Breath-Hold-Triggered BOLD fMRI in Drug-Resistant Nonlesional Focal Epilepsy-A Pilot Study

Abstract

Purpose: Individuals with drug-resistant epilepsy may benefit from epilepsy surgery. In nonlesional cases, where no epileptogenic lesion can be detected on structural magnetic resonance imaging, multimodal neuroimaging studies are required. Breath-hold-triggered BOLD fMRI (bh-fMRI) was developed to measure cerebrovascular reactivity in stroke or angiopathy and highlights regional network dysfunction by visualizing focal impaired flow increase after vasodilatory stimulus. This regional dysfunction may correlate with the epileptogenic zone. In this prospective single-center single-blind pilot study, we aimed to establish the feasibility and safety of bh-fMRI in individuals with drug-resistant non-lesional focal epilepsy undergoing presurgical evaluation.

Methods: In this prospective study, 10 consecutive individuals undergoing presurgical evaluation for drug-resistant focal epilepsy were recruited after case review at a multidisciplinary patient management conference. Electroclinical findings and results of other neuroimaging were used to establish the epileptogenic zone hypothesis. To calculate significant differences in cerebrovascular reactivity in comparison to the normal population, bh-fMRIs of 16 healthy volunteers were analyzed. The relative flow change of each volume of interest (VOI) of the atlas was then calculated compared to the flow change of the whole brain resulting in an atlas of normal cerebral reactivity. Consequently, the mean flow change of every VOI of each patient was tested against the healthy volunteers group. Areas with significant impairment of cerebrovascular reactivity had decreased flow change and were compared to the epileptogenic zone localization hypothesis in a single-blind design.

Results: Acquisition of bh-fMRI was feasible in 9/10 cases, with one patient excluded due to noncompliance with breathing maneuvers. No adverse events were observed, and breath-hold for intermittent hypercapnia was well tolerated. On blinded review, we observed full or partial concordance of the local network dysfunction seen on bh-fMRI with the electroclinical hypothesis in 6/9 cases, including cases with extratemporal lobe epilepsy and those with nonlocalizing 18F-fluorodeoxyglucose positron emission tomography (FDG-PET).

Conclusion: This represents the first report of bh-fMRI in individuals with epilepsy undergoing presurgical evaluation. We found bh-fMRI to be feasible and safe, with a promising agreement to electroclinical findings. Thus, bh-fMRI may represent a potential modality in the presurgical evaluation of epilepsy. Further studies are needed to establish clinical utility.

Keywords: Breath-hold; Cerebrovascular reactivity; Epilepsy surgery; Neuroimaging; Presurgical evaluation.

Fig. 1

Exemplary normalized cerebrovascular reactivity (CVR) maps, shown as twelve representative axial slices for each study participant. a Participant 8. b Participant 6. Images are color-coded to represent the relative change in BOLD fMRI signal after breath-hold maneuvers, with impaired cerebrovascular reactivity shown in red. The color scale representing cerebrovascular reactivity is shown in the plot legend. Regions of interest are labelled (arrows)

Fig. 2

a Cerebellar signal curves during the 7 breath-hold periods (see color code). Note that the stimulus-invoked signal increase occurs well after the breath-hold period: The curve maximum occurs four periods (12 s) after the end of the breath-hold period (shaded red area). b Mean curves of two anatomic labeling atlas volumes-of-interest, the superior temporal (red) and superior temporal pole (blue) regions. Note the relative signal decrease in the left superior temporal regions (light red, light blue) in a patient with left temporal lobe epilepsy (participant 1)

Fig. 3

a FDG-PET/CT of participant 1, axial view. Statistical comparison demonstrated hypometabolism in the left temporal pole (−12%, arrow), left orbitofrontal cortex (−9%) and left insula (−5%). b FDG-PET/MRI of participant 7 demonstrating focal hypometabolism of the right lateral inferior and middle temporal gyrus (arrow), coronal view