Functional Magnetic Resonance Imaging for Preoperative Planning in Brain Tumour Surgery.

BACKGROUND: Functional magnetic resonance imaging (fMRI) is being increasingly used for the preoperative evaluation of patients with brain tumours. METHODS: The study is a retrospective chart review investigating the use of clinical fMRI from 2002 through 2013 in the preoperative evaluation of brain tumour patients. Baseline demographic and clinical data were collected. The specific fMRI protocols used for each patient were recorded. RESULTS: Sixty patients were identified over the 12-year period. The tumour types most commonly investigated were high-grade glioma (World Health Organization grade III or IV), low-grade glioma (World Health Organization grade II), and meningioma. Most common presenting symptoms were seizures (69.6%), language deficits (23.2%), and headache (19.6%). There was a predominance of left hemispheric lesions investigated with fMRI (76.8% vs 23.2% for right). The most commonly involved lobes were frontal (64.3%), temporal (33.9%), parietal (21.4%), and insular (7.1%). The most common fMRI paradigms were language (83.9%), motor (75.0%), sensory (16.1%), and memory (10.7%). The majority of patients ultimately underwent a craniotomy (75.0%), whereas smaller groups underwent stereotactic biopsy (8.9%) and nonsurgical management (16.1%). Time from request for fMRI to actual fMRI acquisition was 3.1±2.3 weeks. Time from fMRI acquisition to intervention was 4.9±5.5 weeks. CONCLUSIONS: We have characterized patient demographics in a retrospective single-surgeon cohort undergoing preoperative clinical fMRI at a Canadian centre. Our experience suggests an acceptable wait time from scan request to scan completion/analysis and from scan to intervention.

Memory loss and memory reorganization patterns in temporal lobe epilepsy patients undergoing anterior temporal lobe resection, as demonstrated by pre-versus post-operative functional MRI.

This study was aimed to longitudinally assess memory function and whole-brain memory circuit reorganization in patients with temporal lobe epilepsy (TLE) by comparing activation potentials before versus after anterior temporal lobe (ATL) resection. Nineteen patients with medically-intractable TLE (10 left TLE, 9 right TLE) and 15 healthy controls were enrolled. Group analyses were conducted pre- and post-ATL of a novelty complex scene-encoding paradigm comparing areas of blood oxygen-level-dependent (BOLD) signal activations on functional magnetic resonance imaging (fMRI). None of the pre-operative patient characteristics we studied predicted the extent of pre- to post-operative memory loss. On fMRI, extra-temporal activations were detected pre-operatively in both LTLE and RTLE, particularly in the frontal lobe. Greater activations also were noted in the contralateral hippocampus and parahippocampus in both groups. Performing within-subject comparisons, post-op relative to pre-op, pronounced ipsilateral activations were identified in the left parahippocampal gyrus in LTLE, versus the right middle temporal gyrus in RTLE patients. Memory function was impaired pre-operatively but declined after ATL resection in both RTLE and LTLE patients. Post-operative fMRI results indicate possible functional adaptations to ATL loss, primarily occurring within the left parahippocampal gyrus versus right middle temporal gyrus in LTLE versus RTLE patients, respectively.

In Vitro Validation of Intratumoral Modulation Therapy for Glioblastoma.

BACKGROUND/AIM: This proof-of-concept study evaluated the antitumor impact of a direct electrical stimulation technique, termed intratumoral modulation therapy (IMT) on glioblastoma (GBM) cells. MATERIALS AND METHODS: An in vitro IMT model comprised of a calibrated electrode to deliver continuous, low-intensity stimulation within GBM preparations. Viability and apoptosis assays were performed in treated immortalized and patient-derived GBM cells, and post-mitotic neurons. IMT was delivered alone and with temozolomide, or gene silencing of the tumor-promoting chaperone, heat-shock protein 27 (HSP27). RESULTS: GBM cells, but not neurons, exhibited >40% loss of viability, caspase-3 activation and apoptosis with IMT. Cell death was modest with temozolomide alone (30%) but increased significantly with concomitant IMT (70%). HSP27 silencing alone produced 30% viability loss, with significant enhancement of target knockdown and GBM cell death (65%), when combined with IMT. CONCLUSION: These findings warrant further evaluation of IMT as a potential novel therapeutic strategy for GBM.

Physiological monitoring of small animals during magnetic resonance imaging.

Maintaining a stable physiologic state is essential when studying animal models of epilepsy with simultaneous electroencephalograph (EEG) and functional magnetic resonance imaging (fMRI) or EEG and magnetic resonance spectroscopy (MRS). To achieve and maintain such stability in rats in the MRI environment, a minimally invasive but comprehensive system was developed to monitor body temperature, heart rate, blood pressure, blood oxygen saturation and end-tidal CO2 (ETCO2) of expired gas. All physiologic parameters were successfully monitored in Sprague-Dawley rats without interfering with EEG recordings during simultaneous fMRI and MRS studies. Body temperature, heart rate, blood pressure, blood oxygen saturation, and ETCO2, were maintained between 36.5 and 37.5 degrees C, 250-450 beats/min, 136+/-17 mmHg, >90%, and 20-35 mmHg, respectively for 6-8 h under inhalational anesthesia. This set-up could be extended to study in vivo applications in other laboratory animals with only minor modifications.

MRI compatible EEG electrode system for routine use in the epilepsy monitoring unit and intensive care unit.

OBJECTIVE: We report on the development of an electroencephalographic (EEG) recording system that is Magnetic Resonance Imaging (MRI) compatible and can safely be left on the scalp during anatomical imaging or used to obtain simultaneous EEG and metabolic or hemodynamic data using functional imaging techniques such as functional MRI or MR spectroscopy. METHODS: We assembled a versatile EEG recording set-up with medically acceptable materials that contained no ferromagnetic components. It was tested for absence of excess heating and distortion of the image quality in a spherical phantom similar in size to average adult human head in a clinical 1.5 T GE scanner. After testing its safety in four volunteers, 100 consecutive patients from our epilepsy long-term monitoring unit were studied. RESULTS: There was no change in the temperature of the EEG electrode discs during the various anatomical MRI sequences used in our routine clinical studies (maximum temperature change was -0.45 degrees C with average head SAR<==1.6 W/Kg in the selected subjects) nor were there any reported complications in the others. The brain images were not distorted by the susceptibility artifact of the EEG electrodes. CONCLUSIONS: Our MRI compatible EEG set-up allows safe and artifact free brain imaging in 1.5T MR scanner with average SAR<==1.6 W/Kg. This EEG system can be used for EEG recording during anatomical MRI studies as well as functional imaging studies in patients requiring continuous EEG recordings.

Functional MRI study of the primary somatosensory cortex in comatose survivors of cardiac arrest.

It is difficult to assess cerebral function in comatose patients. Because earlier functional neuroimaging studies demonstrate associations between cerebral metabolism and levels of consciousness, fMRI in comatose survivors of cardiac arrest could provide further insight into cerebral function during coma. Using fMRI, cerebral activation to somatosensory stimulation to the palm of the hand was measured in 19 comatose survivors of cardiac arrest and in 10 healthy control subjects and was compared to somatosensory-evoked potential (SSEP) testing of the median nerve. Changes in the blood oxygenation-level dependent signal (BOLD) in the primary somatosensory cortex (S1) contralateral to the stimulated hand were quantified. Clinical outcome was assessed using the Glasgow Outcome Scale (GOS) and the modified Rankin Scale at 3 months post-cardiac arrest. Five out of 19 patients were alive at 3 months. Patients who survived cardiac arrest showed greater BOLD in S1 contralateral to somatosensory stimulation of the hand compared to patients who eventually did not. Greater BOLD was also seen in S1 of patients who retained their SSEP N20 waveforms. There were also positive correlations between BOLD in S1 with both levels of consciousness and measures of outcome at 3 months. In summary, this study demonstrates that BOLD in the S1 contralateral to somatosensory stimulation of the hand varies with clinical measures of the level of consciousness during coma.

Functional MRI characteristics of a focal region of cortical malformation not associated with seizure onset.

Neuroimaging studies have demonstrated that heterotopic tissue of patients with "double cortex" is activated during motor and somatosensory tasks. Activation in patients with malformations of cortical development (MCD) has been variable, likely due to the heterogeneity of the disorder. We examined clinical, electroencephalography (EEG), neuropsychological, and functional MRI findings in a patient with intractable epilepsy secondary to MCD in the left temporal cortex. Invasive EEG monitoring revealed that the dysplastic tissue was not involved in ictal onset of seizures. Functional MRI tests of motion and object processing, memory encoding, and language demonstrated no activation within dysplastic tissue. Hemispheric asymmetries in activation for motion and object processing were evident, favoring the right hemisphere--a pattern not evident in controls. These weaker activations in the patient were present in tissue proximal to the seizure focus. Thus, nonepileptogenic dysplastic tissue may not support cognitive functions, with abnormal processing evident in epileptogenic tissue.

Linear aspects of transformation from interictal epileptic discharges to BOLD fMRI signals in an animal model of occipital epilepsy.

Epileptic disorders manifest with seizures and interictal epileptic discharges (IEDs). The hemodynamic changes that accompany IEDs are poorly understood and may be critical for understanding epileptogenesis. Despite a known linear coupling of the neurovascular elements in normal brain tissues, previous simultaneous electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) studies have shown variable correlations between epileptic discharges and blood oxygenation level-dependent (BOLD) response, partly because most previous studies assumed particular hemodynamic properties in normal brain tissue. The occurrence of IEDs in human subjects is unpredictable. Therefore, an animal model with reproducible stereotyped IEDs was developed by the focal injection of penicillin into the right occipital cortex of rats anesthetized with isoflurane. Simultaneous EEG-fMRI was used to study the hemodynamic changes during IEDs. A hybrid of temporal independent component analysis (ICA) of EEG and spatial ICA of fMRI data was used to correlate BOLD fMRI signals with IEDs. A linear autoregression with exogenous input (ARX) model was used to estimate the hemodynamic impulse response function (HIRF) based on the data from simultaneous EEG-fMRI measurement. Changes in the measured BOLD signal from the right primary visual cortex and bilateral visual association cortices were consistently coupled to IEDs. The linear ARX model was applied here to confirm that a linear transform can be used to study the correlation between BOLD signal and its corresponding neural activity in this animal model of occipital epilepsy.

Oropharyngeal stimulation with air-pulse trains increases swallowing frequency in healthy adults.

This study sought to determine whether air-pulse trains delivered to the peritonsillar area would facilitate swallowing in healthy subjects. Trains of unilateral or bilateral air pulses were delivered to the peritonsillar area via tubing embedded in a dental splint, while swallows were simultaneously identified from their associated laryngeal and respiratory movements. Results from four subjects indicated that oropharyngeal air-pulse stimulation evoked an irrepressible urge to swallow, followed by an overt swallow as verified by laryngeal and respiratory movements. Moreover, air-pulse stimulation was associated with a significant increase in swallowing frequency. Mean latency of swallowing following bilateral stimulation tended to be less than the latency of swallowing following unilateral stimulation. These findings in healthy adults suggest the possibility that oropharyngeal air-pulse stimulation may have clinical utility in dysphagic individuals.

Real-time display of artifact-free electroencephalography during functional magnetic resonance imaging and magnetic resonance spectroscopy in an animal model of epilepsy.

Simultaneous recording of electroencephalogram (EEG) and functional MRI (fMRI) or MR spectroscopy (MRS) can provide further insight into our understanding of the underlying mechanisms of neurologic disorders. Current technology for simultaneous EEG and MRI recording is limited by extensive postacquisition processing of the data. Real-time display of artifact-free EEG recording during fMRI/MRS studies is essential in studies that involve epilepsy to ensure that they address specific EEG features such as epileptic spikes or seizures. By optimizing the EEG recording equipment to maximize the common mode rejection ratio of its amplifiers, a unique EEG system was designed and tested that allowed real-time display of the artifact-free EEG during fMRI/MRS in an animal model of epilepsy. Spike recordings were optimized by suppression of the background EEG activity using fast-acting and easily controlled inhalational anesthesia. Artifact suppression efficiency of 70-100% was achieved following direct subtraction of referentially recorded filtered EEG tracings from active electrodes, which were located in close proximity to each other (over homologous occipital cortices) and a reference electrode. Two independent postacquisition processing tools, independent component analysis and direct subtraction of unfiltered digital EEG data in MATLAB, were used to verify the accuracy of real-time EEG display.