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Recording epileptic activity with MEG in a light-weight magnetic shield
Epilepsy Research (2008) 82, 227—231
journal homepage: www.elsevier.com/locate/epilepsyres
SHORT COMMUNICATION
Recording epileptic activity with MEG in a light-weight magnetic shield Xavier De Tiège a,∗, Marc Op de Beeck a, Michael Funke b, Benjamin Legros c, Lauri Parkkonen d, Serge Goldman a, Patrick Van Bogaert a a
Laboratoire de Cartographie Fonctionnelle du Cerveau, ULB-Hôpital Erasme, Brussels, Belgium University of Utah Magnetic Source Imaging, University of Utah, Salt Lake City, UT, USA c Department of Neurology, ULB-Hôpital Erasme, Brussels, Belgium d Brain Research Unit, Low Temperature Laboratory, Helsinki University of Technology, Finland b
Received 15 May 2008; received in revised form 21 August 2008; accepted 22 August 2008 Available online 15 October 2008
KEYWORDS Magnetoencephalography; Light-weight magnetically shielded room; Signal-to-noise ratio; Epilepsy; Presurgical evaluation
Summary Ten patients with focal epilepsy were studied with magnetoencephalography (MEG) to determine if a new light-weight magnetically shielded room (lMSR) provides sufficient attenuation of magnetic interference to detect and localize the magnetic correlates of epileptic activity. Interictal MEG epileptic events co-localizing with the presumed location of the epileptogenic zone were found in all patients. MEG measurements performed in the lMSR provide an adequate signal-to-noise ratio for non-invasive localization of epileptic foci. © 2008 Elsevier B.V. All rights reserved.
Introduction Magnetoencephalography (MEG) is increasingly used in the non-invasive presurgical evaluation of patients with pharmacoresistant epilepsy to localize the epileptic focus although its clinical value compared to other source localization techniques is still under debate (Knowlton, 2006).
∗ Corresponding author at: Magnetoencephalography Unit, Laboratoire de Cartographie Fonctionnelle Cérébrale, ULB-Hôpital Erasme, 808 Lennik Street, 1070 Brussels, Belgium. Tel.: +32 2 555 31 11; fax: +32 2 555 47 01. E-mail address: [email protected] (X. De Tiège).
MEG records the changes in extracranial magnetic fields generated mainly by cortical pyramidal cells. Such fields are extremely weak: 50—10,000 × 10−15 Tesla (T) (Hämäläinen et al., 1993). In clinical environments, the typical ambient magnetic noise level (10−11 to 10−6 T) is several orders of magnitude higher than the neuromagnetic signal. Power-lines, elevators, moving hospital beds, radiological equipments, and even the variation of the Earth’s geomagnetic field contribute to ambient magnetic interferences (Hämäläinen et al., 1993). The most reliable way to reduce external magnetic disturbances is to acquire MEG data in a magnetically shielded room (MSR) (Hämäläinen et al., 1993). MSRs are usually made of several layers of mu-metal and aluminum, resulting in expensive, heavy and bulky constructions. To facilitate
0920-1211/$ — see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.eplepsyres.2008.08.011
228
X. De Tiège et al.
Table 1
Clinical data
Patient
Age/sex/onset
Video-EEG
Structural MRI
FDG-PET
Presumed location of epileptogenic zone
1
10 y/F/3 y
R temp spikes R temp CPS
R MTS
R temp hypo
R mesiotemp
2
11 y/M/6 y
R front SW
R caudate nucleus atrophy R O-front atrophy R front C-S-C abnor
R caudate nucleus hypo
R front
R O-front hypo R ant temp hypo
R front CPS 3
13 y/F/11 y
R par—occi SW R occi SPS
R par—occi atrophy
Not done
R occi
4
15 y/F/3 y
L temp SW L temp SPS & CPS
L temp FCD
L » R temp hypo
L temp
5
22 y/F/8 y
L inf front SW
L inf front atrophy (resection of cavernoma)
L inf front hypo
L inf front
L inf front CPS 6
28 y/F/1 y
L » R temp SW
L MTS, L ant temp FCD L temp CPS
L temp and thal hypo
L mesiotemp
7
32 y/F/12 y
L temp SW
L MTS L temp CPS
L temp hypo
L mesiotemp
8
50 y/M/11 y
R par SW R sensory SPSa
Normal
R sup par
9
53 y/F/8 y
L » R fron—temp SW L fron—temp CPS
R sup par FCD R lentiform nucleus hemorrh L MTS
L temp and thal hypo
L fron—temp
10
53 y/M/35 y
L and R temp SW
L and R temp post-trauma lesions L temp CPS
L temp hypo
L temp
R front post-trauma lesions
y: year; F: female; M: male; R: right; temp: temporal; front: frontal; par: parietal; occi: occipital; CPS: complex partial seizure; SPS: simple partial seizure; SW: spike-wave; MTS: mesiotemporal sclerosis; O-front: orbitofrontal; C-S-C: cortico-sub-cortical; abnor: abnormality; inf: inferior; ant: anterior; sup: superior; hemorrh: hemorraghe; post-trauma: post-traumatic; hypo: hypometabolism; thal: thalamic; mesiotemp: mesiotemporal; FCD: focal cortical dysplasia. a Not localized by EEG.
the siting of MEG systems to clinical environments, Elekta Neuromag Oy (Helsinki, Finland) has developed a lightweight magnetic shielding (lMSR) concept comprising a light-weight passive shielded room characterized by a single shell of interleaved mu-metal/aluminum layers, and active interference cancellation systems acting both inand outside of the shielded room (Parkkonen et al., 2006). This new lMSR concept has been shown to provide sufficient attenuation of magnetic noise to record, with a good signal-to-noise ratio (SNR), magnetic fields evoked by sensory stimuli (Parkkonen et al., 2006). However, this type of MEG measurement uses averaging to improve the SNR. Therefore, it is not guaranteed that lMSR will allow reliable detection and localization of single brain events like epileptic spikes among the residual environmental magnetic noise. A preliminary step to determine the potential clinical interest of this new lMSR in the presurgical evaluation of refractory epilepsy is therefore to demonstrate that MEG using lMSR is able to detect and reliably localize the magnetic correlates of epileptic abnormalities.
Patients and methods Patients Between June and December 2007, 10 patients (10—53 years; 7 females) followed in the presurgical evaluation program of Hôpital Erasme were selected for MEG investigation based on the following criteria: (1) pharmacoresistant symptomatic focal epilepsy, (2) frequent interictal epileptic abnormalities on previous EEG, and (3) well-defined presumed anatomic location of the epileptogenic zone. The presurgical work-up included: clinical evaluation, videoEEG monitoring, structural magnetic resonance imaging (MRI), neuropsychological evaluation and positron emission tomography with [18F]-fluorodeoxyglucose (9 patients). The presumed anatomic location of the seizure focus was determined after multidisciplinary discussion of the presurgical evaluation data. The clinical data of the patients are summarized in Table 1.
MEG acquisition MEG measurements were performed using the whole-head 306-channel Elekta Neuromag® system comprising 204 planar
Recording epileptic activity with MEG in a light-weight magnetic shield Table 2
229
MEG results
Patient
Presumed location of seizure focus
MEG results
Concordance
1 2
R mesiotemp R front
C C+*
3 4 5 6
R occi L temp L inf front L mesiotemp
7 8 9
L mesiotemp R sup par L fron—temp
10
L temp
R post temp spikes R front spikes R ant temp spikes R occi spikes L ant temp polyspikes L inf front spikes L ant temp spikes R post temp Sharp W L ant temp Sharp W R sup par polyspikes L ant temp spikes L post temp spikes L O-front spikes L ant temp spikes R ant temp spikes
C C* C* C+ C C C
C+
R: right; L: left; mesiotemp: mesiotemporal; front: frontal; occi: occipital; temp: temporal; inf: inferior; front: frontal; sup: superior; par: parietal; post: posterior; ant: anterior; W: waves; O-front: orbitofrontal; C: concordant; C+: concordant plus; *: confirmed by invasive EEG monitoring.
gradiometers and 102 magnetometers. MEG data were acquired in the new lMSR (MaxShieldTM , Elekta Neuromag Oy, Helsinki, Finland) which combines three magnetic noise suppression methods: (1) a light-weight single-shell shielded room, (2) an active feedback compensation system (three orthogonal coil pairs driven by the MEG sensors) which further reduces the interference at the sensor array, and (3) the software-based signal-space separation (SSS) method which removes any residual interference (Parkkonen et al., 2006; Taulu et al., 2004). The MSR was located at the basement level of the hospital and close to the sterilization department, the MRI and PET units. For all patients, spontaneous magnetic brain activity (eyesclosed rest, supine position) was recorded for 1 h (sampling frequency 1 kHz, pass-band 0.1—300 Hz).
tized and overlaid on the MRI to ensure an accurate MEG/MRI co-registration.
Assessment of co-localization The presumed anatomical location of the epileptogenic zone was compared to the location of ECDs. The modalities were considered ‘‘co-localized’’ when they pointed towards the same anatomic region for extra-temporal epilepsies and to the same lobe for temporal epilepsies. They were considered ‘‘co-localized plus’’ when ECDs indicated both co-localization and additional distant epileptogenic area.
Results
MEG data analysis Continuous MEG data were preprocessed off-line using the SSS or spatiotemporal SSS methods (Taulu et al., 2004; Taulu and Simola, 2006) to suppress any residual interference, band-pass filtered to 1—40 Hz and visually inspected for epileptic events by X. De Tiège and M. Funke. Sharp signals (duration <200 ms) exceeding 150% of the background signal variance, seen on several neighboring channels and producing clear dipolar magnetic field patterns, were considered as potential epileptic events (Fernandes et al., 2005; Ossenblok et al., 2007). Events related to physiological artifacts or rhythms were rejected. Epileptic events were classified as spikes when their duration was ≤60 ms and as sharp waves when it was 60—200 ms (Fernandes et al., 2005; Ossenblok et al., 2007). Source locations of epileptic events were estimated by conventional dipole modeling tools (Elekta Neuromag Oy) using spherical conductor models determined from individual MRIs. Equivalent current dipoles (ECD) were fitted at the onset and at the peak of epileptic events using a selection of at least 40 channels. Dipole fits were considered valid when the goodness-of-fit was >80% and the 95%-confidence volume was less than 20 mm3 . ECDs were then overlaid on the patient’s MRIs, which were co-registered with MEG using three fiducial landmarks and four head position indicator coils whose locations were digitized prior to the MEG acquisition. Additional points (around 80—100) on the scalp were also digi-
Results of the study are summarized in Table 2. Interictal epileptic abnormalities were found in all 10 patients. ECDs co-localized in 7 patients with the presumed localization of the epileptogenic zone. 3 patients were classified as ‘‘co-localized plus’’ due to additional distinct MEG focus. In 2 of them (patients 6 and 10), the additional MEG focus was reflected also in previous interictal EEG. In 3 patients (patients 2, 4 and 5), the co-localization was confirmed by invasive EEG monitoring and in patient 2, the additional interictal MEG focus was also confirmed by invasive EEG monitoring. In patients with extra-temporal epileptic abnormalities in MEG, the ECDs were clustered on the brain lesion in patients 5 and 8 (Fig. 1), in a single brain area in patients 3 and 9, and scattered around the frontal lobe in patient 2. In patients with temporal epileptic abnormalities in MEG, we found mesiotemporal sources in patient 10, anterior temporal sources with horizontal orientation in five cases (patients 2, 4, 6, 9 and 10) and/or non-anterior temporal sources in four cases (patients 1, 6, 7 and 9); see Fig. 2. In patient 1, the right non-anterior temporal sources, which are usually associated with lateral, posterior or extratemporal epileptogenic zones, were nevertheless classified
230
X. De Tiège et al.
Figure 1 MEG data of patient 5. (A) One second of MEG signal obtained in samples of planar gradiometers grouped by lobes showing a left fronto-temporal interictal spike (RF: right frontal; LF: left frontal; RP: right parietal; LP: left parietal; RT: right temporal; LT: left temporal; RO: right occipital; LO: left occipital). (B) The same second of MEG signal obtained in samples of left fronto-temporal magnetometers showing the left fronto-temporal interictal spike (MAGN: magnetometer). (C) Upper: magnetic field pattern at the peak of the left fronto-temporal interictal spike superimposed on the neuromagnetometer helmet. The sensor array is viewed from the left. The squares show the locations of the sensor elements. The red contours indicate magnetic efflux and the blue contours magnetic influx. The green arrow depicts the surface projection of the equivalent current dipole (ECD) which best explains the field pattern. Middle and lower: ECDs (blue) that best explain the field pattern for the recorded interictal spikes shown on the patient’s co-registered 3D-T1 MRI; the sources of the recorded spikes are located in the left inferior frontal region.
as co-localized with the presumed right mesiotemporal location of the seizure focus as postsurgical follow-up studies have shown that some patients with this type of MEG sources are seizure-free after anterior temporal lobectomy with amygdalo-hippocampectomy (Iwasaki et al., 2002).
Discussion This study shows that the new light-weight magnetic shielding concept employed in a typical hospital environment
provides sufficient attenuation of magnetic interference to detect and reliably localize single epileptic abnormalities on continuous MEG data. The patients included in this study had temporal or extratemporal lobe epilepsy. We found epileptic sources that fit with the presumed location of the epileptogenic zone in all of them. In three patients, the co-localization was confirmed by invasive EEG monitoring. This suggests that MEG performed in the lMSR provides sufficient SNR to be applied in both types of focal epilepsies. In patients with temporal epilepsy, we found the different patterns of temporal
Recording epileptic activity with MEG in a light-weight magnetic shield
231
Figure 2 The different patterns of temporal MEG spikes found in three patients shown on each patient’s co-registered 3D-T1 MRI. Left: right anterior temporal sources with horizontal orientation (blue) found in patient 2. Middle: right mesiotemporal sources found in patient 10. Right: right posterior temporal sources found in patient 6.
lobe MEG spikes as previously reported (Iwasaki et al., 2002). Interestingly, we found clear mesiotemporal MEG sources in one patient, which suggests that the SNR provided by the lMSR is adequate to detect also deep brain sources. These data suggests that MEG with lMSR provides an adequate SNR for the non-invasive localization of epileptic foci. This study represents a preliminary step that warrants further studies comparing MEG using lMSR to simultaneous EEG, invasive EEG monitoring and postsurgical outcome in order to ultimately assess its clinical value. This new, more compact and less expensive magnetic shield should indeed facilitate the development of MEG in clinical environments.
Acknowledgments Xavier De Tiège is supported by a research grant from the ‘‘Fonds Erasme pour la Recherche Médicale’’ (Belgium). This study was supported by research grants from the Fund for Scientific Research (FRS-FNRS, Belgium) and the ‘‘Service Public Fédéral, Politique Scientifique’’ (Belgium).
References Fernandes, J.M., da Silva, A.M., Huiskamp, G., Velis, D.N., Manshanden, I., de Munck, J.C., da Silva, F.L., Cunha, J.P., 2005.
What does an epileptiform spike look like in MEG? Comparison between coincident EEG and MEG spikes. J. Clin. Neurophysiol. 22 (1), 68—73. Hämäläinen, M., Hari, R., Ilmoniemi, R.J., Knuutila, J., Lounasmaa, O.V., 1993. Magnetoencephalography: theory, instrumentation, and applications to noninvasive studies of the working human brain. Rev. Mod. Phys. 65 (2), 413—497. Iwasaki, M., Nakasato, N., Shamoto, H., Nagamatsu, K., Kanno, A., Hatanaka, K., Yoshimoto, T., 2002. Surgical implications of neuromagnetic spike localization in temporal lobe epilepsy. Epilepsia 43 (4), 415—424. Knowlton, R.C., 2006. The role of FDG-PET, ictal SPECT, and MEG in the epilepsy surgery evaluation. Epilepsy Behav. 8 (5), 91—101. Ossenblok, P., de Munck, J.C., Colon, A., Drolsbach, W., Boon, P., 2007. Magnetoencephalography is more successful for screening and localizing frontal lobe epilepsy than electroencephalography. Epilepsia 48 (11), 2139—2149. Parkkonen, L., Simola, J., Taulu, S., Kajola, M., Knuutila, J., Kojo, A., Nenonen, J., Ahonen, A., 2006. A light-weight magnetic shield: performance in real MEG measurements. 15th International Conference on Biomagnetism Biomag 2006, Vancouver, Canada. Taulu, S., Kajola, M., Simola, J., 2004. Suppression of interference and artifacts by the Signal Space Separation Method. Brain Topogr. 16 (4), 269—275. Taulu, S., Simola, J., 2006. Spatiotemporal signal space separation method for rejecting nearby interference in MEG measurements. Phys. Med. Biol. 51 (7), 1759—1768.
journal homepage: www.elsevier.com/locate/epilepsyres
SHORT COMMUNICATION
Recording epileptic activity with MEG in a light-weight magnetic shield Xavier De Tiège a,∗, Marc Op de Beeck a, Michael Funke b, Benjamin Legros c, Lauri Parkkonen d, Serge Goldman a, Patrick Van Bogaert a a
Laboratoire de Cartographie Fonctionnelle du Cerveau, ULB-Hôpital Erasme, Brussels, Belgium University of Utah Magnetic Source Imaging, University of Utah, Salt Lake City, UT, USA c Department of Neurology, ULB-Hôpital Erasme, Brussels, Belgium d Brain Research Unit, Low Temperature Laboratory, Helsinki University of Technology, Finland b
Received 15 May 2008; received in revised form 21 August 2008; accepted 22 August 2008 Available online 15 October 2008
KEYWORDS Magnetoencephalography; Light-weight magnetically shielded room; Signal-to-noise ratio; Epilepsy; Presurgical evaluation
Summary Ten patients with focal epilepsy were studied with magnetoencephalography (MEG) to determine if a new light-weight magnetically shielded room (lMSR) provides sufficient attenuation of magnetic interference to detect and localize the magnetic correlates of epileptic activity. Interictal MEG epileptic events co-localizing with the presumed location of the epileptogenic zone were found in all patients. MEG measurements performed in the lMSR provide an adequate signal-to-noise ratio for non-invasive localization of epileptic foci. © 2008 Elsevier B.V. All rights reserved.
Introduction Magnetoencephalography (MEG) is increasingly used in the non-invasive presurgical evaluation of patients with pharmacoresistant epilepsy to localize the epileptic focus although its clinical value compared to other source localization techniques is still under debate (Knowlton, 2006).
∗ Corresponding author at: Magnetoencephalography Unit, Laboratoire de Cartographie Fonctionnelle Cérébrale, ULB-Hôpital Erasme, 808 Lennik Street, 1070 Brussels, Belgium. Tel.: +32 2 555 31 11; fax: +32 2 555 47 01. E-mail address: [email protected] (X. De Tiège).
MEG records the changes in extracranial magnetic fields generated mainly by cortical pyramidal cells. Such fields are extremely weak: 50—10,000 × 10−15 Tesla (T) (Hämäläinen et al., 1993). In clinical environments, the typical ambient magnetic noise level (10−11 to 10−6 T) is several orders of magnitude higher than the neuromagnetic signal. Power-lines, elevators, moving hospital beds, radiological equipments, and even the variation of the Earth’s geomagnetic field contribute to ambient magnetic interferences (Hämäläinen et al., 1993). The most reliable way to reduce external magnetic disturbances is to acquire MEG data in a magnetically shielded room (MSR) (Hämäläinen et al., 1993). MSRs are usually made of several layers of mu-metal and aluminum, resulting in expensive, heavy and bulky constructions. To facilitate
0920-1211/$ — see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.eplepsyres.2008.08.011
228
X. De Tiège et al.
Table 1
Clinical data
Patient
Age/sex/onset
Video-EEG
Structural MRI
FDG-PET
Presumed location of epileptogenic zone
1
10 y/F/3 y
R temp spikes R temp CPS
R MTS
R temp hypo
R mesiotemp
2
11 y/M/6 y
R front SW
R caudate nucleus atrophy R O-front atrophy R front C-S-C abnor
R caudate nucleus hypo
R front
R O-front hypo R ant temp hypo
R front CPS 3
13 y/F/11 y
R par—occi SW R occi SPS
R par—occi atrophy
Not done
R occi
4
15 y/F/3 y
L temp SW L temp SPS & CPS
L temp FCD
L » R temp hypo
L temp
5
22 y/F/8 y
L inf front SW
L inf front atrophy (resection of cavernoma)
L inf front hypo
L inf front
L inf front CPS 6
28 y/F/1 y
L » R temp SW
L MTS, L ant temp FCD L temp CPS
L temp and thal hypo
L mesiotemp
7
32 y/F/12 y
L temp SW
L MTS L temp CPS
L temp hypo
L mesiotemp
8
50 y/M/11 y
R par SW R sensory SPSa
Normal
R sup par
9
53 y/F/8 y
L » R fron—temp SW L fron—temp CPS
R sup par FCD R lentiform nucleus hemorrh L MTS
L temp and thal hypo
L fron—temp
10
53 y/M/35 y
L and R temp SW
L and R temp post-trauma lesions L temp CPS
L temp hypo
L temp
R front post-trauma lesions
y: year; F: female; M: male; R: right; temp: temporal; front: frontal; par: parietal; occi: occipital; CPS: complex partial seizure; SPS: simple partial seizure; SW: spike-wave; MTS: mesiotemporal sclerosis; O-front: orbitofrontal; C-S-C: cortico-sub-cortical; abnor: abnormality; inf: inferior; ant: anterior; sup: superior; hemorrh: hemorraghe; post-trauma: post-traumatic; hypo: hypometabolism; thal: thalamic; mesiotemp: mesiotemporal; FCD: focal cortical dysplasia. a Not localized by EEG.
the siting of MEG systems to clinical environments, Elekta Neuromag Oy (Helsinki, Finland) has developed a lightweight magnetic shielding (lMSR) concept comprising a light-weight passive shielded room characterized by a single shell of interleaved mu-metal/aluminum layers, and active interference cancellation systems acting both inand outside of the shielded room (Parkkonen et al., 2006). This new lMSR concept has been shown to provide sufficient attenuation of magnetic noise to record, with a good signal-to-noise ratio (SNR), magnetic fields evoked by sensory stimuli (Parkkonen et al., 2006). However, this type of MEG measurement uses averaging to improve the SNR. Therefore, it is not guaranteed that lMSR will allow reliable detection and localization of single brain events like epileptic spikes among the residual environmental magnetic noise. A preliminary step to determine the potential clinical interest of this new lMSR in the presurgical evaluation of refractory epilepsy is therefore to demonstrate that MEG using lMSR is able to detect and reliably localize the magnetic correlates of epileptic abnormalities.
Patients and methods Patients Between June and December 2007, 10 patients (10—53 years; 7 females) followed in the presurgical evaluation program of Hôpital Erasme were selected for MEG investigation based on the following criteria: (1) pharmacoresistant symptomatic focal epilepsy, (2) frequent interictal epileptic abnormalities on previous EEG, and (3) well-defined presumed anatomic location of the epileptogenic zone. The presurgical work-up included: clinical evaluation, videoEEG monitoring, structural magnetic resonance imaging (MRI), neuropsychological evaluation and positron emission tomography with [18F]-fluorodeoxyglucose (9 patients). The presumed anatomic location of the seizure focus was determined after multidisciplinary discussion of the presurgical evaluation data. The clinical data of the patients are summarized in Table 1.
MEG acquisition MEG measurements were performed using the whole-head 306-channel Elekta Neuromag® system comprising 204 planar
Recording epileptic activity with MEG in a light-weight magnetic shield Table 2
229
MEG results
Patient
Presumed location of seizure focus
MEG results
Concordance
1 2
R mesiotemp R front
C C+*
3 4 5 6
R occi L temp L inf front L mesiotemp
7 8 9
L mesiotemp R sup par L fron—temp
10
L temp
R post temp spikes R front spikes R ant temp spikes R occi spikes L ant temp polyspikes L inf front spikes L ant temp spikes R post temp Sharp W L ant temp Sharp W R sup par polyspikes L ant temp spikes L post temp spikes L O-front spikes L ant temp spikes R ant temp spikes
C C* C* C+ C C C
C+
R: right; L: left; mesiotemp: mesiotemporal; front: frontal; occi: occipital; temp: temporal; inf: inferior; front: frontal; sup: superior; par: parietal; post: posterior; ant: anterior; W: waves; O-front: orbitofrontal; C: concordant; C+: concordant plus; *: confirmed by invasive EEG monitoring.
gradiometers and 102 magnetometers. MEG data were acquired in the new lMSR (MaxShieldTM , Elekta Neuromag Oy, Helsinki, Finland) which combines three magnetic noise suppression methods: (1) a light-weight single-shell shielded room, (2) an active feedback compensation system (three orthogonal coil pairs driven by the MEG sensors) which further reduces the interference at the sensor array, and (3) the software-based signal-space separation (SSS) method which removes any residual interference (Parkkonen et al., 2006; Taulu et al., 2004). The MSR was located at the basement level of the hospital and close to the sterilization department, the MRI and PET units. For all patients, spontaneous magnetic brain activity (eyesclosed rest, supine position) was recorded for 1 h (sampling frequency 1 kHz, pass-band 0.1—300 Hz).
tized and overlaid on the MRI to ensure an accurate MEG/MRI co-registration.
Assessment of co-localization The presumed anatomical location of the epileptogenic zone was compared to the location of ECDs. The modalities were considered ‘‘co-localized’’ when they pointed towards the same anatomic region for extra-temporal epilepsies and to the same lobe for temporal epilepsies. They were considered ‘‘co-localized plus’’ when ECDs indicated both co-localization and additional distant epileptogenic area.
Results
MEG data analysis Continuous MEG data were preprocessed off-line using the SSS or spatiotemporal SSS methods (Taulu et al., 2004; Taulu and Simola, 2006) to suppress any residual interference, band-pass filtered to 1—40 Hz and visually inspected for epileptic events by X. De Tiège and M. Funke. Sharp signals (duration <200 ms) exceeding 150% of the background signal variance, seen on several neighboring channels and producing clear dipolar magnetic field patterns, were considered as potential epileptic events (Fernandes et al., 2005; Ossenblok et al., 2007). Events related to physiological artifacts or rhythms were rejected. Epileptic events were classified as spikes when their duration was ≤60 ms and as sharp waves when it was 60—200 ms (Fernandes et al., 2005; Ossenblok et al., 2007). Source locations of epileptic events were estimated by conventional dipole modeling tools (Elekta Neuromag Oy) using spherical conductor models determined from individual MRIs. Equivalent current dipoles (ECD) were fitted at the onset and at the peak of epileptic events using a selection of at least 40 channels. Dipole fits were considered valid when the goodness-of-fit was >80% and the 95%-confidence volume was less than 20 mm3 . ECDs were then overlaid on the patient’s MRIs, which were co-registered with MEG using three fiducial landmarks and four head position indicator coils whose locations were digitized prior to the MEG acquisition. Additional points (around 80—100) on the scalp were also digi-
Results of the study are summarized in Table 2. Interictal epileptic abnormalities were found in all 10 patients. ECDs co-localized in 7 patients with the presumed localization of the epileptogenic zone. 3 patients were classified as ‘‘co-localized plus’’ due to additional distinct MEG focus. In 2 of them (patients 6 and 10), the additional MEG focus was reflected also in previous interictal EEG. In 3 patients (patients 2, 4 and 5), the co-localization was confirmed by invasive EEG monitoring and in patient 2, the additional interictal MEG focus was also confirmed by invasive EEG monitoring. In patients with extra-temporal epileptic abnormalities in MEG, the ECDs were clustered on the brain lesion in patients 5 and 8 (Fig. 1), in a single brain area in patients 3 and 9, and scattered around the frontal lobe in patient 2. In patients with temporal epileptic abnormalities in MEG, we found mesiotemporal sources in patient 10, anterior temporal sources with horizontal orientation in five cases (patients 2, 4, 6, 9 and 10) and/or non-anterior temporal sources in four cases (patients 1, 6, 7 and 9); see Fig. 2. In patient 1, the right non-anterior temporal sources, which are usually associated with lateral, posterior or extratemporal epileptogenic zones, were nevertheless classified
230
X. De Tiège et al.
Figure 1 MEG data of patient 5. (A) One second of MEG signal obtained in samples of planar gradiometers grouped by lobes showing a left fronto-temporal interictal spike (RF: right frontal; LF: left frontal; RP: right parietal; LP: left parietal; RT: right temporal; LT: left temporal; RO: right occipital; LO: left occipital). (B) The same second of MEG signal obtained in samples of left fronto-temporal magnetometers showing the left fronto-temporal interictal spike (MAGN: magnetometer). (C) Upper: magnetic field pattern at the peak of the left fronto-temporal interictal spike superimposed on the neuromagnetometer helmet. The sensor array is viewed from the left. The squares show the locations of the sensor elements. The red contours indicate magnetic efflux and the blue contours magnetic influx. The green arrow depicts the surface projection of the equivalent current dipole (ECD) which best explains the field pattern. Middle and lower: ECDs (blue) that best explain the field pattern for the recorded interictal spikes shown on the patient’s co-registered 3D-T1 MRI; the sources of the recorded spikes are located in the left inferior frontal region.
as co-localized with the presumed right mesiotemporal location of the seizure focus as postsurgical follow-up studies have shown that some patients with this type of MEG sources are seizure-free after anterior temporal lobectomy with amygdalo-hippocampectomy (Iwasaki et al., 2002).
Discussion This study shows that the new light-weight magnetic shielding concept employed in a typical hospital environment
provides sufficient attenuation of magnetic interference to detect and reliably localize single epileptic abnormalities on continuous MEG data. The patients included in this study had temporal or extratemporal lobe epilepsy. We found epileptic sources that fit with the presumed location of the epileptogenic zone in all of them. In three patients, the co-localization was confirmed by invasive EEG monitoring. This suggests that MEG performed in the lMSR provides sufficient SNR to be applied in both types of focal epilepsies. In patients with temporal epilepsy, we found the different patterns of temporal
Recording epileptic activity with MEG in a light-weight magnetic shield
231
Figure 2 The different patterns of temporal MEG spikes found in three patients shown on each patient’s co-registered 3D-T1 MRI. Left: right anterior temporal sources with horizontal orientation (blue) found in patient 2. Middle: right mesiotemporal sources found in patient 10. Right: right posterior temporal sources found in patient 6.
lobe MEG spikes as previously reported (Iwasaki et al., 2002). Interestingly, we found clear mesiotemporal MEG sources in one patient, which suggests that the SNR provided by the lMSR is adequate to detect also deep brain sources. These data suggests that MEG with lMSR provides an adequate SNR for the non-invasive localization of epileptic foci. This study represents a preliminary step that warrants further studies comparing MEG using lMSR to simultaneous EEG, invasive EEG monitoring and postsurgical outcome in order to ultimately assess its clinical value. This new, more compact and less expensive magnetic shield should indeed facilitate the development of MEG in clinical environments.
Acknowledgments Xavier De Tiège is supported by a research grant from the ‘‘Fonds Erasme pour la Recherche Médicale’’ (Belgium). This study was supported by research grants from the Fund for Scientific Research (FRS-FNRS, Belgium) and the ‘‘Service Public Fédéral, Politique Scientifique’’ (Belgium).
References Fernandes, J.M., da Silva, A.M., Huiskamp, G., Velis, D.N., Manshanden, I., de Munck, J.C., da Silva, F.L., Cunha, J.P., 2005.
What does an epileptiform spike look like in MEG? Comparison between coincident EEG and MEG spikes. J. Clin. Neurophysiol. 22 (1), 68—73. Hämäläinen, M., Hari, R., Ilmoniemi, R.J., Knuutila, J., Lounasmaa, O.V., 1993. Magnetoencephalography: theory, instrumentation, and applications to noninvasive studies of the working human brain. Rev. Mod. Phys. 65 (2), 413—497. Iwasaki, M., Nakasato, N., Shamoto, H., Nagamatsu, K., Kanno, A., Hatanaka, K., Yoshimoto, T., 2002. Surgical implications of neuromagnetic spike localization in temporal lobe epilepsy. Epilepsia 43 (4), 415—424. Knowlton, R.C., 2006. The role of FDG-PET, ictal SPECT, and MEG in the epilepsy surgery evaluation. Epilepsy Behav. 8 (5), 91—101. Ossenblok, P., de Munck, J.C., Colon, A., Drolsbach, W., Boon, P., 2007. Magnetoencephalography is more successful for screening and localizing frontal lobe epilepsy than electroencephalography. Epilepsia 48 (11), 2139—2149. Parkkonen, L., Simola, J., Taulu, S., Kajola, M., Knuutila, J., Kojo, A., Nenonen, J., Ahonen, A., 2006. A light-weight magnetic shield: performance in real MEG measurements. 15th International Conference on Biomagnetism Biomag 2006, Vancouver, Canada. Taulu, S., Kajola, M., Simola, J., 2004. Suppression of interference and artifacts by the Signal Space Separation Method. Brain Topogr. 16 (4), 269—275. Taulu, S., Simola, J., 2006. Spatiotemporal signal space separation method for rejecting nearby interference in MEG measurements. Phys. Med. Biol. 51 (7), 1759—1768.