Background and objectiveEstablishing accurate one-to-one morphological correspondence between different hippocampal surfaces is a solid foundation for the analysis of AD-induced hippocampal morphological changes. However, owing to the large variations between hippocampal surfaces, exiting registration work either fails to obtain the accurate matching of local and overall morphological features or does not preserve the bijectivity during parametric mapping. For this reason, this study proposes a hybrid-feature based spherical quasi-conformal registration (HSQR) method that can effectively maintain the diffeomorphic property while meeting the hybrid-feature matching constraints in the spherical parameter domain. MethodsThe HSQR algorithm is primarily achieved through hippocampal surface hybrid feature extraction and spherical quasi-conformal registration. First, hybrid features for a comprehensive morphological description of the hippocampal surface were established, which included essential anatomical features (landmarks) and mean curvature (intensity) features to ensure the accuracy of surface morphology alignment. Second, spherical parameterization was applied to genus-0 closed surfaces, such as the hippocampus, which maximized the preservation of the original local surface morphology through area-preserving properties. Third, a novel spherical quasi-conformal registration algorithm that can handle large deformations is established. It transforms a 3D spherical parameter domain into a 2D plane parameter domain using iterative local stereo projection to improve the efficiency of the registration algorithm. Subsequently, by controlling the Beltramin coefficient, the hybrid morphological features could be aligned while ensuring bijection before and after registration. ResultsUsing a cohort including 161 patients with amyloid-β (Aβ) positive Alzheimer disease (AD), 234 Aβ positive mild cognitive impairment (MCI) and 266 Aβ negative cognitively unimpaired (CU) individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, we set up the experiment which indicated that the HSQR-based whole bilateral hippocampal atrophy features demonstrated the stronger statistical power for group morphological differences of CU vs. MCI with q-value: 0.0453 for left hippocampus and 0.0401 for right hippocampus and group morphological differences of AD vs. MCI with q-value: 0.0282 for left hippocampus and 0.0421 for right hippocampus. ConclusionsOur registration algorithm may provide a solid foundation for the accurate quantification of hippocampal surface morphological changes for the differential diagnosis and tracking of AD.