Lung densitometry: why, how and when

Abstract

Lung densitometry assesses with computed tomography (CT) the X-ray attenuation of the pulmonary tissue which reflects both the degree of inflation and the structural lung abnormalities implying decreased attenuation, as in emphysema and cystic diseases, or increased attenuation, as in fibrosis. Five reasons justify replacement with lung densitometry of semi-quantitative visual scales used to measure extent and severity of diffuse lung diseases: (I) improved reproducibility; (II) complete vs. discrete assessment of the lung tissue; (III) shorter computation times; (IV) better correlation with pathology quantification of pulmonary emphysema; (V) better or equal correlation with pulmonary function tests (PFT). Commercially and open platform software are available for lung densitometry. It requires attention to technical and methodological issues including CT scanner calibration, radiation dose, and selection of thickness and filter to be applied to sections reconstructed from whole-lung CT acquisition. Critical is also the lung volume reached by the subject at scanning that can be measured in post-processing and represent valuable information per se. The measurements of lung density include mean and standard deviation, relative area (RA) at -970, -960 or -950 Hounsfield units (HU) and 1st and 15th percentile for emphysema in inspiratory scans, and RA at -856 HU for air trapping in expiratory scans. Kurtosis and skewness are used for evaluating pulmonary fibrosis in inspiratory scans. The main indication for lung densitometry is assessment of emphysema component in the single patient with chronic obstructive pulmonary diseases (COPD). Additional emerging applications include the evaluation of air trapping in COPD patients and in subjects at risk of emphysema and the staging in patients with lymphangioleiomyomatosis (LAM) and with pulmonary fibrosis. It has also been applied to assess prevalence of smoking-related emphysema and to monitor progression of smoking-related emphysema, alpha1 antitrypsin deficiency emphysema, and pulmonary fibrosis. Finally, it is recommended as end-point in pharmacological trials of emphysema and lung fibrosis.

Keywords: Chronic obstructive pulmonary diseases (COPD); computed tomography (CT); emphysema; lung densitometry; pulmonary fibrosis.

Figure 1

Density histogram indicating the appearance in normal lung and in emphysema, and the derivation of densitometry indexes. The 15th percentile point (Perc15) is defined as the cut-off value, in HU, below which are distributed the 15% of voxels with the lowest density. The voxel index at a threshold of −950 HU (RA950) is shown and is defined as the percentage of voxels with a value less than −950 HU. Adapted and reproduced with permission from reference (55). HU, Hounsfield units.

Figure 2

Low-dose CT image at aortic arch (A) in one subject undergoing lung cancer screening showing multiple areas of decreased attenuation bilaterally. In (B) the pixels with density values below −950 HU (RA950) are outlined in red. Adapted and reproduced with permission from reference (56). CT, computed tomography.

Figure 3

Coronal CT reconstructions and corresponding CT histograms from (A) a healthy individual, (B) a patient with mild lung fibrosis, and (C) a patient with advanced lung fibrosis. In the healthy individual with no lung fibrosis, the CT histogram is sharply peaked and substantially skewed to the left, compared with a Gaussian normal distribution. In the patient with mild fibrosis, the curve is less peaked (less kurtosis) and less skewed. This tendency is even more substantial in the patient with advanced lung fibrosis. Adapted and reproduced with permission from reference (6). CT, computed tomography.

Figure 4

Correlation plot between lung volume and average MLA in 266 smokers or former smokers examined with low-dose CT shows dependency of lung density from lung volume. Adapted and reproduced with permission from reference (56). HU, Hounsfield units; MLA, mean lung attenuation; CT, computed tomography

Figure 5

Relationship between WA% and extent of emphysema (LAA%) in 94 COPD patients and 20 asymptomatic smokers. Horizontal line shows the mean +2SD of LAA% of the asymptomatic smokers. Vertical line shows the mean +2SD of WA% of the asymptomatic smokers. Using these cutoff values, COPD patients can be divided into groups; airway remodeling-dominant group (high WA% and low LAA%), emphysema-dominant group (low WA% and high LAA%), and a mixed group (high WA% and high LAA%). Reproduced with permission from reference (96). WA, wall area; LAA, low attenuation areas; COPD, chronic obstructive pulmonary diseases.

Figure 6

Local histogram-based (CALIPER) analysis of progressive lung fibrosis at baseline and 4 years later. (A) CT sections through the lower lungs show progression (left to right image) of the lung fibrosis; (B) CALIPER analysis with color coding according to CT pattern shows increase in extent of patterns characterized as ground glass abnormality (yellow) and a reduction in the extents of LAA (blue) and normal lung (green); (C) glyph-based analysis summarizes the extent of each pattern of abnormality in each lobe (the same color coding as in part B). The left lower lobe has decreased in volume. A relative increase is shown in extent of fibrotic abnormality (mainly yellow, orange, and red) and a decrease in normal lung (green) during 4 years (left glyph-based analysis to right). Reproduced with permission from reference (6). RU, right upper; LU, left upper; LM, left middle; RM, right middle; LL, left lower; RL, right lower; LAA, low attenuation areas.

Figure 7

COPD phenotypes identified by parametric response mapping (PRM). The strength of PRM to identify functional small airways disease (fSAD) from emphysema is demonstrated in representative coronal PRM images with corresponding inspiratory and expiratory CT scans from four individuals with varying GOLD status. From the three classifications, normal lung tissue is denoted green, fSAD is denoted yellow and emphysema is denoted red. Yellow scale bar indicates 5 cm. Reproduced with permission from reference (130). COPD, chronic obstructive pulmonary diseases.