Evaluation of atlas-based segmentation of hippocampi in healthy humans

Introduction and aim: Region of interest (ROI)-based functional magnetic resonance imaging (fMRI) data analysis relies on extracting signals from a specific area which is presumed to be involved in the brain activity being studied. The hippocampus is of interest in many functional connectivity studies for example in epilepsy as it plays an important role in epileptogenesis. In this context, ROI may be defined using different techniques. Our study aims at evaluating the spatial correspondence of hippocampal ROIs obtained using three brain atlases with hippocampal ROI obtained using an automatic segmentation algorithm dedicated to the hippocampus. Material and methods: High-resolution volumetric T1-weighted MR images of 18 healthy volunteers (five females) were acquired on a 3T scanner. Individual ROIs for both hippocampi of each subject were segmented from the MR images using an automatic hippocampus and amygdala segmentation software called SACHA providing the gold standard ROI for comparison with the atlas-derived results. For each subject, hippocampal ROIs were also obtained using three brain atlases: PickAtlas available as a commonly used software toolbox; automated anatomical labeling (AAL) atlas included as a subset of ROI into PickAtlas toolbox and a frequency-based brain atlas by Hammers et al. The levels of agreement between the SACHA results and those obtained using the atlases were assessed based on quantitative indices measuring volume differences and spatial overlap. The comparison was performed in standard Montreal Neurological Institute space, the registration being obtained with SPM5 (http://www.fil.ion.ucl.ac.uk/spm/). Results: The mean volumetric error across all subjects was 73% for hippocampal ROIs derived from AAL atlas; 20% in case of ROIs derived from the Hammers atlas and 107% for ROIs derived from PickAtlas. The mean false-positive and false-negative classification rates were 60% and 10% respectively for the AAL atlas; 16% and 32% for the Hammers atlas and 6% and 72% for the PickAtlas. Conclusion: Though atlas-based ROI definition may be convenient, the resulting ROIs may be poor representations of the hippocampus in some studies critical to under- or oversampling. Performance of the AAL atlas was inferior to that of the Hammers atlas. Hippocampal ROIs derived from PickAtlas are highly significantly smaller, and this results in the worst performance out of three atlases. It is advisable that the defined ROIs should be verified with knowledge of neuroanatomy before using it for further data analysis

EEG–fMRI mapping of asymmetrical delta activity in a patient with refractory epilepsy is concordant with the epileptogenic region determined by intracranial EEG

We studied a patient with refractory focal epilepsy using continuous EEG-correlated fMRI. Seizures were characterized by head turning to the left and clonic jerking of the left arm, suggesting a right frontal epileptogenic region. Interictal EEG showed occasional runs of independent nonlateralized slow activity in the delta band with right frontocentral dominance and had no lateralizing value. Ictal scalp EEG had no lateralizing value. Ictal scalp EEG suggested right-sided central slow activity preceding some seizures. Structural 3-T MRI showed no abnormality. There was no clear epileptiform abnormality during simultaneous EEG–fMRI. We therefore modeled asymmetrical EEG delta activity at 1–3 Hz near frontocentral electrode positions. Significant blood oxygen level-dependent (BOLD) signal changes in the right superior frontal gyrus correlated with right frontal oscillations at 1–3 Hz but not at 4–7 Hz and with neither of the two frequency bands when derived from contralateral or posterior electrode positions, which served as controls. Motor fMRI activations with a finger-tapping paradigm were asymmetrical: they were more anterior for the left hand compared with the right and were near the aforementioned EEG-correlated signal changes. A right frontocentral perirolandic seizure onset was identified with a subdural grid recording, and electric stimulation of the adjacent contact produced motor responses in the left arm and after discharges. The fMRI localization of the left hand motor and the detected BOLD activation associated with modeled slow activity suggest a role for localization of the epileptogenic region with EEG–fMRI even in the absence of clear interictal discharges

The spatio-temporal mapping of epileptic networks: Combination of EEG–fMRI and EEG source imaging

Simultaneous EEG–fMRI acquisitions in patients with epilepsy often reveal distributed patterns of Blood Oxygen Level Dependant (BOLD) change correlated with epileptiform discharges. We investigated if electrical source imaging (ESI) performed on the interictal epileptiform discharges (IED) acquired during fMRI acquisition could be used to study the dynamics of the networks identified by the BOLD effect, thereby avoiding the limitations of combining results from separate recordings. Nine selected patients (13 IED types identified) with focal epilepsy underwent EEG–fMRI. Statistical analysis was performed using SPM5 to create BOLD maps. ESI was performed on the IED recorded during fMRI acquisition using a realistic head model (SMAC) and a distributed linear inverse solution (LAURA). ESI could not be performed in one case. In 10/12 remaining studies, ESI at IED onset (ESIo) was anatomically close to one BOLD cluster. Interestingly, ESIo was closest to the positive BOLD cluster with maximal statistical significance in only 4/12 cases and closest to negative BOLD responses in 4/12 cases. Very small BOLD clusters could also have clinical relevance in some cases. ESI at later time frame (ESIp) showed propagation to remote sources co-localised with other BOLD clusters in half of cases. In concordant cases, the distance between maxima of ESI and the closest EEG–fMRI cluster was less than 33 mm, in agreement with previous studies. We conclude that simultaneous ESI and EEG–fMRI analysis may be able to distinguish areas of BOLD response related to initiation of IED from propagation areas. This combination provides new opportunities for investigating epileptic networks

Generalized information reuse for optimization under uncertainty with non-sample average estimators

In optimization under uncertainty for engineering design, the behavior of the system outputs due to uncertain inputs needs to be quantified at each optimization iteration, but this can be computationally expensive. Multi-fidelity techniques can significantly reduce the computational cost of Monte Carlo sampling methods for quantifying the effect of uncertain inputs, but existing multi-fidelity techniques in this context apply only to Monte Carlo estimators that can be expressed as a sample average, such as estimators of statistical moments. Information reuse is a particular multi-fidelity method that treats previous optimization iterations as lower-fidelity models. This work generalizes information reuse to be applicable to quantities with non-sample average estimators. The extension makes use of bootstrapping to estimate the error of estimators and the covariance between estimators at different fidelities. Specifically, the horsetail matching metric and quantile function are considered as quantities whose estimators are not sample-averages. In an optimization under uncertainty for an acoustic horn design problem, generalized information reuse demonstrated computational savings of over 60% compared to regular Monte Carlo sampling

Prognostically controlled comparison of dialysis and renal transplantation

Prognostically controlled comparison of dialysis and renal transplantation. Because the comparison of survival in patients with renal failure treated by dialysis and transplantation may be biased by pretreatment prognostic differences in the patients who receive these two therapies, we quantified the pretreatment prognosis of all 430 dialysis and transplant patients who began therapy for end-stage renal disease at two hospitals from 1970 to 1980. Five pretreatment factors had a statistically significant adverse effect on survival: age, duration of diabetes, left ventricular failure, myocardial infarction, and other serious comorbid illness. Dialysis patients had a worse pretreatment prognosis than transplant patients did. When we controlled for these pretreatment differences, the actuarial 5-year patient survivals were 80% for dialysis (D), 79% for cadaver transplantation (CT), and 91% for living donor transplantation (LDT), (P = 0.9 for CT vs. D, and P = 0.05 for LDT vs. D). This similarity in survival with dialysis and cadaver transplantation was quite different from the results obtained when pretreatment prognosis was not controlled; the uncontrolled 5-year patient survivals were 43% for D, 77% for CT, and 89% for LDT (P < 0.001 for CT vs. D, and P < 0.001 for LDT vs. D). Our data suggest that the major factor determining differences in survival with dialysis and renal transplantation is not the relative efficacy of the two treatments but the pretreatment prognostic status of the patients chosen to receive them.Une comparaison contrôlée de façon pronostique entre la dialyse et la transplantation rénale. Puisque la comparaison de la survie des malades en insuffisance rénale traités par dialyse ou par transplantation peut être biaisée par des différences pronostiques pré-thérapeutiques entre les malades qui reçoivent ces deux traitements, nous avons quantifié le pronostic pré-thérapeutique de l'ensemble des 430 malades dialysés et transplantés qui ont commencé le traitement de leur insuffisance rénale dans deux hôpitaux de 1970 à 1980. Cinq facteurs préthérapeutiques possédaient un effet adverse statistiquement significatif sur la survie: l'âge, la durée du diabète, une insuffisance ventriculaire gauche, un infarctus du myocarde, et une autre maladie sérieuse associée. Les dialysés avaient un pronostic pré-thérapeutique plus mauvais que les transplantés. Lorsque nous avons contrôlé ces différences pré-thérapeutiques, la survie actuarielle à 5 ans des malades était de 80% pour la dialyse (D), 79% pour la transplantation cadavérique (CT), et 91% pour la transplantation avec donneur vivant (LDT) (P = 0,9 pour CT contre D, et P = 0,05 pour LDT contre D). Cette similitude de survie en dialyse ou après transplantation cadavérique était très différente des résultats obtenus lorsque le pronostic pré-thérapeutique n'était pas contrôlé; les survies non contrôlées à 5 ans des malades étaient de 43% pour D, 77% pour CT, et 89% pour LDT (P < 0,001 pour CT contre D, et P < 0,001 pour LDT contre D). Nos données suggèrent que le facteur principal déterminant les différences de survie en dialyse ou après transplantation rénale n'est pas l'efficacité relative des deux traitements, mais l'état pronostique pré-thérapeutique des malades choisis pour les recevoir

Phylogenetic analysis of SARS-CoV-2 in Boston highlights the impact of superspreading events

Analysis of 772 complete SARS-CoV-2 genomes from early in the Boston area epidemic revealed numerous introductions of the virus, a small number of which led to most cases. The data revealed two superspreading events. One, in a skilled nursing facility, led to rapid transmission and significant mortality in this vulnerable population but little broader spread, while other introductions into the facility had little effect. The second, at an international business conference, produced sustained community transmission and was exported, resulting in extensive regional, national, and international spread. The two events also differed significantly in the genetic variation they generated, suggesting varying transmission dynamics in superspreading events. Our results show how genomic epidemiology can help understand the link between individual clusters and wider community spread

EEG correlated functional MRI and postoperative outcome in focal epilepsy

Background: The main challenge in assessing patients with epilepsy for resective surgery is localising seizure onset. Frequently, identification of the irritative and seizure onset zones requires invasive EEG. EEG correlated functional MRI (EEG-fMRI) is a novel imaging technique which may provide localising information with regard to these regions. In patients with focal epilepsy, interictal epileptiform discharge (IED) correlated blood oxygen dependent level (BOLD) signal changes were observed in approximately 50% of patients in whom IEDs are recorded. In 70%, these are concordant with expected seizure onset defined by non-invasive electroclinical information. Assessment of clinical validity requires post-surgical outcome studies which have, to date, been limited to case reports of correlation with intracranial EEG. The value of EEG-fMRI was assessed in patients with focal epilepsy who subsequently underwent epilepsy surgery, and IED correlated fMRI signal changes were related to the resection area and clinical outcome. Methods: Simultaneous EEG-fMRI was recorded in 76 patients undergoing presurgical evaluation and the locations of IED correlated preoperative BOLD signal change were compared with the resected area and postoperative outcome. Results: 21 patients had activations with epileptic activity on EEG-fMRI and 10 underwent surgical resection. Seven of 10 patients were seizure free following surgery and the area of maximal BOLD signal change was concordant with resection in six of seven patients. In the remaining three patients, with reduced seizure frequency post-surgically, areas of significant IED correlated BOLD signal change lay outside the resection. 42 of 55 patients who had no IED related activation underwent resection. Conclusion: These results show the potential value of EEG-fMRI in presurgical evaluation