*2.9.1 Shape analysis*

Visualization of hippocampal shape may extend evaluation to details not evident by measurements of hippocampal volume. This technique showed significant inward deviation in the Sommer sector of the sclerotic hippocampi. The analysis of curvature in the hippocampus also revealed medial bending of the posterior hippocampus in patients with TLE, compared with a superomedial shift of the hippocampal body observed in patients with MCD [87].

An extension of shape analysis to adjacent convexities often shows a pathologic relationship. For example, hippocampal malrotation in TLE is associated with increased complexity of the temporolimbic cortices, encompassing parahippocampal, temporopolar, insular, and fronto-opercular regions. This implies that neurodevelopmental factors may play a role in the epileptogenic process [88].

### *2.9.2 Cortical thickness*

Progressive neocortical thinning in the frontal lobes had been found in patients with ongoing seizures than in patients with controlled seizures [89]. This was subsequently echoed in a meta-analysis that showed more marked atrophy in the ipsilateral hippocampus, with moderate effect sizes, in patients with longer epilepsy duration and more frequent seizures [90].

#### *2.9.3 Automatic segmentation*

Increasingly sophisticated automatic segmentation algorithms are developed for the assessment of mesial temporal lobe structures. While the majority of them generally demonstrate an excellent performance in healthy subjects, accuracy in patients drops significantly due to the atypical shape, positioning, and size of the hippocampus secondary to incomplete unfolding (or malrotation which occurs in about 40% of TLE patients) [88, 91, 92]. Automated hippocampal segmentation algorithm which integrates deformable parametric surfaces and multiple templates in a unified framework have been developed [93]. This provides flexibility to model disease-related

shape deformations and atrophy and is important in maintaining a high-level performance regardless of the presence of abnormal morphology [94, 95].

#### *2.9.4 T2 relaxation times*

The sensitivity of VBM can be increased by directly mapping T2 relaxation times. In the vast majority of TLE patients with hippocampal atrophy, T2 relaxation times within the hippocampal gray matter ipsilateral to the focus increased by at least 10ms when compared to controls [96–98]. This may allow mapping of lateralizing information in patients with no evidence of atrophy on MRI [99].
