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A Multimodal Imaging- and Stimulation-based Method of Evaluating Connectivity-related Brain Excitability in Patients with Epilepsy
Published on: November 13, 2016
Ex vivo mesoscopic diffusion MRI correlates with seizure frequency in patients with uncontrolled mesial temporal lobe
Justin Ke1,2, Lesley M Foley3, T Kevin Hitchens3,4
1Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Abstract:
The role of hippocampal connectivity in mesial temporal lobe epilepsy (mTLE) remains poorly understood. The use of ex vivo hippocampal samples excised from patients with mTLE affords mesoscale diffusion magnetic resonance imaging (MRI) to identify individual cell layers, such as the pyramidal (PCL) and granule cell layers (GCL), which are thought to be impacted by seizure activity. Diffusion tensor imaging (DTI) of control (n = 3) and mTLE (n = 7) hippocampi on an 11.7 T MRI scanner allowed us to reveal intra-hippocampal connectivity and evaluate how epilepsy affected mean (MD), axial (AD), and radial diffusivity (RD), as well as fractional anisotropy (FA). Regional measurements indicated a volume loss in the PCL of the cornu ammonis (CA) 1 subfield in mTLE patients compared to controls, which provided anatomical context. Diffusion measurements, as well as streamline density, were generally higher in mTLE patients compared to controls, potentially reflecting differences due to tissue fixation. mTLE measurements were more variable than controls. This variability was associated with disease severity, as indicated by a strong correlation (r = 0.87) between FA in the stratum radiatum and the frequency of seizures in patients. MD and RD of the PCL in subfields CA3 and CA4 also correlated strongly with disease severity. No correlation of MR measures with disease duration was evident. These results reveal the potential of mesoscale diffusion MRI to examine layer-specific diffusion changes and connectivity to determine how these relate to clinical measures. Improving the visualization of intra-hippocampal connectivity will advance the development of novel hypotheses about seizure networks.
Insights
Mesoscale diffusion MRI reveals altered hippocampal connectivity in mesial temporal lobe epilepsy (mTLE). Diffusion measurements in mTLE hippocampi correlated with seizure frequency, offering insights into epilepsy networks.
Area of Science:
- Neuroimaging
- Epilepsy Research
- Diffusion Tensor Imaging
Background:
- The role of hippocampal connectivity in mesial temporal lobe epilepsy (mTLE) is not well understood.
- Ex vivo hippocampal samples from mTLE patients can be studied using mesoscale diffusion MRI.
- This technique allows for the identification of individual cell layers impacted by seizure activity.
Purpose of the Study:
- To investigate intra-hippocampal connectivity in mTLE using mesoscale diffusion MRI.
- To evaluate how epilepsy affects diffusion metrics (MD, AD, RD, FA) and streamline density.
- To correlate diffusion changes with clinical measures of disease severity.
Main Methods:
- Diffusion Tensor Imaging (DTI) was performed on ex vivo control (n=3) and mTLE (n=7) hippocampi using an 11.7 T MRI scanner.
- Regional measurements assessed volume loss in specific hippocampal subfields (e.g., PCL in CA1).
- Diffusion metrics and streamline density were compared between control and mTLE groups.
Main Results:
- Volume loss in the pyramidal cell layer (PCL) of the CA1 subfield was observed in mTLE patients.
- Diffusion measurements and streamline density were generally higher in mTLE hippocampi, potentially due to tissue fixation.
- Variability in mTLE measurements strongly correlated with disease severity, notably FA in the stratum radiatum with seizure frequency (r=0.87).
- Mean diffusivity (MD) and radial diffusivity (RD) in the PCL of CA3 and CA4 also correlated with disease severity.
Conclusions:
- Mesoscale diffusion MRI is a valuable tool for examining layer-specific diffusion changes and connectivity in the hippocampus.
- Observed diffusion changes and variability in mTLE correlate with clinical measures of disease severity, particularly seizure frequency.
- These findings advance the understanding of intra-hippocampal connectivity alterations in epilepsy and can inform novel hypotheses about seizure networks.
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