We describe a new method to automatically discriminate between patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI) and elderly controls, based on multidimensional classification of hippocampal shape features. This approach uses spherical harmonics (SPHARM) coefficients to model the shape of the hippocampi, which are segmented from magnetic resonance images (MRI) using a fully automatic method that we previously developed. SPHARM coefficients are used as features in a classification procedure based on support vector machines (SVM). The most relevant features for classification are selected using a bagging strategy. We evaluate the accuracy of our method in a group of 23 patients with AD (10 males, 13 females, age ±standard-deviation (SD)=73±6 years, mini-mental score (MMS)=24.4±2.8), 23 patients with amnestic MCI (10 males, 13 females, age±SD=74±8 years, MMS=27.3±1.4) and 25 elderly healthy controls (13 males,12 females, age±SD=64±8 years), using leave-one-out cross-validation. For AD vs controls, we obtain a correct classification rate of 94%, a sensitivity of 96%, and a specificity of 92%. For MCI vs controls, we obtain a classification rate of 83%, a sensitivity of 83%, and a specificity of 84%. This accuracy is superior to that of hippocampal volumetry and is comparable to recently published SVM-based whole-brain classification methods, which relied on

Radiomics, which involves the use of high-dimensional quantitative imaging features for predictive purposes, is a powerful tool for developing and testing medical hypotheses. Radiologic and statistical challenges in radiomics include those related to the reproducibility of imaging data, control of overfitting due to high dimensionality, and the generalizability of modeling. The aims of this review article are to clarify the distinctions between radiomics features and other omics and imaging data, to describe the challenges and potential strategies in reproducibility and feature selection, and to reveal the epidemiological background of modeling, thereby facilitating and promoting more reproducible and generalizable radiomics research.