Purpose: To assess whether automated texture analysis of CT images enables discrimination among pathologic classes of lung adenocarcinomas, and thus serves as an in vivo biomarker of lung cancer prognosis. Materials and Methods: Chest CTs of 30 nodules in 30 patients with resected adenocarcinomas were evaluated by a pulmonary pathologist who classified each resected cancer according to the International Association for the Study of
Lung Cancer (IASLC) system. The categories included adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), lepidic-predominant adenocarcinoma (LPA), and other invasive adenocarcinomas (INV). 3D volumes of interest (VOIs) and 2D regions of interest (ROIs) were then constructed for each nodule. A comprehensive set of N=279 texture parameters were computed for both 3D and 2D regions. Clustering and classification of these parameters were performed with linear discriminant analysis (LDA) using features determined by optimal subsets. Results: Of the 30 adenocarcinomas, there were 13 INV, 11 LPA, 3 MIA, and 3 AIS. AIS and MIA groups were analyzed together. With all 3 classes, LDA classified 17 of 30 nodules correctly using the nearest neighbor (k=1) method. When only the two largest classes (INV and LPA) were used, 21 of 24 nodules were classified correctly. With 3 classes and 2D texture analysis, and when using only the two largest groups, LDA was able to correctly classify all nodules. Conclusion: CT texture parameters determined by optimal subsets allows for effective clustering of adenocarcinoma classes. These results suggest the potential use of automated (or computer-assisted) CT image analysis to predict the invasive pathologic character of lung nodules. Our approach overcomes the limitations of current radiologic interpretation, such as subjectivity, inter- and intra-observer variability, and the effect of reader experience.