High-resolution diffusion tensor imaging of the hippocampus in temporal lobe epilepsy

doi:10.1016/j.eplepsyres.2006.05.020

Epilepsy Research

Volume 71, Issues 2–3, October 2006, Pages 102-106

https://doi.org/10.1016/j.eplepsyres.2006.05.020 Get rights and content

Abstract

Purpose

To assess the quantitative diffusion characteristics of the hippocampus with high-resolution diffusion tensor imaging (DTI) in temporal lobe epilepsy (TLE).

Methods

Thirteen controls and seven unilateral TLE patients (six with hippocampal sclerosis, one with normal magnetic resonance imaging (MRI)) were scanned with DTI using a zonally magnified oblique multislice echo planar imaging (ZOOM-EPI) acquisition. Fractional anisotropy (FA) and mean diffusivity (MD) were measured in the hippocampi.

Results

The mean hippocampal MD ipsilateral to the seizure focus was higher than the contralateral MD in patients (p < 0.05) and the mean MD in controls (p < 0.001). Hippocampal FA ipsilateral to the seizure focus was lower than the mean FA in controls (p < 0.05). MD asymmetry indexes were significantly different between the patient and control groups (p < 0.01). All six individual HS patients had ipsilateral hippocampal MD ≥2 standard deviations (S.D.) above the control mean. The patient with normal structural MRI had bilaterally low hippocampal FA and high MD.

Discussion

High-resolution DTI identifies lateralizing abnormalities of MD and FA in TLE patients. This quantitative data on hippocampal integrity may assist in evaluating TLE patients with normal MRI, and in longitudinal studies.

Introduction

Sixty percent of surgically treated temporal lobe epilepsy (TLE) patients become seizure-free if focal pathology such as hippocampal sclerosis (HS) is identified. Conventional magnetic resonance imaging (MRI) is unremarkable in 20–25% with refractory focal epilepsy (Duncan, 2004).

New techniques may give further information on tissue microstructure. Diffusion tensor imaging (DTI) measures the mean diffusivity (MD) and fractional anisotropy (FA; an index of the directionality of diffusion) of water (Basser and Pierpaoli, 1996). Abnormal MD and FA have been reported at epileptic foci (Rugg-Gunn et al., 2001) and diffusion abnormalities have been reported in hippocampi in TLE (Assaf et al., 2003). The aim of this study was to quantify hippocampal diffusion characteristics in unilateral TLE patients and in healthy controls with high-resolution DTI using a zonally magnified oblique multislice echo planar imaging (ZOOM-EPI) acquisition (Wheeler-Kingshott et al., 2002a).

Section snippets

Methods

Thirteen controls (nine females, median age 34) and seven patients (four females, median age 30) with TLE were studied (Table 1). All controls had normal conventional MRI. In the patient group, the diagnosis was based upon clinical semiology, interictal and ictal scalp EEG, neuropsychometry and MRI. Six patients had an MRI diagnosis of unilateral HS (Woermann et al., 1998). The seventh patient had left TLE and normal conventional MRI. No patient had had a complex partial or secondarily

Results

The test–retest reliability was 4% for MD and 9% for FA. Inter-rater reliability was 16% for MD and 19% for FA.

In patients, the hippocampal FA ipsilateral to the seizure focus was lower than in controls (p < 0.05) (Fig. 2A). There was a significant decrease of hippocampal FA from posterior to anterior in the hippocampi ipsilateral to the seizure focus (p < 0.05).

When patients were analyzed individually, patient 5 (Table 1), with left HS, had a low contralateral FA. Patient 3, with normal

Discussion

High-resolution DTI with ZOOM-EPI acquisition detected hippocampal diffusion abnormalities in unilateral TLE patients. The characteristic finding was high MD and low FA in the hippocampus ipsilateral to the seizure focus in TLE. In individual patients, hippocampal MD changes were greater than FA changes.

Our results are in accord with previous data. Diffusion weighted imaging measuring the apparent diffusion coefficient (ADC) demonstrated increased interictal mean ADC values in HS (Wieshmann et

Acknowledgements

We are grateful to Action Medical Research (SP 3772) and the Garfield Weston foundation, the Council of Health Research of the Academy of Finland (55057/200586), Emil Aaltonen Foundation, the Finnish Medical Foundation, Maire Taponen Foundation, Medical Research Council, the Multiple Sclerosis Society of Great Britain and Northern Ireland, the National Society for Epilepsy, the Wellcome Trust and Vaajasalo Foundation for supporting this study, and to Drs. John Stevens and Brian Kendall for

References (18)

P.J. Basser et al.
Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI
J. Magn. Reson. B
(1996)
C.A. Wheeler-Kingshott et al.
Investigating cervical spinal cord structure using axial diffusion tensor imaging
Neuroimage
(2002)
U.C. Wieshmann et al.
Water diffusion in the human hippocampus in epilepsy
Magn. Reson. Imaging
(1999)
B.A. Assaf et al.
Diffusion tensor imaging of the hippocampal formation in temporal lobe epilepsy
AJNR Am. J. Neuroradiol.
(2003)
P.J. Basser et al.
In vivo fiber tractography using DT-MRI data
Magn. Reson. Med.
(2000)
J.S. Duncan
Neuroimaging Clinics of North America-Epilepsy
(2004)
E. Duzel et al.
Measures of hippocampal volumes, diffusion and 1H MRS metabolic abnormalities in temporal lobe epilepsy provide partially complementary information
Eur. J. Neurol.
(2004)
D.A. Feinberg et al.
Inner volume MR imaging: technical concepts and their application
Radiology
(1985)
K. Kantarci et al.
Comparative diagnostic utility of 1H MRS and DWI in evaluation of temporal lobe epilepsy
Neurology
(2002)

There are more references available in the full text version of this article.

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Citation Excerpt :
Methodological differences in DTI measurement technique, neuropsychological testing and statistical handling of multiple comparisons may account for the observed differences between our data—which showed no relationship between changes in diffusion metrics and neuropsychological outcomes—and these prior results. Our results confirm significant preoperative elevation of MD in TLE of the hippocampus ipsilateral to the seizure focus relative to both the contralateral hippocampus and to measures in healthy controls (Assaf et al., 2003; Bernhardt et al., 2016; Hugg et al., 1999; Pereira et al., 2006; Salmenpera et al., 2006). However, we also find significant elevation of FA, AD and RD in the ipsilateral hippocampus in TLE patients prior to surgery relative to both the contralateral hippocampus and healthy controls.
1) Characterize the evolution of microstructural changes in the contralateral, non-operated hippocampus—using longitudinal diffusion tensor imaging (DTI)—following surgery for temporal lobe epilepsy (TLE). 2) Characterize the downstream extra-hippocampal volumetric changes of the fornix and mammillary bodies after TLE surgery. 3) Examine the relationship between these measures and seizure/cognitive outcome.
Serial structural and DTI brain MRI scans were collected in 25 TLE patients pre- and post-surgery (anterior temporal lobectomy, ATL – 13; selective amygdalohippocampectomy, SelAH – 12) and in 12 healthy controls. Contralateral hippocampal fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were computed with manual hippocampal tracings as volumes of interest following co-registration to anatomical images. Fornix and mammillary body volumetry was performed by manual segmentation.
After surgery, the non-resected hippocampus showed significant postoperative decline in FA (p = 0.0001), with increase of MD (p = 0.01) and RD (p = 0.0001). In contrast to the timing of our previously reported volume changes where atrophy is observed in the first week, diffusion changes occurred late, taking 1–3 years to develop and are not significant at one week after surgery. Diffusion changes are accompanied by delayed limbic circuit volume loss in the mammillary bodies (35%; p < 0.0001) and fornix (24%; p < 0.0001) compared to baseline. There was no correlation between postoperative diffusion or structural changes and memory score nor did the degree of postoperative change in hippocampal DTI parameters, mammillary body volume or fornix volume vary significantly based on seizure outcome.
Differences observed in the timing of postoperative volume (first week) and FA/MD (one year) changes would suggest that early contralateral hippocampal atrophy is not secondary to fluid shifts (dehydration) while the late DTI changes suggest ongoing microstructural changes extending beyond the early postoperative period. Postoperative hippocampal diffusion changes are accompanied by delayed mammillary body and fornix volume loss which did not differ when stratified by seizure outcome nor was correlated with degree of hippocampal diffusion change. Finally, we did not identify any significant correlation between postoperative diffusion parameter change and memory performance.
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High-resolution diffusion tensor imaging of the hippocampus in temporal lobe epilepsy

Abstract

Purpose

Methods

Results

Discussion

Introduction

Section snippets

Methods

Results

Discussion

Acknowledgements

J. Magn. Reson. B

Neuroimage

Magn. Reson. Imaging

Diffusion tensor imaging of the hippocampal formation in temporal lobe epilepsy

AJNR Am. J. Neuroradiol.

In vivo fiber tractography using DT-MRI data

Magn. Reson. Med.

Neuroimaging Clinics of North America-Epilepsy

Measures of hippocampal volumes, diffusion and 1H MRS metabolic abnormalities in temporal lobe epilepsy provide partially complementary information

Eur. J. Neurol.

Inner volume MR imaging: technical concepts and their application

Radiology

Comparative diagnostic utility of 1H MRS and DWI in evaluation of temporal lobe epilepsy

Neurology