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PubMed2005

Mixed-effects and fMRI studies.

This note concerns mixed-effect (MFX) analyses in multisession functional magnetic resonance imaging (fMRI) studies. It clarifies the relationship between mixed-effect analyses and the two-stage "summary statistics" procedure (Holmes, A.P., Friston, K.J., 1998. Generalisability, random effects and population inference. NeuroImage 7, S754) that has been adopted widely for analyses of fMRI data at the group level. We describe a simple procedure, based on restricted maximum likelihood (ReML) estimates of covariance components, that enables full mixed-effects analyses in the context of statistical parametric mapping. Using this procedure, we compare the results of a full mixed-effects analysis with those obtained from the simpler two-stage procedure and comment on the situations when the two approaches may give different results.

Brain↗
PubMed2005

A rotation-invariant spherical harmonic decomposition method for mapping intravoxel multiple fiber structures.

A new rotation-invariant spherical harmonic decomposition (SHD) method is proposed in this paper for analyzing high angular resolution diffusion (HARD) imaging. Regular SHD methods have been used to characterize the features of the apparent diffusion coefficient (ADC) profile measured by the HARD technique. However, these regular SHD methods are rotation-variant, i.e., the magnitude and/or the phase of the harmonic components changes with the rotation of the ADC profile. We propose a new rotation-invariant SHD (RI-SHD) method based on the rotation-invariant property of a diffusion tensor model. The basic idea of the proposed method is to reorient the measured ADC profile into a local coordinate system determined by the three eigenvectors of the diffusion tensor in each imaging voxel, and then apply a SHD to the ADC profile. Both simulations and in vivo experiments were carried out to validate the method. Comparisons were made between the component maps from a regular SHD method, diffusion circular spectrum mapping (DCSM) method and the proposed RI-SHD method. The results indicate that the regular SHD maps vary significantly with the rotation of the diffusion-encoding scheme, whereas the maps of the DCSM and the proposed method remain unchanged. In particular, the (0,0)-th, (2,2)-th and (4,4)-th component maps from the RI-SHD method exhibited good consistency with the 0th, 2nd and 4th order maps of the DCSM method, respectively. Compared with the regular SHD methods used in HARD imaging, the proposed RI-SHD method is superior in characterizing the diffusion patterns of multiple fiber structures between different brain regions or across subjects.

Adult↗
PubMed2006

Lagged covariance structure models for studying functional connectivity in the brain.

Most cognitive processes are supported by large networks of brain regions. To describe the operation of these networks, it is critical to understand how individual areas are functionally connected. Here, we establish a statistical framework for studying effective and functional brain connectivity, using data obtained with a relatively new neuroimaging method, the event-related optical signal (EROS). The novelty of our approach is the use of timing information (in the form of lagged cross-correlations) in interpreting the connections between areas. Interpretation of lagged cross-correlations exploits the combination of spatial and temporal resolution provided by EROS. In this paper, we apply dynamic factor analysis as a method for testing various structural models on the lagged covariance matrices derived from the EROS data. We first illustrate the approach by testing a simple path model of neural activity propagation from area V1 to V3 in a visual stimulation task. We then build more complex structural equation models with latent variables, describing both within-hemisphere integrity, and interactions between the two hemispheres, to interpret data from a second task involving inter-hemispheric competition. The results demonstrate how the integrity of anatomical connections between the two hemispheres explains different patterns of cross-hemispheric interactions. This approach allows for fitting brain imaging data to complex models that capture dynamic cognitive processes as they rapidly evolve over time.

Adolescent↗
PubMed2006

76-space analysis of grey matter diffusivity: methods and applications.

Diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) allow in vivo investigation of molecular motion of tissue water at a microscopic level in cerebral gray matter (GM) and white matter (WM). DWI/DTI measure of water diffusion has been proven to be invaluable for the study of many neurodegenerative diseases (e.g., Alzheimer's disease and Creutzfeldt-Jakob disease) that predominantly involve GM. Thus, quantitative analysis of GM diffusivity is of scientific interest and is promised to have a clinical impact on the investigation of normal brain aging and neuropathology. In this paper, we propose an automated framework for analysis of GM diffusivity in 76 standard anatomic subdivisions of gray matter to facilitate studies of neurodegenerative and other gray matter neurological diseases. The computational framework includes three enabling technologies: (1) automatic parcellation of structural MRI GM into 76 precisely defined neuroanatomic subregions ("76-space"), (2) automated segmentation of GM, WM and CSF based on DTI data, and (3) automatic measurement of the average apparent diffusion coefficient (ADC) in each segmented GM subregion. We evaluate and validate this computational framework for 76-space GM diffusivity analysis using data from normal volunteers and from patients with Creutzfeldt-Jakob disease.

Adult↗
PubMed2006

Analysis of EEG-fMRI data in focal epilepsy based on automated spike classification and Signal Space Projection.

Simultaneous acquisition of EEG and fMRI data enables the investigation of the hemodynamic correlates of interictal epileptiform discharges (IEDs) during the resting state in patients with epilepsy. This paper addresses two issues: (1) the semi-automation of IED classification in statistical modelling for fMRI analysis and (2) the improvement of IED detection to increase experimental fMRI efficiency. For patients with multiple IED generators, sensitivity to IED-correlated BOLD signal changes can be improved when the fMRI analysis model distinguishes between IEDs of differing morphology and field. In an attempt to reduce the subjectivity of visual IED classification, we implemented a semi-automated system, based on the spatio-temporal clustering of EEG events. We illustrate the technique's usefulness using EEG-fMRI data from a subject with focal epilepsy in whom 202 IEDs were visually identified and then clustered semi-automatically into four clusters. Each cluster of IEDs was modelled separately for the purpose of fMRI analysis. This revealed IED-correlated BOLD activations in distinct regions corresponding to three different IED categories. In a second step, Signal Space Projection (SSP) was used to project the scalp EEG onto the dipoles corresponding to each IED cluster. This resulted in 123 previously unrecognised IEDs, the inclusion of which, in the General Linear Model (GLM), increased the experimental efficiency as reflected by significant BOLD activations. We have also shown that the detection of extra IEDs is robust in the face of fluctuations in the set of visually detected IEDs. We conclude that automated IED classification can result in more objective fMRI models of IEDs and significantly increased sensitivity.

Cerebral Cortex↗
PubMed2006

Normal pituitary volumes in chronic schizophrenia.

Pituitary volumes were shown to be abnormally large in pre- or first-psychotic episode patients and abnormally reduced in established schizophrenia by magnetic resonance imaging (MRI) studies. We present here the results of the second ever published MRI study exploring pituitary size in a large population of patients with chronic schizophrenia recruited from the geographically defined catchment area of South Verona, Italy. No significant differences for pituitary volumes were reported between 65 subjects with chronic schizophrenia and 65 normal individuals (mean age+/-S.D.=42.31+/-11.44 and 40.54+/-11.12 years). In contrast to Pariante et al. (2004), normal pituitary size was found in our population of chronic schizophrenia. Discrepancies between these two studies may partially be accounted by sample age and gender. Considering increased pituitary volumes in pre- or first-psychotic episode patients, we put forward the hypothesis that pituitary size may normalize or reduce with the progression of the illness as a result of reduced numbers of acute episodes and consequent diminished hypothalamus-pituitary-adrenal axis activity. To better test this hypothesis, future large MRI studies should investigate pituitary volumes in chronic schizophrenia longitudinally, also collecting pituitary hormones and cortisol, and comparing the effects of typical and atypical antipsychotics on pituitary size in a randomized trial.

Adult↗
PubMed2000

DNA rings with multiple energy minima.

Within the context of DNA rings, we analyze the relationship between intrinsic shape and the existence of multiple stable equilibria, either nicked or cyclized with the same link. A simple test, based on a perturbation expansion of symmetry breaking within a continuum elastic rod model, provides good predictions of the occurrence of such multiple equilibria. The reliability of these predictions is verified by direct computation of nicked and cyclized equilibria for several thousand DNA minicircles with lengths of 200 and 900 bp. Furthermore, our computations of equilibria for nicked rings predict properties of the equilibrium distribution of link, as calculated by much more computationally intensive Monte Carlo simulations.

Computer Simulation↗
PubMed2001

A comparison between EGS4 and MCNP computer modeling of an in vivo X-ray fluorescence system.

The Monte Carlo computer codes EGS4 and MCNP were used to develop a theoretical model of a 180 degrees geometry in vivo X-ray fluorescence system for the measurement of platinum concentration in head and neck tumors. The model included specification of the photon source, collimators, phantoms and detector. Theoretical results were compared and evaluated against X-ray fluorescence data obtained experimentally from an existing system developed by the Swansea In Vivo Analysis and Cancer Research Group. The EGS4 results agreed well with the MCNP results. However, agreement between the measured spectral shape obtained using the experimental X-ray fluorescence system and the simulated spectral shape obtained using the two Monte Carlo codes was relatively poor. The main reason for the disagreement between the results arises from the basic assumptions which the two codes used in their calculations. Both codes assume a "free" electron model for Compton interactions. This assumption will underestimate the results and invalidates any predicted and experimental spectra when compared with each other.

Computer Simulation↗
PubMed1998

Classification and identification of proteins by means of common and specific amino acid n-tuples in unaligned sequences.

Unaligned amino acid sequences can be characterized by their composition of amino acid n-tuples (i.e. doublets, triplets, quadruplets, etc.). In this study we investigated the performance of two statistics, termed commonality and specificity, that are derived from n-tuple counts using a set of G-protein coupled receptor (GPCR) sequences. The commonality of a tuple is defined as its relative occurrence in the sequences that belong to a given GPCR subtype. The specificity of a tuple is derived from its relative occurrence in the sequences of a given GPCR subtype and from its relative non-occurrence in the sequences that do not belong to this subtype. A graphical presentation, termed 'polygram', is described for the visualization of common and specific tuples. The method can be applied to the classification of unknown GPCR sequences. It can also be applied to the identification of fragments of GPCRs, such as may occur in chimeric receptors. The method is generally applicable to other protein families and other types of coding.

Amino Acid Sequence↗
PubMed1998

Link between fertilization-induced Ca2+ oscillations and relief from metaphase II arrest in mammalian eggs: a model based on calmodulin-dependent kinase II activation.

Mammalian eggs are ovulated in metaphase II of meiosis, in a state characterized by high levels of cyclin B and of active maturation promoting factor (MPF). This arrest is mediated by an activity referred to as cytostatic factor (CSF) which prevents the degradation of cyclin. Fertilization triggers a train of Ca2+ spikes which is responsible for the decrease in activity of both MPF and CSF. The decline in MPF however much precedes that in CSF. Experimental observations on mammalian eggs indicate that the kinetics of cell cycle resumption much depends on the temporal pattern of the repetitive Ca2+ spikes. Here, we propose a theoretical model which accounts for Ca(2+)-induced relief from metaphase II arrest in mammalian eggs. The model is based on the fact that Ca2+/calmodulin kinase II (CaMKII) activation is the primary event leading to inactivation of both CSF and MPF. To account for experimental observations, it has to be assumed that CaMKII activation affects the level of the active form of the anaphase promoting complex (APC), which initiates the degradation of cyclin, through two pathways characterized by different time scales. Thus, we hypothesize that CaMKII activation by Ca2+ leads to the transformation of a mediator protein from a form which stimulates the inactivation of the APC into a form which gradually and indirectly induces the deactivation of CSF. In consequence, a sufficient number of Ca2+ spikes first triggers the decrease of MPF, thus allowing the egg to enter in interphase, and later that of CSF. Finally, when CSF is low and when Ca2+ oscillations have stopped, the level of MPF can increase again, a phenomenon that would correspond to the first mitosis. This model also accounts for the observed dependence of the time of entry in interphase (marked by the appearance of the pronuclei) on the frequency of Ca2+ spikes, as well as for the possible entry in metaphase III arrest, a pathological state of the egg which results from an insufficient activation by Ca2+. This study provides some theoretical prediction as to the time of the first mitosis as a function of the temporal pattern of Ca2+ oscillations.

Animals↗
PubMed2003

Mixed blocked/event-related designs separate transient and sustained activity in fMRI.

Recent functional magnetic resonance imaging (fMRI) studies using mixed blocked/event-related designs have shown activity consistent with separable sustained task-related processes and transient trial-related processes. In the mixed design, control blocks are intermixed with task blocks, during which trials are presented at varying intervals. Two studies were conducted to assess the ability of this design to detect and dissociate sustained task-related from transient trial-related activity. Analyses on both simulated and empirical data were performed by using the general linear model with a shape assumed for sustained effects, but not transient effects. In the first study, simulated data were produced with sustained time courses, transient time courses, and the sum of both together. Analyses of these data showed appropriate parsing of sustained and transient activity in all three cases. For the empirical fMRI experiment, counterphase-flickering checkerboard stimuli were constructed to produce sustained, transient, and combined sustained and transient responses in visual cortex. As with the simulation, appropriate parsing of sustained and transient activity was seen in all three cases; i.e., sustained stimuli produced sustained time courses and transient stimuli produced transient time courses. Combined stimuli produced both transient and sustained time courses. Critically, transient stimuli alone did not produce spurious positive sustained responses; sustained stimuli alone produced negligible spurious transient time courses. The results of these two studies along with supplemental simulations provide strong evidence that mixed designs are an effective tool for separating transient, trial-related activity from sustained activity in fMRI experiments. Mixed designs can allow researchers a means to examine brain activity associated with sustained processes, potentially related to task-level control signals.

Attention↗
PubMed2003

Gray matter features of schizotypal disorder patients exhibiting the schizophrenia-related code types of the Minnesota Multiphasic Personality Inventory.

OBJECTIVE: Previous studies have suggested that several code types of the Minnesota Multiphasic Personality Inventory (MMPI) are useful markers for identifying schizophrenia. We hypothesized that schizotypal disorder (STD) patients with such schizophrenia-related code types have the morphological brain abnormalities associated with schizophrenia. METHOD: Voxel-based morphometric analysis with statistical parametric mapping (SPM) 99 software was used to investigate the differences in brain morphology between 14 STD patients with the schizophrenia-related code types of the MMPI and 28 normal individuals. RESULTS: The STD patients showed significantly decreased gray matter volume in the insular regions bilaterally and in the left entorhinal cortex, compared with the controls. CONCLUSION: Our findings suggest that STD patients with the schizophrenia-related code types have volume reductions in these regions as an endophenotype that overlaps with schizophrenia.

Adolescent↗
PubMed1992

Categorical versus coordinate spatial relations: computational analyses and computer simulations.

Results of 4 sets of neural network simulations support the distinction between categorical and coordinate spatial relations representations: (a) Networks that were split so that different hidden units contributed to each type of judgment performed better than unsplit networks; the reverse was observed when they made 2 coordinate judgments. (b) Both computations were more difficult when finer discriminations were required; this result mirrored findings with human Ss. (c) Networks with large, overlapping "receptive fields" performed the coordinate task better than did networks with small, less overlapping receptive fields, but vice versa for the categorical task; this suggests a possible basis for observed cerebral lateralization of the 2 kinds of processing. (d) The previously observed effect of stimulus contrast on this hemispheric asymmetry could reflect contributions of more neuronal input in high-contrast conditions.

Computer Simulation↗
PubMed2002

[II: Difference plots or scattergram--when to use which?].

Sometimes the statistical comparison of diagnostic measurement methods or subsequent measurement series in the same individuals is based on bivariate scattergrams; correlation coefficients and linear regression lines are provided in addition. However, this strategy for data representation must be considered inappropriate, as soon as the measurement series under consideration show the same physical index (e.g. repeated measurement of the intraocular pressure [mm Hg] 2 and 4 weeks after glaucoma surgery). Such data can be handled by computation of the intraindividual difference of an individual's measurement. The resulting series of intraindividual deviations can then be analysed using standard strategies: description can be based on the intraindividual differences' median and quartiles, graphical representation on the differences' distribution's box whisker plot. This procedure is particularly attractive for data arising from ophthalmological studies, when two eyes of one patient are to be compared. The statistical comparison of diagnostic methods can further be based on the Bland/Altman diagram, which not only illustrates the distribution of differences, but also motivates a dependence between the order of deviations and the absolute order of the measurement values. Whereas a box plot of intraindividual differences and a Bland/Altman diagram illustrate the concordance of two measurement series, the correlation scattergram rather visualizes their reproducibility.

Computer Graphics↗
PubMed2003

[Registration using three-dimensional laser surface scanning for navigation in oral and craniomaxillofacial surgery].

INTRODUCTION: Recent innovations in laser scanning technology provide a potentially useful tool for three-dimensional surface registration for image-guided surgery. The purpose of this study is to evaluate the clinical reliability of this technique in oral and maxillofacial surgical procedures using image-guided navigation. METHODS: In an experimental step, a stable anthropomorphic skull model with prelabeled markers was scanned and registered with laser surface scanning (z-touch, BrainLAB) and marker- based algorithms. The registration protocol was then repeated 25-times. Root mean square error (RMSE) and target difference values were compared for their suitability for this application. Twelve patients with different indications for oral and maxillofacial surgery were planned for image-guided surgery using a passive infrared surgical navigation system (VectorVision, BrainLAB). Preoperative computed tomography (CT) scans were carried out with newest 16-line multisclice CT-scanner (Siemens Somatom Sensation 16). The new markerless laser surface scanning technique was applied in all intraoperative patient registrations. Registration error was noted. The clinical application accuracy was determined for anatomical landmark localization deviation. RESULTS: In the experimental protocol a mean registration error (RMSE) or target difference of 1.3 (0.14) or 2.08 (0.49) mm for laser scanning and 0.38 (0.01) or 0.99 (0.15) mm for marker registration was found. The differences for RMSE and target localization were statistically significant (p < 0.005). Furthermore, a strong correlation between RMSE and target difference was found for laser scanning (r = 0.96) and marker registration (r = 0.95). During various clinical procedures involving oral and maxillofacial surgery, the overall error of the registration procedure determined as RMSE was 1.21 (0.34) mm. Intraoperatively, the mean clinical application accuracy was found to be 1.8 (0.5) mm. CONCLUSION: Three-dimensional laser surface scanning technique may be a interesting and useful approach to register the patient for image-guided procedures, particularly during oral and craniomaxillofacial surgery.

Cephalometry↗
PubMed2003

[Multislice TrueFISP-MR imaging for identifying stress-induced myocardial functional disturbances in coronary heart disease].

PURPOSE: This study assesses the left ventricular function using a new multislice cine sequence and determines the diagnostic accuracy of stress-induced wall motion abnormalities in patients with coronary artery disease (CAD). MATERIALS AND METHODS: 15 patients (mean age 57.7 years) with angiographically proven CAD were examined on a 1.5 T whole body system (Magnetom Sonata, Siemens, Erlangen) at rest and during dipyridamole-induced (0.56 mg/kg body weight) stress. Left ventricular function was determined using a multislice (steady-state) sequence (TR 2.3 ms, TE 1.15 ms, slice thickness 10 mm, temporal resolution 77 ms) as well as a standard single-slice true FISP 2D sequence (TR 3.2 ms, TE 1.6 ms, slice thickness 5 mm, temporal resolution 45 ms) as reference. RESULTS: Both cine sequences provide high sensitivity and excellent correlation (r = 0.95) with angiographic findings for the detection of regional wall motion abnormalities. However, the measurement of functional parameters yielded significant differences. End-systolic left ventricular volumes (ESV) were systematically overestimated in the multislice images (mean 78 ml, + 5.8 %) compared with the reference single-slice images (mean 74 ml) (p < 0.05). This resulted in underestimation of the ejection fraction with multislice images (mean 40 %, - 11.3 %) compared with single-slice images (mean 46 %) (p < 0.05). CONCLUSION: The multislice sequence results in a substantial reduction of imaging time and breath-hold periods necessary to cover the left ventricle for functional assessment. The multislice sequence yields adequate images, especially for qualitative determination of wall motion abnormalities. Due to the reduced spatial and temporal resolution of the multi-slice sequence, however, some uncertainty concerning the functional parameters has to be taken into account.

Adult↗
PubMed2003

[Computer-assisted planning and corrective osteotomy in distal radius malunion].

Corrective osteotomy of the malunited distal radius following fracture was performed in six patients using virtual planning and computer-assisted surgery. Radius joint angles and ulnar variance were assessed by CT scan and compared with the uninvolved wrist. Dorsal tilt was improved by 6 degrees, radial inclination by 3 degrees, radius rotation by 7 degrees and ulnar variance by 4.6 mm. Results were almost equivalent to the noninvolved radius. Corrective osteotomy in extraarticular malunited distal radius fracture was optimized by computer-assisted planning and surgery.

Adult↗
PubMed2004

How much information can one store in a nonequilibrium medium?

It has recently been emphasized again that the very existence of stationary stable localized structures with short-range interactions might allow one to store information in nonequilibrium media, opening new perspectives on information storage. We show how to use generalized topological entropies to measure aspects of the quantities of storable and nonstorable information. This leads us to introduce a measure of the long-term stably storable information. As a first example to illustrate these concepts, we revisit a mechanism for the appearance of stationary stable localized structures that is related to the stabilization of fronts between structured and unstructured states (or between differently structured states).

Computers, Molecular↗