BRIEF COMMUNICATION

Triggered Seizures for Ictal SPECT Imaging: A Case Series

and Feasibility Study
Sabry L. Barlatey1, Camille G. Mignardot2, Cecilia Friedrichs-Maeder2, Kaspar Schindler2, Roland Wiest3,
Andreas Nowacki1, Matthias Haenggi4, Werner J. Z’Graggen1, Claudio Pollo1, Axel Rominger5, Thomas Pyka*5, and
Maxime O. Baud*2
1
Department of Neurosurgery, University Hospital of Bern, Bern, Switzerland; 2Sleep-Wake-Epilepsy Center and NeuroTec, Center for
Experimental Neurology, Department of Neurology, University Hospital of Bern, Bern, Switzerland; 3Support Center for Advanced
Neuroimaging, University Institute of Diagnostic and Interventional Neuroradiology, University Hospital of Bern, Bern, Switzerland;
4
Department of Intensive Care Medicine, University Hospital of Bern, Bern, Switzerland; and 5Department of Nuclear Medicine,
University Hospital of Bern, Bern, Switzerland

radiotracer over days incurs issues with isotope production, trans-

Ictal SPECT is an informative seizure imaging technique to tailor epi-
lepsy surgery. However, capturing the onset of unpredictable seizures
is a medical and logistic challenge. Here, we sought to image planned
seizures triggered by direct stimulation of epileptic networks via ste-
reotactic electroencephalography (sEEG) electrodes. Methods: In this
case series of 3 adult participants with left temporal epilepsy, we iden-
tified and stimulated sEEG contacts able to trigger patient-typical sei-
zures. We administered 99mTc-HMPAO within 12 s of ictal onset and
acquired SPECT images within 40 min without any adverse events.
Results: Ictal hyperperfusion maps partially overlapped concomitant
sEEG seizure activity. In both participants known for periictal aphasia,
SPECT imaging revealed hyperperfusion in the speech cortex lacking
sEEG coverage. Conclusion: Triggering of seizures for ictal SPECT
complements discrete sEEG sampling with spatially complete images
of early seizure propagation. This readily implementable method revives
interest in seizure imaging to guide resective epilepsy surgery.
Key Words: human epilepsy; seizure imaging; ictal SPECT; seizure
triggering; stereotactic electroencephalography
J Nucl Med 2024; 65:470–474
DOI: 10.2967/jnumed.123.266515
port and storage, as well as radioprotection (5). Thus, because of
growing cost and time constraints in health care, most epilepsy
centers, including ours, abandoned this informative technique (6).
Here, we conducted a feasibility study modifying the original
ictal SPECT method to address these practical issues. In most
patients with epilepsy undergoing invasive stereotactic electroen-
cephalography (sEEG) monitoring, patient-typical seizures can be
triggered using direct electric stimulation (7). This procedure con-
tributes to localizing ictogenic tissue but also offers temporal con-
trol over the occurrence of seizures. We used this untapped
opportunity to image planned seizures.
MATERIALS AND METHODS
Participants
Three male participants undergoing invasive sEEG investigations
for the clinical purpose of localizing their seizures gave their written
informed consent in accordance with the Declaration of Helsinki. The
Ethics Committee of the Canton Bern, Switzerland, approved this pro-
spective feasibility study (KEK 2021-01337).

Electrophysiology
sEEG leads (DIXI Medical) were implanted under general anesthe-

D elineating brain areas of seizure onset and propagation is a

necessary step toward tailoring surgery for focal epilepsy (1). Ictal
SPECT is a key method to capture a spatially complete view of
propagating seizures by imaging areas of accompanying parenchy-
mal hyperperfusion (1–3). However, the unpredictable timing of
fleeting seizures renders ictal SPECT acquisitions logistically chal-
lenging and resource-intensive.
In practice, neurologists reduce antiseizure medications to has-
ten the occurrence of seizures. Their prompt detection requires
continuous visual monitoring of the electroencephalogram. Until
then, nuclear medicine staff must stand ready to inject a radio-
tracer, critically within seconds of seizure onset, which rarely suc-
ceeds without delay (4). Moreover, maintaining ready-to-inject
Received Aug. 7, 2023; revision accepted Dec. 4, 2023.
For correspondence or reprints, contact Maxime O. Baud (maxime.baud.
neuro@gmail.com).
*Contributed equally to this work.
Published online Jan. 11, 2024.
COPYRIGHT ß 2024 by the Society of Nuclear Medicine and Molecular Imaging.
sia in cerebral areas of interest for recording (Natus Quantum), map-
ping, and stimulation (ISIS neurostimulator; Inomed Medizintechnik
GmbH). We systematically screened all gray-matter sEEG contacts for
minimal stimulation parameters able to trigger the patient-typical sei-
zure (biphasic 1-ms square pulses; frequency, 60 Hz; duration, 1–4 s;
intensity, 2–6 mA; Table 1). Epileptiform discharges without symp-
toms and symptoms without epileptiform discharges were disregarded.
Seizure Triggering and SPECT Acquisition
One day after triggering a first patient-typical seizure (confirmed as
such against spontaneous seizures), stimulation was repeated at the
identified trigger site with a connected syringe containing the freshly
produced 99mTc-hexamethylpropyleneamine oxime (HMPAO) (medeo
AG; Table 1). Upon the onset of an electroclinical seizure, the radio-
tracer was injected, followed by SPECT imaging within 21–39 min on
a prebooked Symbia Intevo Bold system (Siemens Healthineers) (Fig.
1A). Potential spillover was assessed with a Geiger counter.
Imaging Data
Postoperative CT images were coregistered to a preoperative
T1-weighted MRI scan using the Lead-DBS toolbox (version 2.5.2) in

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 TABLE 1
Characteristics of Participants, Trigger Parameters, SPECT Acquisition Data, and Clinical Value

Category Characteristic Participant 1 Participant 2 Participant 3

Participants and Age and sex 20-y-old man 50-y-old man 48-y-old man
their epilepsy
Epilepsy Left mesiotemporal Left mesiotemporal Left laterotemporal
Etiology Hippocampal sclerosis Hippocampal sclerosis Posthemorragic
Seizure onset zone Entorhinal cortex, anterior Anterior hippocampus Temporal pole
from sEEG and posterior hippocampus
Spontaneous seizure Gustatory aura ! oral and Rising epigastric Paresthesia in neck !
symptoms* manual automatisms ! sensation ! de ja
-vu ! familiar voices and
aphasia aphasia music ! tunnel
vision ! aphasia
Triggered seizures Symptoms Identical up to aphasia Identical up to aphasia Identical up to
tunnel vision
Antiseizure medication Half-dose None Full-dose
Triggering bipole Entorhinal cortex Entorhinal cortex Temporal pole
Stimulation intensity 2 mA 2 mA 6 mA
Stimulation duration 1s 2s 4s
Loss of awareness Yes No No
Seizure duration 151 s 94 s 188 s
Seizure aborted No No Yes, clonazepam, 1 mg
Propagation* Entorhinal ! anterior and Amygdala ! anterior Temporal pole !
posterior hippocampus ! and posterior anterior hippocampus
amygdala ! temporal pole hippocampus ! insula ! fusiform
gyrus
SPECT Delay
Seizure onset to 12 s 9s 7s
injection
Injection to image 21 min 22 min 39 min
Radiotracer 3 h 13 min 2 h 26 min 1 h 38 min
production to
image
Dose 406 MBq 489 MBq 511 MBq
Hyperperfusion Mesiotemporal, superior Mesiotemporal, superior Temporal pole,
temporal, frontobasal temporal hippocampus,
insula anterior
Surgery Resection Selective None because of Selective polectomy
amygdalohippocampectomy, cognitive risk and amygdalectomy
left
Seizure outcome Engel class ID at 1 y NA Engel class IV at 1 y
Cognitive outcome Improved NA Unchanged

*Arrows indicate sequence of symptoms or involved areas, which can be complete or partial across seizures in same participant.
NA 5 not applicable.

MATLAB 2020a (The MathWorks) to compute the coordinates of sEEG
contacts. We computed a SPECT deviation map for each participant and
detected volumes with a z-value of at least 2.25 as hyperperfusion clusters
using a normal database (8)—that is, normalization to whole-brain activ-
ity—provided by the Hermes BRASS software (version 6.1.3; Hermes
Medical Solutions; Fig. 1B) as a reference. We computed patient-specific
cortical reconstruction with FreeSurfer (Harvard) for covisualization with
the hyperperfusion clusters and sEEG contacts (Fig. 2).
Electrophysiologic Data
We computed bipolar traces of adjacent contacts and filtered signals
with a 1- to 410-Hz bandpass filter. To estimate seizure power per
bipolar contact, a z-value was calculated as follows: ðLL post 2LL pre Þ/
(SDðLLpre Þ), where LL is the line length of the sEEG signal over a
running window of 1 s, averaged over 60 s before (pre) and after
(post) seizure onset (9). Seizure-triggering stimulation was excluded
from this calculation.
RESULTS
Within a few attempts over 3–8 min, we successfully triggered
seizures in 3 participants, replicating the patient-typical seizure
semiology and electrographic pattern on sEEG (Table 1). In each
case, we injected 99mTc-HMPAO (,520 MBq) within 9–12 s of

TRIGGERED SEIZURES FOR ICTAL SPECT
Barlatey et al. 471

 DISCUSSION

To our knowledge, this is the first study

establishing the feasibility of triggering
ictal SPECT on demand with direct electric
stimulation of the epileptic cortex. Trigger-
ing seizures for SPECT imaging was pre-
viously explored in psychiatric patients
undergoing electroconvulsive therapy (10)
and epileptic patients receiving pentylene-
tetrazole (11). However, these prior meth-
ods did not generalize, given the unclear
clinical utility and safety of these proce-
dures. With this case series, we show that
triggering of seizures with direct electric
stimulation for ictal SPECT imaging is
convenient, spares resources, and can be
clinically useful.
The presented method is limited to
patients with epilepsy undergoing invasive
sEEG monitoring. As such, it cannot guide
electrode placement but may contribute to
the planning of resective surgery. Of note,
we used a normal non–age-matched data-
FIGURE 1. Schematic of triggered ictal SPECT and data processing. (A) Previously screened and base for the calculation of deviation maps.
selected sEEG bipolar contact is stimulated to trigger patient-typical seizure. Directly after seizure Although we could identify ictal hyperper-
onset, confirmed through sEEG signals and semiology, systemic bolus of radiotracer (99mTc-
fusion areas, further optimization with the
HMPAO) is administered. Planned SPECT is acquired within less than 1 h. (B) Raw data processing
from left to right (dataset from participant 3 as example). Postimplantation CT and preimplantation
subtraction of patient-specific interictal
T1-weighted MRI are coregistered for sEEG lead localization. Raw SPECT images are coregistered SPECT is required. To establish the clini-
to T1-weighted MRI sequence. SPECT deviation map is computed and anatomically colocalized with cal value, future studies should compare
sEEG signals. triggered and spontaneous ictal SPECT as
predictors of postsurgical outcomes, as
well as delineate their added value over
unequivocal seizure onset (Fig. 1), enabling a planned ictal SPECT 18F-FDG PET (12) or electroencephalography/functional MRI (13).
acquisition with a prebooked g-camera. The participants did not Moreover, the advent of digital SPECT using 360 cadmium-zinc-
have any adverse events: triggered seizures were controlled and telluride detectors offers a promising opportunity to enhance the
without secondary generalization, and radioprotection was ensured performance of ictal SPECT imaging with greater sensitivity and
(absence of radiotracer spillover). In all 3 participants, the ictal improved quantitation (14).
SPECT contributed to characterizing periictal aphasia (Fig. 2). As proposed by previous retrospective work (15,16), the maxi-
Participant 1 reported his typical gustatory aura and showed mum ictal hyperperfusion did not overlap perfectly with the seizing
oral and manual automatisms followed by loss of awareness and parenchyma (Fig. 2), suggesting a potential regional impairment of
postictal aphasia. sEEG revealed a seizure onset zone in the left neurovascular coupling (17) and potential ictal hypoperfusion areas
entorhinal cortex and posterior hippocampus. Hyperperfusion (16). As shown here, delineating ictogenic parenchyma with high
involved the ipsilateral posterior temporal lobe and contralateral temporal resolution (sEEG) and spatial continuity (ictal SPECT)
mesiotemporal lobe (Fig. 2A). Participant 2 reported his typical may offer a deeper understanding of seizure propagation pathways
rising epigastric sensation and had ictal aphasia without loss of and help plan resections around eloquent cortex.
awareness. sEEG located the seizure onset zone in the left anterior
hippocampus. Hyperperfusion involved the same structure and the CONCLUSION
ipsilateral posterior temporal lobe (Fig. 2B). Participant 3 reported
his typical paresthesia in the neck followed by familiar voices and Nuclear medicine and sEEG for recording and stimulation are
tunnel vision, but the seizure did not progress to his occasional broadly available at specialized epilepsy centers. In our opinion,
ictal aphasia. sEEG located the seizure onset zone in the left tem- SPECT imaging of seizures can be rapidly readopted in controlled
poral pole. Hyperperfusion was restricted to this structure, without conditions that mitigate its previous logistic drawbacks. Novel
any additional early propagation (Fig. 2C). data generated with this technique in larger cohorts could contrib-
Thus, despite stimulation in the same brain area (left mesiotem- ute to refinement of resection planning, improving seizure and
poral), each triggered seizure was patient-specific and the imaged cognitive outcomes in epilepsy surgery.
early seizure propagation unique. In the first 2 cases, ictal SPECT
DISCLOSURE
offered complementary information to sEEG and revealed early
involvement of brain areas lacking electrode coverage to limit the Maxime Baud holds shares with Epios, Ltd., a medical device
risk of complications in potentially eloquent cortex. In the third company based in Geneva. No other potential conflict of interest
case, sEEG and ictal SPECT provided overlapping information. relevant to this article was reported.

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FIGURE 2. sEEG–SPECT comparison: patient-specific cortex reconstruction (FreeSurfer, left-hemisphere, frontal and inferior view) with sEEG bipolar
contacts and SPECT deviation map (orange to yellow, more intense) for participants 1 (A), 2 (B), and 3 (C). Amygdala and hippocampus contours
(adapted from FreeSurfer) are shown as dark gray overlays. sEEG bipolar contacts (plotted at anatomic centers of bipoles) are color-coded from white to
blue according to amount of ictal activity recorded over 1 min (line length relative to baseline). Red bolt depicts stimulated bipole. sEEG traces are shown
for selected channels of interest with their anatomic location. Brackets regroup channels from same lead. Note relationship between stimulus artifacts
and direct beginning of epileptic discharges. A 5 amygdala; Ent 5 entorhinal cortex; HippA 5 hippocampus anterior; HippP 5 hippocampus posterior;
P-1 5 participant 1; P-2 5 participant 2; P-3 5 participant 3; Parahipp 5 parahippocampal gyrus; STG 5 superior temporal gyrus; TP 5 temporal pole;
WM 5 white matter.

TRIGGERED SEIZURES FOR ICTAL SPECT
Barlatey et al. 473

ACKNOWLEDGMENT
We thank Sandy Feruglio for setting up the clinical database for
this study.
KEY POINTS
QUESTION: Is ictal SPECT able to map seizures triggered by
direct electric stimulation?
PERTINENT FINDINGS: We successfully triggered and imaged
patient-typical seizures with SPECT in a prospective case series
of 3 participants with left temporal epilepsy. Our combined
sEEG/SPECT approach revealed early seizure propagation
pathways, beyond discrete electrophysiologic exploration.
IMPLICATIONS FOR PATIENT CARE: Triggering of patient-
typical seizures for on-demand ictal SPECT may broadly reinstate
this often-abandoned imaging technique and help tailor resective
epilepsy surgeries.
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March 2024