7T MR spectroscopic imaging in the localization of surgical epilepsy

For the neurosurgical evaluation of intractable epilepsy, localization of seizure onset is a critical step. Achieving localization is commonly the result of an integrated analysis of multiple lines of evidence, including semiology, electroencephalography (EEG; scalp and intracranial), imaging, and cognitive performance. Nonetheless, the challenges of identifying seizure onset are well known, given the varying clinical expression of different brain regions and the strong possibility for rapid seizure propagation. It remains that identification with intracranial EEG data of seizure onset with accuracy that is sufficient for surgery is the goal for many magnetic resonance imaging (MRI)–negative (or MRI–ambiguous) patients. Given this, a more practical goal for improving seizure localization would be to more accurately assess candidate regions for electrode placement. In the past, MR spectroscopy and spectroscopic imaging have been suggested to be informative for localization (Connelly et al., 1994; Kuzniecky et al., 1997; Maudsley et al., 2010a); this is premised on the known role that N-acetyl aspartate (NAA) plays for neuronal mitochondrial function (Bates et al., 1996; Pan & Takahashi, 2005). As suggested by Connett (1988); the use of total creatine (Cr, being a key component of phosphocreatine that serves as a buffer for ATP) in the normalization of bioenergetics parameters is highly informative over a cross-section of species and within a given tissue type. Therefore, many groups have used the ratio of NAA/Cr as a normalized parameter, which we characterize as the bioenergetics of the neuronal/glial unit (“bGNU”), finding it to be informative for identifying regions of energetic and neuronal dysfunction (Suhy et al., 2000; Munoz Maniega et al., 2008; Guevara et al., 2010). However, MR spectroscopic imaging has been challenging (Goelman et al., 2007; Maudsley et al., 2010a,b) because of the need to cover wide brain territories, because available localization may be lobar or hemispheric. In addition, studies need to be done with sufficient spatial resolution to sensitively identify dysfunctional areas, that is, to avoid extensive partial volume effects that could otherwise dilute small abnormalities. Because of these issues, it is evident that single voxel spectroscopy is not adequate for seizure localization. With spectroscopic imaging, the technical factors of adequate signal-to-noise (SNR), consistency of coverage, and study duration have been problematic, continuing improvements in imaging technology have been made. In this report we describe the systematic use of ultra-high field (7T) MR spectroscopic imaging to evaluate seizure localization in a range of temporal and neocortical localization-related epilepsy eases. 7T is used because of the goal for high SNR in the face of relatively small voxel sizes (Vaughan et al., 2001; Inglese et al., 2006). Because of challenges intrinsic to the 7T field strength and its implementation in humans (Vaughan et al., 2001; Van de Moortele et al., 2005), this study made use of several advances in B0 shimming and radiofrequency (RF) technology to achieve consistent spectroscopic imaging performance (Avdievich et al., 2009; Hetherington et al., 2010; Pan et al., 2012a). We report on 25 patients who were included in this analysis if there was a surgical resection (rather than solely transection or device-based therapy) and there was regional overlap between the MRSI data and surgically executed plan. We assessed the concordance (complete, partial, or discordant) between the region of surgical resection and the MRSI data, and determined how this concordance related to available outcome data.