MRI + iEEG for Epilepsy

Overseen By Kathryn A Davis, MD, MSTR

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Pennsylvania

Disqualifiers: Pregnancy, Metal implants, Claustrophobia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

290 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the trial is for patients with medication-refractory epilepsy, it might be assumed that you can continue your current epilepsy medications.

What data supports the effectiveness of the treatment MRI + iEEG for Epilepsy?

Research shows that using 7 Tesla MRI, which provides clearer images of the brain, can detect more abnormalities in epilepsy patients compared to standard MRI. This improved detection can help in planning surgeries and potentially lead to better outcomes for patients with epilepsy. ^{1 2 3 4 5}

Is it safe to use MRI with intracranial EEG for epilepsy?

Studies have shown that using MRI with intracranial EEG (iEEG) at 1.5T and 3T is generally safe, with no significant risks like electrode movement or dangerous heating, as long as specific safety guidelines are followed. ^{1 6 7 8 9}

How does the MRI + iEEG treatment for epilepsy differ from other treatments?

The MRI + iEEG treatment for epilepsy is unique because it combines intracranial electroencephalography (iEEG) with functional magnetic resonance imaging (fMRI) to detect smaller brain activity changes that are not visible with standard scalp EEG-fMRI. This approach helps to better understand the brain mechanisms involved in seizures, offering a more detailed view than traditional methods. ^{1 6 7 10 11}

Research Team

Kathryn A Davis, MD, MSTR

Principal Investigator

University of Pennsylvania

Eligibility Criteria

This trial is for individuals with drug-resistant epilepsy who are scheduled to have intracranial EEG (IEEG) placement and are thought to have temporal lobe epilepsy. It's not suitable for those with non-diagnostic IEEG results, contraindications to MRI like metal implants or claustrophobia, pregnant individuals, or those who've had prior brain surgery.

Inclusion Criteria

You are planning to have electrodes placed in your brain for EEG testing.

I am believed to have epilepsy originating in the temporal lobe.

My epilepsy does not improve with medication.

Exclusion Criteria

Clinical features that typically preclude the use of IEEG (e.g. pregnancy)

Your EEG results do not show clear information about where seizures start in your brain.

I have had brain surgery or a device implanted in my brain.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-implant Imaging

Patients undergo diffusion tensor imaging (DTI) and resting-state functional MRI (rsfMRI) prior to stereotactic IEEG

4 weeks

2 visits (in-person)

IEEG Monitoring

Patients undergo stereotactic IEEG to map seizure onset and propagation

4-6 weeks

Inpatient monitoring

Follow-up

Participants are monitored for safety and effectiveness after IEEG monitoring and potential surgical intervention

8 weeks

2 visits (in-person)

Treatment Details

Interventions

• 3T Magnetic Resonance Imaging
• 7T Magnetic Resonance Imaging
• Intracranial electroencephalography recordings

Trial Overview The study tests the use of high-resolution MRIs at 7T and standard 3T alongside IEEG recordings to develop imaging biomarkers that could predict the outcomes of epilepsy surgery. The goal is to improve surgical strategies for seizure control in people with focal drug-resistant epilepsy.

Participant Groups

Group I: Epilepsy patient volunteers Experimental Treatment 3 Interventions

Patients recruited for the study with intractable epilepsy who are anticipated to undergo epilepsy surgery

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Medical University of South Carolina

Collaborator

Trials

994

Recruited

7,408,000+

Findings from Research

Combining intracranial electroencephalography (iEEG) with functional magnetic resonance imaging (fMRI) at 3 Tesla is safe and effective, as demonstrated by the absence of adverse events in two subjects and the successful recording of numerous interictal discharges.

The study revealed significant blood oxygen level-dependent (BOLD) signal changes associated with interictal discharges, indicating that focal epileptiform activity can influence widespread cortical and subcortical areas, suggesting a novel mechanism of action in epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial EEG-fMRI analysis of focal epileptiform discharges in humans. Cunningham, CB., Goodyear, BG., Badawy, R., et al.[2012]

7 Tesla MRI significantly improves the detection and delineation of morphologic abnormalities in patients with epilepsy, achieving a detection rate of 65% compared to only 22% with conventional 1.5T or 3.0T MRI, based on a review of 25 studies involving 467 patients.

The majority of studies were case series or case studies, indicating a need for more robust cohort studies to further validate the clinical outcomes and effectiveness of 7T MRI in epilepsy diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utility of 7 Tesla Magnetic Resonance Imaging in Patients With Epilepsy: A Systematic Review and Meta-Analysis. Park, JE., Cheong, EN., Jung, DE., et al.[2021]

7T MRI can significantly improve the detection of structural brain lesions in patients with drug-resistant focal onset epilepsy, which is crucial for predicting seizure freedom after surgery, as conventional MRI (1.5 and 3T) only identifies lesions in 60%-85% of cases.

The 7T Epilepsy Task Force, consisting of experts from 21 centers and over 2,000 patient scans, provides practical recommendations for the clinical use of 7T MRI, including patient selection, acquisition protocols, and interpretation guidelines to enhance epilepsy management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

7T Epilepsy Task Force Consensus Recommendations on the Use of 7T MRI in Clinical Practice. Opheim, G., van der Kolk, A., Markenroth Bloch, K., et al.[2022]

In a study of 47 patients with MRI-negative frontal lobe epilepsy, those who underwent presurgical evaluation with 3D intracranial EEG (3D-iEEG) had a better chance of achieving seizure freedom after surgery, with 48.9% of patients being seizure-free at 24 months post-surgery.

The analysis revealed that patients who did not achieve seizure freedom had more widespread seizure onset and shorter latencies to seizure spread, indicating that detailed 3D-iEEG monitoring can help predict surgical outcomes in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-dimensional intracranial EEG monitoring in presurgical assessment of MRI-negative frontal lobe epilepsy. Yang, PF., Shang, MC., Lin, Q., et al.[2021]

In a study of 13 patients with drug-resistant temporal lobe epilepsy (TLE), ultra-high field 7T MRI showed concordance with clinical assessments in 61.5% of cases, revealing additional abnormalities not seen on standard 1.5T MRI in some patients.

Despite the improved resolution of 7T MRI, only 15.4% of patients had anatomical findings that directly explained the EEG abnormalities, indicating that while 7T MRI can enhance detection of structural issues, it may not always correlate with EEG findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultra-High Field 7-Tesla Magnetic Resonance Imaging and Electroencephalography Findings in Epilepsy. Salehi, F., Nadeem, IM., Kwan, BYM., et al.[2022]

The study assessed the safety of combining intracranial electroencephalography (icEEG) with functional magnetic resonance imaging (fMRI) in a clinical setting, finding that RF-induced heating of electrodes remained below the 1°C safety limit during a 70-minute session.

No significant risks were identified regarding electrode movement or induced voltage, indicating that icEEG-fMRI can be safely performed, although high specific absorption ratio sequences like fast spin echo (FSE) should be avoided to minimize heating risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the Safety of Simultaneous Intracranial Electroencephalography and Functional Magnetic Resonance Imaging Acquisition Using a 3 Tesla Magnetic Resonance Imaging Scanner. Fujita, Y., Khoo, HM., Hirayama, M., et al.[2022]

Integrating intracranial EEG (iEEG) with functional MRI (iEEG-fMRI) at 3T poses a low risk for electrode displacement and temperature increase during standard imaging sequences, making it feasible for clinical use.

However, high specific absorption rate (SAR) sequences can cause significant heating of the electrodes, exceeding safe limits, and fMRI signal intensity is reduced near the electrodes, which may affect imaging quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of an intracranial EEG-fMRI protocol at 3T: risk assessment and image quality. Boucousis, SM., Beers, CA., Cunningham, CJ., et al.[2012]

Simultaneous intracranial EEG and fMRI (icEEG-fMRI) can provide valuable information for epilepsy patients, but safety concerns regarding potential hazards like tissue heating and mechanical forces on electrodes need to be addressed.

Experimental evaluations showed that while heating can exceed safety guidelines, it can be controlled to remain below 1.0 degrees Celsius by using specific techniques, indicating that icEEG-fMRI can be performed safely with proper precautions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of simultaneous intracranial EEG-fMRI in humans: a safety study. Carmichael, DW., Thornton, JS., Rodionov, R., et al.[2022]

A review of 165 patients with intracranial EEG electrodes showed that MRI scans at both 1.5 T and 3 T were safe, with no adverse events or complications reported during or after the scans.

The study confirmed that avoiding high specific energy absorption rate sequences during MRI prevents electrode heating, ensuring that patients with implanted electrodes can safely undergo MRI without worsening pre-existing complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical safety of intracranial EEG electrodes in MRI at 1.5 T and 3 T: a single-center experience and literature review. Peedicail, JS., Poulin, T., Scott, JN., et al.[2021]

The study evaluated different processing methods for magnetic resonance encephalography (MREG) in analyzing interictal epileptic discharges (IEDs) and found that using a generalized linear model (GLM) with 24 head motion components significantly improved the reliability of activation maps.

The analysis indicated that employing a canonical hemodynamic response function (HRF) was more effective than variable or patient-specific HRFs, enhancing the accuracy of identifying brain activation areas related to IEDs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subject-level reliability analysis of fast fMRI with application to epilepsy. Hao, Y., Khoo, HM., von Ellenrieder, N., et al.[2018]

Simultaneous multi-modal MR-PET-EEG imaging at 3 T and 9.4 T offers complementary advantages, combining the structural and functional imaging capabilities of MRI, the molecular insights from PET, and the temporal resolution of EEG, enhancing overall diagnostic accuracy.

Hybrid imaging at ultra-high field strengths like 9.4 T allows for ultra-high resolution structural imaging and improved metabolic imaging, as demonstrated by high-resolution sodium distribution images and tumor imaging examples, paving the way for more precise clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in multimodal neuroimaging: hybrid MR-PET and MR-PET-EEG at 3 T and 9.4 T. Shah, NJ., Oros-Peusquens, AM., Arrubla, J., et al.[2016]

References

1. United States pubmed.ncbi.nlm.nih.gov

Intracranial EEG-fMRI analysis of focal epileptiform discharges in humans. [2012]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Utility of 7 Tesla Magnetic Resonance Imaging in Patients With Epilepsy: A Systematic Review and Meta-Analysis. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

7T Epilepsy Task Force Consensus Recommendations on the Use of 7T MRI in Clinical Practice. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Three-dimensional intracranial EEG monitoring in presurgical assessment of MRI-negative frontal lobe epilepsy. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Ultra-High Field 7-Tesla Magnetic Resonance Imaging and Electroencephalography Findings in Epilepsy. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluating the Safety of Simultaneous Intracranial Electroencephalography and Functional Magnetic Resonance Imaging Acquisition Using a 3 Tesla Magnetic Resonance Imaging Scanner. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Feasibility of an intracranial EEG-fMRI protocol at 3T: risk assessment and image quality. [2012]

8. United States pubmed.ncbi.nlm.nih.gov

Feasibility of simultaneous intracranial EEG-fMRI in humans: a safety study. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Clinical safety of intracranial EEG electrodes in MRI at 1.5 T and 3 T: a single-center experience and literature review. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Subject-level reliability analysis of fast fMRI with application to epilepsy. [2018]

11. United States pubmed.ncbi.nlm.nih.gov

Advances in multimodal neuroimaging: hybrid MR-PET and MR-PET-EEG at 3 T and 9.4 T. [2016]