Introduction: Several methods offer free volumetry services for MR data that adequately quantify volume differences in the hippocampus and its subregions. These methods are frequently used to assist in clinical diagnosis of suspected hippocampal sclerosis in temporal lobe epilepsy. A strong association between severity of histopathological anomalies and hippocampal volumes was reported using MR volumetry with a higher diagnostic yield than visual examination alone. Interpretation of volumetry results is challenging due to inherent methodological differences and to the reported variability of hippocampal volume. Furthermore, normal morphometric differences are recognized in diverse populations that may need consideration. To address this concern, we highlighted procedural discrepancies including atlas definition and computation of total intracranial volume that may impact volumetry results. We aimed to quantify diagnostic performance and to propose reference values for hippocampal volume from two well-established techniques: FreeSurfer v.06 and volBrain-HIPS.Methods: Volumetry measures were calculated using clinical T1 MRI from a local population of 61 healthy controls and 57 epilepsy patients with confirmed unilateral hippocampal sclerosis. We further validated the results by a state-of-the-art machine learning classification algorithm (Random Forest) computing accuracy and feature relevance to distinguish between patients and controls. This validation process was performed using the FreeSurfer dataset alone, considering morphometric values not only from the hippocampus but also from additional non-hippocampal brain regions that could be potentially relevant for group classification. Mean reference values and 95% confidence intervals were calculated for left and right hippocampi along with hippocampal asymmetry degree to test diagnostic accuracy.Results: Both methods showed excellent classification performance (AUC:> 0.914) with noticeable differences in absolute (cm3) and normalized volumes. Hippocampal asymmetry was the most accurate discriminator from all estimates (AUC:1~0.97). Similar results were achieved in the validation test with an automatic classifier (AUC:>0.960), disclosing hippocampal structures as the most relevant features for group differentiation among other brain regions.Conclusion: We calculated reference volumetry values from two commonly used methods to accurately identify patients with temporal epilepsy and hippocampal sclerosis. Validation with an automatic classifier confirmed the principal role of the hippocampus and its subregions for diagnosis.

The development of techniques for the acquisition of high-resolution 3D images, such as computed tomography and magnetic resonance imaging, has opened new avenues to the study of complex morphologies. Detailed descriptions of internal and external traits can be now obtained, allowing the intensive sampling of surface points. In this paper, we introduce a morphometric and statistical framework, grounded on Procrustes and Procrustes-like techniques as well as standard spatial statistics, to explicitly describe and incorporate the spatial pattern of these surface points into the analyses. We exemplified this approach by analyzing ontogenetic changes in a sample of human brain endocasts and inter-specific differences between primate skulls. An intensive sampling of points on 3D surfaces was performed by automatic techniques and the morphometric variation among specimens was measured by the residuals obtained after the alignment of points. Our results showed that shape changes in both examples are spatially structured. Different results were attained by using methods that incorporate or not the spatial structure in the evaluation of the effect of specific biological factors on shape variation. Particularly, these analyses indicated that the effect of biological factors acting at local scales can be confounded with more systemic factors (by example, the effect of the diet on the facial skeleton) if the spatial structure is not taken into account. Overall, our results suggest that the intensive description of shape differences among structures using densely sampled points on 3D surfaces combined with spatial statistical methods can be used to explore problems not widely addressed in morphological studies.