Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy with 60-75% of cases reported in surgical series. The hippocampus is involved in the genesis of the seizures and hippocampal sclerosis (HS) is the most frequent neuropathological finding observed in surgical samples. However extra-hippocampal neocortical structures may also be involved and the focal cortical dysplasia (FCD) is the most common second alteration frequently associated with HS. Aim of this project was to clarify, both at radiological and neuropathological level, the abnormalities frequently observed in the temporal pole of many TLE patients as the focal cortical dysplasia, the hippocampal sclerosis and the radiological alteration of grey/white matter boundary called “blurring”. The study was performed on surgical specimens of human temporal cortices and hippocampi from TLE patients and autoptic hippocampi at different stage of development submitted first to high resolution (7T) MRI and then processed for histological analysis. Comparison between 7T MRI data with corresponding histological and immunohistochemical features was done. The first part of this study demonstrates that thanks to differences in MRI signal intensities, depending on different density and distribution of cells and myelin fibres, high-resolution ex-vivo MRI enables to visualize the intracortical organization in normal and pathological areas and can detect the subtle architectural alterations in samples presenting dysplastic cortex. The temporo-polar blurring has demonstrated to be due to a great degeneration of fibre bundles in the white matter and, since the age at epilepsy onset is earlier in patients with blurring in comparison to those without blurring, these data suggest that it consists in a slowly evolving chronic degeneration process with the redistribution of the remaining fibres. The comparative imaging-histology investigation on healthy hippocampal specimens shows that 7T MRI can identify the main anatomical structures and the sublayers of the normal hippocampus along its anterior-posterior axis. In sclerotic surgical hippocampi high resolution MRI reveals areas of anomalous hyperintensity of signal associated to marked loss of neurons and intense gliosis as visualized by histological analysis for neuronal and glial cells. Moreover the investigation of intrahippocampal projections performed using fractional anisotropy and fiber tracking, demonstrates a disorganization of fibers in sclerotic samples in comparison to normal hippocampi. The same experimental protocol applied to healthy autoptic hippocampi at different stage of development reveals that during fetal period the MRI signal is related to the cellular density, in fact the regions characterized by densely packed neurons are easily recognizable on ex vivo high field MRI as hypointense areas, while in post-natal specimens the MRI signal is still linked to the cell density but, with the appearance and the progressive increase of the myelin fibers content, this correlation becomes less obvious and the myelin represent the histological component which mainly contributes on MRI signal intensity. This study shows the potential utility of ex-vivo high-field MRI in the understanding of temporal cortical and hippocampal abnormalities, included developmental hippocampal changes, and suggests its possible application in vivo in the near future for the study of several disorders.

(2014). Temporal lobe epilepsy: a combined study with high field (7T) Magnetic Resonance Imaging and optical and ultrastructural histopathology. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2014).

Temporal lobe epilepsy: a combined study with high field (7T) Magnetic Resonance Imaging and optical and ultrastructural histopathology

MILESI, GLORIA
2014

Abstract

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy with 60-75% of cases reported in surgical series. The hippocampus is involved in the genesis of the seizures and hippocampal sclerosis (HS) is the most frequent neuropathological finding observed in surgical samples. However extra-hippocampal neocortical structures may also be involved and the focal cortical dysplasia (FCD) is the most common second alteration frequently associated with HS. Aim of this project was to clarify, both at radiological and neuropathological level, the abnormalities frequently observed in the temporal pole of many TLE patients as the focal cortical dysplasia, the hippocampal sclerosis and the radiological alteration of grey/white matter boundary called “blurring”. The study was performed on surgical specimens of human temporal cortices and hippocampi from TLE patients and autoptic hippocampi at different stage of development submitted first to high resolution (7T) MRI and then processed for histological analysis. Comparison between 7T MRI data with corresponding histological and immunohistochemical features was done. The first part of this study demonstrates that thanks to differences in MRI signal intensities, depending on different density and distribution of cells and myelin fibres, high-resolution ex-vivo MRI enables to visualize the intracortical organization in normal and pathological areas and can detect the subtle architectural alterations in samples presenting dysplastic cortex. The temporo-polar blurring has demonstrated to be due to a great degeneration of fibre bundles in the white matter and, since the age at epilepsy onset is earlier in patients with blurring in comparison to those without blurring, these data suggest that it consists in a slowly evolving chronic degeneration process with the redistribution of the remaining fibres. The comparative imaging-histology investigation on healthy hippocampal specimens shows that 7T MRI can identify the main anatomical structures and the sublayers of the normal hippocampus along its anterior-posterior axis. In sclerotic surgical hippocampi high resolution MRI reveals areas of anomalous hyperintensity of signal associated to marked loss of neurons and intense gliosis as visualized by histological analysis for neuronal and glial cells. Moreover the investigation of intrahippocampal projections performed using fractional anisotropy and fiber tracking, demonstrates a disorganization of fibers in sclerotic samples in comparison to normal hippocampi. The same experimental protocol applied to healthy autoptic hippocampi at different stage of development reveals that during fetal period the MRI signal is related to the cellular density, in fact the regions characterized by densely packed neurons are easily recognizable on ex vivo high field MRI as hypointense areas, while in post-natal specimens the MRI signal is still linked to the cell density but, with the appearance and the progressive increase of the myelin fibers content, this correlation becomes less obvious and the myelin represent the histological component which mainly contributes on MRI signal intensity. This study shows the potential utility of ex-vivo high-field MRI in the understanding of temporal cortical and hippocampal abnormalities, included developmental hippocampal changes, and suggests its possible application in vivo in the near future for the study of several disorders.
FINOCCHIARO, GAETANO
GARBELLI, RITA
temporal lobe epilepsy, hippocampus, neuropathology, high resolution 7T MRI, immunohistochemistry and histology
BIO/13 - BIOLOGIA APPLICATA
English
22-gen-2014
Scuola di Dottorato in Medicina Traslazionale e Molecolare
SCUOLA DI DOTTORATO IN MEDICINA TRASLAZIONALE E MOLECOLARE (DIMET) - 72R
26
2012/2013
open
(2014). Temporal lobe epilepsy: a combined study with high field (7T) Magnetic Resonance Imaging and optical and ultrastructural histopathology. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2014).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/80943
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