Quantitative Assessment and Comparative Analysis of Longitudinal Lung CT Scans of Chest-Irradiated Nonhuman Primates

Computed tomography (CT) imaging has been used to diagnose radiation-induced lung injury for decades. However, histogram-based quantitative tools have rarely been applied to assess lung abnormality due to radiation-induced lung injury (RILI). Here, we used first-order summary statistics to derive and assess threshold measures extracted from whole lung histograms of CT radiodensity in rhesus macaques. For the present study, CT scans of animals exposed to 10 Gy of whole thorax irradiation were utilized from a previous study spanning 2-9 months postirradiation. These animals were grouped into survivors and non-survivors based on their clinical and experimental endpoints. We quantified the change in lung attenuation after irradiation relative to baseline using three density parameters; average lung density (ALD), percent change in hyper-dense lung volume (PCHV), hyperdense volume as a percent of total volume (PCHV/TV) at 2-month intervals and compared each parameter between the two irradiated groups (non-survivors and survivors). We also correlated our results with histological findings. All the three indices (ALD, PCHV, PCHV/TV) obtained from density histograms showed a significant increase in lung injury in non-survivors relative to survivors, with PCHV relatively more sensitive to detect early RILI changes. We observed a significant positive correlation between histologic pneumonitis scores and each of the three CT measurements, indicating that CT density is useful as a surrogate for histologic disease severity in RILI. CT-based three density parameters, ALD, PCHV, PCHV/TV, may serve as surrogates for likely histopathology patterns in future studies of RILI disease progression.