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Analysis of ischemic stroke MR images by means of brain atlases of anatomy and blood supply territories.

RATIONALE AND OBJECTIVES: A method for atlas-assisted analysis of stroke magnetic resonance images that is a part of a stroke computer-assisted diagnosis system supporting rapid and quantitative checking of thrombolysis conditions is presented. MATERIALS AND METHODS: Two brain atlases are used for analysis: atlas of anatomy (AA) and atlas of blood supply territories (BSTs). To map these atlases onto scans, two methods are used at present: (1) fast Talairach transformation and (2) midsagittal plane and brain's bounding box matching. After atlas-to-scan mapping, both atlases are superimposed onto the studied images and can be used to get their underlying anatomy and BSTs. To speed up the process of analysis, the system automatically analyzes entire regions occupied by the infarct and penumbra. RESULTS: By using both atlases, the system calculates the following values for each infarct and penumbra region: (1) names of all anatomic structures and BSTs within the region, (2) volumes of occupancy for each structure and territory, and (3) percentages of occupancy for each structure and territory. In addition, the system calculates the infarct-middle cerebral artery (MCA) territory ratio for diffusion-weighted images and the penumbra-MCA territory ratio for perfusion images. Atlas-assisted analysis is fast, and calculations take less than 10 seconds. CONCLUSION: This method potentially facilitates and speeds up stroke data analysis, as well as supports decision making.

Atlases as Topic↗

Improved programs for the affected-pedigree-member method of linkage analysis.

The affected-pedigree-member (APM) method is a non-parametric method of linkage analysis, which requires no assumptions about how the trait of interest is inherited [Weeks and Lange, 1988, 1991, 1992; Lange and Weeks, 1990; Weeks et al., 1992]. The APM method uses only the affected members of each pedigree who are typed for the marker(s). Based on the affected members' marker genotypes and the relationships of the affecteds to each other, the APM method computes a statistic which provides a measure of marker similarity. If the affected members are significantly more similar at the marker locus than expected by chance, then one may conclude that the marker is not segregating independently of the disease. Since the APM method tests a hypothesis about marker similarity, and not about recombination between the marker and disease, it makes and requires no assumptions about the mode of inheritance of the disease. For this reason, the APM method has been used for complex diseases such as Alzheimer's, breast cancer, and melanoma [Pericak-Vance et al., 1989, 1990; Haile et al., 1990; Hall et al., 1990; St George-Hyslop et al., 1990; Cannon-Albright et al., 1992]. We would like to announce the availability of a much improved version of the APM program package. This version has been improved in several ways, as outlined below.

Bias↗

Permutation tests for factorially designed neuroimaging experiments.

Permutation methods for analysis of functional neuroimaging data acquired as factorially designed experiments are described and validated. The F ratio was estimated for main effects and interactions at each voxel in standard space. Critical values corresponding to probability thresholds were derived from a null distribution sampled by appropriate permutation of observations. Spatially informed, cluster-level test statistics were generated by applying a preliminary probability threshold to the voxel F maps and then computing the sum of voxel statistics in each of the resulting three-dimensional clusters, i.e., cluster "mass." Using simulations comprising two between- or within-subject factors each with two or three levels, contaminated by Gaussian and non-normal noise, the voxel-wise permutation test was compared to the standard parametric F test and to the performance of the spatially informed statistic using receiver operating characteristic (ROC) curves. Validity of the permutation-testing algorithm and software is endorsed by almost identical performance of parametric and permutation tests of the voxel-level F statistic. Permutation testing of suprathreshold voxel cluster mass, however, was found to provide consistently superior sensitivity to detect simulated signals than either of the voxel-level tests. The methods are also illustrated by application to an experimental dataset designed to investigate effects of antidepressant drug treatment on brain activation by implicit sad facial affect perception in patients with major depression. Antidepressant drug effects in left amygdala and ventral striatum were detected by this software for an interaction between time (within-subject factor) and group (between-subject factor) in a representative two-way factorial design.

Algorithms↗

Design and analysis of fMRI studies with neurologically impaired patients.

Functional neuroimaging can be used to characterize two types of abnormality in patients with neurological deficits: abnormal functional segregation and abnormal functional integration. In this paper we consider the factors that influence the experimental design, analysis, and interpretation of such studies. With respect to experimental design, we emphasize that: 1) task selection is constrained to tasks the patient is able to perform correctly, and 2) the most sensitive designs entail presenting stimuli of the same type close together. In terms of data preprocessing, prior to statistical analysis, we note that structural pathology may call for constraints on nonlinear transformations, used by spatial normalization, to prevent distortion of intact tissue. This means that one may have to increase spatial smoothing to reduce the impact of inaccurate normalization. Important issues in statistical modeling concern the first level of analysis (estimation of activation within subject), which has to distinguish correct from incorrect responses. At the second level (between subjects), inference should be based on between-subjects variance. Provided that these and other constraints are met, deficits in functional segregation are indicated when activation in one or a set of regions is higher or lower in patients relative to control subjects. In contrast, deficits in functional integration are implied when the influence of one brain region on another is stronger or weaker in patients relative to control subjects.

Brain↗

Multimodal image coregistration and partitioning--a unified framework.

This paper presents a method for the coregistration and partitioning (i.e., tissue segmentation) of brain images that have been acquired in different modalities. The basic idea is that instead of matching two images directly, one performs intermediate within-modality registrations to two template images that are already in register. One can use a least-squares minimization to determine the affine transformations that map between the templates and the images. By incorporating suitable constraints, a rigid body transformation which directly maps between the images can be extracted from these more general affine transformations. A further refinement capitalizes on the implicit normalization of both images into a standard space. This facilitates segmentation or partitioning of both original images into homologous tissue classifications. Once partitioned, the partitions can be jointly matched, further increasing the accuracy of the coregistration. In short, these techniques reduce the between-modality problem to a series of simpler within-modality problems. These methods are relatively robust, address a number of problems in image transformations, and require no manual intervention.

Brain↗

Assessment of spatial normalization of PET ligand images using ligand-specific templates.

Recent advances allow robust computation of parametric maps of ligand-receptor binding from PET data sets. Parametric maps may be statistically analyzed at the voxel level, given suitable techniques for both the spatial normalization of image data into a standard space and the application of appropriate statistical tests. The purpose of this study was to spatially normalize parametric maps of [carbonyl-11C]WAY-100635 and [11C]raclopride binding using SPM 96 and ligand-specific templates. Ligand-specific templates were created from integral images taken from healthy subjects. For this, a MRI-based spatial normalization was used: T1-weighted MRI scans were coregistered to the PET integral images, and the spatial normalization of the MRI to the SPM 96 T1 MRI template was applied to the integral images. These integral images were meaned and smoothed to form [carbonyl-11C]WAY-100635 and [11C]raclopride templates. Reliability of spatial normalization using the ligand template method and the previous MRI-based spatial normalization was investigated by using a second set of integral images taken from a different cohort: Landmark coordinates were defined on all spatially normalized integral images. Mean coordinates were found in order to produce an overall (average) landmark for each location. For each image, at each location, the distance from the landmark coordinates to the overall landmark were found. A multivariate analysis of variance was used to examine the effects of observer variance, landmark location, and the method used. Visually acceptable templates were created. While observer variance was not significant, the landmark x method interaction was significant. The ligand template method had significantly smaller distances: Among the landmark locations with this method, the mean distances between individual image landmarks and overall image landmarks ranged from 1. 1 to 4.9 mm. The ligand template method provides a reliable approach for spatial normalization of PET ligand images.

Algorithms↗

Could neuroimaging help us to interpret the clinical effects of acupuncture?

One of the problems in assessing acupuncture efficacy has been the lack of a standardised placebo/control. Despite the lack of 'proof', acupuncture is widely used; hence it would seem that a large proportion of the public are not too concerned with the question of efficacy. Patients and researchers approach the issue of whether acupuncture "works" in an entirely different way. It may be that the management of chronic pain as a whole is largely context driven and non-specific. Therefore, research should focus on areas such as pragmatic/comparative trials and the non-specific effects of treatment. Improving our understanding of the neural mechanisms and substrates of acupuncture, placebo and non-specific effects might enable us to better define a "true placebo" and improve trial design. Imaging studies, however, need to be much more pragmatic. Because of the large overlap in areas of brain activated through acupuncture, pain, placebo and non-specific factors, separating these out in an attempt to pinpoint the mechanisms behind acupuncture will be difficult. Ultimately we need a balance between efficacy, comparative and mechanistic trials using imaging work to inform the whole picture. A broader view of research is therefore necessary to yield meaningful answers and we need to look at the whole package that acupuncture delivers.

Acupuncture Therapy↗

[Functional neuroimaging in psychotherapy research].

Only recently has functional neuroimaging been used increasingly in the context of psychotherapy research. Based on a literature survey, procedures, methodological underpinnings and paradigms relevant for psychotherapy research are explored regarding functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). Current studies on changes of brain functions and potential mechanisms are presented based on obsessive-compulsive disorders, depression, phobia, panic and borderline personality disorders. Findings and implications are discussed regarding the use of functional neuroimaging in psychotherapy research. Systematic changes of brain activation were demonstrated following successful psychotherapy, partially resembling and partially differing from those induced by psychopharmacological treatments. Thus the traditional split between pharmacological procedures "acting on the brain" and psychological procedures making the patient "feel better" has been rendered obsolete. Procedures of functional neuroimaging have been developed to such an extent that they can be used to study issues of great relevance for psychotherapy, e. g. biological underpinnings of psychiatric disorders, plasticity of neural networks, mechanisms of change and prognostic factors of psychotherapy, etc.

Biomedical Research↗

[One decade of functional imaging in schizophrenia research. From visualisation of basic information processing steps to molecular-genetic oriented imaging].

Modern neuroimaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) have contributed tremendously to our current understanding of psychiatric disorders in the context of functional, biochemical and microstructural alterations of the brain. Since the mid-nineties, functional MRI has provided major insights into the neurobiological correlates of signs and symptoms in schizophrenia. The current paper reviews important fMRI studies of the past decade in the domains of motor, visual, auditory, attentional and working memory function. Special emphasis is given to new methodological approaches, such as the visualisation of medication effects and the functional characterisation of risk genes.

Biomarkers↗

[Functional magnetic resonance imaging and antipsychotics. Overview and own data].

Recently, there has been growing interest in using functional magnetic resonance imaging (fMRI) for the evaluation of psychopharmacological drugs. fMRI studies in healthy human volunteers and psychiatric patients focus on cerebral activity following acute drug administration (single challenge) and on adaptive effects on neural networks due to long-term medication. In our own fMRI studies, the effects of olanzapine or amisulpride in never treated or medication-free schizophrenic patients using robust motor, visual, and acoustic tasks was longitudinally examined. In agreement with previous reports in the literature it could be shown that, in contrast to traditional neuroleptics, atypical drugs do not decrease the activation of the sensorimotor cortex but rather normalize the reduced frontoparietal activation as well as the neuropsychological test results. This encourages the assumption that atypical antipsychotics seem to support the recovery or normalization of frontoparietal brain dysfunction in schizophrenia. However, with these new opportunities additional methodological considerations and limitations emerge.

Antipsychotic Agents↗

[Functional imaging of neurocognitive dysfunction in attention deficit hyperactivity disorder].

Attention Deficit Hyperactivity Disorder (ADHD) is a neurobiological disorder of early childhood onset. Defining symptoms are chronic impairments of attention, impulse control and motor hyperactivity that frequently persist until adulthood. Miscellaneous causes of the disorder have been discussed. Accumulating evidence from imaging- and molecular genetic studies strengthened the theory of ADHS being a predominantly inherited disorder of neurobiological origin. In the last 15 years, non-invasive brain imaging methods were successfully implemented in pediatric research. Functional magnetic resonance imaging studies gave major insight into the neurobiological correlates of executive malfunction, inhibitory deficits and psychomotoric soft signs. These findings are in good accordance with brain morphometric data indicating a significant volumetric decrease of major components of striato-thalamo-cortical feedback loops, primarily influencing prefrontal executive functioning (e.g. basal ganglia). Empirical evidence points to a broad array of associated behavioral disturbances like deficient visuomotor abilities and oculomotor dysfunctions. This paper reviews the current empirical evidence derived from prior imaging studies. Special emphasis is given to the relevance of oculomotor dysfunctions in clinical and research settings, as well as their assessment in the MR environment.

Attention Deficit and Disruptive Behavior Disorder↗

[Functional imaging of emotional disorders and experiences in schizophrenia patients].

Functional imaging of normal and dysfunctional emotional processes is an important tool for a better understanding of the pathophysiology of affective symptoms in schizophrenia patients. These symptoms are still poorly characterized with respect to their neural correlates.Comparisons of cerebral activation during emotional paradigms offered the possibility for a better characterization of cerebral dysfunctions during emotional processing in schizophrenia. Abnormal activation patterns reveal a complex dysfunctional subcortical-cortical network. This is modulated by respective genotypes as well as psycho- and pharmacotherapy.

Affective Symptoms↗

Mapping of taiep rat phenotype to rat Chromosome 9.

The taiep mutant rat was first described in a colony of Sprague-Dawley rats at the University of Puebla in 1989, with an autosomal recessive inherited pattern. taiep is an acronym for the progressive neurologic deficits that the rat develops, i.e., t = trembling (3-4 weeks), a = ataxia (at 4 months), i = immobility (5-6 months), e = epilepsy (5-6 months), andp = paresis (7 months onwards). Thus, mutant rats are first identified by a tremor at 3-4 weeks of age that is followed by a progressive neurological worsening (Holmgren et al. 1989; Lunn et al. 1997). The cause of the neurological symptoms is an early failure of normal myelination of the central nervous system (CNS) followed by progressive demyelination of certain CNS tracts (Lunn et al. 1997). We have been exploring the underlying pathophysiology of the mutant and have determined that the myelin defect results from the progressive accumulation of microtubules in oligodendrocytes, the myelin-producing cells of the CNS (Song et al. 1999). Microtubules are the major component of the cytoskeleton of this and many other cells of the body, and microtubule-based transport of protein and mRNA is essential for normal cell function. There is no direct human counterpart of the taiep rat. Nonetheless, providing an understanding of the control of microtubule dynamics in the oligodendrocyte will be highly relevant to our knowledge of the cell biology of the myelinating cell of the CNS. This information is of great relevance to the function of the cell in human myelin disorders and in experimental remyelination. As the taiep rat apparently has a primary disorder in the oligodendrocyte cytoskeleton, it is an ideal model in which to study this process. This information may also be a key to the complete understanding of the mechanism of microtubule assembly/disassembly in many cell types.

Animals↗

Haplotype frequencies of eight Y-chromosome STR loci in Barcelona (North-East Spain).

Haplotype frequencies for eight Y-chromosomal short tandem repeat (STR) loci were determined in paragraph signa population sample from Barcelona (NE Spain). After PCR amplification and denaturing PAGE electrophoresis, DYS19, DYS388, DYS389 I/II, DYS390, DYS391, DYS392 and DYS393 loci were typed. Complete eight paragraph signY-chromosomal STRs haplotypes could be formed for 223 subjects, among which 137 different haplotypes were observed. The most common haplotype was shared by 13% of the sample, while 108 haplotypes were unique. The discrimination capacity was 61.5% and the gene diversity was 0.978. From the forensic point of view the combined polymorphisms provide a high diagnostic efficiency.

Base Sequence↗

Y-Chromosomal STR haplotypes in a population from north west Germany.

We present a German Y-chromosome short tandem repeat (STR)-haplotype database consisting of the loci DYS19, DXYS156-Y, subtypes of DYS389, DYS390, DYS391, DYS392 and as well as DYS393. 104 haplotypes were observed in 179 unrelated Germans, the haplotype diversity is 98.06%. This database is a prerequisite for the forensic application of these new markers.

Chromosome Mapping↗

DNA commission of the International Society of Forensic Genetics: recommendations on forensic analysis using Y-chromosome STRs.

During the past few years the DNA commission of the International Society of Forensic Genetics has published a series of documents providing guidelines and recommendations concerning the application of DNA polymorphisms to the problems of human identification. This latest report addresses a relatively new area, namely Y-chromosome polymorphisms, with particular emphasis on short tandem repeats (STRs). This report addresses nomenclature, use of allelic ladders, population genetics and reporting methods.

Alleles↗