Evaluating the Safety of Simultaneous Intracranial Electroencephalography and Functional Magnetic Resonance Imaging Acquisition Using a 3 Tesla Magnetic Resonance Imaging Scanner

Background: The unsurpassed sensitivity of intracranial electroencephalography (icEEG) and the growing interest in understanding human brain networks and ongoing activities in health and disease have make the simultaneous icEEG and functional magnetic resonance imaging acquisition (icEEG-fMRI) an attractive investigation tool. However, safety remains a crucial consideration, particularly due to the impact of the specific characteristics of icEEG and MRI technologies that were safe when used separately but may risk health when combined. Using a clinical 3-T scanner with body transmit and head-receive coils, we assessed the safety and feasibility of our icEEG-fMRI protocol. Methods: Using platinum and platinum-iridium grid and depth electrodes implanted in a custom-made acrylic-gel phantom, we assessed safety by focusing on three factors. First, we measured radio frequency (RF)-induced heating of the electrodes during fast spin echo (FSE, as a control) and the three sequences in our icEEG-fMRI protocol. Heating was evaluated with electrodes placed orthogonal or parallel to the static magnetic field. Using the configuration with the greatest heating observed, we then measured the total heating induced in our protocol, which is a continuous 70-min icEEG-fMRI session comprising localizer, echo-planar imaging (EPI), and magnetization-prepared rapid gradient-echo sequences. Second, we measured the gradient switching-induced voltage using configurations mimicking electrode implantation in the frontal and temporal lobes. Third, we assessed the gradient switching-induced electrode movement by direct visual detection and image analyses. Results: On average, RF-induced local heating on the icEEG electrode contacts tested were greater in the orthogonal than parallel configuration, with a maximum increase of 0.2°C during EPI and 1.9°C during FSE. The total local heating was below the 1°C safety limit across all contacts tested during the 70-min icEEG-fMRI session. The induced voltage was within the 100-mV safety limit regardless of the configuration. No gradient switching-induced electrode displacement was observed. Conclusion: We provide evidence that the additional health risks associated with heating, neuronal stimulation, or device movement are low when acquiring fMRI at 3 T in the presence of clinical icEEG electrodes under the conditions reported in this study. High specific absorption ratio sequences such as FSE should be avoided to prevent potential inadvertent tissue heating

An Exploratory Trial of EPI-589 in Amyotrophic Lateral Sclerosis (EPIC-ALS) : Protocol for a Multicenter, Open-Labeled, 24-Week, Single-Group Study

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, with its currently approved drugs, including riluzole and edaravone, showing limited therapeutic effects. Therefore, safe and effective drugs are urgently necessary. EPI-589 is an orally available, small-molecule, novel redox-active agent characterized by highly potent protective effects against oxidative stress with high blood-brain barrier permeability. Given the apparent oxidative stress and mitochondrial dysfunction involvement in the pathogenesis of ALS, EPI-589 may hold promise as a therapeutic agent. Objective: This protocol aims to describe the design and rationale for the EPI-589 Early Phase 2 Investigator-Initiated Clinical Trial for ALS (EPIC-ALS). Methods: EPIC-ALS is an explorative, open-labeled, single-arm trial that evaluates the safety and tolerability of EPI-589 in patients with ALS. This trial consists of 12-week run-in, 24-week treatment, and 4-week follow-up periods. Patients will receive 500 mg of EPI-589 3 times daily over the 24-week treatment period. Clinical assessments include the mean monthly change of Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised total score. The biomarkers are selected to analyze the effect on oxidative stress and neuronal damage. The plasma biomarkers are 8-hydroxy-2′-deoxyguanosine (8-OHdG), 3-nitrotyrosine (3-NT), neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (pNfH), homocysteine, and creatinine. The cerebrospinal fluid biomarkers are 8-OHdG, 3-NT, NfL, pNfH, and ornithine. The magnetic resonance biomarkers are fractional anisotropy in the corticospinal tract and N-acetylaspartate in the primary motor area. Results: This trial began data collection in September 2021 and is expected to be completed in October 2023. Conclusions: This study can provide useful data to understand the characteristics of EPI-589

Multiple blood flow measurements before and after carotid artery stenting via phase-contrast magnetic resonance imaging: An observational study.

After carotid artery stenting, the procurement of information about blood flow redistribution among brain-feeding arteries and its time trend is essential to understanding a patient's physiological background and to determine their care regimen. Cerebral blood flow has been measured twice following carotid artery stenting in few previous studies, with some discrepancies in the results. The purpose of this study was to measure cerebral blood flow at multiple time points after carotid artery stenting, and to elucidate the time trend of cerebral blood flow and redistribution among arteries. Blood flow rates in 11 subjects were measured preoperatively, at one day, one week, and about three months, respectively after carotid artery stenting by using phase-contrast magnetic resonance imaging. The target vessels were the bilateral internal carotid arteries, the basilar artery, and the bilateral middle cerebral arteries. Lumen was semi-automatically defined using an algorithm utilizing pulsatility. The results showed that blood flow rates in the stented internal carotid artery and the ipsilateral middle cerebral artery increased following carotid artery stenting. Blood flow rates in the contralateral internal carotid artery and the basilar artery gradually declined, and they were lower than the preoperative values at three months after stenting. The sum of blood flow rates of the bilateral internal carotid arteries and the basilar artery increased after carotid artery stenting, and then decreased over the next three months. There was no significant change in the blood flow rate in the contralateral middle cerebral artery. From these results, it was concluded that redistribution among the bilateral internal carotid arteries and the basilar artery occurs after carotid artery stenting, and that it takes months thereafter to reach another equilibrium

Prediction and Visualization of Non-Enhancing Tumor in Glioblastoma via T1w/T2w-Ratio Map

One of the challenges in glioblastoma (GBM) imaging is to visualize non-enhancing tumor (NET) lesions. The ratio of T1- and T2-weighted images (rT1/T2) is reported as a helpful imaging surrogate of microstructures of the brain. This research study investigated the possibility of using rT1/T2 as a surrogate for the T1- and T2-relaxation time of GBM to visualize NET effectively. The data of thirty-four histologically confirmed GBM patients whose T1-, T2- and contrast-enhanced T1-weighted MRI and 11C-methionine positron emission tomography (Met-PET) were available were collected for analysis. Two of them also underwent MR relaxometry with rT1/T2 reconstructed for all cases. Met-PET was used as ground truth with T2-FLAIR hyperintense lesion, with >1.5 in tumor-to-normal tissue ratio being NET. rT1/T2 values were compared with MR relaxometry and Met-PET. rT1/T2 values significantly correlated with both T1- and T2-relaxation times in a logarithmic manner (p < 0.05 for both cases). The distributions of rT1/T2 from Met-PET high and low T2-FLAIR hyperintense lesions were different and a novel metric named Likeliness of Methionine PET high (LMPH) deriving from rT1/T2 was statistically significant for detecting Met-PET high T2-FLAIR hyperintense lesions (mean AUC = 0.556 ± 0.117; p = 0.01). In conclusion, this research study supported the hypothesis that rT1/T2 could be a promising imaging marker for NET identification

Subjects' demographic data.

<p>Subjects' demographic data.</p

Imaging plane for blood flow rate measurement in the bilateral internal carotid arteries and the basilar artery.

<p>The plane is set as close to perpendicular as possible to these three arteries using the lateral view of the maximum intensity projection image of a three-dimensional magnetic resonance angiograph. Thus, the blood flow rates were measured in the presellar or posterior vertical segment of the cavernous portion of the internal carotid artery and basilar artery. The arteries in these anatomical locations run in a fairly straight manner and have low turbulence.</p

Flow rates of the stented internal carotid artery (solid line) and contralateral internal carotid artery (dotted line).

<p>Horizontal bars and boxes represent mean and mean +/- standard deviation, respectively. Compared to preoperative values, the flow rates of the stented internal carotid artery after carotid artery stenting (CAS) are significantly larger. Compared to preoperative values, the flow rate of the contralateral carotid artery at 3 months after CAS is significantly smaller.</p

Sum of flow rates of the bilateral internal carotid arteries (ICAs) and the basilar artery.

<p>The sum increases after CAS, then decreases over the next 3 months.</p