Background:Accurate segmentation of individual tooth and their substructures including enamel, pulp, and dentin from cone-beam computed tomography (CBCT) images is essential for dental diagnosis and treatment planning in digital dentistry. Existing methods for tooth segmentation based on CBCT images have achieved substantial progress; however, techniques for further segmentation into substructures are yet to be developed. Purpose:We aim to propose a novel three-stage progressive deep-learning-based framework for automatically segmenting 3D tooth from CBCT images, focusing on finer substructures, i.e., enamel, pulp, and dentin. Methods:In this paper, we first detect each tooth using its centroid by a clustering scheme, which efficiently determines each tooth detection by applying learned displacement vectors from the foreground tooth region. Next, guided by the detected centroid, each tooth proposal, combined with the corresponding tooth map, is processed through our tooth segmentation network. We also present an attention-based hybrid feature fusion mechanism, which provides intricate details of the tooth boundary while maintaining the global tooth shape, thereby enhancing the segmentation process. Additionally, we utilize the skeleton of the tooth as a guide for subsequent substructure segmentation. Results:Our algorithm is extensively evaluated on a collected dataset of 314 patients, and the extensive comparison and ablation studies demonstrate superior segmentation results of our approach. Conclusions:Our proposed method can automatically segment tooth and finer substructures from CBCT images, underlining its potential applicability for clinical diagnosis and surgical treatment.