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Purpose: Topological texture features were compared in their ability to classify “honeycombing,” a morphological pattern that is considered indicative for the presence of fibrotic interstitial lung disease in high-resolution computed tomography (HRCT) images. Methods: For 14 patients with known occurrence of honeycombing, a stack of 70 axial, lung kernel reconstructed images was acquired from HRCT chest exams. A set of 964 regions of interest of both healthy and pathological (356) lung tissue was identified by an experienced radiologist. Texture features were extracted using statistical features (Stat), six properties calculated from gray-level co-occurrence matrices (GLCMs), Minkowski dimensions (MDs), and three Minkowski functionals (MFs) (e.g., MF.Euler). A naive Bayes (NB) and k-nearest-neighbor (k-NN) classifier, a multilayer radial basis functions network (RBFN), and a support vector machine with a radial basis function (SVMrbf) kernel were optimized in a tenfold cross-validation for each texture vector, and the classification accuracy was calculated on independent test sets as a quantitative measure of automated tissue characterization. A Wilcoxon signed-rank test was used to compare two accuracy distributions and the significance thresholds were adjusted for multiple comparisons by the Bonferroni correction. Results: The best classification results were obtained by the MF features, which performed significantly better than all the standard Stat, GLCM, and MD features (p |