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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests MRI techniques and brain wave recordings to improve epilepsy surgery outcomes. Researchers aim to discover new, noninvasive methods to predict and map seizure spread. This could lead to more targeted treatments for epilepsy patients unresponsive to medication. Individuals with medication-resistant epilepsy planning to undergo brain recordings before surgery might be suitable for this trial. As an Early Phase 1 trial, this research focuses on understanding how these new techniques work in people, offering participants a chance to contribute to groundbreaking advancements in epilepsy treatment.

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 prior data suggests that MRI and iEEG are safe for epilepsy patients?

A previous study demonstrated that 3T MRI is safe and effective for epilepsy, providing clearer images than lower-strength scanners. This clarity helps doctors better observe changes in the brain. Safety data for 3T MRI confirm its safe use in both clinical and research settings.

Research indicates that 7T MRI is also well-tolerated and offers even more detailed images, aiding in the understanding of epilepsy. Studies have examined its safety and found 7T MRI to be safe for patients of different ages.

Intracranial electroencephalography (iEEG) has been safely used in many patients. While there are some risks, such as a small chance of bleeding or temporary symptoms, long-lasting problems are rare. Overall, iEEG is considered safe for monitoring brain activity.

These findings suggest that the treatments in this study are generally safe. However, as with any medical procedure, some risks are involved. Participants should discuss any concerns with the trial team. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using 3T and 7T Magnetic Resonance Imaging (MRI) alongside intracranial electroencephalography (iEEG) recordings for epilepsy because these techniques offer a much more detailed view of brain activity than current standard treatments like medication or surface EEG. Unlike typical imaging, 3T and 7T MRI provide high-resolution images, making it easier to pinpoint the exact areas of the brain involved in seizures. The addition of iEEG, which involves placing electrodes directly on the brain, offers real-time monitoring of electrical activity with greater accuracy. These advanced methods could lead to more precise surgical decisions and potentially improve outcomes for patients with drug-resistant epilepsy.

What evidence suggests that MRI and iEEG are effective for epilepsy?

Research has shown that a 3T MRI effectively identifies structural issues in epilepsy, providing clearer images and detecting more lesions than the standard 1.5T MRI. In this trial, participants will undergo either 3T or 7T MRI. The 7T MRI offers even higher detail, aiding in the detection of small abnormalities that might be missed, especially in cases where medication is ineffective. Additionally, intracranial electroencephalography (iEEG) recordings, which participants in this trial will also undergo, are crucial for predicting surgical success in epilepsy. They help locate the brain areas where seizures begin, guiding successful surgeries. Together, these tools aim to improve treatment and surgical outcomes for people with epilepsy. ^{1 3 6 7 8}

Who Is on the Research Team?

Kathryn A Davis, MD, MSTR

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4557590/

Partial epilepsy: A pictorial review of 3 TESLA magnetic ... Furthermore, several studies showed that MRI at 3 T performed better than 1.5-T in image quality, detection and characterization of structural lesions, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1464155/

MR Imaging and Epilepsy—3T or not 3T? That Is the ... Experienced, unblinded review of 3T PA-MRI studies yielded additional diagnostic information in 48% (19/40) compared to routine clinical reads at 1.5T. In 37.5% ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2213158221000462

Ultra-high field magnetic resonance imaging in human ... Seizure freedom was achieved in 73% of operated patients; no seizure outcome comparison was made between 7T MRI positive, 7T negative and 3T positive patients.

4. ajronline.org ajronline.org/doi/10.2214/AJR.07.3933

Qualitative Comparison of 3-T and 1.5-T MRI in the Evaluation ... In evaluation of epilepsy, MRI at 3 T performed better than 1.5-T MRI in image quality, detection of structural lesions, and characterization of lesions. High- ...

5. healthcare-bulletin.co.uk healthcare-bulletin.co.uk/article/role-of-3-tesla-magnetic-resonance-imaging-in-evaluation-of-epilepsy-among-patients-in-tertiary-care-teaching-hospital-in-western-uttar-pradesh-3846/

Role of 3 Tesla Magnetic Resonance Imaging in ... Conclusion: 3 Tesla MRI significantly enhances detection of structural abnormalities in epilepsy, especially in patients with partial seizures.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0967586825003650

Application, utility and safety of intraoperative 3T magnetic ... This study evaluates the application, utility, and safety of intraoperative 3T MRI in pediatric epilepsy surgery over a ten-year period.

7. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1684/epd.2020.1174

MRI essentials in epileptology: a review from the ILAE ... This review contains information on basic MRI principles, sequences, field strengths and safety, when to perform and repeat an MRI, epilepsy MRI ...

8. karger.com karger.com/doi/10.1159/000542725

Phantom Safety Assessment of 3 Tesla Magnetic ... Conclusion: These phantom safety data show that both clinically used MRI sequences and research sequences such as fMRI can be successfully ...