The overarching aim of our research is to more directly image the cerebral discharges underlying epilepsy than has been achievable using standard techniques. Epilepsy patients often have abnormal neuronal discharges between seizures, called interictal spikes. Although their presence can be detected using EEG, the source of these spikes remains difficult to identify. We are developing a novel set of imaging tools and analysis methods to help us detect these discharges via their effect on MR images (encephalographic magnetic resonance imaging, or eMRI). The technique is based upon simultaneous high-speed acquisition of electroencephalography (EEG) and gradient-echo echo-planar MR images, with the EEG signal used to identify the images acquired during electrically active epochs. In a small cohort of patients with epilepsy, we have demonstrated fast responses in the MR images, nearly simultaneous with the interictal spikes seen on EEG. Our goals here are to extend eMRI as a tool with clinical utility for precise localization of the foci of epileptiform activity. Our first specific aim is to image pediatric patients with benign epilepsy with centrotemporal spikes (BECTS), in whom spikes are frequent and exquisitely well localized anatomically. The spatial extent of the regions involved by the interictal spikes will be studied, in order to determine if this correlates with the presence of neuropsychiatric or developmental abnormalities in this group of patients. Our second specific aim is to use eMRI to assess a cohort of patients with medically intractable epilepsy, in whom invasive cortical electrodes will be implanted intracranially as the first step in their epilepsy surgery. The regions identified by the invasive electrodes will be compared with the regions identified by eMRI. Finally, our third specific aim is to systematically vary the imaging parameters used in the eMRI acquisition, and make use of an electric current phantom, in order to optimize our protocol and to elucidate the mechanisms underlying the fast MR responses we have observed. eMRI has the potential to improve presurgical localization and to transform epilepsy resection into a one-stage surgical procedure, avoiding the need for prolonged intracranial recordings. More broadly, the technique would potentially allow for more efficacious deployment of antiepileptic medical therapy in the individual patient, as well as providing a means for testing novel agents, by directly demonstrating treatment effects on interictal activity. This work is likely to deepen our understanding of the pathophysiology of epileptiform discharges and their spread.

Public Health Relevance

A technique, such as eMRI, that allows for more direct imaging of epileptiform discharges than is currently possible, is likely to be a powerful diagnostic tool for presurgical seizure focus localization, potentially transforming epilepsy resection into a one-stage surgical procedure, avoiding the need for prolonged intracranial recordings. More broadly, such an imaging tool would potentially allow for more efficacious deployment of antiepileptic medications in the individual patient, as well as providing a means for testing novel agents, by directly demonstrating their effects on cortical electrical discharges. This work is likely to deepen our understanding of the pathophysiology of epilepsy discharges and their spread.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21NS076859-02
Application #
8320870
Study Section
Special Emphasis Panel (ZRG1-DTCS-U (81))
Program Officer
Fureman, Brandy E
Project Start
2011-09-01
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2012
Total Cost
$281,779
Indirect Cost
$119,837
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
Pinto, Anna L R; Fernández, Iván S; Peters, Jurriaan M et al. (2014) Localization of sleep spindles, k-complexes, and vertex waves with subdural electrodes in children. J Clin Neurophysiol 31:367-74
Sanchez Fernandez, Ivan; Abend, Nicholas S; Agadi, Satish et al. (2014) Gaps and opportunities in refractory status epilepticus research in children: a multi-center approach by the Pediatric Status Epilepticus Research Group (pSERG). Seizure 23:87-97
Sanchez Fernandez, Ivan; Abend, Nicholas S; Arndt, Daniel H et al. (2014) Electrographic seizures after convulsive status epilepticus in children and young adults: a retrospective multicenter study. J Pediatr 164:339-46.e1-2
Berg, Anne T; Baca, Christine B; Loddenkemper, Tobias et al. (2013) Priorities in pediatric epilepsy research: improving children's futures today. Neurology 81:1166-75
Fernandez, Ivan Sanchez; Chapman, Kevin E; Peters, Jurriaan M et al. (2013) The tower of Babel: survey on concepts and terminology in electrical status epilepticus in sleep and continuous spikes and waves during sleep in North America. Epilepsia 54:741-50
Mane, Ketan K; Loddenkemper, Tobias; Fernandez, Ivan Sanchez et al. (2013) Visual aids to medical data and computational diagnostics: new frontiers in pediatric neurology. Epilepsy Behav 28:258-60
Fernandez, Ivan Sanchez; Peters, Jurriaan; Takeoka, Masanori et al. (2013) Patients with electrical status epilepticus in sleep share similar clinical features regardless of their focal or generalized sleep potentiation of epileptiform activity. J Child Neurol 28:83-9
Sanchez, Sarah M; Carpenter, Jessica; Chapman, Kevin E et al. (2013) Pediatric ICU EEG monitoring: current resources and practice in the United States and Canada. J Clin Neurophysiol 30:156-60
Mulkern, Robert V; Balasubramanian, Mukund; Orbach, Darren B et al. (2013) Incorporating reversible and irreversible transverse relaxation effects into Steady State Free Precession (SSFP) signal intensity expressions for fMRI considerations. Magn Reson Imaging 31:346-52
Sanchez Fernandez, Ivan; Peters, Jurriaan M; An, Sookee et al. (2013) Long-term response to high-dose diazepam treatment in continuous spikes and waves during sleep. Pediatr Neurol 49:163-170.e4

Showing the most recent 10 out of 12 publications