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Year : 2022  |  Volume : 20  |  Issue : 2  |  Page : 69-73

The role of ictal brain single photon-emission tomography in refractory epilepsy complementary to magnetic resonance imaging and electroencephalogram – Our experience

1 Department of Nuclear Medicine, Christian Medical College, Vellore, Tamil Nadu, India
2 Department of Radiology, Christian Medical College, Vellore, Tamil Nadu, India
3 Department of Paediatric Neurology, Christian Medical College, Vellore, Tamil Nadu, India

Date of Submission08-Dec-2021
Date of Decision05-Feb-2022
Date of Acceptance25-Mar-2022
Date of Web Publication07-May-2022

Correspondence Address:
Dr. Julie Hephzibah
Department of Nuclear Medicine, Christian Medical College, Vellore - 632 004, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/cmi.cmi_107_21

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Background: Correct identification of the epileptogenic zone (EZ) is essential for surgical success for focal epilepsy. There are multiple modalities which are available for detecting the anatomical and the functional abnormalities. The purpose of this study was to determine the complementary role of ictal brain single photon-emission tomography (SPECT) in delineating the EZ in addition to electroencephalogram (EEG) and magnetic resonance imaging (MRI). Methodology: Clinical and diagnostic data from patients with refractory epilepsy undergoing ictal brain SPECT (IEBS), EEG, MRI between 2014 and 2019 were analyzed retrospectively. Tc99m-ethyl cysteinate dimer was administered intravenously during or within 30 s of onset of seizure activity. Results: Eighty-nine patients aged: Four months-32 years (median age: Eight years) were studied. The concordance of IEBS with MRI and EEG were studied. Among them, EEG was normal in 22 and abnormal in 67 (multifocal: 40, unifocal: 8, generalized: 19). MRI was normal in 36, abnormal in 26, nonspecific in 24 and not done in three patients. Of the 80 patients showing tracer uptake in IEBS, 14-multifocal uptake and 66-unifocal uptake (EEG and MRI were not showing any abnormality in 15 and 27 patients, respectively). Unifocal uptake in IEBS was concordant with EEG in 11 (16.67%) and MRI in 15 (27.72%). The concordance and nonconcordance of the results among the two imaging modalities or EEG assuming surgical site as the gold standard was noted. Twenty-two had undergone surgical removal of the EZ, 15 was conformable with MRI or IEBS. Conclusion: In patients with noncontributory EEG and MRI, IEBS could detect the epileptogenic focus. Therefore, depending entirely on EEG and MRI may limit its diagnosis. IEBS, MRI and EEG are complementary to each other in the detecting the epileptogenic focus.

Keywords: Electroencephalogram, epilepsy, ictal single photon-emission tomography, magnetic resonance imaging, m-ethyl cysteinate dimer

How to cite this article:
Benjamin J, Sunny SS, Hephzibah J, Mathew D, Jasper A, Thomas M, Shanthly N, Oommen R. The role of ictal brain single photon-emission tomography in refractory epilepsy complementary to magnetic resonance imaging and electroencephalogram – Our experience. Curr Med Issues 2022;20:69-73

How to cite this URL:
Benjamin J, Sunny SS, Hephzibah J, Mathew D, Jasper A, Thomas M, Shanthly N, Oommen R. The role of ictal brain single photon-emission tomography in refractory epilepsy complementary to magnetic resonance imaging and electroencephalogram – Our experience. Curr Med Issues [serial online] 2022 [cited 2023 Feb 2];20:69-73. Available from: https://www.cmijournal.org/text.asp?2022/20/2/69/344925

  Introduction Top

Epilepsy is characterized by seizures due to anomalous, excessive, and synchronic neuronal activity in the brain.[1] Epilepsy affects people of all ages and is the one of the more common brain disorders in almost every country of the world.[2] Estimates say that in Indian population, there are more than 1 crore persons with epilepsy. It is prevalent in about 1% of the Indian population.[3] The causes of epilepsies are varied and multifaceted in many of the cases.[4] Therefore, study of the primary causes of seizures will depend on the clinical setting, in particular, the type of set of symptoms, age of onset, forms of seizures, accompanying diseases, whether progressive or static motor and cognitive dysfunction, among other factors. Medical management, when tolerable, can lead to control of seizures in a large number of patients having epilepsy. However, it is that estimated that 20%–30% of epileptic patients are refractory to all forms of medical management.[5]

Imaging of the brain is essential to the assessment of patients with epilepsy to detect any underlying anatomical brain abnormality that may be the origin of the epilepsy. Those with focal seizures refractory to drugs, who have to be treated surgically need particular attention. Magnetic resonance imaging (MRI) and electroencephalogram (EEG) are helpful in diagnosing possible etiology of epilepsy. Single photon-emission tomography (SPECT) of the brain is useful in planning preoperatively for refractory epilepsy to medicines and to detect the laterality and localization of an epileptogenic zone (EZ) before surgery. It is not necessarily used in the initial diagnosis or assessment of recent-onset epilepsy.[6] MRI is frequently negative or equivocal in detecting the epileptogenic focus. In addition, multiple lesions in MRI may pose a diagnostic challenge in detecting the same. EEG may also be ambivalent or disagreeing with the anatomical imaging. In view of this radionuclide imaging is found to be particularly useful. The blood flow in the epileptogenic region during the ictal state obviously increases proportional to the electrical hyperactivity. The radiopharmaceutical (RP) is injected, for ictal SPECT via intravenous administration either instantly during or after the onset of seizure.


To study the complementary role of ictal brain SPECT (IEBS) in localizing EZ in addition to EEG and MRI.

  Methodology Top

Study design

Retrospective study.


This study was conducted in the department of nuclear medicine of our hospital with the data of patients with refractory epilepsy undergoing ictal brain SPECT.


Between November 2014 and November 2019.

Inclusion criteria

All patients on more than two antiepileptic drugs. All had undergone EEG and MRI and whenever essential SPECT images were fused with MRI images for structural localization to help for precise surgical removal if necessary. Tc99m-ethyl cysteinate dimer (ECD) was administered intravenously during or within 30 s of onset of seizure activity.

Magnetic resonance imaging

MRI was performed using 1.5-T or 3.0-T units. The minimal protocol consisted of fast spin echo (FSE) T2-weighted sequences in the axial and coronal planes with slice thickness of 5 mm and interslice gap of 1 mm. In addition, the temporal lobe protocol consisted of FSE T2-weighted and (fluid attenuation inversion recovery) sequences with 3 mm thick slices in the oblique coronal plane, individually fitted perpendicular to the long axis of the hippocampus. Three-dimensional volumetric acquisition using T1-weighted FSE sequences was performed with reconstruction in axial, sagittal, and coronal planes. To a 25-cm field of view, a 256 × 256 matrix was applied. Additional sequences or gadolinium- diethylenetriamine pentaacetateenhancement were performed in selected cases.

Single photon-emission tomography perfusion imaging

Ictal SPECT scans were performed using 99 mTc ECD, BRIT India, Tomography was performed about 45–60 min after injecting the RP. Where appropriate, tracer dose was adjusted for weight and age-based upon an adult dose of 740 MBq. Dual-headed gamma cameras equipped with high-resolution collimators were used.

  • Images were acquired over 360°
  • Step-and-shoot mode
  • Step angle of 3° into 128 × 128 acquisition matrix
  • Zoom 1.3
  • Tc99m primary window at 140Kev +/‒10%
  • Scatter correction with window kept at 120Kev
  • Data reconstruction employed iterative Ordered Subsets Expectation Maximization (OSEM) with attenuation and scatter corrections
  • Attenuation correction was performed using the standard Chang's method
  • Images were reoriented along the orbito-meatal line to generate transaxial, coronal, and sagittal slices
  • Additional slices, aligned parallel to the longitudinal axis of the temporal lobes, were also generated to better evaluate possible temporal lobe epilepsies
  • On seizure onset, ECD was immediately injected. SPECT was considered to be ictal study if injection occurred within <1 min of seizure onset
  • In the majority of cases, seizure was detected by the presence of aura or onset of seizure activity
  • Postprocessing with Butterworth filter with critical frequency of 0.5 mm and power factor of 10, OSEM reconstruction method was employed with attenuation and scatter correction with 8 subsets and 4 iterations, the reconstructed images are then re-angulated to OM plane
  • No subtraction analysis was used.<

Imaging and electroencephalogram reporting

EEG recordings were reported by the Neurologist while MRI images were reviewed by the Radiologist. Ictal ECD brain SPECT (IEBS) was analyzed by an experienced Nuclear Medicine physician. Foci of uptake in hyper-perfused areas in IEBS were recorded. The unifocal uptake was assigned the appropriate lateralization to a cerebral hemisphere and localization to the cerebral lobe [Figure 1]. More than one site of uptake on IEBS was considered multifocal uptake [Figure 2].
Figure 1: Unifocal uptake: 2-year-old male child – recurrent myoclonic epilepsy; Single photon emission tomography – R frontal, magnetic resonance imaging – R middle frontal gyrus, electroencephalogram – normal, Op – Right fronto-parietal, Biopsy– focal cortical dysplasia R Superior frontal gyrus

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Figure 2: Multifocal uptake: 1/F: Refractory right focal motor seizures; Ictal ECD brain SPECT: L frontal, parietal, magnetic resonance imaging: focal cortical dysplasia-L frontal, caudate, ant putamen, electroencephalogram: L hemispheric epileptiform activity, Op: L frontotemporal craniotomy, periinsular hemispherotomy; Biopsy: L lobe focal cortical dysplasia

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Statistical analysis

The localization and lateralization of the seizure in all the modalities were recorded. For each diagnostic test, sensitivity values were calculated taking the surgical site as the gold standard in cases where surgery was done. Cross tabulation was used to determine the concordance and nonconcordance of the results among the two imaging modalities or EEG. In the remaining nonoperated cases, concordance of IEBS with either MRI or EEG was analyzed.

Ethical consideration

Institutional Review Board approved the study with IRB Min. No. 14096 (Retro) dated 30.06.2021. The waiver of consent was obtained from the IRB/ethics committee before commencement of the study.

  Results Top

Eighty-nine patients aged between 4 months and 32 years (median age: Eight years) were included. EEG, MRI, and IEBS were done in these patients. The concordance of IEBS with MRI and EEG was studied.

Of these 89 patients, EEG was normal in 22 and abnormal in 67 (multifocal: 40, unifocal: 8, generalized: 19). There was generalized epileptiform activity in 19 of them, 8 had unifocal epileptiform activity, 40 had multifocal epileptiform activity, and 22 were found to be having normal EEG.

MRI was normal in 36, abnormal in 26 (including focal cortical dysplasia [FCD]: 8), nonspecific in 24 and not done in three patients [Figure 3].
Figure 3: (a) Unifocal uptake in left frontal region on ictal ethyl cysteinate dimer brain SPECT but missed on magnetic resonance imaging and electroencephalogram (8/F: Refractory epilepsy). (b) Unifocal uptake in the left frontal region on ictal ethyl cysteinate dimer brain SPECT concordant with focal cortical dysplasia in the corresponding magnetic resonance imaging (red arrow) and epileptiform activity on frontal and anterior temporal regions on electroencephalogram (4/F: Recurrent right focal motor seizures)

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Eighty patients had tracer uptake in IEBS, of which 66 patients had uptake in single focus [Table 1] and 14 had uptake in multiple foci [Table 2]. It was localized to the following lobes: frontal–25, fronto-parietal – 5, fronto-temporal – 6, parietal – 21, temporal – 2, temporo-parietal – 3, and occipital – 4. It was lateralized to the left side in 34 patients and right side in 32 patients.
Table 1: Unifocal site on ictal Tc99m-ethyl cysteinate dimer brain single photon emission tomography (n=66)

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Table 2: Multifocal site on ictal Tc99m-ethyl cysteinate dimer brain single photon emission tomography (n=14)

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Among the patients had uptake in single focus, EEG and MRI was negative in 15 and 27 patients, respectively. Unifocal uptake in IEBS was concordant with EEG in 11 (16.67%) patients and MRI in 15 (27.72%). Due to multifocal epileptiform activity on EEG, 6 ictal foci identified on IEBS was missed on EEG. Among the 2 ictal foci that were missed on MRI, one was reported as normal and the other was mislocalized.

The concordance and nonconcordance of the results among the two imaging modalities or EEG assuming surgical site as the gold standard, has been depicted in [Table 3]. Twenty-two patients had surgical removal of the epileptogenic focus, 15 were agreeable with MRI or IEBS. The biopsy from three out of twenty-two patients was reported as FCD and remaining as astrocytosis and gliosis. On follow-up, it was found that among those who had unifocal uptake (n = 16), 2 of them were seizure free, 8 of them were on anti-epileptic drugs, 6 had persistent seizures; and among those who had multifocal uptake (n = 5), 2 were seizure free, 1 each were on antiepileptic drugs, had persistent seizures, respectively and one was lost to follow-up.
Table 3: Inter-modality agreements among ictal Tc99m-ethyl cysteinate dimer brain single photon emission tomography, electroencephalogram, or magnetic resonance imaging for correct localization or lateralization of a seizure focus assuming surgical site as gold standard

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  Discussion Top

In complex cases of epilepsy, gamma camera neuroimaging techniques can actively improve decision-making process. The present study analyzed all the patients with refractory epilepsy undergoing brain SPECT between November 2014 and November 2019. Brain SPECT studies use perfusion RPs that should be capable of crossing the blood brain barrier with desirable characteristics of lipophilicity and smaller molecular size.[7] Those that are labelled with Tc-99 m have superior imaging characteristics. The distribution in the brain tissue is proportional to the blood flow and remains sufficiently long in the brain tissue for adequate time to image the patient (more than 30 min).

At present, Tc99m-ECD and Tc-99 m-hexamethylpropyl eneamine-oxime (HMPAO) are regularly used. Within 2 min after the injection these agents reach optimum level in the brain tissue and stay in the tissue for about 2 h and imaging can be performed during this period of time. Tc-99 m-ECD has a higher target-to-background ratio, because there is fast clearance from the extracerebral regions. It also has reasonable in vitro stability for up to 8 h, which is optimal for ictal SPECT studies, and therefore, it was used in the current study.

Terence et.al. demonstrated that Tc99m ECD had higher specificity and sensitivity in localizing seizures in refractory epilepsy due to its short injection latency than with unstabilised 99 mTc-HMPAO.[8]

In the subset of patients where the ictal foci are localized, IEBS serves as an accurate roadmap for surgical management, which is notably effective. However, the diagnostic challenge is accurate delineation of the epileptogenic focus, as a result of which only a few ultimately undergo surgery.

In the past, cortical, scalp and depth EEG were utilized for the purpose of localization of epileptogenic focus. However, it has been noted that, the accuracy of scalp EEG is compromised due to dependency on low spatial resolution and cortical surface effects. This can result in mislocalization of epileptogenic foci. In addition, spatial sampling area is limited in cortical EEG and only those regions that are accessible by the electrode placed can be assessed. Although signals from deeper structures are detected by depth EEG, it can cause surgical complications as it is an invasive procedure.[9]

Various noninvasive neuroimaging methods, such as SPECT and MRI, have changed evaluation of epileptic patients presurgically. MRI may be considered for the assessment of patients with new-onset seizure in an outpatient setting when we want to look for an underlying structural cause.[10] However, only SPECT has the ability to image functional changes in the blood flow that are associated with seizures. It is used to assess the pathology when neurological symptoms may not be detectable by structural neuroimaging results.[11] Although functional MRI could also be used for this purpose, it may not be practical in cases where there is significant patient movement during seizures. This problem is not a limitation in SPECT imaging due to its optimal timing and technique.

The blood flow in the cerebrum changes rapidly, depending on the origin, type and mode of propagation of the seizure. Therefore, the radiotracer injection should be administered early during the seizure to capture the changes in the blood flow. In our study, we followed the protocol of injection of the radiotracer (within 30 s of the seizure onset). In order to correctly interpret the SPECT images, it is important to know the exact time of injection and duration of the seizure. Delayed injection of radiotracer shows variability in the pattern of blood flow as the seizure evolves along with variation in the pattern of propagation of the seizure leading to secondary generalisation.

During the ictal phase, an increase of up to 300% is noted in the blood flow in the epileptic region which is observed as a focus of hyperperfusion on ictal SPECT.[10] The focal perfusion abnormalities on SPECT is concordant with other noninvasive investigations in 95% of the cases.[12],[13] Ictal SPECT can correctly localize the epileptogenic focus in 70%–90% of cases with unilateral temporal lobe epilepsy.[14],[15] The sensitivity of ictal SPECT (70%–90%) has also been reported to be greater than that of interictal SPECT.[16] In our study, there were 80/89 (≈90%) scans showing tracer uptake in irritable bowel syndrome.

The greatest challenge is accurate localization with a single modality, but with multimodal imaging, identification of epileptogenic focus is increased. 8/22 (36.36%) of them picked up by IEBS were either missed on MRI or EEG. In a study done by John et.al., it was found that IEBS can be used in presurgical evaluation of patients with refractory focal epilepsy who have MRI that is normal or discordant with clinical and EEG data.[17] SPECT can reveal focal perfusion abnormalities concordant with other noninvasive presurgical examinations in up to 95% of patients. In our study, we found that IEBS, MRI, and EEG were contributing to detecting epileptogenic focus in 19/22 of them (86.36%).

Limitations of the study

  • Single center retrospective study
  • Biopsy confirmation was not possible in all patients
  • Small sample size.

  Conclusion Top

The diagnostic localization of the epileptogenic focus is limited when only MRI and EEG are utilized. In patients with noncontributory EEG and MRI, IEBS is a useful modality for diagnosis. Hence, IEBS, MRI, and EEG are complementary to each other.

Research quality and ethics statement

Every author of this manuscript affirm that this scientific study is in compliance with prescribed reporting guidelines laid down by the EQUATOR Network. The authors endorse that this study required Institutional Review Board review, and hence, former approval was attained-IRB Min. No. 14096 (Retro) dated 30.06.2021. We also affirm that we did not plagiarize the contents of this manuscript and have made a Plagiarism Check.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2], [Table 3]


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