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Chapter 29 Comparison between preoperative and intraoperative localization of cortical function in patients with brain tumors
Functional Neuroscience: Evoked Potentials and Related Techniques (Supplements to Clinical Neurophysiology, Vol. 59) Editors: C. Barber, S. Tsuji, S. Tobimatsu, T. Uozumi, N. Akamatsu, A. Eisen © 2006 Elsevier B.V. All rights reserved
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Chapter 29
Comparison between preoperative and intraoperative localization of cortical function in patients with brain tumors J. P. Mäkelä* Brain Research Unit, Low Temperature Laboratory, Helsinki University of Technology, P.O. Box 2200, FIN-02015 Espoo (Finland), Department of Neurology, Central Military Hospital, P.O. Box 50, FIN-00301 Helsinki (Finland) and BioMag Laboratory, Helsinki University Central Hospital, P.O. Box 340, FIN-00029 HUS, Helsinki (Finland)
1. Introduction During the last decade functional landmarks, produced by various neuroimaging methods and depicting eloquent brain areas, have been suggested to be a valuable planning adjunct before surgery of brain tumors (e.g. Rezai et al., 1996; Hund et al., 1997; Bittar et al., 1999; Ganslandt et al., 1999; Lehericy et al., 2000; Kober et al., 2001; Mäkelä et al., 2001; Inoue et al., 2004). These landmarks may encourage operations in the cases where key cortical areas are moved away but are unaffected by tumor masses, or suggest selection of alternative treatment strategies in patients with tumor invasion of the crucial cortical regions. They also allow maximum resection in tumors abutting eloquent cortex. The distance between these landmarks and operated region has also been shown to predict the risk of complications (Hund et al., 1997). One possibility to produce such functional landmarks is to measure magnetoencephalographic (MEG)
*Correspondence to: J. P. Mäkelä, BioMag Laboratory, Helsinki University Central Hospital, P.O. Box 340, FIN-00029 HUS, Helsinki, Finland. Tel: +358-9-47172096; Fax: +358-9-47175781; E-mail: [email protected]
signals produced by brain electric activity. Modern whole-head MEG instruments allow fast localization of brain areas producing somatosensory, auditory and visual responses, and localization of the motor cortical areas producing spontaneous brain activity coherent with EMG of a contracted muscle. Excellent temporal resolution allows follow-up of brain activation sequences with millisecond time separation. For example, it is feasible to study the spread of somatosensory activation from the primary sensory cortex at 20 ms to secondary somatosensory and posterior parietal cortices at about 90–110 ms (Hari and Forss, 1999). These activation sites can be overlaid on 3-dimensional (3D) MRI reconstructions of the brain of an individual patient. Resemblance to the actual field of view during the operation can be enhanced by depicting the cortical veins, which often produce useful visual cues for orientation. In our experience, MEG source locations of evoked responses overlaid on these 3D MRI reconstructions aid in pinpointing functionally irretrievable areas before neurosurgery, assist in presurgical planning, and ease orientation in a limited field of view available during surgery (Mäkelä et al., 2001). To avoid complications, it is at present important to localize the eloquent cortical areas also intraoperatively using, for example, cortical electric stimulation,
214 or recording evoked electric potentials directly from the exposed cortex. Preoperative functional landmarks serve as “intraoperative road maps,” speeding up selection of stimulation sites or electrode grid positions for intraoperative monitoring. Comparison of the preoperative and intraoperative source localizations gives an estimate of accuracy of these preoperative functional landmarks, but also an idea of the general validity of source identification by functional brain imaging. We have made a comparison of preoperative MEG landmarks and intraoperative localization in a series of patients going through a brain tumor operation (Mäkelä et al., 2001). 2. Patients and methods Eleven patients underwent awake craniotomy due to a brain tumor. Four patients had a primary glioma, and four a recurrent GII or GIII glioma, one had a metastatic neurofibrosarcoma, one a hemangioma, and one an arteriovenous malformation in the vicinity of the somatomotor strip. Before the operation, evoked fields to median and tibial nerve and lip stimuli were recorded with a whole-scalp 122-channel neuromagnetometer (Neuromag 122TM; Ahonen et al., 1993) to identify hand, foot, and face representations in the somatosensory cortex. Oscillatory cortical activity, coherent with surface electromyogram during isometric muscle contraction, was analyzed to reveal the hand and foot representations in the precentral motor cortex. The source locations were coregistered with standard magnetic resonance images (MRI) of individual subjects. Particular care was taken to make the coregistration as accurate as possible. For example, we used four coils instead of the typical three, attached to the scalp in locating the patient’s head with respect to the sensors. The locations of the coils with respect to the nasion and periauricular points were determined with a 3D digitizer. Before digitization, these fiduciary points were marked on the skin, and the nasion and the auricular folds were photographed with a digital camera to allow a more exact comparison with MR images. The MR images (1.5 T Siemens Magnetom system) were acquired using regular T1-weighted MPRAGE
sequence for head images and gadolinium-enhanced MPRAGE sequence for visualizing the venous system and tumor enhancement. To depict the veins on the brain surface, the contrast-enhanced MR images were segmented along the inner surface of the skull. The software for the visualization of the segmented images was developed in low temperature laboratory by M. Seppä. The MEG source locations were visualized as colored dots on top of the ray-traced raster images. The equivalent current dipoles (ECDs) were generally located at some depth within a sulcus, and the ambiguity caused by parallax distortion in projecting them to the brain surface was solved by identifying the appropriate sulcus from traditional MR images in three planes and following it onto the cortical surface. During the operation, cortical somatosensory evoked potentials (SEPs) were recorded from five patients (8-channel Viking IV recorder; NicoletTM; Table 2) to median nerve stimulation. The responses were recorded from two first rows of a 4 × 5 electrode grid (PMT Inc., Minnesota, USA). The grid was placed over the central sulcus hand region. The cortical area around and over the tumor region was mapped for motor and sensory function in seven patients, using 50 Hz 0.2 ms 9–18 mA unipolar electric pulses. The optimum response site was not searched for. The cortical surface, location of stimulation sites, and the SEP grid position were photographed for comparison with preoperative findings. To provide a rough estimate of the locational accuracy of the SEF sources, the sensory cortical areas identified by intraoperative cortical stimulation and by the sites of cortical electrodes displaying maximum negative SEP deflections in 20–25 ms range were superimposed on the surface of the individual 3D MRI reconstructions. The MEG sources were projected to the nearest brain surface. The distance between the identified stimulation points or electrode sites and the SEF sources was then measured (Fig. 1). We also tested a notion of a broader precentral motor than postcentral somatosensory gyrus at the vertex by measuring the width of precentral and postcentral gyrus 3 mm lateral from the medial border of the hemispheric cortex in the longitudinal fissure from the 3D MRI reconstructions of the patients.
215
Fig. 1. Left: 3D reconstruction of the brain of a patient before reoperation of a left-sided GII oligodendroglioma. Sources of somatosensory evoked fields (SEFs) to the right median nerve (white circle) and tibial nerve (black circle) stimulation are overlaid on the reconstruction. Right: intraoperative photograph shows tags marking cortical stimulation sites. Foot movements were elicited in stimulation under tag 6 and finger movements under tag 3. A prominent gyrus is labeled with an asterisk in both figures.
In a parallel set of experiments, SEF sources were also compared with functional MR imaging (fMRI) of activity generated by repetitive wrist flexions in the localization of central sulcus. In 15 patients, intraoperative verification of central sulcus location by cortical mapping was available (Korvenoja et al., in press). 3. Results The mean distance between the somatosensory evoked field (SEF) source and the SEP electrode picking up the maximum 20 ms response was 10 mm (range 5–18 mm). In one patient, the distance was 18 mm along the postcentral gyrus, and thus did not affect the identification of the central sulcus. In other subjects, the difference varied between 5 and 10 mm. In three patients, the mean distance between the site
producing sensory response in cortical stimulation and SEF source was 8 mm. In 7 out of 11 patients, the MEG–EMG coherence maxima were identified with a satisfactory goodness of fit of the single-dipole model. These results thus provided an additional independent measure to confirm the location of the central sulcus. The source locations indicated motor cortex activation in all patients. The comparison between preoperative hand motor cortex location, as defined by coherence analysis, and intraoperative motor cortex stimulation was possible only in one patient; the difference was 6 mm. A wider precentral than postcentral gyrus was observed in 9 out of 12 affected and in 10 out of 12 non-affected hemispheres. The precentral vs. postcentral gyrus widths 3 mm lateral from the longitudinal fissure were, on average, 10 ± 5 mm vs. 7 ± 3 mm
216 ( p < 0.02) in the left hemisphere, and 11 ± 4 mm vs. 7 ± 3 mm ( p < 0.01) in the right hemisphere. SEF sources agreed with intraoperative somatosensory cortex localization in all 15 patients. Localization of the motor cortex by fMRI agreed with intraoperative findings in 11 out of 15 patients. In patients with erroneous localization, maximum fMRI activation was seen posterior to the motor cortex in the region of postcentral sulcus. In addition, multiple non-primary cortical areas were activated in fMRI, with considerable individual variation (Korvenoja et al., in press). 4. Discussion Preoperative functional localization with MEG generally agrees with intraoperative findings of the active somatosensory and motor cortical areas. This is delightful to an MEG scientist. The MEG source localization deals with solving the “inverse problem,” deducing the source location from the externally measured magnetic field, which, in general form, has no unique solution. However, these examples, in line with previous work (Gallen et al., 1993, 1995; Kamada et al., 1993; Rezai et al., 1996; Ganslandt et al., 1997; Hund et al., 1997; Nakasato et al., 1997), show that presuppositions included in dipole modelling of the inverse problem match with the physiological reality in localization of the early SEF sources. Our mean accuracy of about 1 cm agrees with 13 ± 1 mm accuracy reported by Schiffbauer et al. (2002) in a larger series of patients. These results certainly compare favorably with estimations of accuracy of motor cortex localization based on anatomic landmarks, recently described to be on average 25 mm (Towle et al., 2003). Furthermore, central sulcus localization with MEG compares favorably with that obtained by fMRI activation of motor cortex elicited by a standard motor paradigm (Korvenoja et al., in press). Although several studies have reported an excellent match between fMRI and intraoperative central sulcus localization, some have not. For example, the fMRI and MEG localization of the central sulcus in the same patients differed in about 20% of the affected hemispheres; the MEG localizations were confirmed by intraoperative SEP recordings (Inoue et al., 1999).
Mean difference of SEF source location and somatosensory elicited activation has been reported to be 15 ± 5 mm, which may exceed the gyral width (see above); unfortunately, no comparison with the intraoperative recordings were made in this study (Kober et al., 2001). The sensory fMRI activation was reported to be anterior to motor one in 9 out of 21 hemispheres (Towle et al., 2003). Due to slowness of hemodynamic response, activation of multiple non-primary areas may complicate interpretation of fMRI results; this drawback is avoided by MEG’s millisecond temporal sensitivity. The comparison of preoperative and intraoperative cortical functional localization in millimeter accuracy is fraught with several problems. SEF sources typically are located within a sulcus whereas cortical stimulation and recordings are performed from the gyral surface. It is perfectly feasible to model sources of SEPs recorded from the cortical surface. However, this procedure would require more recording channels than we had at our disposal. Indeed, it was not possible to define unequivocal orientation of polarity inversion line of SEPs in all our subjects. This inversion line would be a more appropriate site for comparison of preoperative and intraoperative somatosensory localization than the site of the electrode picking up the maximum SEP response. The size of recording instruments produces limits to the comparison accuracy. In our electrode grid, electrode diameter was 6.5 mm and electrode separation was 3 mm. The tip of the electrode used in cortical stimulation had a 4 mm diameter, and tags used to mark the stimulation site were 10 × 7 mm in size. Optimal site for eliciting responses in cortical stimulation was not searched for due to the limited time available during the operation. Furthermore, there is no clear information about the spread of the stimulation current within the cortex. Schiffbauer et al. (2002) observed that intraoperative sites at which stimulation evoked the same response had a spatial variation of 11 ± 1 mm. A neuronavigator system could have ameliorated some of the described problems. Schiffbauer et al. (2002), using neuronavigation, demonstrated a 21 ± 2 mm 3D difference between preoperative SEF
217 localization and intraoperative stimulation sites. However, additional problems for pre- and intraoperative site comparison could have been introduced by neuronavigation as well. It has been shown that the cortical surface shifts 5–10 mm after dural opening in the surgery. The direction of the main shift follows gravity and its effect on the brain depends on head position during the operation (Roberts et al., 1998). The largest shift occurs near the center of the craniotomy, usually in the brain region of greatest interest (Hill et al., 2000), and most probably adds to the difference in comparison between preoperative and intraoperative source areas. Four of our patients suffered from recurrent glioma, and in some of them ferromagnetic dust from the drilling in previous operations produced considerable noise to the signals. The largest difference between the preoperative and intraoperative localization occurred in one of these patients. Most recent technical developments may alleviate this type of problems in the future. Continuous head position monitoring (Uutela et al., 2001), in combination with signal space separation algorithm, may allow the separation of direct current artifacts due to moving magnetic objects from brain signals (Taulu et al., 2004). To conclude, it is usually possible to identify somatosensory and motor cortex preoperatively with about 1 cm accuracy using MEG recordings in patients with brain tumors in close vicinity of the sensorimotor strip. This accuracy compares favorably with localization results with fMRI, and suggests that the presuppositions underlying dipole modelling of the primary sensorimotor responses are sensible. 5. Acknowledgements I thank Prof. R. Hari for comments on this chapter. References Ahonen, A., Hämäläinen, M., Kajola, M., Knuutila, J., Laine, P., Lounasmaa, O., Parkkonen, L., Simola, J. and Tesche, C. (1993) 122-channel SQUID instrument for investigating the magnetic signals from human brain. Physica Scripta, T49: 198–205. Bittar, R., Olivier, A., Sadikot, A., Andermann, F., Comeau, R., Cyr, M., Peters, T. and Reutens, D. (1999) Localization of somatosensory
function by using positron emission tomography scanning; a comparison with intraoperative cortical stimulation. J. Neurosurg., 90: 478–483. Gallen, C., Sobel, D., Waltz, T., Aung, M., Copeland, B., Schwartz, B., Hirschkoff, E. and Bloom, F. (1993) Noninvasive presurgical mapping of somatosensory cortex. Neurosurgery, 33: 260–268. Gallen, C., Schwartz, B. and Bucholz, R. (1995) Presurgical localization of functional cortex using magnetic source imaging. J. Neurosurg., 82: 988–994. Ganslandt, O., Steinmeier, R., Kober, H., Vieth, J., Kassubeck, J., Romstöck, J., Strauss, C. and Fahlbusch, R. (1997) Magnetic source imaging combined with image-guided frameless stereotaxy: a new method in surgery around the motor strip. Neurosurgery, 41: 621–628. Ganslandt, O., Fahlbusch, R., Nimsky, C., Kober, H., Möller, M., Steinmeier, R., Römstock, J. and Vieth, J. (1999) Functional neuronavigation with magnetoencephalography: outcome in 50 patients with lesions around the motor cortex. J. Neurosurg., 91: 73–79. Hari, R. and Forss, N. (1999) Magnetoencephalography in the study of human somatosensory cortical processing. Phil. Trans. Roy. Soc. Lond., B 354: 1145–1154. Hill, D., Castellano Smith, A., Simmons, A., Maurer, C., Cox, T., Elwes, R., Brammer, M., Hawkes, D. and Polkey, C. (2000) Sources of error in comparing functional magnetic resonance imaging and invasive electrophysiological recordings. J. Neurosurg., 93: 214–223. Hund, M., Rezai, A., Kronberg, E., Cappell, J., Zoneshayn, M., Ribary, U., Kelly, P. and Llinas, R. (1997) Magnetoencephalographic mapping: basis of new functional risk profile in the selection of patients with cortical brain lesions. Neurosurgery, 40: 936–943. Inoue, T., Shimizu, H., Nakasato, N., Kumabe, T. and Yoshimoto, T. (1999) Accuracy and limitation of functional magnetic resonance imaging for identification of the central sulcus: comparison with magnetoencephalography in patients with brain tumors. Neuroimage, 10: 738–748. Inoue, T., Fujimura, M., Kumabe, T., Nakasato, N., Higano, S. and Tominaga, T. (2004) Combined three-dimensional aniotropy contrast imaging and magnetoencephalography guidance to preserve visual function in a patient with an occipital lobe tumor. Minim. Invas. Neurosurg., 47: 249–252. Kamada, K., Takeuchi, F., Kuriki, S., Oshiro, O., Houkin, K. and Abe, H. (1993) Functional neurosurgical simulation with brain surface magnetic resonance images and magnetoencephalography. Neurosurgery, 33: 269–273. Kober, H., Nimsky, C., Møller, M., Hastreiter, P., Fahlbusch, R. and Ganslandt, O. (2001) Correlation of sensorimotor activation with functional magnetic resonance imaging and magnetoencephalography in presurgical functional imaging: a spatial analysis. Neuroimage, 14: 1214–1228. Korvenoja, A., Kirveskari, E., Aronen, H.J., Avikainen, S., Brander, A., Huttunen, J., Illmoniemi, R.J., Jääskeläinen, J., Kovala, T., Mäkelä, J.P., Salli, E. and Seppä, M. Localization of primary sensorimotor cortex: comparison of magnetoencephalography, functional MR imaging and intraoperative cortical mapping. Radiology, in press. Lehericy, S., Duffay, H., Cornu, P., Capelle, L., Pidoux, B., Carpentier, A., Auliac, S., Clemenceau, S., Sichez, J.-P., Bitar, A.,
218 Valery, C.-A., Van Effenterre, R., Faillot, T., Srour, A., Fohanno, D., Philippon, J., LeBihan, D. and Marsault, C. (2000) Correspondence between functional magnetic resonance imaging somatotopy and individual brain anatomy of the central region: comparison with intraoperative stimulation in patients with brain tumors. J. Neurosurg., 92: 589–598. Mäkelä, J.P., Kirveskari, E., Seppä, M., Hämäläinen, M., Forss, N., Avikainen, S., Salonen, O., Salenius, S., Kovala, T., Randell, T., Jääskeläinen, J. and Hari, R. (2001) Three-dimensional integration of brain anatomy and function to facilitate intraoperative navigation around the sensorimotor strip. Hum. Brain Mapp., 12: 180–192. Nakasato, N., Kumabe, T., Kanno, A., Ohtomo, S., Mizoi, K. and Yoshimoto, T. (1997) Neuromagnetic evaluation of cortical auditory function in patients with temporal lobe tumors. J. Neurosurg., 86: 610–618. Rezai, A., Hund, M., Kronberg, E., Zoneshayn, M., Cappell, J., Ribary, U., Kall, B., Llinas, R. and Kelly, P. (1996) The interactive use of magnetoencephalography in stereotactic image-guided neurosurgery. Neurosurgery, 39: 92–102.
Roberts, D., Hartov, A., Kennedy, F., Miga, M. and Paulsen, K. (1998) Intraoperative brain shift and deformation: a quantitative analysis of cortical displacement in 28 cases. Neurosurgery, 42: 749–760. Schiffbauer, H., Berger, M., Ferrari, P., Freudenstein, D., Rowley, H. and Roberts, T. (2002) Preoperative magnetic source imaging for brain tumor surgery: a quantitative comparison with intraoperative sensory and motor mapping. J. Neurosurg., 97: 1333–1342. Taulu, S., Kajola, M. and Simola, J. (2004) Suppression of interference and artifacts by the signal space separation method. Brain Topogr., 16: 269–275. Towle, V., Khorasani, L., Uftring, S., Pelizzari, C., Erickson, R., Spire, J.-P., Hoffman, K., Chu, D. and Scherg, M. (2003) Noninvasive identification of human central sulcus: a comparison of gyral morphology, functional MRI, dipole localization, and direct cortical mapping. Neuroimage, 19: 684–697. Uutela, K., Taulu, S. and Hämäläinen, M. (2001) Detecting and correcting for head movements in neuromagnetic measurements. Neuroimage, 14: 1424–1431.
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Chapter 29
Comparison between preoperative and intraoperative localization of cortical function in patients with brain tumors J. P. Mäkelä* Brain Research Unit, Low Temperature Laboratory, Helsinki University of Technology, P.O. Box 2200, FIN-02015 Espoo (Finland), Department of Neurology, Central Military Hospital, P.O. Box 50, FIN-00301 Helsinki (Finland) and BioMag Laboratory, Helsinki University Central Hospital, P.O. Box 340, FIN-00029 HUS, Helsinki (Finland)
1. Introduction During the last decade functional landmarks, produced by various neuroimaging methods and depicting eloquent brain areas, have been suggested to be a valuable planning adjunct before surgery of brain tumors (e.g. Rezai et al., 1996; Hund et al., 1997; Bittar et al., 1999; Ganslandt et al., 1999; Lehericy et al., 2000; Kober et al., 2001; Mäkelä et al., 2001; Inoue et al., 2004). These landmarks may encourage operations in the cases where key cortical areas are moved away but are unaffected by tumor masses, or suggest selection of alternative treatment strategies in patients with tumor invasion of the crucial cortical regions. They also allow maximum resection in tumors abutting eloquent cortex. The distance between these landmarks and operated region has also been shown to predict the risk of complications (Hund et al., 1997). One possibility to produce such functional landmarks is to measure magnetoencephalographic (MEG)
*Correspondence to: J. P. Mäkelä, BioMag Laboratory, Helsinki University Central Hospital, P.O. Box 340, FIN-00029 HUS, Helsinki, Finland. Tel: +358-9-47172096; Fax: +358-9-47175781; E-mail: [email protected]
signals produced by brain electric activity. Modern whole-head MEG instruments allow fast localization of brain areas producing somatosensory, auditory and visual responses, and localization of the motor cortical areas producing spontaneous brain activity coherent with EMG of a contracted muscle. Excellent temporal resolution allows follow-up of brain activation sequences with millisecond time separation. For example, it is feasible to study the spread of somatosensory activation from the primary sensory cortex at 20 ms to secondary somatosensory and posterior parietal cortices at about 90–110 ms (Hari and Forss, 1999). These activation sites can be overlaid on 3-dimensional (3D) MRI reconstructions of the brain of an individual patient. Resemblance to the actual field of view during the operation can be enhanced by depicting the cortical veins, which often produce useful visual cues for orientation. In our experience, MEG source locations of evoked responses overlaid on these 3D MRI reconstructions aid in pinpointing functionally irretrievable areas before neurosurgery, assist in presurgical planning, and ease orientation in a limited field of view available during surgery (Mäkelä et al., 2001). To avoid complications, it is at present important to localize the eloquent cortical areas also intraoperatively using, for example, cortical electric stimulation,
214 or recording evoked electric potentials directly from the exposed cortex. Preoperative functional landmarks serve as “intraoperative road maps,” speeding up selection of stimulation sites or electrode grid positions for intraoperative monitoring. Comparison of the preoperative and intraoperative source localizations gives an estimate of accuracy of these preoperative functional landmarks, but also an idea of the general validity of source identification by functional brain imaging. We have made a comparison of preoperative MEG landmarks and intraoperative localization in a series of patients going through a brain tumor operation (Mäkelä et al., 2001). 2. Patients and methods Eleven patients underwent awake craniotomy due to a brain tumor. Four patients had a primary glioma, and four a recurrent GII or GIII glioma, one had a metastatic neurofibrosarcoma, one a hemangioma, and one an arteriovenous malformation in the vicinity of the somatomotor strip. Before the operation, evoked fields to median and tibial nerve and lip stimuli were recorded with a whole-scalp 122-channel neuromagnetometer (Neuromag 122TM; Ahonen et al., 1993) to identify hand, foot, and face representations in the somatosensory cortex. Oscillatory cortical activity, coherent with surface electromyogram during isometric muscle contraction, was analyzed to reveal the hand and foot representations in the precentral motor cortex. The source locations were coregistered with standard magnetic resonance images (MRI) of individual subjects. Particular care was taken to make the coregistration as accurate as possible. For example, we used four coils instead of the typical three, attached to the scalp in locating the patient’s head with respect to the sensors. The locations of the coils with respect to the nasion and periauricular points were determined with a 3D digitizer. Before digitization, these fiduciary points were marked on the skin, and the nasion and the auricular folds were photographed with a digital camera to allow a more exact comparison with MR images. The MR images (1.5 T Siemens Magnetom system) were acquired using regular T1-weighted MPRAGE
sequence for head images and gadolinium-enhanced MPRAGE sequence for visualizing the venous system and tumor enhancement. To depict the veins on the brain surface, the contrast-enhanced MR images were segmented along the inner surface of the skull. The software for the visualization of the segmented images was developed in low temperature laboratory by M. Seppä. The MEG source locations were visualized as colored dots on top of the ray-traced raster images. The equivalent current dipoles (ECDs) were generally located at some depth within a sulcus, and the ambiguity caused by parallax distortion in projecting them to the brain surface was solved by identifying the appropriate sulcus from traditional MR images in three planes and following it onto the cortical surface. During the operation, cortical somatosensory evoked potentials (SEPs) were recorded from five patients (8-channel Viking IV recorder; NicoletTM; Table 2) to median nerve stimulation. The responses were recorded from two first rows of a 4 × 5 electrode grid (PMT Inc., Minnesota, USA). The grid was placed over the central sulcus hand region. The cortical area around and over the tumor region was mapped for motor and sensory function in seven patients, using 50 Hz 0.2 ms 9–18 mA unipolar electric pulses. The optimum response site was not searched for. The cortical surface, location of stimulation sites, and the SEP grid position were photographed for comparison with preoperative findings. To provide a rough estimate of the locational accuracy of the SEF sources, the sensory cortical areas identified by intraoperative cortical stimulation and by the sites of cortical electrodes displaying maximum negative SEP deflections in 20–25 ms range were superimposed on the surface of the individual 3D MRI reconstructions. The MEG sources were projected to the nearest brain surface. The distance between the identified stimulation points or electrode sites and the SEF sources was then measured (Fig. 1). We also tested a notion of a broader precentral motor than postcentral somatosensory gyrus at the vertex by measuring the width of precentral and postcentral gyrus 3 mm lateral from the medial border of the hemispheric cortex in the longitudinal fissure from the 3D MRI reconstructions of the patients.
215
Fig. 1. Left: 3D reconstruction of the brain of a patient before reoperation of a left-sided GII oligodendroglioma. Sources of somatosensory evoked fields (SEFs) to the right median nerve (white circle) and tibial nerve (black circle) stimulation are overlaid on the reconstruction. Right: intraoperative photograph shows tags marking cortical stimulation sites. Foot movements were elicited in stimulation under tag 6 and finger movements under tag 3. A prominent gyrus is labeled with an asterisk in both figures.
In a parallel set of experiments, SEF sources were also compared with functional MR imaging (fMRI) of activity generated by repetitive wrist flexions in the localization of central sulcus. In 15 patients, intraoperative verification of central sulcus location by cortical mapping was available (Korvenoja et al., in press). 3. Results The mean distance between the somatosensory evoked field (SEF) source and the SEP electrode picking up the maximum 20 ms response was 10 mm (range 5–18 mm). In one patient, the distance was 18 mm along the postcentral gyrus, and thus did not affect the identification of the central sulcus. In other subjects, the difference varied between 5 and 10 mm. In three patients, the mean distance between the site
producing sensory response in cortical stimulation and SEF source was 8 mm. In 7 out of 11 patients, the MEG–EMG coherence maxima were identified with a satisfactory goodness of fit of the single-dipole model. These results thus provided an additional independent measure to confirm the location of the central sulcus. The source locations indicated motor cortex activation in all patients. The comparison between preoperative hand motor cortex location, as defined by coherence analysis, and intraoperative motor cortex stimulation was possible only in one patient; the difference was 6 mm. A wider precentral than postcentral gyrus was observed in 9 out of 12 affected and in 10 out of 12 non-affected hemispheres. The precentral vs. postcentral gyrus widths 3 mm lateral from the longitudinal fissure were, on average, 10 ± 5 mm vs. 7 ± 3 mm
216 ( p < 0.02) in the left hemisphere, and 11 ± 4 mm vs. 7 ± 3 mm ( p < 0.01) in the right hemisphere. SEF sources agreed with intraoperative somatosensory cortex localization in all 15 patients. Localization of the motor cortex by fMRI agreed with intraoperative findings in 11 out of 15 patients. In patients with erroneous localization, maximum fMRI activation was seen posterior to the motor cortex in the region of postcentral sulcus. In addition, multiple non-primary cortical areas were activated in fMRI, with considerable individual variation (Korvenoja et al., in press). 4. Discussion Preoperative functional localization with MEG generally agrees with intraoperative findings of the active somatosensory and motor cortical areas. This is delightful to an MEG scientist. The MEG source localization deals with solving the “inverse problem,” deducing the source location from the externally measured magnetic field, which, in general form, has no unique solution. However, these examples, in line with previous work (Gallen et al., 1993, 1995; Kamada et al., 1993; Rezai et al., 1996; Ganslandt et al., 1997; Hund et al., 1997; Nakasato et al., 1997), show that presuppositions included in dipole modelling of the inverse problem match with the physiological reality in localization of the early SEF sources. Our mean accuracy of about 1 cm agrees with 13 ± 1 mm accuracy reported by Schiffbauer et al. (2002) in a larger series of patients. These results certainly compare favorably with estimations of accuracy of motor cortex localization based on anatomic landmarks, recently described to be on average 25 mm (Towle et al., 2003). Furthermore, central sulcus localization with MEG compares favorably with that obtained by fMRI activation of motor cortex elicited by a standard motor paradigm (Korvenoja et al., in press). Although several studies have reported an excellent match between fMRI and intraoperative central sulcus localization, some have not. For example, the fMRI and MEG localization of the central sulcus in the same patients differed in about 20% of the affected hemispheres; the MEG localizations were confirmed by intraoperative SEP recordings (Inoue et al., 1999).
Mean difference of SEF source location and somatosensory elicited activation has been reported to be 15 ± 5 mm, which may exceed the gyral width (see above); unfortunately, no comparison with the intraoperative recordings were made in this study (Kober et al., 2001). The sensory fMRI activation was reported to be anterior to motor one in 9 out of 21 hemispheres (Towle et al., 2003). Due to slowness of hemodynamic response, activation of multiple non-primary areas may complicate interpretation of fMRI results; this drawback is avoided by MEG’s millisecond temporal sensitivity. The comparison of preoperative and intraoperative cortical functional localization in millimeter accuracy is fraught with several problems. SEF sources typically are located within a sulcus whereas cortical stimulation and recordings are performed from the gyral surface. It is perfectly feasible to model sources of SEPs recorded from the cortical surface. However, this procedure would require more recording channels than we had at our disposal. Indeed, it was not possible to define unequivocal orientation of polarity inversion line of SEPs in all our subjects. This inversion line would be a more appropriate site for comparison of preoperative and intraoperative somatosensory localization than the site of the electrode picking up the maximum SEP response. The size of recording instruments produces limits to the comparison accuracy. In our electrode grid, electrode diameter was 6.5 mm and electrode separation was 3 mm. The tip of the electrode used in cortical stimulation had a 4 mm diameter, and tags used to mark the stimulation site were 10 × 7 mm in size. Optimal site for eliciting responses in cortical stimulation was not searched for due to the limited time available during the operation. Furthermore, there is no clear information about the spread of the stimulation current within the cortex. Schiffbauer et al. (2002) observed that intraoperative sites at which stimulation evoked the same response had a spatial variation of 11 ± 1 mm. A neuronavigator system could have ameliorated some of the described problems. Schiffbauer et al. (2002), using neuronavigation, demonstrated a 21 ± 2 mm 3D difference between preoperative SEF
217 localization and intraoperative stimulation sites. However, additional problems for pre- and intraoperative site comparison could have been introduced by neuronavigation as well. It has been shown that the cortical surface shifts 5–10 mm after dural opening in the surgery. The direction of the main shift follows gravity and its effect on the brain depends on head position during the operation (Roberts et al., 1998). The largest shift occurs near the center of the craniotomy, usually in the brain region of greatest interest (Hill et al., 2000), and most probably adds to the difference in comparison between preoperative and intraoperative source areas. Four of our patients suffered from recurrent glioma, and in some of them ferromagnetic dust from the drilling in previous operations produced considerable noise to the signals. The largest difference between the preoperative and intraoperative localization occurred in one of these patients. Most recent technical developments may alleviate this type of problems in the future. Continuous head position monitoring (Uutela et al., 2001), in combination with signal space separation algorithm, may allow the separation of direct current artifacts due to moving magnetic objects from brain signals (Taulu et al., 2004). To conclude, it is usually possible to identify somatosensory and motor cortex preoperatively with about 1 cm accuracy using MEG recordings in patients with brain tumors in close vicinity of the sensorimotor strip. This accuracy compares favorably with localization results with fMRI, and suggests that the presuppositions underlying dipole modelling of the primary sensorimotor responses are sensible. 5. Acknowledgements I thank Prof. R. Hari for comments on this chapter. References Ahonen, A., Hämäläinen, M., Kajola, M., Knuutila, J., Laine, P., Lounasmaa, O., Parkkonen, L., Simola, J. and Tesche, C. (1993) 122-channel SQUID instrument for investigating the magnetic signals from human brain. Physica Scripta, T49: 198–205. Bittar, R., Olivier, A., Sadikot, A., Andermann, F., Comeau, R., Cyr, M., Peters, T. and Reutens, D. (1999) Localization of somatosensory
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