CT Measurements of Lung Density in Life Can Quantitate Distal Airspace Enlargement—An Essential Defining Feature of Human Emphysema

Abstract

We used a computerized microscopic image analysis system to directly measure the surface area of distal air spaces in methacrylate-embedded blocks randomly selected from inflation-fixed lobes that were resected from 45 patients as treatment of their peripheral lung tumors. In 28 of these patients, a preoperative computer tomography (CT) scan, at 6 and 10 cm below the sternal notch, was used to generate frequency histograms of CT numbers (measured as EMI units), a measure of lung density, in pixels from the lung or lobe that was subsequently resected. A similar CT number histogram was also derived from the lateral two fifths of the area of lobe/lung that was to be resected. The EMI unit that defined the lowest fifth percentile of this latter histogram correlated (n = 28, r = -0.77, p less than 0.001) with the mean value of the surface area of the walls of distal airspaces per unit lung volume (AWUV) in the five 1 mm x 1 mm microscopic fields with the lowest AWUV values, out of the 20 to 35 such fields examined in each patient. In the 34 of the 45 patients in whom we also measured volume-corrected diffusing capacity (DLCO/VA), this also correlated (n = 34, r = 0.84, p less than 0.001) with this value of AWUV, which measures the surface area of airspaces distal to the terminal bronchioles--reflecting an increase in airspace size, a defining characteristic of emphysema. However, a low DLCO/VA is nonspecific, whereas an abnormally low regional lung density is more likely to be specific for emphysema. In addition, highlighting those pixels of the CT display with low CT numbers (i.e., EMI units -500 [air] to -450, where zero = water) can locate areas of macroscopic emphysema, as shown by subsequent pathologic examination. Thus the quantitative CT scan can diagnose, quantitate, and locate mild to moderate emphysema, in humans, in life, noninvasively.

Report of a workshop: quantitative computed tomography scanning in longitudinal studies of emphysema

“…GOULD et al [33] reported the first successful application of a quantitative CT technique that correlated well with pathological evidence of emphysema.…”

Quantitative Computed Tomography Assessment of Airway Wall Dimensions: Current Status and Potential Applications for Phenotyping Chronic Obstructive Pulmonary Disease

“…Ever since the work by Hayhurst and coworkers (31), Gould and coworkers (32), and Mü ller and coworkers (33) showed that the extent of emphysema could be measured using CT, these techniques have been applied to studies of COPD. These early studies showed that by using either a threshold technique whereby any lung voxels with X-ray attenuation values less than a given cutoff (e.g., 2910 HU) (33) or the X-ray attenuation value (measured in HU) at a given percentile point of the distribution of X-ray attenuation values (e.g., 5th percentile point) (31,32) correlated with extent of emphysema measured using quantitative pathology.…”

“…These early studies showed that by using either a threshold technique whereby any lung voxels with X-ray attenuation values less than a given cutoff (e.g., 2910 HU) (33) or the X-ray attenuation value (measured in HU) at a given percentile point of the distribution of X-ray attenuation values (e.g., 5th percentile point) (31,32) correlated with extent of emphysema measured using quantitative pathology. These original studies have been refined over the years with different threshold points being redefined (9,34,35), as CT scanners and image reconstruction techniques have evolved but the basic principle remains the same, that low attenuating areas on CT are indicative of lung tissue destruction ( Figure 5).…”

Reproducibility of spirometrically controlled CT lung densitometry in a clinical setting

“…Mean lung density, however, is not the only densitometric parameter which can be extracted from the CT data. Pixel index analysis [3,4,14] and the lowest 10th percentile of the frequency distribution of densities [15] have shown promising results in the assessment of emphysema.If densitometry of the lung is used for diagnosis and follow-up of pulmonary emphysema or interstitial lung disease, the overall precision of the procedure has to be established. Reproducibility errors due to instrumental and technical factors have generally been considered to be smaller than patient-related factors.…”

“…Mean lung density, however, is not the only densitometric parameter which can be extracted from the CT data. Pixel index analysis [3,4,14] and the lowest 10th percentile of the frequency distribution of densities [15] have shown promising results in the assessment of emphysema.…”