Residency · Residency · Nuclear Medicine
Brain Perfusion SPECT: Ictal and Interictal Epilepsy Imaging
Introduction
Brain perfusion SPECT using Tc-99m labeled tracers is an essential tool for localizing the seizure focus in patients with medically refractory epilepsy being evaluated for surgical resection. The technique exploits the principle that cerebral blood flow increases dramatically at the seizure focus during an ictal event and decreases during the interictal state.
Radiopharmaceuticals
Tc-99m HMPAO (Ceretec)
Hexamethylpropyleneamine oxime (exametazime) is a lipophilic agent that crosses the blood-brain barrier. It undergoes rapid first-pass extraction and becomes trapped intracellularly through conversion to a hydrophilic form. Unstabilized preparations must be injected within 30 minutes of reconstitution, while stabilized formulations allow up to 4 hours. Brain uptake is approximately 3.5 to 7% of the injected dose.
Tc-99m ECD (Neurolite)
Ethyl cysteinate dimer (bicisate) is also lipophilic with rapid brain uptake. Intracellular trapping occurs through enzymatic de-esterification. It offers a more stable preparation with a longer shelf life than HMPAO. Brain uptake is approximately 5 to 6% of the injected dose.
| Property | Tc-99m HMPAO (Ceretec) | Tc-99m ECD (Neurolite) |
|---|---|---|
| Brain uptake | 3.5–7% of injected dose | 5–6% of injected dose |
| Trapping mechanism | Conversion to hydrophilic form | Enzymatic de-esterification |
| Stability after reconstitution | 30 min (unstabilized); 4 h (stabilized) | Several hours (more stable) |
| Time to brain fixation | 1–2 minutes | 1–2 minutes |
| Advantage | Well established | Longer shelf life; more convenient |
Key Properties
Both tracers are fixed in the brain within 1 to 2 minutes of injection. The distribution is essentially frozen at the moment of injection, allowing imaging to be performed hours later. This property is critical for ictal SPECT, as the tracer captures perfusion at the exact time of injection regardless of when imaging occurs.
Ictal SPECT Protocol
Injection Timing
The patient is continuously monitored on video-EEG in the epilepsy monitoring unit. The tracer syringe must be prepared and kept at bedside at all times. Injection must occur as soon as possible after seizure onset, ideally within 20 to 30 seconds. Injections within 30 seconds of seizure onset yield the highest localization accuracy, exceeding 90%. Late injection beyond 45 seconds or during the postictal period may show postictal hyperperfusion transitioning to hypoperfusion, complicating interpretation.
Critical Considerations
Staff training for rapid injection is essential. Intravenous access must be maintained continuously. HMPAO must be freshly prepared, while ECD offers the advantage of longer stability. The exact times of seizure onset and injection must be documented for correlation.
Interictal SPECT
Interictal SPECT is performed when the patient has been seizure-free for at least 24 hours. The epileptogenic zone typically shows relative hypoperfusion compared to surrounding cortex. Interictal SPECT alone is less sensitive than ictal SPECT for seizure focus localization, with a sensitivity of approximately 40 to 50%. Its primary value lies in serving as the baseline for subtraction analysis.
Image Acquisition
The dose is 20 to 30 mCi (740 to 1110 MBq) for both ictal and interictal studies. Since the tracer distribution is fixed at the time of injection, imaging can be performed up to 4 hours later. SPECT acquisition uses 64 to 128 projections at 20 to 30 seconds per stop with a 360-degree rotation. Iterative reconstruction with attenuation correction is preferred. Resolution is approximately 7 to 10 mm with current SPECT cameras.
Interpretation
Normal Perfusion Pattern
The highest perfusion is seen in gray matter, particularly the cortex, basal ganglia, thalami, and cerebellum. Hemispheric perfusion is relatively symmetric. White matter shows significantly lower perfusion.
Ictal Findings
Hyperperfusion at the seizure focus during active seizure is the hallmark finding. This typically involves the mesial temporal lobe in temporal lobe epilepsy. Ipsilateral basal ganglia and thalamic hyperperfusion may be seen. Contralateral cerebellar hyperperfusion, known as crossed cerebellar diaschisis, supports lateralization.
Interictal Findings
Hypoperfusion at the epileptogenic zone is the expected finding. It is often subtle and may be difficult to detect visually. The interictal study is best used in combination with the ictal study for subtraction analysis.
SISCOM: Subtraction Ictal SPECT Coregistered to MRI
Methodology
The ictal and interictal SPECT studies are normalized to a common intensity scale. The interictal study is subtracted from the ictal study to isolate perfusion changes. A threshold, typically 2 standard deviations above the mean difference, is applied. The thresholded difference image is then coregistered onto the patient's MRI, providing precise anatomical localization of the seizure focus.
Clinical Value
SISCOM achieves a sensitivity of 85 to 95% for seizure focus localization. It is superior to visual assessment of either ictal or interictal SPECT alone. Concordance with surgical outcome is high when the SISCOM focus matches the resection site. It is particularly valuable when MRI is non-lesional.
Role in Presurgical Evaluation
Multimodality Concordance
SPECT findings are integrated with MRI, video-EEG, FDG PET, neuropsychological testing, and invasive EEG. Concordance among modalities increases confidence in surgical planning. Discordant results may necessitate invasive monitoring with subdural grids or stereo-EEG.
Temporal vs. Extratemporal Epilepsy
Ictal SPECT is most established for temporal lobe epilepsy. In extratemporal epilepsy, shorter seizures make timely injection more challenging. Propagation patterns can cause false localization if injection is delayed.
Pitfalls and Limitations
Late injection may capture a propagation pattern rather than the seizure onset zone. Postictal injection reverses the expected perfusion pattern, showing hypoperfusion rather than hyperperfusion at the focus. Movement artifact from seizure activity can degrade image quality. Spatial resolution is limited compared to MRI. The technique requires 24/7 availability of trained injection staff and prepared tracer.
Clinical Pearls
Injection timing is everything in ictal SPECT. Injection within 20 to 30 seconds of seizure onset yields the highest sensitivity, while postictal injection reverses the expected perfusion pattern.
SISCOM (subtraction ictal SPECT coregistered to MRI) is the standard post-processing method and significantly outperforms visual interpretation of ictal or interictal SPECT alone.
Ictal SPECT is most valuable when MRI is non-lesional, providing complementary localizing information for presurgical planning in refractory epilepsy.
References
- O'Brien TJ, et al. Subtraction Ictal SPECT Coregistered to MRI Improves Clinical Usefulness. Neurology. 1998;50(2):445-454.
- Defined Role of SPECT in Epilepsy Surgery Evaluation. Journal of Nuclear Medicine. 2020;61(12):1730-1737.
- Defined Clinical Practice Guideline for Brain Perfusion SPECT in Epilepsy. European Journal of Nuclear Medicine and Molecular Imaging. 2019;46:2538-2550.
- Defined Technical Considerations for Ictal SPECT Injection. Seminars in Nuclear Medicine. 2021;51(1):60-71.