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.

Public Health Relevance

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.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Neuroscience and Ophthalmic Imaging Technologies Study Section (NOIT)
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Whittemore, Vicky R
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Wayne State University
Schools of Medicine
United States
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John, Flóra; Maqbool, Mohsin; Jeong, Jeong-Won et al. (2018) Deep cerebral vein expansion with metabolic and neurocognitive recovery in Sturge-Weber syndrome. Ann Clin Transl Neurol 5:502-506
Kim, Jeong-A; Jeong, Jeong-Won; Behen, Michael E et al. (2018) Metabolic correlates of cognitive function in children with unilateral Sturge-Weber syndrome: Evidence for regional functional reorganization and crowding. Hum Brain Mapp 39:1596-1606
Motoi, Hirotaka; Miyakoshi, Makoto; Abel, Taylor J et al. (2018) Phase-amplitude coupling between interictal high-frequency activity and slow waves in epilepsy surgery. Epilepsia 59:1954-1965
Nakai, Yasuo; Nagashima, Akari; Hayakawa, Akane et al. (2018) Four-dimensional map of the human early visual system. Clin Neurophysiol 129:188-197
Nakai, Yasuo; Jeong, Jeong-Won; Brown, Erik C et al. (2017) Three- and four-dimensional mapping of speech and language in patients with epilepsy. Brain 140:1351-1370
Kambara, Toshimune; Brown, Erik C; Jeong, Jeong-Won et al. (2017) Spatio-temporal dynamics of working memory maintenance and scanning of verbal information. Clin Neurophysiol 128:882-891
Jeong, Jeong-Won; Asano, Eishi; Kumar Pilli, Vinod et al. (2017) Objective 3D surface evaluation of intracranial electrophysiologic correlates of cerebral glucose metabolic abnormalities in children with focal epilepsy. Hum Brain Mapp 38:3098-3112
Pilli, Vinod K; Chugani, Harry T; Juhász, Csaba (2017) Enlargement of deep medullary veins during the early clinical course of Sturge-Weber syndrome. Neurology 88:103-105
Dhakar, Monica B; Ilyas, Mohammed; Jeong, Jeong-Won et al. (2016) Frontal Aslant Tract Abnormality on Diffusion Tensor Imaging in an Aphasic Patient With 49, XXXXY Syndrome. Pediatr Neurol 55:64-7
Jeong, Jeong-Won; Sundaram, Senthil; Behen, Michael E et al. (2016) Relationship between genotype and arcuate fasciculus morphology in six young children with global developmental delay: Preliminary DTI stuy. J Magn Reson Imaging 44:1504-1512

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