Interictal functional ultrasound imaging in human epilepsy resection and responsive neurostimulation surgery

K. A. Agyeman; D. Lee; B. P. Lee; R. J. McGinn; A. Abedi; J. Russin; K. Wu; w. Choi; C. Liu; V. N. Christopoulos

doi:10.64898/2026.10.15.26365563

AI summary · DOI: 10.64898/2026.10.15.26365563 · medRxiv: Neurology

Interictal functional ultrasound imaging in human epilepsy resection and responsive neurostimulation surgery

K. A. Agyeman, D. Lee, B. P. Lee, R. J. McGinn, A. Abedi, J. Russin, K. Wu, w. Choi,

and 2 more authors

C. Liu, V. N. Christopoulos

How to read this summary? Illustrated guide

The essentials

In nine epilepsy surgery patients, intraoperative functional ultrasound distinguished interictal cortical dynamics and detected hemodynamic changes following seizure-onset zone resection and responsive neurostimulation.

Based on the abstract only: check the details in the original paper.

Question

Can intraoperative functional ultrasound distinguish interictal activity in seizure-onset zones from surrounding cortex in drug-resistant focal epilepsy? Can it also assess cortical responses associated with resection and responsive neurostimulation?

Method

Functional ultrasound signals were acquired directly from exposed cortex during standard-of-care surgery in nine patients with drug-resistant focal epilepsy. The authors developed six ultrafast power Doppler-based interictal activity markers to distinguish seizure-onset zone cortex from peri-resection zone cortex and quantify treatment-associated changes following resection and responsive neurostimulation.

Findings

Result The interictal activity markers revealed distinct hemodynamic dynamics between seizure-onset zone and peri-resection zone cortex.
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The IaMs revealed distinct interictal hemodynamic dynamics between SOZ and PRZ cortex.
Result All six markers changed significantly in surrounding peri-resection zone cortex following seizure-onset zone resection.
See the passage in the paper
Following SOZ resection, all six markers changed significantly within the surrounding PRZ.
Result Responsive neurostimulation modulated cortical hemodynamic dynamics in a stimulation paradigm-dependent manner.
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RNS also induced robust, stimulation paradigm-dependent modulation of cortical hemodynamic dynamics.
Result Responsive neurostimulation and resection produced changes in the same direction for five of the six markers.
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Notably, RNS and surgical resection produced concordant directional changes across five of the six IaMs, despite representing fundamentally different therapeutic interventions.
Authors’ interpretation The authors interpret these findings as demonstrating the feasibility of intraoperative functional ultrasound for distinguishing interictal cortical dynamics and assessing treatment-associated responses.
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Together, these findings demonstrate the feasibility of intraoperative fUSI for characterizing and distinguishing interictal dynamics within SOZ and PRZ cortex and assessing treatment-associated cortical responses during human epilepsy surgery.

Limitations

The study's scope is limited to nine patients with drug-resistant focal epilepsy undergoing intraoperative imaging of exposed cortex.

Why it matters

The authors propose functional ultrasound as a complementary high-resolution imaging approach alongside established clinical methods for seizure-onset zone localization and intraoperative functional assessment.

Written by AI from the paper. Passages are checked word for word against the text we analysed; the rest may contain errors.

AI-generated keywords: Functional ultrasound imaging; Drug-resistant epilepsy; Seizure-onset zone; Interictal activity; Responsive neurostimulation

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Comprehensive Summary
Layman's Summary
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Original abstract

This medRxiv preprint examines whether functional ultrasound imaging (fUSI) can characterize abnormal brain activity between seizures and measure immediate responses to epilepsy treatment during surgery. More than 30% of patients with epilepsy do not respond adequately to medication and may require surgery or neuromodulation. Identifying the seizure-onset zone (SOZ)—the region where seizures begin—remains challenging. Existing approaches may involve invasive monitoring, prolonged hospitalization, adjustments to antiseizure medication, and recordings of actual seizures. The authors therefore investigated whether intraoperative fUSI could provide complementary information without requiring a seizure during imaging. The study included nine patients with drug-resistant focal epilepsy undergoing standard-of-care surgery. Researchers acquired fUSI signals directly from the exposed cortex to examine interictal activity, or activity between seizures. Because fUSI measures blood-flow-related signals, it reflects hemodynamic changes rather than directly recording neuronal electrical activity. The team developed six interictal activity markers (IaMs) using ultrafast power Doppler imaging. They used these markers to compare SOZ tissue with cortex in the peri-resection zone (PRZ), the region surrounding the resection area, and to assess changes associated with SOZ removal and responsive neurostimulation (RNS). The authors report that the six markers revealed distinct interictal hemodynamic dynamics in SOZ and PRZ cortex. These findings support the feasibility of obtaining potentially useful information about epileptic tissue without recording seizures. However, the abstract provides no numerical classification accuracy, sensitivity, specificity, or other diagnostic-performance measures. The reported regional differences therefore do not establish how reliably fUSI could localize the SOZ in clinical practice. After SOZ resection, all six markers changed significantly in the surrounding PRZ, indicating that removal was associated with detectable changes in nearby cortical hemodynamics. RNS also produced changes the authors describe as robust, with responses varying by stimulation paradigm. Notably, RNS and resection produced changes in the same direction for five of the six markers. This agreement suggests that fUSI may detect shared features of treatment-associated cortical responses, but it does not establish identical mechanisms or equivalent clinical benefits. The authors conclude that intraoperative fUSI is feasible for characterizing interictal cortical dynamics, distinguishing SOZ from surrounding cortex, and assessing immediate treatment responses during epilepsy surgery. They propose it as a complementary, high-resolution functional imaging method rather than a replacement for established clinical approaches. The evidence remains preliminary. The study is a preprint involving only nine patients, and this summary is based solely on the title, authors, and abstract; the stated license did not permit access to the full text. The abstract does not identify the six markers or provide patient counts for each intervention, effect sizes, exact statistical results, or stimulation settings. It also does not report whether marker changes predicted subsequent seizure control. Because imaging was performed directly on exposed cortex, the demonstrated application is limited to the intraoperative setting. Larger studies incorporating diagnostic-performance measures and long-term clinical outcomes are needed to determine whether fUSI improves treatment decisions or patient outcomes.

Listening Between Seizures: Ultrasound’s Potential Role in Epilepsy Surgery

For people with drug-resistant epilepsy, one of the hardest questions is also one of the most important: where do seizures begin? More than 30% of patients with epilepsy do not respond adequately to medication, and some may need surgery or neuromodulation. Yet identifying the seizure-onset zone, or SOZ, can require invasive monitoring, extended hospital stays, medication adjustments, and recordings of actual seizures.

A preliminary study explores whether functional ultrasound imaging, known as fUSI, could offer useful information during surgery without waiting for a seizure. The medRxiv preprint, “Interictal functional ultrasound imaging in human epilepsy resection and responsive neurostimulation surgery,” by K. A. Agyeman, D. Lee, B. P. Lee, R. J. McGinn, A. Abedi, J. Russin et al., examines both activity between seizures and immediate responses to treatment.

Why Look Between Seizures?

Seizures provide crucial clues about where abnormal brain activity starts. But capturing them is not always straightforward. An imaging method that reveals useful differences between brain regions during interictal periods—the intervals between seizures—could complement existing approaches to surgical assessment.

Functional ultrasound measures blood-flow-related signals rather than neuronal electrical activity directly. These hemodynamic signals offer a different window into cortical function. The key question is whether their patterns can help characterize epileptic tissue and reveal how the surrounding brain responds when treatment is delivered.

What the Researchers Did

The study included nine patients with drug-resistant focal epilepsy undergoing standard-of-care surgery. Researchers acquired fUSI recordings directly from the exposed cortex, making this an investigation of intraoperative imaging rather than a demonstration of imaging through an intact skull.

Using ultrafast power Doppler imaging, the team developed six interictal activity markers, abbreviated as IaMs. These markers were used to examine regional differences and treatment-associated changes. The researchers focused on three questions:

Did the markers differ between the SOZ and cortex in the peri-resection zone, or PRZ, surrounding the resection area?
Did the surrounding cortex show marker changes after removal of the SOZ?
Could the markers capture responses to responsive neurostimulation, or RNS?

This approach examined whether blood-flow dynamics could provide complementary information about both tissue characteristics and immediate treatment responses.

What the Study Found

Regional Differences Without Recording Seizures

The authors report that the six markers revealed distinct interictal hemodynamic dynamics in SOZ and PRZ cortex. That finding supports the feasibility of detecting potentially informative regional differences without recording a seizure during imaging.

However, detecting differences is not the same as proving reliable localization. The abstract provides no numerical classification accuracy, sensitivity, specificity, or other diagnostic-performance measures. It therefore does not establish how consistently fUSI could identify the SOZ in clinical practice.

Changes After Resection

After SOZ removal, all six markers changed significantly in the surrounding PRZ. This suggests that resection was associated with detectable changes in nearby cortical hemodynamics, not simply the removal of tissue from the imaging field.

These findings raise the possibility of using fUSI to assess immediate physiological responses during surgery. But the abstract does not report whether those changes predicted later seizure control. A measurable response should not yet be interpreted as evidence of a successful long-term outcome.

Responses to Neurostimulation

RNS also produced changes that the authors describe as robust, with responses varying according to the stimulation paradigm. Notably, RNS and resection produced changes in the same direction for five of the six markers.

This agreement suggests that fUSI may capture shared features of treatment-associated cortical responses. It does not show that stimulation and resection work through identical mechanisms or provide equivalent clinical benefits. Similar marker directions are an intriguing observation, not proof that the treatments are interchangeable.

Important Limits to Keep in View

The evidence remains preliminary. This is a preprint involving only nine patients. This article is based solely on the supplied title, author information, and abstract; the stated license did not permit access to the full text.

The abstract does not identify the six markers, specify how many patients received each intervention, or provide effect sizes, exact statistical results, or stimulation settings. Those missing details limit assessment of the findings’ magnitude, consistency, and reproducibility.

The setting also matters. Because imaging was performed on exposed cortex, the demonstrated application is restricted to surgery. The study does not establish fUSI as a noninvasive screening tool or a replacement for established epilepsy investigations.

A Promising Complement, Not a Proven Decision Tool

The study offers an early demonstration that intraoperative fUSI can characterize interictal cortical dynamics and detect immediate changes associated with resection and neurostimulation. Its potential lies in adding high-resolution functional information to the tools clinicians already use.

The next step is to determine whether that information improves decisions and outcomes. Larger studies need to measure localization performance and connect intraoperative marker changes with long-term seizure control. For now, fUSI is a promising complementary research approach—not yet a proven guide to epilepsy treatment.

Created on 27 Oct. 2026

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Weekly letter Presented in "Brain and behaviour this week" of 26 October 2026. Brain and behaviour this week: Lowering a protein, finding a memory, catching a rhythm

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Interictal functional ultrasound imaging in human epilepsy resection and responsive neurostimulation surgery

The essentials

Question

Method

Findings

Limitations

Why it matters

Read further

Definitions

Listening Between Seizures: Ultrasound’s Potential Role in Epilepsy Surgery

Why Look Between Seizures?

What the Researchers Did

What the Study Found

Regional Differences Without Recording Seizures

Changes After Resection

Responses to Neurostimulation

Important Limits to Keep in View

A Promising Complement, Not a Proven Decision Tool

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