Clinical utility of functional magnetic resonance imaging for brain mapping in epilepsy surgery
Introduction
fMRI, which measures the blood oxygen level-dependent (BOLD) response (Ogawa et al., 1990) is a noninvasive methodology that is commonly used to localize functional brain areas. In the clinical setting, fMRI is increasingly being used to lateralize language function and to localize motor and language function (Hirsch et al., 2000, Ruge et al., 1999, Binder et al., 1996, Binder et al., 1997, Carpentier et al., 2001, Desmond et al., 1995, Gaillard et al., 2004, Rosenberger et al., 2009). However, the utility of fMRI in guiding surgical decision-making remains unclear. The ability to validate fMRI signal analysis with a more direct invasive method may help resolve this issue. Staged epilepsy surgery, where invasive electrodes are implanted in order to define the ictal onset and functional zones, provides an opportunity to correlate the noninvasive BOLD signal to more invasively obtained methods such as electrical stimulation mapping (ESM) in the extraoperative setting (Carpentier et al., 2001).
A good correlation has been demonstrated between language lateralization assessed using fMRI and the intracarotid amytal (Wada) test (Gaillard et al., 2004, Thesen et al., 2007). Localization of the motor cortex using BOLD signal has been accurate in some studies (Ruge et al., 1999). However, factors such as brain shift may limit their utility in patients undergoing electrode implantation for staged epilepsy surgery (Hill et al., 2000). Prior studies have shown poor sensitivity, specificity and predictive values of the location of the BOLD signal to areas defined by language using intraoperative ESM (Roux et al., 2003). The present study aims to assess the clinical utility of fMRI in the circumstance of extraoperative ESM with additional image processing is performed to account for the brain shift caused by the electrodes. Use of extraoperative ESM allows for more accurate integration and coregistration of intracranial electrodes while accounting for brain shift. In addition, time is permitted to perform reliability testing and to integrate ESM and fMRI data prior to the operative intervention that involves the possibility of resection.
Some studies have examined the effect of varying the threshold for activation for language localization in efforts to reduce Type 1 and Type 2 error, but no standard criteria exist (Loring et al., 2002). This type of analysis is critical for determining the clinical utility of fMRI and may be explored by examining the relationship between ESM and fMRI across a range of statistical values. A further analysis beyond the traditional post hoc analysis would be focused upon determining which ESM-positive sites do not show fMRI activation in order to determine whether certain areas should always be tested via ESM, regardless of fMRI activation. The present study investigates these issues in order to determine the clinical utility of fMRI language mapping in predicting the effects of extraoperative ESM.
Section snippets
Subjects
Four patients were used as subjects for this study. Demographics are shown in Table 1. All patients, after undergoing video electroencephalographic testing, MRI and neuropsychological assessment, were deemed candidates for epilepsy surgery based upon medication-resistant partial complex epilepsy. All subjects had normal MRI with no lesions, dysplasia or masses, and therefore, electrodes were implanted primarily in order to assess seizure localization. When electrodes were near regions of
Motor cortex
67 sites were tested with ESM for motor function of the hand in 2 subjects. ESM at 8 sites elicited motor response of the contralateral hand. For these sites, using a threshold of a T score of 2.5 (p < .01 corrected FDR), sensitivity for hand motor cortex was 1.0 and specificity was .96 for the two subjects where electrode contacts lay over the hand area of motor cortex (Fig. 1). PPV and NPV were 0.8 and 1.0, respectively. In the two remaining subjects an additional 10 sites were found on ESM
Sensitivity and specificity
Comparing the results of fMRI and ESM is complicated by the fact that fMRI involves the observation of normal function while ESM involves interference with function. Therefore, it may be hypothesized that fMRI could show participation of brain areas that are involved in, but not critical to, language function and that these areas overlap with critical sites identified by ESM. If this were the case, then the sensitivity would be high and the specificity would be low. Thus, the BOLD response may
Acknowledgements
Funding support is from the Page and Otto Marx Foundation. Additional support provided by the Feinstein Institute for Medical Research NSLIJ General Clinical Research Center, Grant #M01 RR018535 from the National Center for Research Resources (NCRR).
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