It is generally considered that the hazy increased density and consolidation seen on high resolution lung CT (HRCT) scans in patients with diffuse interstitial lung disease reflect tissue inflammation, whereas a predominance of linear structures corresponds to tissue fibrosis. The purpose of this study was to determine whether abnormalities observed by HRCT in the lungs of bleomycin-treated rabbits correlated with specific pathologic abnormalities seen on morphometric analysis of lung tissue. Bleomycin was instilled into the lungs of intubated rabbits and followed by inhalation of 100% oxygen. In different animals on Days 14, 28, or 56 after bleomycin, 1 or 1.5 mm HRCT scans were obtained at 8-mm intervals. Subsequently, the right lungs were processed for histology, and the left lungs were processed for determination of hydroxyproline content. Using a morphometric technique, the volume density of normal lung parenchyma, hazy increased density, consolidation, nodules, and central or peripheral lines was determined on each HRCT scan. After the rabbits were killed, the volume density of normal lung parenchyma, intra-alveolar cells, intra-alveolar amorphous material, and thickened interstitium (cellular or acellular) was also determined morphometrically in multiple lung tissue sections in each rabbit, There was a correlation between the volume densities of consolidation on HRCT scans and intra-alveolar cells and amorphous material on tissue morphometry (r = 0.90, p = 0.0001) over the 56-day period after bleomycin/oxygen administration. There was no correlation between the volume density of hazy increased lung density (HRCT) and the volume density of these same or any other individual or combined parameters (tissue morphometry) over the 56 days. At all time points after bleomycin administration, central and peripheral lines quantitated by HRCT morphometry correlated with thickened interstitium on tissue morphometry (r = 0.72, p = 0.0003). The lung content of hydroxyproline at Day 56 after bleomycin/oxygen correlated with the volume density of thickened interstitium on tissue morphometry (r = 0.94, p = 0.0002) and with the volume density of peripheral lines alone on HRCT scan morphometry (r = 0.86, p = 0.003). These data suggest that during bleomycin/oxygen-induced lung injury/inflammation: (1) hazy increased density on HRCT scans was a nonspecific finding and did not correlate with the accumulation of cells and/or amorphous material in the alveolar space or with any other parameter measured by tissue morphometry; (2) consolidation on HRCT scans, most evident during a more acute phase (Day 14) of this process, reflected the accumulation of cells and amorphous material in the alveolar space; (3) central and peripheral lines on HRCT scans reflected thickened interstitium as defined by tissue morphometry, but they could not distinguish between thickening caused by an increased cell content, an increase in components other than cells (i.e., collagen), or both; (4) peripheral lines alone observed by HRCT scanning correlated with an increased hydroxyproline content in the lung at all time points after bleomycin administration.
