We propose to investigate clinical applications of our novel methods using diffusion weighted imaging (DWI) tractography to improve the accuracy of localization of motor and language areas (often referred to as 'eloquent cortex') for minimizing postoperative deficits in children undergoing brain surgery. Although the current gold standard for identifying motor and language areas is electrical stimulation mapping (ESM), and functional MRI (fMRI) is used as a complementary tool for adult patients, ESM and fMRI fail to localize the 'eloquent cortex' of interest in 30-40% of surgical cases. Furthermore, both ESM and fMRI are inherently unable to localize crucial white matter pathways associated with eloquent cortex, and these pathways also may be at risk for damage during surgery. Thus, there is a real need, especially in children, for identification of these cortical regions and their pathways preoperatively. As a non-invasive alternative modality, we recently developed a state-of-the-art DWI tractography technique, referred to as maximum a posteriori probability (DWI-MAP) classifier. Our central hypothesis is that this novel DWI approach can serve as an accurate localizing tool in young children and can be used to estimate the occurrence of postoperative deficits in motor and language functions. Specifically, we will determine whether separate pathways of 'finger', 'leg', 'face motor' and 'language' areas determined by our DWI-MAP classifier are concordant with the functionally-important sites determined by ESM in children regardless of the presence of lesions seen on MRI. Also, we will investigate whether Kalman filter analysis combined with DWI-MAP classifier can estimate the probability of postoperative deficit as a function of resection margin in children undergoing epilepsy surgery. Finally, we will determine whether in children whose ESM fails to localize 'finger', 'leg', 'face motor', 'comprehension', and 'expressive language' areas, Kalman filter-determined resection margin preserving DWI-MAP pathways will lead to successful preservation of these specific functions. We believe that the proposed aims will significantly impact an objective decision making when benefits of removing epileptic brain regions vs. risks of severe deficits are being weighed or when there is no alternative to map these eloquent sites. Importantly, this proposal will provide a critical translational step to clinical applications by yielding objective tools that are not curretly available to precisely tailor surgical margins and prevent specific motor and language deficits. At the end of the funding period we anticipate novel DWI methods that are non-invasive and do not require patient cooperation (unlike fMRI), which can be easily applied in uncooperative patients. DWI can be acquired as part of the clinical MRI. It is cost-effective and can be readily applied in other centers.
This proposal presents an innovative imaging tool for young children undergoing epilepsy surgery who are insensitive to electrical stimulation mapping. This project will translate into preoperative decision-making in order to preserve crucial brain tissues which may be at risk to be damaged or resected during surgery.
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