Mapping interictal discharges using intracranial EEG-fMRI to predict postsurgical outcomes.

Various subjective and objective methods have been proposed to identify which interictal epileptiform discharge (IED)-related EEG-fMRI results are more likely to delineate seizure generating tissue in patients with drug-resistant focal epilepsy for the purposes of surgical planning. In this intracranial EEG-fMRI study, we evaluated the utility of these methods to localize clinically relevant regions pre-operatively and compared the extent of resection of these areas to post-operative outcome. Seventy patients admitted for intracranial video-EEG monitoring were recruited for a simultaneous intracranial EEG-fMRI study. For all analyses of blood oxygen level-dependent responses associated with IEDs, an experienced epileptologist identified the most Clinically Relevant brain activation cluster using available clinical information. The Maximum cluster (the cluster with the highest z-score) was also identified for all analyses and assigned to one of three confidence levels (low, medium, or high) based on the difference of the peak z-scores between the Maximum and Second Maximum cluster (the cluster with the second highest peak z-value). The distance was measured and compared between the peak voxel of the aforementioned clusters and the electrode contacts where the interictal discharge and seizure onset were recorded. In patients who subsequently underwent epilepsy surgery, the spatial concordance between the aforementioned clusters and the area of resection was determined and compared to post-operative outcome. We evaluated 106 different IEDs in 70 patients. Both subjective (identification of the Clinically Relevant cluster) and objective (Maximum cluster much more significant than the second maximum cluster) methods of culling non-localizing EEG-fMRI activation maps increased the spatial concordance between these clusters and the corresponding IED or seizure onset zone contacts. However, only the objective methods of identifying medium and high confidence maps resulted in a significant association between resection of the peak voxel of the Maximum cluster and post-operative outcome. Resection of this area was associated with good post-operative outcomes but was not sufficient for seizure freedom. On the other hand, we found that failure to resect the medium and high confidence Maximum clusters was associated with a poor post-surgical outcome (negative predictive value = 1.0, sensitivity = 1.0). Objective methods to identify higher confidence EEG-fMRI results are needed to localize areas necessary for good post-operative outcomes. However, resection of the peak voxel within higher confidence Maximum clusters is not sufficient for good outcomes. Conversely, failure to resect the peak voxel in these clusters is associated with a poor post-surgical outcome.

In situ theranostic platform combining highly localized magnetic fluid hyperthermia, magnetic particle imaging, and thermometry in 3D.

Theranostic platforms, combining diagnostic and therapeutic approaches within one system, have garnered interest in augmenting invasive surgical, chemical, and ionizing interventions. Magnetic particle imaging (MPI) offers a quite recent alternative to established radiation-based diagnostic modalities with its versatile tracer material (superparamagnetic iron oxide nanoparticles, SPION). It also offers a bimodal theranostic framework that can combine tomographic imaging with therapeutic techniques using the very same SPION. Methods: We show the interleaved combination of MPI-based imaging, therapy (highly localized magnetic fluid hyperthermia (MFH)) and therapy safety control (MPI-based thermometry) within one theranostic platform in all three spatial dimensions using a commercial MPI system and a custom-made heating insert. The heating characteristics as well as theranostic applications of the platform were demonstrated by various phantom experiments using commercial SPION. Results: We have shown the feasibility of an MPI-MFH-based theranostic platform by demonstrating high spatial control of the therapeutic target, adequate MPI-based thermometry, and successful in situ interleaved MPI-MFH application. Conclusions: MPI-MFH-based theranostic platforms serve as valuable tools that enable the synergistic integration of diagnostic and therapeutic approaches. The transition into in vivo studies will be essential to further validate their potential, and it holds promising prospects for future advancements.

Topography-Related EEG-fMRI in Surgically Confirmed Epileptic Foci: A Comparison to Spike-Related EEG-fMRI in Clinical Practice.

EEG-fMRI has gained increasing importance in epilepsy pre-surgical diagnosis. However, 40-70% of EEG-fMRI recordings in patients lack interictal epileptiform discharges (IEDs) during the scan, which could be overcome by detecting matching topography maps. We tried to validate this method in clinical settings taking various electroclinical factors into consideration. Eleven patients who had undergone EEG-fMRI during pre-surgical evaluation for drug-resistant epilepsy and who had had clinical long-term video-EEG were studied. Spike-related blood oxygen level-dependent (BOLD) maps were created using IEDs occurring during the EEG-fMRI scan. Separate maps were then generated from IEDs marked on the clinical long-term EEG recordings, which were averaged to produce topographical IED maps and correlated with the EEGs recorded inside the scanner yielding a correlation coefficient time course. Epileptogenic zones were defined by an expert panel during pre-surgical evaluation and validated by an epilepsy surgery resulting in a good outcome. Both techniques' performance was evaluated according to factors including arousal during IED recording, IED topography and lateralization, lesion type, and localization. Topography-related EEG-fMRI yielded more specific results compared to the spike-related method. Superficial lesion location and ipsilateral IED seem to result in a higher concordance of BOLD maps. The polarity of BOLD responses may be lesion-dependent, and both positive and negative BOLD changes may be associated with the irritative zone. Topography-related EEG-fMRI may show improved specificity especially for superficial lesions producing ipsilateral spikes. This method can be used as an alternative either in the absence of spikes during the simultaneous EEG-fMRI acquisition or to sharpen a diffusely activated BOLD-map.

Comparison of Left Atrial Measurements Using 2- and 3-Dimensional Transesophageal Echocardiography.

OBJECTIVES: To assess the correlation between left atrial measurements using 2- and 3-dimensional transesophageal echocardiography. DESIGN: Prospective, observational study. SETTING: Single, tertiary care, academic medical center. PARTICIPANTS: The study comprised 63 consecutive patients undergoing cardiac surgery with cardiopulmonary bypass and intraoperative transesophageal echocardiography. INTERVENTIONS: In addition to the standard comprehensive intraoperative transesophageal examination, study images were obtained by designated anesthesiologists from the study team. MEASUREMENTS AND MAIN RESULTS: The 2-dimensional transesophageal echocardiography views included 4-chamber, 2-chamber, aortic valve short axis, and aortic valve long axis. For the 3-dimensional images, full-volume (90 × 90) data sets were acquired from 4-chamber and aortic valve short-axis views over 4 beats with apnea. Left atrial height, mediolateral length, anteroposterior length, and area were measured in 2- and 3-dimensional images. Left atrial length in the short- and long-axis views of the aortic valve also were measured in 2- and 3-dimensional images. Results indicate that for all patients in this study, the 2- and 3-dimensional measurements correlate well and the 2 observers were in agreement with each other. CONCLUSIONS: Two- and 3-dimensional measurements of the left atrium correlated well. Measurements made using 3-dimensional transesophageal echocardiography were subject to similar limitations as those made using 2-dimensional echocardiography. The benefits of 3-dimensional transesophageal echocardiography and multiplanar reconstruction could be expanded by improvements in ultrasound technology and software.

The identification of distinct high-frequency oscillations during spikes delineates the seizure onset zone better than high-frequency spectral power changes.

OBJECTIVE: Interictal high-frequency oscillations (HFOs, 80-500Hz) can predict the seizure onset zone (SOZ), but visual detection of HFOs is time consuming. Time-frequency analysis can reveal large high-frequency (HF) power changes (80-500Hz) associated with inter-ictal spikes. The present study determines how well the rate of HFOs and spike-related HF power changes were co-localized with SOZ. METHODS: We analyzed 583 channels (68 in the SOZ) sampled from 14 patients who underwent intracranial EEG recording. We determined if the rate of visually-marked HFOs and spike-related HF power changes differed between SOZ and non-SOZ. RESULTS: Significantly higher rates of HFOs were found in SOZ. The degree of spike-related HF power augmentation failed to differ between SOZ and non-SOZ, whereas that of post-spike HF power attenuation was significantly more severe in SOZ compared to in non-SOZ. Regions showing HFOs and large spike-related HF-changes showed a partial overlap in distribution in 7/14 patients. CONCLUSIONS: Strong HF augmentation during spikes and high HFO rates occurred over different brain locations. The rate of HFOs showed the best performance in identifying SOZ. Post-spike HF power attenuation may represent increased inhibition in these channels and should be investigated further. SIGNIFICANCE: Strong HF power changes during spikes and HFOs per se seem to reflect distinct phenomena.

High frequency oscillations mirror disease activity in patients with focal cortical dysplasia.

PURPOSE: The study analyzes the occurrence of high frequency oscillations in different types of focal cortical dysplasia in 22 patients with refractory epilepsy. High frequency oscillations are biomarkers for epileptic tissue, but it is unknown whether they can reflect increasingly dysplastic tissue changes as well as epileptic disease activity. METHODS: High frequency oscillations (80-450 Hz) were visually marked by two independent reviewers in all channels of intracranial implanted grid, strips, and depth electrodes in patients with focal cortical dysplasia and refractory epilepsy. Rates of high frequency oscillations in patients with pathologically confirmed focal cortical dysplasia of Palmini type 1a and b were compared with those in type 2a and b. KEY FINDINGS: Patients with focal cortical dysplasia type 2 had significantly more seizures than those with type 1 (p < 0.001). Rates of high frequency oscillations were significantly higher in patients with focal cortical dysplasia type 2 versus type 1 (p < 0.001). In addition, it could be confirmed that rates of high frequency oscillations were significantly higher in presumed epileptogenic areas than outside (p < 0.001). SIGNIFICANCE: Activity of high frequency oscillations mirrors the higher epileptogenicity of focal cortical dysplasia type 2 lesions compared to type 1 lesions. Therefore, rates of high frequency oscillations can reflect disease activity of a lesion. This has implications for the use of high frequency oscillations as biomarkers for epileptogenic areas, because a detailed analysis of their rates may be necessary to use high frequency oscillations as a predictive tool in epilepsy surgery.

Independent component analysis reveals dynamic ictal BOLD responses in EEG-fMRI data from focal epilepsy patients.

INTRODUCTION: Seizures occur rarely during EEG-fMRI acquisitions of epilepsy patients, but can potentially offer a better estimation of the epileptogenic zone than interictal activity. Independent component analysis (ICA) is a data-driven method that imposes minimal constraints on the hemodynamic response function (HRF). In particular, the investigation of HRFs with clear peaks, but varying latency, may be used to differentiate the ictal focus from propagated activity. METHODS: ICA was applied on ictal EEG-fMRI data from 15 patients. Components related to seizures were identified by fitting an HRF to the component time courses at the time of the ictal EEG events. HRFs with a clear peak were used to derive maps of significant BOLD responses and their associated peak delay. The results were then compared with those obtained from a general linear model (GLM) method. Concordance with the presumed epileptogenic focus was also assessed. RESULTS: The ICA maps were significantly correlated with the GLM maps for each patient (Spearman's test, p<0.05). The ictal BOLD responses identified by ICA always included the presumed epileptogenic zone, but were also more widespread, accounting for 20.3% of the brain volume on average. The method provided a classification of the components as a function of peak delay. BOLD response clusters associated with early HRF peaks were concordant with the suspected epileptogenic focus, while subsequent HRF peaks may correspond to ictal propagation. CONCLUSION: ICA applied to EEG-fMRI can detect areas of significant BOLD response to ictal events without having to predefine an HRF. By estimating the HRF peak time in each identified region, the method could also potentially provide a dynamic analysis of ictal BOLD responses, distinguishing onset from propagated activity.

High frequency oscillations in intracranial EEGs mark epileptogenicity rather than lesion type.

High frequency oscillations (HFOs) called ripples (80-250 Hz) and fast ripples (FR, 250-500 Hz) can be recorded from intracerebral EEG macroelectrodes in patients with intractable epilepsy. HFOs occur predominantly in the seizure onset zone (SOZ) but their relationship to the underlying pathology is unknown. It was the aim of this study to investigate whether HFOs are specific to the SOZ or result from pathologically changed tissue, whether or not it is epileptogenic. Patients with different lesion types, namely mesial temporal atrophy (MTA), focal cortical dysplasia (FCD) and nodular heterotopias (NH) were investigated. Intracranial EEG was recorded from depth macroelectrodes with a sampling rate of 2000 Hz. Ripples (80-250 Hz) and Fast Ripples (250-500 Hz) were visually marked in 12 patients: five with MTA, four with FCD and three with NH. Rates of events were statistically compared in channels in four areas: lesional SOZ, non-lesional SOZ, lesional non-SOZ and non-lesional non-SOZ. HFO rates were clearly more linked to the SOZ than to the lesion. They were highest in areas in which lesion and SOZ overlap, but in patients with a SOZ outside the lesion, such as in NHs, HFO rates were clearly higher in the non-lesional SOZ than in the inactive lesions. No specific HFO pattern could be identified for the different lesion types. The findings suggest that HFOs represent a marker for SOZ areas independent of the underlying pathology and that pathologic tissue changes alone do not lead to high rates of HFOs.

APEP-Anesthesiology Preceptorship Enrichment Program: A Curriculum for First and Second Year Medical Students An Early Look.

BACKGROUND: The purpose of this educational innovation was to create a program for first and second year medical students (MS1s and MS2s) that would: (1) Provide students with early clinical exposure to the subspecialty field of anesthesiology, (2) Expose MS1s and MS2s to dedicated anesthesiologists serving as preceptors, (3) Enrich the students' basic science knowledge in a practical way using an integrated curriculum with clinical correlates and (4) Convey an accurate depiction of anesthesiology as a possible career choice. METHODS: The Anesthesiology Preceptorship Enrichment Program (APEP) was designed for MS1s and MS2s as a seven month curriculum for each level, integrated with basic science course content. APEP students shadowed faculty from the Department of Anesthesiology (APEP preceptors). Guided by handouts, preceptors reviewed basic science concepts with clinical correlates. APEP encounters from October 2006-April 2007, October 2007-April 2008, and October 2008-April 2009 were documented and students completed a questionnaire about their experience. RESULTS: After three years, APEP has become a successful program, as evidenced by the increasing numbers of interested incoming students, active students and returning students. According to the end of program questionnaire, 38-68% of the APEP students used the APEP handouts to guide discussions with their preceptor, enhance intra-operative teaching, and/or refer to while studying for basic science course exams. According to the questionnaire, 71-80% of the APEP students were more interested in the field of anesthesiology after participating in APEP, 10-16% were neither more or less interested, and 4-19% were less interested. CONCLUSIONS: Early clinical exposure to anesthesiology with APEP was viewed as a very positive experience, increasing interest in anesthesiology at the MS1 and MS2 level. The APEP handouts were deemed a useful aid for discussion and created opportunities for teaching clinical correlates of basic science knowledge.

Late-onset epilepsy in a surgically-treated Sturge-Weber patient.

Sturge-Weber syndrome is a rare, congenital, neurocutaneous disorder. It can be associated with a variety of symptoms including severe epilepsy. Patients often become symptomatic during childhood and the severity of the epilepsy correlates with the patient's neurological outcome. The patient reported here remained asymptomatic until age 24, when he started to experience migraine accompanied by visual scotoma and hemiparesis. Ten years later, he developed severe, refractory epilepsy, with prolonged postictal neurological deficits and ictal as well as post-ictal headaches. It became increasingly difficult to distinguish between migraines and seizures as both could last for several hours, as demonstrated in the two video EEGs. Both the epilepsy and the migraine may therefore have contributed to the patient's severe, neurological deterioration, probably by accelerating the progressive neuronal damage. Surgery improved the situation, but lesional areas were too extensive for complete removal. Late-onset symptoms in Sturge-Weber syndrome may thus result in a severe course for the disease. Early intervention and surgical treatment options are discussed.