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Diffusion constant of K+ inside Gramicidin A: a comparative study of four computational methods.

The local diffusion constant of K(+) inside the Gramicidin A (GA) channel has been calculated using four computational methods based on molecular dynamics (MD) simulations, specifically: Mean Square Displacement (MSD), Velocity Autocorrelation Function (VACF), Second Fluctuation Dissipation Theorem (SFDT) and analysis of the Generalized Langevin Equation for a Harmonic Oscillator (GLE-HO). All methods were first tested and compared for K(+) in bulk water--all predicted the correct diffusion constant. Inside GA, MSD and VACF methods were found to be unreliable because they are biased by the systematic force exerted by the membrane-channel system on the ion. SFDT and GLE-HO techniques properly unbias the influence of the systematic force on the diffusion properties and predicted a similar diffusion constant of K(+) inside GA, namely, ca. 10 times smaller than in the bulk. It was found that both SFDT and GLE-HO methods require extensive MD sampling on the order of tens of nanoseconds to predict a reliable diffusion constant of K(+) inside GA.

Cations, Monovalent↗

A supervised method for calculating perfusion/diffusion mismatch volume in acute ischemic stroke.

Diffusion and perfusion (MR) imaging modalities identify overlapping but not identical areas of tissue as lesion following a stroke. It is thought that the 'mismatch' between modalities may represent tissue that could be recovered with proper (thrombolytic) treatment. We have designed a tool for semi-automated segmentation of the images and calculation of the mismatch volume. We present results from software phantoms and clinical data. Phantom results show our mismatch volume calculations are unbiased at realistic noise levels. Clinical data show that raters using our tool are consistent, fast (15min per subject) and indistinguishable from an expert using manual segmentation.

Adult↗

Explicit parameterization of sleep EEG transients.

Adaptive time-frequency approximations, implemented via the matching pursuit algorithm, offer description of local signals structures in terms of their time occurrence and width, frequency and amplitude. This allows to construct explicit filters for finding EEG waveforms, known from the visual analysis, in the matching pursuit decomposition of signals. In such a way detectors of relevant structures of both transient and oscillatory nature can be constructed in the space of physically meaningful parameters. This study presents evaluation of changes of power and frequency of sleep spindles and delta waves, related to the depth of the sleep, which were previously assessed in a qualitative way. We confirm quantitatively the decrease of frequencies of sleep spindles and delta waves with the depth of the sleep.

Algorithms↗

Computational tools for modeling electrical activity in cardiac tissue.

Computer models offer many attractive benefits. However, the modeling of cardiac tissue is computationally expensive due to several physical constraints which result in fine spatiotemporal discretization over large spatiotemporal regions. Our laboratory has been actively trying to develop new techniques to make large scale cardiac simulations tractable over the past 15 years. This paper describes the latest modeling software that our group has developed, called Carp (Cardiac arrhythmias research package). It is designed to run in both shared memory and clustered computing environments. Carp aims to be modular and flexible by following a plug-in framework. This allows the latest models and most efficient solvers to be incorporated as well as enabling run-time selection of techniques. Performance results are given for a large-scale simulation which utilized a comprehensive membrane ionic current description.

Action Potentials↗

Three-dimensional analysis of enlarging aneurysms after endovascular abdominal aortic aneurysm repair in the Gore Excluder Pivotal clinical trial.

OBJECTIVE: Recent reports have raised concern about the percentage of enlarging abdominal aortic aneurysms (AAAs) after endovascular repair with the Gore Excluder device. As part of the investigation into this issue, a morphologic analysis was performed on enlarging aneurysms in the Excluder Pivotal clinical trial. METHODS: Computed tomographic scans were evaluated on all patients identified with enlarging aneurysms (5-mm increase by Core laboratory or site) and at least 4 years of follow-up in the Excluder Pivotal clinical trial. Three-dimensional reconstruction, a set of 24 standard morphologic measurements, and analysis of potential enlargement mechanisms were performed. RESULTS: Of 112 trial patients with 4 years of follow-up, 38 AAAs (34%) were identified as enlarging. Data were obtained from 196 computed tomographic scans (the mean interval was 47 months from first to last scan). Of the 158 scans with a prior scan for comparison, 41% demonstrated growth relative to the initial scan by diameter criteria, but 79% demonstrated growth relative to the initial scan by 3-dimensional volume criteria (P < .0001 vs diameter; chi2 analysis). This difference was most evident at early time points: at 1 year, diameter criteria indicated that 8% of these AAAs were enlarging, but 56% were already enlarging by volume criteria. On average, enlargement was detected by volume 18 months before it was detected by diameter (P < .0001), and at a smaller diameter (55 +/- 1 mm vs 60 +/- 1 mm; P < .0001). Only 19% of scans (39% of patients) had apparent endoleaks. Scans with apparent endoleaks demonstrated a greater interval rate of growth as compared with those without apparent endoleak (3.6 +/- 0.8 mm vs 1.9 +/- 0.3 mm [P < .02] by diameter; 23 +/- 4 cm3 vs 11 +/- 1 cm3 [P < .001] by volume). Although the etiology of enlargement may be endotension or device permeability in up to 74% of patients, other potential causes of aneurysm enlargement included neck apposition length less than 15 mm (15 patients; 39%), large aortic diameter relative to device (18%), large iliac diameter (5%), and iliac apposition length less than 15 mm (20%). Multiple potential etiologies of enlargement were present in 53% of AAAs. CONCLUSIONS: The etiology of aneurysm enlargement in the Excluder Pivotal trial is likely multifactorial, including endoleak, inadequate attachment site length, and endotension or device permeability. Even by conservative criteria, a substantial percentage of aneurysm growth with the original device is likely due to material permeability. Three-dimensional volume criteria detected aneurysm enlargement more frequently, at a smaller diameter, and on average 18 months sooner than standard diameter criteria, thus suggesting a role in further investigation of this issue.

Angioplasty↗

A knowledge-driven algorithm for a rapid and automatic extraction of the human cerebral ventricular system from MR neuroimages.

A knowledge-driven algorithm for a rapid, robust, accurate, and automatic extraction of the human cerebral ventricular system from MR neuroimages is proposed. Its novelty is in combination of neuroanatomy, radiological properties, and variability of the ventricular system with image processing techniques. The ventricular system is divided into six 3D regions: bodies and inferior horns of the lateral ventricles, third ventricle, and fourth ventricle. Within each ventricular region, a 2D region of interest (ROI) is defined based on anatomy and variability. Each ventricular region is further subdivided into subregions, and conditions detecting and preventing leakage into the extra-ventricular space are specified for each subregion. The algorithm extracts the ventricular system by (1) processing each ROI (to calculate its local statistics, determine local intensity ranges of cerebrospinal fluid and gray and white matters, set a seed point within the ROI, grow region directionally in 3D, check anti-leakage conditions, and correct growing if leakage occurred) and (2) connecting all unconnected regions grown by relaxing growing conditions. The algorithm was validated qualitatively on 68 and quantitatively on 38 MRI normal and pathological cases (30 clinical, 20 MGH Brain Repository, and 18 MNI BrainWeb data sets). It runs successfully for normal and pathological cases provided that the slice thickness is less than 3.0 mm in axial and less than 2.0 mm in coronal directions, and the data do not have a high inter-slice intensity variability. The algorithm also works satisfactorily in the presence of up to 9% noise and up to 40% RF inhomogeneity for the BrainWeb data. The running time is less than 5 s on a Pentium 4, 2.0 GHz PC. The best overlap metric between the results of a radiology expert and the algorithm is 0.9879 and the worst 0.9527; the mean and standard deviation of the overlap metric are 0.9723 and 0.01087, respectively.

Adolescent↗

Voxel-based relaxometry: a new approach for analysis of T2 relaxometry changes in epilepsy.

The measurement of the T2 relaxation time (T2 relaxometry) had been established as a reliable tool for the assessment of certain conditions such as temporal lobe epilepsy. The standard procedure for analysis of T2 data uses manually drawn regions of interest (ROIs). This approach is limited by its subjective nature and its restricted scope of investigation within selected regions of the brain. In this study, we introduce a voxel-based analysis approach termed voxel-based relaxometry (VBR). Tissue signal changes were assessed in 19 patients with hippocampal sclerosis (HS) and in 38 healthy controls using (i) conventional ROI-based analysis with several bilateral ROIs and also (ii) the VBR method in which the T2 maps are warped to a stereotactic space, smoothed and statistically compared. Conventional ROI analysis identified the expected T2 increase in the sclerotic hippocampus in all HS patients. Furthermore, 13 of the 19 patients displayed a T2 increase in at least one of the other ROIs. The VBR analysis showed a similar pattern of statistically significant areas of increased T2 within the sclerotic hippocampus. In addition, extrahippocampal areas of increased T2 were apparent including the anterior temporal lobe white matter and the parahippocampal gyrus. The results of the VBR analysis are in agreement with the conventional ROI analysis. The VBR analysis has the advantage of providing an even-handed assessment of T2 differences through the brain. We recommend VBR as an alternative means of relaxometry data analysis that provides an objective assessment of differences between subjects.

Adult↗

Optimisation of the 3D MDEFT sequence for anatomical brain imaging: technical implications at 1.5 and 3 T.

An algorithm for the optimisation of 3D Modified Driven Equilibrium Fourier Transform (MDEFT) sequences for T1-weighted anatomical brain imaging is presented. Imaging parameters are optimised for a clinical whole body scanner and a clinical head scanner operating at 1.5 and 3 T, respectively. In vivo studies show that the resulting sequences allow for the whole brain acquisition of anatomical scans with an isotropic resolution of 1 mm and high contrast-to-noise ratio (CNR) in an acceptable scan time of 12 min. Typical problems related to the scanner-specific hardware configurations are discussed in detail, especially the occurrence of flow artefacts in images acquired with head transmit coils and the enhancement of scalp intensities in images acquired with phased array receive coils. It is shown both theoretically and experimentally that these problems can be avoided by using spin tagging and fat saturation.

Adult↗

Dopaminergic effects on electrophysiological and functional MRI measures of human cortical stimulus-response power laws.

Power laws have been widely used to formulate relationships between objective intensity of stimulation and subjective intensity of sensation. We investigated the effects of dopaminergic drug treatment (sulpiride) on the relationship between somatosensory stimulus intensity and cortical response measured electrophysiologically by somatosensory-evoked potentials (SEP) and functional magnetic resonance imaging (fMRI). The intensity of stimulation was related by a simple power law to both electrophysiological and fMRI measures of cortical response, with overlapping confidence intervals for both power law exponents. Sulpiride did not modulate the power law exponent, but significantly attenuated the "gain" of both stimulus-response functions. Using path analysis we decomposed dopaminergic effects on fMRI data into an indirect component (16%), predictable by drug effects on SEP, and a direct component (84%), not explained electrophysiologically. Results indicate that sulpiride has comparable effects on power law parameters estimated from SEP and fMRI, but fMRI has superior sensitivity to detect drug effects on somatosensory cortical recruitment by graded stimulation.

Adult↗

Effect of white matter hyperintensities on cortical cerebral blood volume using perfusion MRI.

White matter hyperintensities (WMHs) are commonly seen on brain magnetic resonance imaging (MRI) scans of elderly individuals, but their functional significance remains controversial. We used perfusion-weighted MRI to determine the impact of WMHs on cortical regional cerebral blood volume (rCBV). We studied 24 elderly stroke patients and 27 control subjects with conventional MRI which included T2-weighted FLAIR coronal slices through whole brain and gadolinium-DTPA (0.2 mmol/kg)-based perfusion MRI (pMRI) with echo planar imaging. Volumes of WMHs, including deep WMHs and periventricular hyperintensities (PVHs), were computed by an automated method after excluding regions of infarction. Partial correlations between WMH and corresponding cortical rCBV were determined after correction for age and atrophy. The relative rCBV of gray matter was higher in control subjects and there was no significant hemispheric asymmetry. When both stroke and control groups were included, there were significant correlations among frontal cortical rCBV and frontal WMHs, temporal cortical rCBV with temporal WMHs, and cortical rCBV with both total deep WMHs and PVHs. Although the trends of correlation still existed when the two groups were analyzed separately, they were not significant. The correlations between cortical rCBV and WMHs in the same lobe were significant for subjects with more severe hyperintensities irrespective of the group. In conclusion, T2-weighted WMHs are associated with reduced rCBV in the cerebral cortex, particularly in individuals with extensive hyperintensities.

Age Factors↗

Correction for intracranial volume in analysis of whole brain atrophy in multiple sclerosis: the proportion vs. residual method.

Two techniques that correct (normalize) regional and whole brain volumes according to head size-the proportion method (tissue-to-intracranial volume ratio) and the residual method (regression-based predicted brain tissue volumes)-are used pervasively in neuroimaging research, but have received little critical evaluation or direct comparison. Using a quantitatively derived MRI data set of patients with multiple sclerosis (n = 18) and age-/sex-matched normal controls (n = 18), we introduced various types of error into estimates of intracranial volume (ICV) and absolute parenchymal volume (APV) to observe how this error affected the final outcome of normalized brain measures and their ability to detect group differences, as computed by a proportion (brain parenchymal fraction [BPF]) and residual method (predicted parenchymal volume [PPV]). The results indicated that systemic error in ICV and APV values considerably affected BPF means based on the proportion method, except with dependent-related systematic APV error, but essentially did not change statistical power associated with group differences in BPF. Random error altered BPF means to a much smaller extent, but was associated with moderate reductions in statistical power. On the other hand, PPV estimates based on the residual method were unaffected by these same ICV and APV errors, except with dependent-related systematic APV error, and were not associated with reductions in statistical power. Our findings suggest that head size correction of brain regions with the residual method generally may provide advantages over the proportion method.

Adult↗

Quantitative analysis of temporal lobe white matter T2 relaxation time in temporal lobe epilepsy.

The objective of this study was to assess temporal lobe white matter (WM) quantitatively using T2 relaxometry in patients with pharmacologically intractable temporal lobe epilepsy (TLE). T2 relaxometry was performed using a dual-echo sequence with 23 contiguous oblique coronal slices in 56 consecutive TLE patients and in 30 healthy subjects. Averages of six slices were chosen to calculate T2 relaxation time in the temporal lobe WM (WM-T2) and the hippocampus (Hippo-T2). Twenty-seven patients had unilateral hippocampal atrophy (HA), and twenty-nine patients had normal hippocampal volumes (NV) on volumetric MRI. Mean WM-T2 was increased ipsilateral to the seizure focus in TLE patients with HA and those with NV (P < 0.001). Contralateral mean WM-T2 was increased in left and right TLE with HA (P < 0.001) and in right TLE with NV (P = 0.001). There was a positive correlation between WM-T2 and Hippo-T2. Individual analysis showed a prolongation of WM-T2 in about 70% of TLE patients with HA and NV. In half of the patients, WM-T2 increase was bilateral and symmetric. However, in 33% of patients with NV and bilateral symmetric increase in Hippo-T2, WM-T2 provided a correct lateralization of the seizure focus. Regardless of the pattern of T2 abnormalities, that is, bilateral symmetric or ipsilateral, the majority of patients with HA became seizure-free after surgery, while those with NV did not have a favorable outcome. In patients with NV, WM-T2 measurement may provide additional lateralizing information compared to Hippo-T2.

Adolescent↗

Visuospatial attention: how to measure effects of infrequent, unattended events in a blocked stimulus design.

This fMRI study investigates the differences between a blocked and event-related analysis in a cued target detection task, the so-called Posner paradigm, using a hybrid design. Validly and invalidly cued trials were presented intermingled in different blocks containing 50%, 75%, or 100% valid trials. Four analyses were conducted: (i) an event-related analysis comparing invalid and valid trials, (ii) a blocked analysis comparing blocks with 50% valid and invalid trials to blocks with 100% valid trials, (iii) a blocked analysis detecting differences between block models when modeled as epochs or chains of events, and (iv) a blocked analysis that modeled blocks as chains of events to scale regressors equally to the event-related analysis. Irrespective of the type of analysis (blocked or event related), significant activation of the right intraparietal sulcus was observed. A larger cluster size was evident in the blocked analysis, which can be attributed to higher efficiency. In addition to this common right parietal activation, the event-related analysis revealed activations in right superior parietal cortex and left intraparietal sulcus. In contrast, the blocked analysis yielded additional activity in the right occipitoparietal junction. No influences of the block model (epoch versus chain of events) were found in regions activated in the blocked or event-related analysis, respectively. In summary, using a hybrid design and both event-related and blocked analysis techniques, we show both sustained and transient neural processes underlying reorienting of visuospatial attention.

Adult↗

ROC-based assessments of 3D cortical surface-matching algorithms.

Algorithms for the semi-automated analysis of brain surfaces have recently received considerable attention, and yet, they rarely receive a rigorous assessment of their performance. We present a method for the quantitative assessment of performance across differing surface analysis algorithms and across various modifications of a single algorithm. The sensitivity and specificity of an algorithm for detecting known deformations added synthetically to the brains being studied are assessed using curves for Receiver Operating Characteristics (ROC). We also present a method for the isolation of sources of variance in MRI data sets that can contribute to degradation in performance of surface-matching algorithms. Isolation of these sources of variance allows determination of whether degradation in performance of surface-matching algorithms derives primarily from errors in registration of brains to a common coordinate space, from errors in placement of the known deformation, or from interindividual or between-group variability in morphology of the cortical surface. We apply these methods to the study of surface-matching algorithms that are based on fluid flow (FF) deformation, geodesic (GD) interpolation, or nearest neighbor (NN) proximity. We show that the performances of surface-matching algorithms depend on the presence of interindividual and between-group variability in the surfaces surrounding the cortical deformation. We also show that, in general, the FF algorithm performs as well as or better than the GD and NN algorithms. The large variance in identifying point correspondences across brain surfaces using the GD and the NN algorithms suggests strongly that these point correspondences are less valid than those determined by the FF algorithm. The GD and NN algorithms, moreover, are both vulnerable to detecting false-positive activations at points of high curvature, particularly along large fissures, cisterns, and cortical sulci.

Algorithms↗

A full-size MRI-compatible keyboard response system.

Two commercially available plastic keyboards were contrasted in the degree to which they interfered with echo planar imaging. One keyboard (GrandTec USA's "Virtually Indestructible Keyboard") caused significantly less temporally variant and invariant signal loss and was integrated into a MRI interface system for recording participants' manual motor responses. The response recording system is safe, accurately records reaction time behavioral data, and does not interfere with functional data collection. Implementing this MRI-compatible keyboard allows the collection of motor responses from complex manual behaviors (i.e., typing) and thus represents a valuable tool for functional MRI (fMRI) studies.

Adult↗

Voxel-based analysis of multiple-system atrophy of cerebellar type: complementary results by combining voxel-based morphometry and voxel-based relaxometry.

Voxel-based relaxometry (VBR) is a novel morphometric method that analyses the relaxation rate R2 derived from multi-echo T2-weighted images on a voxel-by-voxel basis. We used VBR to study the brain morphology of 14 patients suffering from multiple-system atrophy of cerebellar type (MSA-C) and compared the results with those obtained by voxel-based morphometry (VBM) of T1-weighted images. VBR analysis revealed reduction of relaxation rate R2 in the cerebellum and brainstem reflecting infratentorial brain atrophy. The affected regions largely corresponded to those regions in which VBM showed reductions of grey and white matter. In addition, R2 was increased in the putamen, a region in which VBM did not show abnormalities. Our data show that the combination of VBR and VBM provided convergent and complimentary information about the brain morphology of MSA-C.

Atrophy↗

Valid conjunction inference with the minimum statistic.

In logic a conjunction is defined as an AND between truth statements. In neuroimaging, investigators may look for brain areas activated by task A AND by task B, or a conjunction of tasks (Price, C.J., Friston, K.J., 1997. Cognitive conjunction: a new approach to brain activation experiments. NeuroImage 5, 261-270). Friston et al. (Friston, K., Holmes, A., Price, C., Buchel, C., Worsley, K., 1999. Multisubject fMRI studies and conjunction analyses. NeuroImage 10, 85-396) introduced a minimum statistic test for conjunction. We refer to this method as the minimum statistic compared to the global null (MS/GN). The MS/GN is implemented in SPM2 and SPM99 software, and has been widely used as a test of conjunction. However, we assert that it does not have the correct null hypothesis for a test of logical AND, and further, this has led to confusion in the neuroimaging community. In this paper, we define a conjunction and explain the problem with the MS/GN test as a conjunction method. We present a survey of recent practice in neuroimaging which reveals that the MS/GN test is very often misinterpreted as evidence of a logical AND. We show that a correct test for a logical AND requires that all the comparisons in the conjunction are individually significant. This result holds even if the comparisons are not independent. We suggest that the revised test proposed here is the appropriate means for conjunction inference in neuroimaging.

Arousal↗

The BOLD onset transient: identification of novel functional differences in schizophrenia.

Blood oxygen level dependent (BOLD) signals characteristically exhibit an overshoot (transient signal increase) at the beginning of fMRI task blocks. This onset transient has often been overlooked as an independent measure of neuronal activity, but it may represent unique functional processes. We examined onset transient responses in normal subjects and individuals with schizophrenia performing three cognitive tasks. These analyses revealed a regionally specific and task specific attenuation of the onset transient in individuals with schizophrenia during performance of a working memory task. Furthermore, this attenuation was often not accompanied by a corresponding population difference in the sustained response, and is missed through conventional fMRI analysis techniques. Relevance of these findings to both an interpretation of the onset transient and the pathology of schizophrenia are discussed.

Adult↗