Manjari Murthy, Director of Product Management

Epilepsy is a neurological disorder that affects 4 million people in North America (CDC, Canada.ca), 6 million people in Europe (Linehan et al, 2021), and over 50 million globally (WHO, 2020), and is considered to be one of the leading causes of disability (Linehan et al, 2021). Administration of antiseizure drugs is the first line of treatment; however, these are not always successful: 30-40% of patients are considered to be medically refractory, or unresponsive to two drugs either in isolation or in combination. In these instances, alternative treatments must be considered, many of which require surgery to remove the seizure focus or implant devices to control seizures.

Development of a presurgical plan is complex. The patient must undergo a number of investigations, including neuropsychological and psychosociological testing, electroencephalography (EEG), magnetoencephalography (MEG), magnetic resonance imaging (MRI) and positron emission tomography (PET). The latter two are the principal modalities used to assess structure and function in the brain. MRI provides a 3D anatomical map of soft tissue in the brain, while PET provides information about areas of abnormal activity (function) towards identifying areas that are critical to a presurgical plan, whether it be to remove the origin (focus) of the seizure, map out thermal therapy targets, or identify candidate regions for device implantation. Combining them is a key component of the presurgical planning process. A CT scan is almost always done during a PET scan; it helps to delineate bone anatomy but is only useful insofar as providing information for correction of PET signal that is distorted (attenuated) by bone. However, CT exposes the patient to unnecessary radiation. With this information in mind, in recent years, doctors have turned to a powerful imaging technology to do structural and functional imaging in a safer, most streamlined fashion, and with greater precision: combined PET/MRI.

The many benefits of PET/MRI in presurgical planning for epilepsy have been well documented. Most broadly, conducting the PET and MRI scans simultaneously allows for perfect co-registration of the data from each modality, which can dramatically improve a surgeon’s confidence in their plan. A 2020 paper by Traub-Weidinger and colleagues demonstrated that PET/MR imaging allowed for the identification of areas of abnormal activity in 53% of patients studied, and that it “increased the confidence in the original clinical readings in 33% of […] cases” (Traub-Weidinger et al, 2020). PET/MRI also can help provide critical pieces of the puzzle in cases where information from other modalities are not in agreement. A 2021 study showed that in 60 patients with discordant presurgical workups, hybrid PET/MR significantly altered the care plans in 19/60 cases, in some cases making patients eligible for curative surgery and in others, avoiding surgery which would have had minimal success (Toth et al, 2021).

The data derived from PET/MRI has also been shown to improve surgical outcomes. Lin and colleagues demonstrated that use of quantitative PET/MRI data to identify subtle epileptic foci was associated with improved surgical outcomes in patients with focal cortical dysplasia, the commonest cause of intractable epilepsy (Lin et al 2018). Oldan and colleagues showed that hybrid PET and MRI allowed more epileptic foci to be visualized as targets for resection, increasing the chance that surgery would result in total remission, and that the increased sensitivity that results from the combination of PET and MRI allowed readers to identify lesions of greater significance. They also noted that the increased number of lesions identified could have an important impact on the placement of subdural electrodes for EEG monitoring (Oldan et al, 2018). Relatedly, Zhang and colleagues showed that hybrid PET/MRI-guided iEEG electrode placement successfully identified seizure onset zones in 38/42 cases, in concordance with EEG-identified lesions, and that this agreement was significantly predictive of successful surgical outcome (Zhang et al, 2020).

From a technical perspective, hybrid PET/MR imaging enables MR-driven PET data optimization. For example, MRI allows for partial volume effect correction of the PET image, helping to improve quantitative PET and PET spatial resolution, as well as allowing the user to correct for motion occurring during a scanning session (Zhu and Zhu, 2019). Hybrid imaging also opens the door for dynamic imaging, which tracks the concentration of radiotracer in a patient’s blood in real time during a scan and can be used to get a better idea of activity and uptake. The use of arterial input function to measure dynamic glucose metabolism, either through arterial blood sampling or MR-image derived methods, allows for more accurate assessment of primary and secondary seizure focus activity, both hypo- and hyper-metabolic (Paldino et al, 2017). This makes an even more compelling case for the adoption of PET/MRI as the hybrid structural/functional method of choice.

Finally – and most importantly – PET/MR benefits the patients by helping to streamline care, improving comfort and convenience, which can help to alleviate the stress of multiple hospital visits during an already trying time. Taken together, the benefits of PET/MRI in the epilepsy presurgical planning process make a compelling case for its integration into routine clinical practice when caring for patients with epilepsy, laying clear groundwork for a push towards improved access to this powerful technology.

References

1. Lin, Y. et al. 2018. Quantitative positron emission tomography-guided magnetic resonance imaging postprocessing in magnetic resonance imaging-negative epilepsies. Epilepsia 59(8): 1583-1594
2. Linehan, C. et al. 2021. Exploring the prevalence and profile of epilepsy across Europe using a standard retrospective chart review: Challenges and opportunities. Epilepsia 62(11): 2651-2666
3. Oldan, J.D. et al. 2018. Subsequent experience in hybrid PET-MRI for evaluation of refractory focal onset epilepsy. Seizure 61: 128-134
4. Paldino, M.J. et al. 2017. Comparison of the diagnostic accuracy of PET/MRI to PET/CT-acquired FG brain exams for seizure focus detection: a prospective study. Pediatr Radiol 47(11): 1500-1507
5. Public Health Agency of Canada. 2019. Epilepsy in Canada. https://www.canada.ca/en/public-health/services/publications/diseases-conditions/epilepsy.html
6. Toth, M. et al. 2021. The role of hybrid FDG-PET/MRI on decision-making in presurgical evaluation of drug-resistant epilepsy. BMC Neurol 21:363
7. Traub-Weidinger, T. et al. 2020. Utility of Absolute Quantification in Non-Lesional Extratemporal Lobe Epilepsy Using FDG PET/MR Imaging. Front Neurosci 11(54)
8. US Centers for Disease Control and Prevention. 2020. Epilepsy Data and Statistics. https://www.cdc.gov/epilepsy/data/index.html
9. Zhang M. et al. 2020. Utility of hybrid PET/MRI multiparametric imaging in navigating SEEG placement in refractory epilepsy. Seizure 81: 295-303
10. Zhu, Y., Zhu, X. 2019. MRI-Driven PET Image Optimisation for Neurological Applications. Front Neurosci 13: 782