Manual Hippocampal Subfield Segmentation Using High-Field MRI: Impact of Different Subfields in Hippocampal Volume Loss of Temporal Lobe Epilepsy Patients.

Jose Eduardo Peixoto-Santos,Roland Coras,Caio Cesar Marconato Simoes Matias,Renata Caldo Scandiuzzi,Ingmar Blümcke,Antonio Carlos Dos Santos,Paula Rejane Beserra Diniz,Joao Alberto Assirati,Joao Pereira Leite,Carlos Ernesto Garrido Salmon,Luciana Estefani Drumond De Carvalho,Marcio Flavio D Moraes,Ludmyla Kandratavicius,Carlos Gilberto Carlotti,Tonicarlo R Velasco

doi:10.3389/fneur.2018.00927

Abstract

In patients with temporal lobe epilepsy (TLE), presurgical magnetic resonance imaging (MRI) often reveals hippocampal atrophy, while neuropathological assessment indicates the different types of hippocampal sclerosis (HS). Different HS types are not discriminated in MRI so far. We aimed to define the volume of each hippocampal subfield on MRI manually and to compare automatic and manual segmentations for the discrimination of HS types. The T2-weighted images from 14 formalin-fixed age-matched control hippocampi were obtained with 4.7T MRI to evaluate the volume of each subfield at the anatomical level of the hippocampal head, body, and tail. Formalin-fixed coronal sections at the level of the body of 14 control cases, as well as tissue samples from 24 TLE patients, were imaged with a similar high-resolution sequence at 3T. Presurgical three-dimensional (3D) T1-weighted images from TLE went through a FreeSurfer 6.0 hippocampal subfield automatic assessment. The manual delineation with the 4.7T MRI was identified using Luxol Fast Blue stained 10-μm-thin microscopy slides, collected at every millimeter. An additional section at the level of the body from controls and TLE cases was submitted to NeuN immunohistochemistry for neuronal density estimation. All TLE cases were classified according to the International League Against Epilepsy's (ILAE's) HS classification. Manual volumetry in controls revealed that the dentate gyrus (DG)+CA4 region, CA1, and subiculum accounted for almost 90% of the hippocampal volume. The manual 3T volumetry showed that all TLE patients with type 1 HS (TLE-HS1) had lower volumes for DG+CA4, CA2, and CA1, whereas those TLE patients with HS type 2 (TLE-HS2) had lower volumes only in CA1 (p ≤ 0.038). Neuronal cell densities always decreased in CA4, CA3, CA2, and CA1 of TLE-HS1 but only in CA1 of TLE-HS2 (p ≤ 0.003). In addition, TLE-HS2 had a higher volume (p = 0.016) and higher neuronal density (p < 0.001) than the TLE-HS1 in DG + CA4. Automatic segmentation failed to match the manual or histological findings and was unable to differentiate TLE-HS1 from TLE-HS2. Total hippocampal volume correlated with DG+CA4 and CA1 volumes and neuronal density. For the first time, we also identified subfield-specific pathology patterns in the manual evaluation of volumetric MRI scans, showing the importance of manual segmentation to assess subfield-specific pathology patterns.

Highlights

Epilepsy affects 0.6–1.5% of the world’s population [1]
The clinical variables investigated were the age at death and cause of death for control and age at surgery, epilepsy duration, age at epilepsy onset, seizure frequency for Temporal lobe epilepsy (TLE) patients, and variables related to epilepsy
The TLE-HS1 and TLE-HS2 groups had no differences with regard to initial precipitating injury (IPI) occurrence, IPI type, age at IPI, age at seizure recurrence, seizure frequency, seizure generalization, seizure clustering, the occurrence of status epilepticus, familiar history of epilepsy, surgical outcome, or presence and type of other presurgical Magnetic resonance imaging (MRI) findings (Table 1)

Summary

Introduction

Epilepsy affects 0.6–1.5% of the world’s population [1]. Temporal lobe epilepsy (TLE) is the most frequent focal epilepsy in adults, and drug-resistance is common in these patients [2]. Resection of the epileptogenic zone, when indicated by the presurgical evaluation, is the main treatment for drug-resistant cases [3]. In most TLE cases, MRI often reveals hippocampal atrophy in T1weighted imaging and increased signal in T2-weighted imaging [5, 7,8,9,10]. The postsurgical histological assessment of the resected hippocampus frequently reveals hippocampal sclerosis (HS), characterized by differential neuronal cell loss and gliosis [11,12,13,14,15,16,17]. Quantitative studies correlated the severity of neuronal loss and gliosis to the degree of hippocampal atrophy measured in MRI [7, 9, 18, 19], there is no consent about which hippocampal subfield has a more significant impact on the hippocampal atrophy. It is essential to evaluate the contribution of each hippocampal subfield for the hippocampal volume in control cases, to better define volume loss in TLE cases

Objectives

Methods

Results

Conclusion