Clinical trial NCT04649008: Localizing Epileptic Networks Using MRI and iEEG
Official title: Optimized Intracranial EEG Targeting in Focal Epilepsy Based Upon Neuroimaging Connectomics
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Epilepsy
Epilepsy Intractable
Epilepsy, Temporal Lobe
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: Medical University of South Carolina
First posted: 2020-12-02
Enrollment: 290
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.

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)

Primary outcomes:
measure: Structure-function coupling
timeFrame: Measure will be assessed upon collection of patient pre-implant MRI study and iEEG recordings, and control MRI
Secondary outcomes:
measure: Correlate iEEG seizure onset and propagation with 7T rsfMRI
timeFrame: Measure will be assessed upon collection of patient pre-implant 7T rsfMRI and iEEG recordings, and control 7T MRI
measure: Imaging biomarkers for seizure onset
timeFrame: Measure will be assessed upon collection of patient pre-implant 3T and 7T MRI studies and iEEG recordings, and control MRI
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Kathryn A Davis, MD, MSTR
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Wolf RL, Alsop DC, Levy-Reis I, Meyer PT, Maldjian JA, Gonzalez-Atavales J, French JA, Alavi A, Detre JA. Detection of mesial temporal lobe hypoperfusion in patients with temporal lobe epilepsy by use of arterial spin labeled perfusion MR imaging. AJNR Am J Neuroradiol. 2001 Aug;22(7):1334-41.
citation: Detre JA, Sirven JI, Alsop DC, O'Connor MJ, French JA. Localization of subclinical ictal activity by functional magnetic resonance imaging: correlation with invasive monitoring. Ann Neurol. 1995 Oct;38(4):618-24. doi: 10.1002/ana.410380410.
citation: Verma G, Woo JH, Chawla S, Wang S, Sheriff S, Elman LB, McCluskey LF, Grossman M, Melhem ER, Maudsley AA, Poptani H. Whole-brain analysis of amyotrophic lateral sclerosis by using echo-planar spectroscopic imaging. Radiology. 2013 Jun;267(3):851-7. doi: 10.1148/radiol.13121148. Epub 2013 Jan 29.
citation: Maudsley AA, Domenig C, Ramsay RE, Bowen BC. Application of volumetric MR spectroscopic imaging for localization of neocortical epilepsy. Epilepsy Res. 2010 Feb;88(2-3):127-38. doi: 10.1016/j.eplepsyres.2009.10.009. Epub 2009 Nov 17.
citation: Dlugos D, Worrell G, Davis K, Stacey W, Szaflarski J, Kanner A, Sunderam S, Rogawski M, Jackson-Ayotunde P, Loddenkemper T, Diehl B, Fureman B, Dingledine R; Epilepsy Benchmark Stewards. 2014 Epilepsy Benchmarks Area III: Improve Treatment Options for Controlling Seizures and Epilepsy-Related Conditions Without Side Effects. Epilepsy Curr. 2016 May-Jun;16(3):192-7. doi: 10.5698/1535-7511-16.3.192. No abstract available.
citation: Khambhati AN, Davis KA, Lucas TH, Litt B, Bassett DS. Virtual Cortical Resection Reveals Push-Pull Network Control Preceding Seizure Evolution. Neuron. 2016 Sep 7;91(5):1170-1182. doi: 10.1016/j.neuron.2016.07.039. Epub 2016 Aug 25.