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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurol. | doi: 10.3389/fneur.2018.00927

Manual hippocampal subfield segmentation on high-field MRI: impact of different subfields in hippocampal volume loss of temporal lobe epilepsy patients

 José Eduardo Peixoto-Santos1, 2,  Luciana Estefani D. Carvalho3,  Ludmyla Kandratavicius1, Paula Rejane B. Diniz4, Renata C. Scandiuzzi1,  Roland Coras2, Ingmar Blümcke2, João A. Assirati5, Carlos G. Carlotti5, Caio Cesar M. Matias5,  Carlos E. Garrido Salmon6, Antônio C. Santos7, Tonicarlo R. Velasco1, Márcio Flávio D. Moraes8 and  João P. Leite1*
  • 1Departamento de Neurociências e Ciências do Comportamento, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brazil
  • 2Neuropathologisches Institut, Universitätsklinikum Erlangen, Germany
  • 3Universidade Federal de São João del-Rei, Brazil
  • 4Hospital das Clínicas, Universidade Federal de Pernambuco, Brazil
  • 5Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brazil
  • 6Departamento de Física, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Brazil
  • 7Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brazil
  • 8Centro de Tecnologia e Pesquisa em Magneto-Ressonância, Universidade Federal de Minas Gerais, Brazil

In patients with temporal lobe epilepsy (TLE), the presurgical magnetic resonance imaging (MRI) often reveals hippocampal atrophy, while neuropathological assessment may show differential patterns of neuronal cell loss across hippocampal subfields. However, currently used methods to assess hippocampal subfield volume on MRI have difficulties to correctly identify the anatomic subfield borders. Our aim was to co-register histological and MRI data to 1) define the volume of each hippocampal subfield on MRI, 2) to correlate neuronal density and volume of each subfield with gross hippocampal volume. The latter will help to better understand the contribution and impact of each individual subfield when hippocampal atrophy is reported by clinical examination. T2-weighted images from six formalin-fixed control hippocampi were obtained at 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 25 TLE patients, were imaged with a similar MRI sequence at 3T. Anatomical subfield delineation at 4.7T MRI was informed by 10-µm-thin microscopy slides, collected at every millimeter from control cases, and stained for Luxol Fast Blue. An additional section was collected at the level of the body from controls and TLE groups and submitted to NeuN immunohistochemistry for the evaluation of neuronal cell density. Whole hippocampal volumetric assessment in control cases revealed that the dentate gyrus (DG)+CA4 region, CA1, and subiculum accounted for almost 90% of the hippocampal volume, with larger variations across the hippocampal head, body, and tail. Compared to control cases, all TLE patients had significantly lower subfield volumes for DG/CA4, CA3, CA2, CA1, and the subiculum. Neuronal cell densities were always decreased in CA4, CA3, CA2, and CA1. Total hippocampal volume correlated, however, most significantly with DG and CA1 volumes and neuronal density. For the first time, we identified also subfield specific pathology patterns in volumetric MRI scans. Our data reinforced the importance of CA1 to the hippocampal volume of TLE patients and the importance of manual segmentation of anatomical boundaries to assess subfield-specific pathology patterns.

Keywords: High-field MRI, hippocampal subfield volumetry, neuron density, Hippocampal Sclerosis (HS), Ex vivo imaging

Received: 13 Jul 2018; Accepted: 12 Oct 2018.

Edited by:

Fernando Cendes, Universidade Estadual de Campinas, Brazil

Reviewed by:

Liankun Ren, Xuanwu Hospital, Capital Medical University, China
Irene Wang, Cleveland Clinic, United States  

Copyright: © 2018 Peixoto-Santos, Carvalho, Kandratavicius, Diniz, Scandiuzzi, Coras, Blümcke, Assirati, Carlotti, Matias, Garrido Salmon, Santos, Velasco, Moraes and Leite. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. João P. Leite, Departamento de Neurociências e Ciências do Comportamento, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirao Preto, 14049-900, Brazil,