) images of three-dimensional (3D) anatomical structures. CT technology overcomes this drawback by rotating the conventional x-ray tube around a patient to construct a 3D volume of the region of interest. The 3D volume created from the CT scan is made up of voxels (volume elements), each of which has a Hounsfield Unit (HU) associated with it based on the attenuation of x-rays through that region. The HU scale uses water as a reference, where water has a HU = 0, air has HU = -1000 and solid structures such as bone have HU > +1000 (72). Ultimately, CT provides 3D images of the anatomy based on density and since many tissues and organs within the body have different densities, good contrast can be achieved with conventional CT imaging.

As described in Section 1.2, one pathophysiological phenotype of COPD is emphysema. When the alveoli are destroyed, alveolar ducts and sacs coalesce and the distal airspaces

enlarge to ultimately cause a decrease in parenchymal density. Therefore, on CT images, emphysematous regions within the lung have attenuation values close to that of air (≤- 950HU) and appear darker than the higher density parenchyma surrounding them. Extensive research and debate is ongoing to determine an optimal HU threshold to define emphysema on CT. Currently, the most commonly used HU threshold to identify emphysema is -950HU, whereby regions of the lung with attenuation ≤-950HU are considered to be emphysematous. This threshold has been confirmed to correspond to emphysematous lesions on pulmonary histology of macroscopic (73) and microscopic (74) emphysema. Figure 1-7 shows emphysematous lung regions ≤-950HU on CT in a healthy volunteer and a COPD patient. It is important to note that other thresholds are also in use for the purpose of identifying mild emphysema (-910HU) and gas trapping on expiratory CT (-856HU) (75-77). Another method for quantifying emphysema on CT is focused on the HU below which fifteen percent of all x-ray attenuation values fall (PD15).

Using this method, the measurement of emphysema is a HU not a percent of the lung as it is with the threshold cutoff. While both the threshold and percentile methods are widely used and considered appropriate for cross-sectional studies, the 15th percentile analysis is recommended for longitudinal studies because it is less sensitive to changes in CT scanner technology that may occur over time (78). At the same time, methods for quantitatively describing the size and distribution of emphysematous clusters (regions of RA950) on CT have also emerged (79). The value of measuring these low attenuation

clusters (LAC) relies on the concept that emphysematous lesions tend to coalesce and form larger clusters (bullae) as emphysema progresses. The total number of emphysematous clusters (clusters of voxels <-950HU) is plotted against the cluster size in the log-log domain. The slopes of the plots can then be described by the power law and the value of the slope is obtained by linear regression and used to quantify the LAC. In this manner subjects with early or mild forms of emphysema have smaller and more emphysematous clusters and subsequently have a more negative LAC (higher slope) while COPD subjects who have larger emphysematous bullae and fewer total clusters have a more positive LAC (flatter slope).

Along with regionally mapping and quantifying emphysema within the lung, thoracic CT is also used to evaluate airway structure. By measuring the cross section of the airways,

measurements of the airway lumen and wall thickness can be assessed. The measurements of airway wall area percent (WA%) and lumen area (LA) were the first to be shown to significantly correlate with measures of lung function in COPD patients where the airway wall thickness increased and airway lumen area decreased as FEV1

decreased (80). However this early work focused predominantly on measuring the large and central airways which do not reflect the main site of airflow obstruction in COPD. Subsequent studies have transitioned to measuring higher generation airways (81), counting the number of airways visible on CT (82) and estimating small airway dimensions (83). Figure 1-7 shows CT airway trees in a healthy volunteer and COPD patient. Visibly, the COPD subject has few and thinner airways than the healthy subject.

Figure 1-7. Thoracic CT and segmented airway tree of a healthy volunteer and a COPD patient.

Emphysema, or areas of the lung ≤-950HU on CT are shown in yellow. Compared to the healthy subject, the COPD patient has more severe emphysema and fewer airways present as measured by CT.

Lastly, an important consideration for using CT to evaluate and monitor COPD is the radiation dose associated with each scan. In COPD, longitudinal monitoring is necessary for evaluating disease progression or response to treatment or surgery. The radiation dose associated with a single conventional chest CT is estimated to be ~7 mSv which is equivalent to 2.8yr of natural background radiation (84). Therefore, if CT is the only option available for pulmonary imaging at a specific centre or within a region, it is clear that careful planning is required in order to longitudinally image a COPD patient because of the risk of radiation-induced cancers from cumulative dose of serial CT scans. One potential solution to the burden of radiation dose associated with chest CT scanning is the further development of iterative reconstruction techniques and their incorporation into clinical use instead of, or along with, filtered back projection (FBP) reconstruction approaches. Unlike FBP which is rapid and requires little computational processing, iterative approaches correct image data using a variety of models and require long computing times (85). Current iterative reconstruction techniques can produce thoracic CT images of similar or better quality (based on signal-to-noise ratio) using a lower dose than images acquired using FBP (86). The downside is that the reconstructive approach used during acquisition influences quantitative (and potentially qualitative) measurements of emphysema and airways disease. Therefore, scientists and clinicians would need to meet and overcome the challenge of standardizing reconstructive approaches across academic centres where large-scale and long-term follow-up studies are ongoing in order to compare and concatenate data.