Complementing Epilepsy Imaging by Seizure Imaging
Until today, MRI in epilepsy has focused on neurostructural pathologies causing seizures, whereas the epileptic seizures as such, albeit being the pathognomonic symptoms of epilepsy, have not received any attention. Here, we want to establish functional MR imaging of epileptic seizures by sensitizing our MRI signal and data postprocessing for what is commonly known as transient peri-ictal MRI changes. As epileptic seizures of patients may not directly be observed in the scanner for pragmatic reasons, the idea is to post-hoc visualize microstructural processes anatomically and temporally related to individual seizures, such as peri-ictal blood-brain barrier dysfunction (Rüber, David et al., 2018) or postictal hypoperfusion (Gaxiola-Valdez et al., 2017). First studies in our group have confirmed that peri-ictal blood-brain barrier dysfunction may be measured by means of post-ictal quantitative MRI after ictal injection of Gadolinium and could be visualized peri-focally after elaborate postprocessing on a single-subject level (see figure). The ictal injection of Gadolinum, however, is time-consuming and the medical harmlessness of Gadolinium itself is in the focus of a controversial scientific debate. In collaboration with Professor Tony Stöcker from the Bonn DZNE, an Arterial Spin Labeling MR sequence is being developed which may measure both at the same time: blood-brain barrier permeability and perfusion by means of an endogenous tracer, i.e. without exogenous contrast agent application (and, thus, without the need for a technical-assistant observing the patient to ensure strictly ictal injection of contrast agent).
Modulating the Blood-Brain-Barrier using TMS
Transcranial magnetic stimulation (TMS) is a neurophysiological technique that allows the induction of a current in the brain using a magnetic field. In TMS, a current passes through a coil of copper wire that is held over the subject's head. As the current passes through the coil it generates a magnetic field that can penetrate the subject's scalp and skull, and in turn induce a current in the subject's brain. Repetitive TMS (rTMS) includes trains of multiple stimuli per second. In a recent, study our group has found evidence for the hypothesis that epileptic seizures lead to a dysfunction of the blood-brain barrier (Rüber, David et al., 2018). On the background of the neurophysiological analogy between epileptic seizures and rTMS, we aim to investigate whether rTMS is also capable of modulating the blood-brain barrier. In case rTMS can modulate the blood-brain barrier, it could be applied for targeted drug delivery.
ΔT1 indicating postictal enhancement of gadolinium-based contrast agent in three patient. ΔT1computed by subtracting postictal qT1 from interictal qT1. Higher ΔT1 values, thus, reflect a greater postictal enhancement of contrast agent.
Patient 1: MRI: hippocampal sclerosis, ictal EEG onset: left temporal, presumed seizure onset zone: left mesio-temporal, patient showed focal seizure
Patient 2: MRI: resected cavernoma in left temporal lobe, ictal EEG onset: left temporal, presumed seizure onset zone: left temporal, patient showed focal seizure
Patient 3: MRI: negative, showed ictal EEG onset: right frontal, presumed SOZ: right frontal, patient showed generalized seizure