Master student project: (Bio)Medical Engineering
Supervisors:
Pauly Ossenblok, PhD (OssenblokP@kempenhaeghe.nl) Epilepsy Center Kempenhaeghe,
Heeze
Anna Vilanova, PhD (a.vilanova@tue.nl), WH 2.103, 2475416, BMT/TUe, Eindhoven
Olaf Schijns, PhD (o.schijns@mumc.nl), neurochirurgie, MUMC+, Maastrich
Location: Epilepsy Center Kempenhaeghe and Biomedical Image Analysis Lab of the TU/e
Identifying the structural basis of epileptic
and functional networks in candidates for
anterior temporal lobe resection
Background
Recently it has been reported that combined EEG-fMRI and DWI tractography has the
potential to identify both the extent and interactions within an epileptogenic network [1],
while fMRI seeded tractography may be a predictor of memory decline [2] and may predict
the risk of a visual field deficit (VFD) due to disruption of the anterior part of the optic
radiation (Meyers loop) following an anterior temporal lobe resection (ATLR) [3]. An ATLR
is the most frequently performed resection in patients with drug-resistant partial epilepsy.
Failure of resection in these patients with temporal lobe epilepsy (TLE) may be due to the
complexity of interactions between mesial and neocortical temporal structures, particularly
when a standardized surgical procedure, limited to the mesial or anterior temporal lobe is
performed [4,5]. Therefore, a better understanding of the inter-structural relationships
sustaining TLE networks is important not only to be able to predict outcome of surgery but
also to better understand the potential consequences of an ATLR on functions, mainly
memory and visual functions.
In recent studies we evaluated and optimized the potential of EEG-fMRI in the preoperative
planning of lesion-related epilepsy surgery [6,7]. We showed that EEG-fMRI identifies and
may delineate the epileptogenic network that reflects the site of onset and propagation of the
interictal epileptiform discharges (IEDs) The description of these networks is based on the
concept of a trigger onset zone and propagation towards distinct brain regions involved in the
discharges. Figure 1shows the EEG-fMRI analysis results reflecting positive activations in the
left temporal lobe, probably related to the trigger onset zone of the IEDs, whereas a negative
activated area was obtained in the parietal region near the lesion of the patient.
These results show that EEG-fMRI leads to a better understanding of the onset and
propagation patterns of the epileptic discharges, however, little is known about the pathways
for propagation of these discharges. For example, it is well known that propagation speed in
human seizures may be quite variable. There may be slow contiguous spread via horizontal
cortical layers, propagation from the cortex to the thalamic relay neurons has also been
described, while in humans, slower cortico-cortical propagation to ipsilateral or contralateral
Pauly Ossenblok, June 10, 2011
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Figure 1 The IEDs of the patient are shown at the left. Event related fMRI analyses using the
IED density function yielded the regions of significant BOLD as shown in the middle of the
figure. In our approach the haemodynamic response function (HRF) is estimated out of the
data for each voxel of the brain. It appears that the shape of the HRFs of adjacent voxels are
similar (HRFs of the same color (insert right part of the figure) as the significant voxels).
homotopic or heterotopic areas has been observed [8,9]. The latter suggests non-contiguous
spread patterns via white matter tracts such as connections through corpus callosum and the
anterior commissure or other major white matter tracts. These white matter tracts may be
visualized by diffusion-weighted (DWI) tractography [10]. DWI tractography is a recently
introduced MR technology which allows for the assessment of the amplitude (diffusivity) and
the directionality of diffusion (anisotropy) of water molecules within tissue [11]. It is a
powerful tool for interrogating white matter integrity and allows for the identification of the
white matter tracts with particular attention to the tracts that connect the interictal epileptic
network nodes [1], e.g. the significant BOLD regions as determined by EEG-fMRI (see figure
1). It was shown at the Biomedical Imaging Analysis group of the TU/e that the use of a more
simple model for DWI tractography results in the same information gain as high angular
resolution diffusion imaging (HARDI) by using contextual information [12,13], thus reaching
accurate high resolution reconstructions with a clinical useful DWI protocol. In an attempt to
predict the risk of a VFD after an ATLR we already showed (figure 2) that the strength and
paths of the optic radiation can be assessed with DWI tractography [14]. It was shown that the
ConTrack probabilistic fiber tracking algorithm can be successfully used to reconstruct the
optic radiation based on two regions of interest (ROI). The first ROI is the LGN which was
manually localized from the anatomical T1 image, the second ROI was the primary visual
cortex that was automatically extracted from blood oxygen level dependent (BOLD)
responses generated from selective stimulation with a visual checkerboard stimulus. The
challenge in this research project is to estimate the structural basis of both the epileptic
network and the functional networks involved (memory and visual network) using similar
models for DWI tractography. These, supplementary structural data may improve
preoperative planning of ATL resections , while potentially obviating the need for invasive
recordings and resulting in a more favorable outcome with respect to seizure freedom.
Pauly Ossenblok, June 10, 2011
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R
Figure 2 The preoperative DWI tractography results shown relative to the right temporal
lesion (indicated by the red arrow).
Project description
The main objective of this study is to optimize the reliability and accuracy of combined DWI
and fMRI analysis in order to improve the potentiality of this technique for the assessment of
the interactions in an epileptogenic network involved in TLE in relation to memory and visual
function. This brings us to the following research questions:
1) Can we identify the structural basis of an interictal epileptiform network as described by
EEG-fMRI?
2) Is the reliability and accurateness of DWI tractography of the white matter tracts
connecting the functional brain areas sufficient to predict the risk of postoperative memory
or visual impairment after ATLR?
Tasks
 Literature study.
 Investigate the possibilities for reconstruction of the structural network connecting the
functional nodes of the network (regions of significant BOLD) as obtained by EEG-fMRI
for patients who are candidates for an ATLR (epileptic network) using DWI tractography.
This includes:
o Participation in the acquisition and analysis of simultaneously recorded EEG and fMRI
data for patients who are candidates for an ATLR;
o Pre-processing steps that are needed to generate the fMR images (network of significant
BOLD regions) related to the IEDs;
o Using the significant BOLD regions as seedpoint for DWI tractography analysis;
o Display the results in 3D MRI.
 Investigate the sensitivity of the methodology as described in the master thesis of Jacobs
(2010) and currently further developed by Chantal Tax for user input parameters and how
these affect the output result and investigate the plausibility and reproducibility of the
epileptic network reconstructions in comparison to the results guided by published
anatomical data of white matter tracts [15] and by the extensive amount of literature
describing the TLE networks as studied by invasive recordings [4.5].
 Participate in the fMRI seeded DTI study aimed at the prediction of memory impairments
and VFDs as result of an ATLR.
Pauly Ossenblok, June 10, 2011
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 Investigate the possibilities of the methodology as described in the master thesis of Jacobs
(2010) for reconstruction of the memory network and apply the methodology in close
collaboration with the neuropsychologist working on the project in a small study of healthy
volunteers (n= 5) and patients (n=5).
 Registration and visualization of the functional (memory and visual) networks together
with the epileptic network.
 Investigate the potential of the methodology to improve the planning and outcome of
ATLR, by analysis of the patients pre- and post- surgery data (n=5).
Supervision in Kempenhaeghe
The trainee will be based at the department of Clinical Physics and will work in close
collaboration with the students working at prediction of visual and memory impairment after
an ATLR (Chantal Taxs and Nikita Frankenmolen) and with Petra van Houdt, who currently
is a PhD student working at the EEG-fMRI research project to improve pre-surgical planning
of epilepsy patients. The supervisor in Kempenhaeghe is Dr. Pauly Ossenblok, medical
physicist of Epilepsy Center Kempenheaghe (e-mail: OssenblokP@Kempenhaeghe.nl). The
project will be done in close collaboration with the department of neurology of
Kempenhaeghe and the MRI department.
References
[1] Yogarajah and Duncan, Epilepsia 2008; [2] Bettus et al., Hum Brain Mapp 2009; [3]
Yogarajah et al., Brain 2009; [4] Bartolemei et al. Brain 2008; [5] Bartolemei et al., Epilepsia
2010; [6] Van Houdt et al., Hum Brain Mapp, 2010a; [7] Van Houdt et al. Magn Reson
Imaging. 2010; [8] Baumgartner et al., Neurology 1996; [9] Blume et al., Epilepsia 1996;
[10] Diehl et al., Epilepsy research, 2010; [11] Kim and Kim, Ann NY Acad Sci 2005; [12]
Prckovska et al., IEEE Trans Vis Comput Graph, 2010; [13] Prckovska et al., IEEE Trans Vis
Comput Graph, 2010; [14] Jacobs, Master thesis, 2010; [ 15] Mori and Zhang, Ann. Neurol.,
2006;
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