|
|
||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Neuroradiology |
1 From the Functional Brain Imaging Unit, Helsinki Brain Research Center, Medical Imaging Center, University of Helsinki, Helsinki, Finland (A.K., H.J.A., E.S.); Brain Research Unit, Low Temperature Laboratory, Helsinki University of Technology, Espoo, Finland (E.K., S.A., J.P.M., M.S.); BioMag Laboratory, Helsinki Brain Research Center, Engineering Centre (A.K., R.J.I.) and Department of Clinical Neurophysiology (E.K., J.H., T.K.), Helsinki University Central Hospital, Helsinki, Finland; Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland (J.E.J.); and Department of Radiology, Hyvinkää Hospital, Hospital District of Helsinki and Uusimaa, Hyvinkää, Finland (A.B.). From the 2000 RSNA Annual Meeting. Received May 10, 2005; revision requested July 8; revision received September 8; accepted October 14; final version accepted November 23. Supported by grants from the Finnish Radiological Society, Maire Taponen Foundation, Maud Kuistila Foundation, Finnish Cancer Organization, Helsinki University Central Hospital, Academy of Finland, Nordic Cancer Union, Sigrid Juselius Foundation, and Helsinki University Hospital Clinical Research Institute. Address correspondence to A.K., Radiology Department, Biomedicum Helsinki, PO Box 700, FI-00029 HUS, Helsinki, Finland (e-mail: antti.korvenoja{at}helsinki.fi).
| ABSTRACT |
|---|
|
|
|---|
Materials and Methods: Fifteen patients (six men, nine women; age range, 2558 years) with a lesion near the primary sensorimotor cortex (13 gliomas, one cavernous hemangioma, and one meningioma) were examined after institutional review board approval and written informed consent from each patient were obtained. At MEG, evoked magnetic fields to median nerve stimulation were recorded; at functional MR imaging, hemodynamic responses to self-paced palmar flexion of the wrist were imaged. General linear model analysis with contextual clustering (P < .01) was used to analyze functional MR imaging data, and dipole modeling was used to analyze MEG data. MEG and functional MR localizations were compared with intraoperative cortical mappings. The distance from the area of functional MR imaging activation to the tumor margin was compared between the patients with discordant and those with concordant intraoperative mapping findings by using unpaired t testing.
Results: MEG depicted the central sulcus correctly in all 15 patients, as verified at intraoperative mapping. The functional MR imaging localization results agreed with the intraoperative mappings in 11 patients. In all four patients with a false localization, the primary activation was in the postcentral sulcus region, but it did not differ significantly from the primary activation in the patients with correct localization with respect to proximity to the tumor (P = .38). Furthermore, at functional MR imaging, multiple nonprimary areas were activated, with considerable interindividual variation.
Conclusion: Although both MEG and functional MR imaging can provide useful information for neurosurgical planning, in the present study, MEG proved to be superior for locating the central sulcus. Activation of multiple nonprimary cerebral areas may confound the interpretation of functional MR imaging results.
© RSNA, 2006
| INTRODUCTION |
|---|
|
|
|---|
In the search for noninvasive methods that yield this information, magnetoencephalography (MEG) (1,513) and functional magnetic resonance (MR) imaging (2,8,9,1230) have been particular focuses of interest. MEG and functional MR imaging have been compared in a clinical setting for their effectiveness in central sulcus localization in only a few studies (8,9,12,13). Although the performances of these two methods have been consistent with each other and with those of invasive cortical mapping in most cases, discrepancies have been reported (9). Thus, the purpose of this study was to prospectively evaluate MEG and functional MR imaging, as compared with intraoperative cortical mapping, for identification of the central sulcus.
| MATERIALS AND METHODS |
|---|
|
|
|---|
Patients
Fifteen patients (six men, nine women; age range, 2558 years) with a lesion near the primary sensorimotor cortex (13 gliomas, one cavernous hemangioma, and one meningioma) were examined after institutional review board approval and written informed consent from each patient were obtained. Subjects who were consecutive patients of one neurosurgeon (J.E.J.), had a lesion near the primary sensorimotor cortex, and were scheduled for surgery by means of awake craniotomy and monitoring with intraoperative cortical mapping were recruited from February 1998 through November 1999. The area of the primary sensorimotor cortex that controls hand function was mapped preoperatively with functional MR imaging and MEG and was mapped intraoperatively by means of cortical stimulation and/or recording of the cortical somatosensory evoked potentials.
MR Image Acquisition and Data Analysis
MR images were acquired with a 1.5-T Vision system (Siemens Medical Systems, Erlangen, Germany) by using a standard head coil. One transverse, one coronal, and three sagittal localizer images were acquired for section positioning. In each patient, a set of 1-mm-thick contiguous sagittal T1-weighted whole-head images (field of view, 256 mm; matrix, 256 x 256) was obtained by using a three-dimensional (3D) magnetization-prepared rapid gradient-echo sequence (repetition time msec/echo time msec/inversion time msec, 9.7/4/20; flip angle, 10°) before and after the administration of a gadolinium-based contrast agent: gadopentetate dimeglumine (Magnevist; Schering, Berlin, Germany) or gadoterate meglumine (Dotarem; Guerbet, Roissy, France). In each patient, 16 3-mm-thick contiguous transverse functional MR image sections were obtained by using a gradient-echo echo-planar sequence (repetition time msec/echo time msec, 3500/70; flip angle, 90°; field of view, 256 mm; matrix, 128 x 128) to cover the area of the primary sensorimotor cortex that controls hand function. The functional MR imaging paradigm included periods of self-paced palmar hand flexions contralateral to the lesion, which were alternated with rest. A time series of 91128 volumes of gradient-echo echo-planar images was acquired.
For functional MR imaging analysis and coregistration of the functional images with the structural images, we used FSL 3.1 (Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, John Radcliffe Hospital, Headington, Oxford, England) and in-house software. The images were first corrected for motion (31). To reach a steady state of longitudinal magnetization, we discarded the first two image volumes. Mean-based intensity normalization of all volumes, performed by using the same factor, and nonlinear high-pass temporal filtering (ie, Gaussian-weighted least-squares straight-line fitting,
= 52.5 seconds) were performed. Thereafter, statistical images were generated. Functional MR imaging results were visualized by showing them as pseudocolor overlays on three orthogonal views and on 3D reconstructions of segmented (32) images by using MRIcro software written by Chris Rorden (http://www.sph.sc.edu/comd/rorden/mricro.html) (33). The software is distributed as freeware by the author. By using the atlas of Duvernoy (34), one of the authors (A.K., with 10 years experience in brain MR imaging) labeled the activation according to the nearest sulcus and gyrus. The location of the central sulcus determined intraoperatively served as the reference. The same author (A.K.) manually outlined the tumor. Thereafter, the shortest Euclidian distance between the area of the peak statistical value in the central sulcus and the tumor margin was calculated.
MEG Recordings and Data Analysis
With use of a 122- or 306-channel helmet-shaped magnetometer (Neuromag 122 and Neuromag VectorView, respectively; Elekta Neuromag) in a magnetically shielded room (Euroshield, Eura, Finland), MEG responses to median nerve stimulation contralateral to the lesion were recorded. Constant-current 0.2-msec pulses were delivered at 2 Hz to the wrist at an intensity slightly above the motor threshold. The signals were band-pass filtered (0.03320.00 Hz) before sampling at 987 Hz. The sweep duration of 550 msec included a 50-msec prestimulus baseline. Epochs containing MEG amplitudes higher than 3000 fT/m or electric ocular or muscle artifacts exceeding 150 µV were rejected from the averaging. About 200 responses were recorded for each averaged trace.
The preauricular points and the nasion, as well as four head-position indicator coils attached to the patient's head, were located with a 3D digitizer (Polhemus, Colchester, Vt). The anatomic landmarks were marked on the skin with a pen and photographed for later reference. We determined the head position within the magnetometer helmet by allowing a current to pass through the indicator coils and recording the induced magnetic signals.
The head was modeled by a spherical conductor that matched the local curvature of the inner surface of the skull in the region of interest. A least-squares search revealed the equivalent current dipole (ECD) that best accounted for the measured magnetic fields at the given time point. The search was performed over a time window that corresponded to the first cortical somatosensory evoked response component (N20m). A local subset of 2744 channels was used for fitting.
The data for patient 4 were digitally high-pass filtered at 10 Hz to remove slow artifacts that arose from magnetic items inside the head (ie, steel splinters from surgical drills). For patients 1 and 15, respectively, 145- and 140-Hz low-pass filters were used to remove 150-Hz noise. For patient 1, a 50-Hz notch filter was used to remove 50-Hz noise.
One author (A.K.) coregistered the MEG coordinate space with the T1-weighted 3D magnetization-prepared rapid gradient-echo MR images by identifying the digitized anatomic landmarks on these images. A 3D volume-rendered image was created from the contrast agentenhanced image set that depicted the cortical surface, cortical veins, and ECD.
Intraoperative Monitoring
Intraoperative electrophysiologic monitoring was performed during awake craniotomy (E.K., T.K., and J.E.J., with 1, 3, and 3 years experience, respectively). Somatosensory evoked potential recording and cortical stimulation were performed in seven patients. Only cortical stimulation was performed in seven patients. In one patient, only somatosensory evoked potential recording was performed.
Cortical stimulation and evoked potential recording were performed by using an eight-channel Viking IV recorder (Nicolet Biomedical, Madison, Wis). For somatosensory evoked potential recording, the median nerve was stimulated at the wrist with 0.2-msec constant-current pulses at 4 Hz, with the stimulus intensity exceeding the motor threshold. Responses were recorded from the first two rows of a 4 x 5-electrode grid (PMT, Chanhassen, Minn) with 3-mm spacing and 6.5-mm-diameter silversilver chloride electrodes. A reference needle electrode was inserted into the temporal muscle on the surgically treated side. At cortical stimulation, 50-Hz electric pulses (duration, 0.2 msec; intensity, 613 mA) were used.
Delineation of the Central Sulcus
The ECD locations determined by using MEG were superimposed on the MR image sections. If the ECD was located in a gyrus, the sulcus nearest to this location in the dipolar direction was labeled as the central sulcus. If the ECD was located in a sulcus, this sulcus was considered to be the central sulcus.
At functional MR imaging, two criteria were used separately to identify the central sulcus: the sulcus with the largest number of activated voxels and the sulcus nearest to the area of the maximal z-statistic value. At electrocorticography, the central sulcus was identified by using the phase reversal of the 2025-msec response between the electrodes located frontally and parietally.
During the cortical stimulation, the motor responses were monitored and the patients were asked to report their sensations. The central sulcus was identified as the sulcus posterior to the gyrus from which the stimulation elicited motor responses. The exposed cortex was photographed before and after application of the tags or the corticographic electrode grid.
The central sulcus was delineated at MEG and functional MR imaging by A.K. and was delineated intraoperatively by A.K., E.K., and J.E.J. in consensus. The Euclidian distance from the N20m ECD to both the nearest functional MR imaging activation voxel and the maximal z-score voxel was considered the measure of the MEG and functional MR imaging overlap.
Statistical Analyses
Statistical analysis of the functional MR imaging data was performed by using a general linear model with local autocorrelation correction (35). z-Statistic (ie, Gaussianized t) images were segmented into activated and nonactivated regions by means of contextual clustering (36,37). Parameters (initial thresholding z > 1.6, neighborhood weighting ß = 0.427) (33) that would yield an approximate global false-positive rate of 0.01 in a search volume of the brain on the echo-planar MR images were chosen. For analysis of the MEG data, the percentage of variance explained by ECDsthat is, the goodness of fitand the 95% confidence volume for ECD location were calculated (38). The distance from the area of maximal functional MR imaging activation near the central sulcus to the tumor margin was measured in each patient. The difference in this distance between the patients with functional MR imaging results concordant with intraoperative mapping and those with discordant results was evaluated by using an unpaired one-sided t test.
| RESULTS |
|---|
|
|
|---|
|
|
|
|
|
|
More rostrally, activation was observed in the superior (seven patients), middle (three patients), and inferior frontal (two patients) sulci. In addition, parietal activations were observed in the superior parietal, angular, and supramarginal gyri within the intraparietal sulcus in 12 patients. Activations were observed in the supramarginal gyri within the lateral sulcus in five patients.
Ipsilaterally, activations were seen in the precentral wall (11 patients) and on the postcentral side (six patients) of the central sulcus. Precentral gyrus activations in the precentral sulcus and activations in the postcentral, superior parietal, and supramarginal gyri within the postcentral sulcus were seen in nine patients. In addition, activations were seen in the ipsilateral superior (10 patients), middle (four patients), and inferior (four patients) frontal sulci, as well as in the intraparietal (12 patients) and lateral (six patients) sulci.
Within the interhemispheric fissure, activations were seen in either or both hemispheres in the medial aspect of the superior frontal gyrus (13 patients) and the fissural part of the superior frontal gyrus (11 patients) in the cingulate sulcus. Activation was seen also in the paracentral lobule (n = 6), cingulate gyrus (n = 9), and fissural part of the postcentral gyrus (three patients) in the cingulate sulcus.
| DISCUSSION |
|---|
|
|
|---|
The superiority of MEG in the temporal domain is due to the fact that this examination enables one to directly measure neuronal electrical activity in a millisecond time scale, whereas functional MR imaging is based on the measurement of hemodynamic responses that reflect neuronal activation, which are much longer than the underlying neuronal activity, lasting up to 15 seconds after a stimulus (42).
In suitable conditionsfor example, when a single spatially confined source area is activated5-mm spatial resolution can be achieved with MEG in practical applications (43,44). Typical spatial resolutions at functional MR imaging studies of presurgical mapping have ranged from 3 to 4 mm in a plane with a section thickness of 56 mm (45). Hence, although the spatial resolution achieved with both techniques can be high, functional MR imaging can be considered superior in the spatial domain. This is especially evident in the capability of functional MR imaging to reveal spatial details of the activationeven at the cortical column level (46)and activations extending over large areas of the cortex. At MEG, the ECD represents an estimate of the center of gravity of the underlying activation, which may have considerable dimensions (38). Even the use of more sophisticated source models, such as minimum-norm estimates, has not enabled reliable reproduction of the spatial details of the underlying activation at MEG examinations.
The spatial specificity of functional MR imaging, however, depends on the type of technique used. Gradient-echo MR imaging of the oxygenation state is known to be sensitive to signals arising from the veins that drain the activated cortex. Approaches based on imaging of the cerebral blood flow or volume offer better spatial specificity (47)but at the price of a lower signal-to-noise ratio, which has limited practical use with these techniques. This better spatial specificity, however, does not solve the problem of the activation in adjacent nonprimary functional areas. The analysis methods used also influence the sensitivity and spatial specificity of functional MR imaging.
The spatial accuracies of MEG and functional MR imaging are dependent on the procedures used to coregister the functional data with the structural image data. Spatial distortions due to susceptibility effects are common with functional MR imaging. On the other hand, the landmark-based registration used with MEG can involve human-induced errors.
Despite the limited spatial resolution of MEG compared with the spatial resolution of functional MR imaging, our results confirm the amply documented suitability of somatosensory evoked magnetic fields for localization of the central sulcus (1,5,6,813,48,49). In fact, in all 175 patients examined in previous studies (1,5,6,813,48,49) and in all 15 patients examined in our study, localization of the central sulcus with MEG was correct. The localization information gleaned from somatosensory evoked magnetic field recording can even be corroborated with the information obtained at primary motor cortex localization by measuring the coherence between cortical oscillations and electromyography (10).
With functional MR imaging, the activation of multiple nonprimary areas during a motor task is an expected finding, according to previous imaging results for healthy subjects (5052). However, the effect of these activations on the interpretation of functional MR imaging motor activation patterns has received little attention in previous studies involving patients. Data in the bulk of the current literature suggest that the primary sensorimotor cortex can be located reliably with functional MR imaging by using a motor task (2,8,1218,20,21,23,2530,53), and nonprimary activations are not appreciated as a confounding factor in these reports. In contrast, the results of this study, in agreement with the findings of some previous studies involving limited numbers of patients (9,17,19), indicate that widespread functional MR imaging activation may render identification of the central sulcus difficult.
Even simple limb movements require the concerted action of multiple motor and somatosensory cortical areas. In the motor cortical network, primary motor, premotor, and supplementary motor areas are activated to a variable degree in most subjects. Somatosensory afferent signals provide indispensable feedback information that is necessary for the execution of all kinds of movements. Also, simple flexion-extension movements, such as those used in our study and in most previous studies, necessarily activate different types of afferent nerve fibers, including proprioceptive afferent fibers. In the cortex, the proprioceptive afferent fibers are largely relayed to Brodmann areas 2 and 5 (54), which are located in the postcentral sulcus region. It is therefore not surprising that functional MR imaging activations extended toand in some patients occurred predominantly inthe postcentral sulcus area.
The observed interindividual variations in functional MR imaging activation patterns could have also reflected the variable strategies used to perform the motor tasks among the patients with brain lesions. It has been suggested that brain abnormalities may also contribute to variations in activation by means of either mechanical effects (27) or modulation of the neurovascular coupling through neurotransmitters and tumor invasion of the functional cortex. There have also been observations that contradict these views (54,55). In this study, there was no difference in the proximity of the lesion to the central sulcus between the patients with false and those with correct localization results.
The interpreter of the functional MR imaging results can use previous experience and knowledge of anatomic landmarks in combination with the functional map of the sensorimotor network. This kind of a priori information, however, is not always availablefor example, in cases in which the anatomy has been distorted by a lesion or lesions. It is in these cases that information about the functional anatomy is most valuable.
Our study had limitations. It included a small patient group. The types and locations of the lesions varied considerably. These factors hinder the evaluation of the contribution of possible tumor-induced neurovascular uncoupling effects to the false localization results. Because stereotactic neuronavigation was not available at the time of the study, our investigation was limited to the identification of the central sulcus; no quantitative measurements of the overlap of intraoperative mapping with noninvasive methods were made.
The results of our study emphasize that the limited temporal resolution must be appreciated when interpreting functional MR imaging results. Because functional MR imaging is more accessible than is MEG, it will likely remain the primary method used for noninvasive functional mapping. Ultimately, it may be beneficial to use both methods, if feasible (9,56), to achieve the most complete and reliable characterization of the functional anatomy.
| ADVANCES IN KNOWLEDGE |
|---|
|
|
|---|
| ACKNOWLEDGMENTS |
|---|
| FOOTNOTES |
|---|
Abbreviations: ECD = equivalent current dipole MEG = magnetoencephalography N20m = first cortical somatosensory evoked response component 3D = three-dimensional
See Materials and Methods for pertinent disclosures.
Author contributions: Guarantors of integrity of entire study, A.K., H.J.A., J.H.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, A.K., E.K., H.J.A., S.A., J.H., R.J.I., J.E.J., J.P.M.; clinical studies, A.K., E.K., S.A., A.B., J.E.J., T.K., J.P.M.; statistical analysis, A.K., E.K., H.J.A., S.A., J.P.M., E.S., M.S.; and manuscript editing, all authors
| References |
|---|
|
|
|---|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| RADIOLOGY | RADIOGRAPHICS | RSNA JOURNALS ONLINE |