Localizing Epileptic Networks Using MRI and iEEG

Official title

Optimized Intracranial EEG Targeting in Focal Epilepsy Based Upon Neuroimaging Connectomics

Overview

Upon successful completion of this study, the investigators expect the study's contribution to be the development of noninvasive imaging biomarkers to predict IEEG functional dynamics and epilepsy surgical outcomes. Findings from the present study may inform current and new therapies to map and alter seizure spread, and pave the way for less invasive, better- targeted, patient-specific interventions with improved surgical outcomes. This research is relevant to public health because over 20 million people worldwide suffer from focal drug-resistant epilepsy and are potential candidates for cure with epilepsy surgical interventions.

Detailed description

Despite recent advances in neuroimaging, approximately 2/3 of intractable epilepsy patients that undergo surgical evaluation continue to require intracranial EEG (IEEG), arguably the most invasive diagnostic test in medicine. Clinicians currently lack methods to quantitatively map noninvasive imaging measures of structure and function to IEEG. Specifically, there is a critical need to validate whole-brain noninvasive neuroimaging network- based biomarkers to guide precise placement of electrodes and translate noninvasive network neuroimaging to change the paradigms of clinical care. The long-term goal of this study is to predict IEEG functional dynamics and surgical outcomes using noninvasive MRI-based measures of structure and function. The investigators' overall objective, which is the next step toward attaining the study's long-term goal, is to develop open-source noninvasive imaging tools that map epileptic networks by integrating MRI and IEEG data. The central hypothesis is that noninvasive measures of structure and function relate to and can predict the intricate functional dynamics captured on IEEG. The central hypothesis will be tested in patients undergoing IEEG targeting the temporal lobe network by pursuing three specific aims: 1) To map the patient specific structural connectome to IEEG seizure onset and propagation, 2) To correlate seizure onset and propagation on IEEG with network measures derived from resting state functional MRI (rsfMRI), and 3) To integrate the structural (Aim 1) and functional (Aim 2) connectome with standard qualitative clinical data to predict IEEG network dynamics and surgical outcomes. Under the first aim patients will undergo diffusion tensor imaging (DTI) prior to stereotactic IEEG, an IEEG method that inherently samples long range networks. The functional IEEG network will be mapped to DTI thus defining how seizures are constrained by the underlying structural connectome as they propagate. Under the second aim patients with temporal lobe epilepsy will undergo rsfMRI on 7T MRI prior to stereotactic IEEG. Functional network measures from rsfMRI and IEEG will be coregistered and rsfMRI will be used to predict functional EEG ictal and interictal networks. In the third aim two models predicting IEEG network dynamics and epilepsy surgical outcomes will be created building off of methods developed in Aims 1 and 2. This research is innovative because it represents a substantive departure from the status quo by directly connecting noninvasive multimodal imaging with measures of functional network dynamics in IEEG. This research is also significant because it is expected that successful completion of these aims will yield personalized strategies for IEEG targeting based on noninvasive neuroimaging.

Interventions

• Diagnostic test 3T Magnetic Resonance Imaging
  Magnetic resonance imaging acquired at a field strength of 3 Tesla.
• Diagnostic test Intracranial electroencephalography recordings
  Epilepsy patients may undergo implantation of intracranial electroencephalography (iEEG) electrodes for localization of epileptogenic foci, which also provide a means to record localized brain activity during memory or other tasks for research purposes.
• Diagnostic test 7T Magnetic Resonance Imaging
  Magnetic resonance imaging acquired at a field strength of 7 Tesla.

Primary outcome measures

• Structure-function coupling [Time frame: Measure will be assessed upon collection of patient pre-implant MRI study and iEEG recordings, and control MRI]

Secondary outcome measures (2)

• Correlate iEEG seizure onset and propagation with 7T rsfMRI [Time frame: Measure will be assessed upon collection of patient pre-implant 7T rsfMRI and iEEG recordings, and control 7T MRI]
• Imaging biomarkers for seizure onset [Time frame: Measure will be assessed upon collection of patient pre-implant 3T and 7T MRI studies and iEEG recordings, and control MRI]

Eligibility criteria

Inclusion criteria

• Patients with medication-refractory epilepsy
• Planned intracranial EEG (IEEG) placement
• Hypothesized to have temporal lobe epilepsy

Exclusion criteria

• Contraindication to 3T MRI (e.g. metal implants or claustrophobia), clinical features that typically preclude the use of IEEG (e.g. pregnancy), prior intracranial surgery or device, and IEEG findings that are non-diagnostic (e.g. seizure onset zone(s) not identified)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

United States · 1 center

• University of Pennsylvania — Philadelphia

Publications

• Jette N, Wiebe S. Update on the surgical treatment of epilepsy. Curr Opin Neurol. 2013 Apr;26(2):201-7. doi: 10.1097/WCO.0b013e32835ef345. PMID 23449171
• Wiebe S. Epilepsy. Outcome patterns in epilepsy surgery--the long-term view. Nat Rev Neurol. 2012 Jan 31;8(3):123-4. doi: 10.1038/nrneurol.2012.9. PMID 22290572
• de Tisi J, Bell GS, Peacock JL, McEvoy AW, Harkness WF, Sander JW, Duncan JS. The long-term outcome of adult epilepsy surgery, patterns of seizure remission, and relapse: a cohort study. Lancet. 2011 Oct 15;378(9800):1388-95. doi: 10.1016/S0140-6736(11)60890-8. PMID 22000136
• Widdess-Walsh P, Diehl B, Najm I. Neuroimaging of focal cortical dysplasia. J Neuroimaging. 2006 Jul;16(3):185-96. doi: 10.1111/j.1552-6569.2006.00025.x. PMID 16808819
• Tassi L, Colombo N, Garbelli R, Francione S, Lo Russo G, Mai R, Cardinale F, Cossu M, Ferrario A, Galli C, Bramerio M, Citterio A, Spreafico R. Focal cortical dysplasia: neuropathological subtypes, EEG, neuroimaging and surgical outcome. Brain. 2002 Aug;125(Pt 8):1719-32. doi: 10.1093/brain/awf175. PMID 12135964
• Raybaud C, Shroff M, Rutka JT, Chuang SH. Imaging surgical epilepsy in children. Childs Nerv Syst. 2006 Aug;22(8):786-809. doi: 10.1007/s00381-006-0132-5. Epub 2006 Jul 13. PMID 16838193
• Colombo N, Tassi L, Galli C, Citterio A, Lo Russo G, Scialfa G, Spreafico R. Focal cortical dysplasias: MR imaging, histopathologic, and clinical correlations in surgically treated patients with epilepsy. AJNR Am J Neuroradiol. 2003 Apr;24(4):724-33. PMID 12695213
• Mathern GW. Challenges in the surgical treatment of epilepsy patients with cortical dysplasia. Epilepsia. 2009 Oct;50 Suppl 9:45-50. doi: 10.1111/j.1528-1167.2009.02294.x. PMID 19761453

Identifiers

NCT: NCT04649008 · 819126

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗