Biomedical subjects

Alan C Evans

Publications and source records attributed to Alan C Evans.

35 records · Page 2Linked to original sources

PubMed2005

Focal brain matter differences associated with lifetime alcohol intake and visual attention in male but not in female non-alcohol-dependent drinkers.

The purpose of this study was to investigate whether current or lifetime alcohol intake is related to focal gray and white matter in healthy non-alcohol-dependent drinkers, and, if so, whether these densities are related to functional brain activity associated with visual attention. Voxel-based morphometric analyses of gray- and white-matter densities, and event-related potentials in response to a visual-attention task were determined in 47 male drinkers (current alcohol intake 20 drinks per week, lifetime alcohol intake 240 kg) and 44 female drinkers (current alcohol intake 15 drinks per week, lifetime alcohol intake 170 kg). All participants had a negative personal and family history of alcohol dependence to reduce possible confounding by genetic factors related to alcohol dependence. In males, mean lifetime alcohol intake was negatively associated with gray-matter density and positively associated with white-matter density in the right frontal gyrus (BA 6) and the right parietal region (BA 40). Right frontal (but not right parietal) gray and white matter in males correlated with the P3 amplitude of the event-related potentials elicited in a visual-attention task. In females, mean lifetime alcohol intake was not associated with gray- or white-matter density. Current alcohol intake was unrelated to gray or white matter in both males and females. In conclusion, lifetime alcohol intake is associated with focal gray-matter decreases and white-matter increases in the right frontal and right parietal brain regions in non-alcohol-dependent males, but not in females. These alcohol-related differences in focal brain matter in males are associated with differences in brain function related to visual attention. As the confounding effects of genetic factors were reduced, the present results may selectively relate to the effects of alcohol intake on focal brain matter.

Alcohol Drinking↗

PubMed2005

Brain imaging in drug R&D.

Magnetic resonance imaging (MRI), used as a clinical diagnostic tool since the early 1980s, is rapidly gaining traction as an integral part of the drug development process. Brain imaging research spans a wide area, covering both structure and function, and ranging from the physics and physiology associated with novel acquisition techniques, to the development of sophisticated image processing algorithms. This paper briefly describes two methods on either end of this spectrum: the "pipeline" framework for the fully automated morphometric analysis of brain imaging data, and molecular MRI, which holds promise for the non-invasive detection of molecular targets of new pharmacological compounds. The potential use of these technologies is illustrated by examples of their applications in multiple sclerosis, Alzheimer's disease, and oncology.

Algorithms↗

PubMed2004

Focal decline of cortical thickness in Alzheimer's disease identified by computational neuroanatomy.

Alzheimer's disease (AD) is characterized by a heterogeneous distribution of pathological changes throughout the brain. Magnetic resonance imaging can be used to investigate the regional distribution of cortical atrophy in AD in vivo. One marker for the disease-specific atrophy is the thickness of the cortical mantle across the brain, obtained with automated 3-D image processing. Here, we present data from 36 subjects (17 controls and, 19 patients diagnosed as probable AD) investigated for cortical thickness across the entire brain. We show significant cortical thickness decline in AD in temporal, orbitofrontal and parietal regions, with the most pronounced changes occurring in the allocortical region of the medial temporal lobes, outlining the parahippocampal gyrus, and representing a loss of >1.25 millimeters of cortical thickness. Moreover, focal cortical areas decline with progression of the disease as measured by time from baseline scan as well as the Mini-Mental State Exam. The results demonstrate the ability of this method to detect changes in cortical thickness in AD, across the entire brain, without need of prior anatomical definitions. The regional distribution of changes reported here is consistent with independent findings on the distribution of neuropathological alterations in AD. Using cortical thickness, moreover, we provide a direct quantitative index of atrophy in the disease.

Aged↗

PubMed2004

A voxel-based morphometric study to determine individual differences in gray matter density associated with age and cognitive change over time.

Voxel-based morphometry (VBM) was used to examine the relation between age and gray matter density cross-sectionally and to study the association between gray matter density and longitudinal decline in performance on cognitive tests in healthy, non-demented elderly individuals. Participants were neuropsychologically tested at baseline and again after 3 years. Thirty-seven subjects (mean age 72.5 years) who showed a decline in cognitive test performance at follow-up were compared with 38 individually matched control subjects (mean age 71.8 years) whose performance did not change over time. Magnetic resonance imaging scans were acquired at follow-up and individual differences in regional gray matter density were examined with VBM. The largest age effects were found in various regions in the prefrontal cortex, the (medial) temporal lobes and the striate cortex. Longitudinal cognitive decline was associated with decreased gray matter density in prefrontal areas, the (medial) temporal lobes and the posterior parietal cortex. These findings suggest that prefrontal and temporal cortical regions are of particular relevance both in aging and age-related cognitive decline in healthy elderly individuals.

Adult↗

PubMed2004

Tuning and comparing spatial normalization methods.

Spatial normalization is a key process in cross-sectional studies of brain structure and function using MRI, fMRI, PET and other imaging techniques. A wide range of 2D surface and 3D image deformation algorithms have been developed, all of which involve design choices that are subject to debate. Moreover, most have numerical parameters whose value must be specified by the user. This paper proposes a principled method for evaluating design choices and choosing parameter values. This method can also be used to compare competing spatial normalization algorithms. We demonstrate the method through a performance analysis of a nonaffine registration algorithm for 3D images and a registration algorithm for 2D cortical surfaces.

Algorithms↗

PubMed2004

Focal white matter density changes in schizophrenia: reduced inter-hemispheric connectivity.

Gray matter changes have been demonstrated in several regions in schizophrenia. Particularly, the frontal and temporal cortices and amygdala-hippocampal region have been found decreased in volume and density in magnetic resonance imaging (MRI) studies. These abnormalities may reflect an aberrant neuronal network in schizophrenia, suggesting that white matter fibers connecting these regions may also be affected. However, it is unclear if particular white matter areas are (progressively) affected in schizophrenia and if these are related to the gray matter changes. Focal white matter changes in schizophrenia were studied in whole brain magnetic resonance images acquired from 159 patients with schizophrenia or schizophreniform disorder and 158 healthy comparison subjects using voxel-based morphometry. White matter density changes in the patients with schizophrenia were correlated to gray matter density changes and to illness severity. In the patients with schizophrenia, significant decreases in white matter density were found in the genu and truncus of the corpus callosum in the left and right hemisphere, in the right anterior internal capsule and in the right anterior commissure. No interactions between diagnosis and age were found. Increased illness severity was correlated with low density of the corpus callosum and anterior commissure. Decreased corpus callosum density correlated with decreased density of thalamus, lateral inferior frontal and insular gray matter in patients and controls and with decreased density of medial orbitofrontal and superior temporal gyri in patients. Decreased internal capsule and anterior commissure density correlated with increased caudate, and globus pallidus density in patients and controls. These findings suggest aberrant inter-hemispheric connectivity of anterior cortical and sub-cortical brain regions in schizophrenia, reflecting decreased hemispheric specialisation in schizophrenia.

Adult↗

PubMed2003

Deformation-based surface morphometry applied to gray matter deformation.

We present a unified statistical approach to deformation-based morphometry applied to the cortical surface. The cerebral cortex has the topology of a 2D highly convoluted sheet. As the brain develops over time, the cortical surface area, thickness, curvature, and total gray matter volume change. It is highly likely that such age-related surface changes are not uniform. By measuring how such surface metrics change over time, the regions of the most rapid structural changes can be localized. We avoided using surface flattening, which distorts the inherent geometry of the cortex in our analysis and it is only used in visualization. To increase the signal to noise ratio, diffusion smoothing, which generalizes Gaussian kernel smoothing to an arbitrary curved cortical surface, has been developed and applied to surface data. Afterward, statistical inference on the cortical surface will be performed via random fields theory. As an illustration, we demonstrate how this new surface-based morphometry can be applied in localizing the cortical regions of the gray matter tissue growth and loss in the brain images longitudinally collected in the group of children and adolescents.

Adolescent↗

PubMed2003

Automatic volumetric segmentation of human visual retinotopic cortex.

Previous identification of early visual cortical areas in humans with phase-encoded retinotopic mapping techniques have relied on an accurate cortical surface reconstruction. Here a 3D phase-encoded retinotopic mapping technique that does not require a reconstruction of the cortical surface is demonstrated. The visual field sign identification is completely automatic and the method directly supplies volumes for a region-of-interest analysis, facilitating the application of cortical mapping to a wider population. A validation of the method is provided by simulations and comparison to cortical surface-based methodology.

Adult↗

PubMed2003

Statistical mapping analysis of lesion location and neurological disability in multiple sclerosis: application to 452 patient data sets.

In multiple sclerosis (MS), the correlation between disability and the volume of white matter lesions on magnetic resonance imaging (MRI) is usually weak. This may be because lesion location also influences the extent and type of functional disability. We applied an automatic lesion-detection algorithm to 452 MRI scans of patients with relapsing-remitting MS to identify the regions preferentially responsible for different types of clinical deficits. Statistical parametric maps were generated by performing voxel-wise linear regressions between lesion probability and different clinical disability scores. There was a clear distinction between lesion locations causing physical and cognitive disability. Lesion likelihood correlated with the Expanded Disability Status Scale (EDSS) in the left internal capsule and in periventricular white matter mostly in the left hemisphere. Pyramidal deficits correlated with only one area in the left internal capsule that was also present in the EDSS correlation. Cognitive dysfunction correlated with lesion location at the grey-white junction of associative, limbic, and prefrontal cortex. Coordination impairment correlated with areas in interhemispheric and pyramidal periventricular white matter tracts, and in the inferior and superior longitudinal fascicles. Bowel and bladder scores correlated with lesions in the medial frontal lobes, cerebellum, insula, dorsal midbrain, and pons, areas known to be involved in the control of micturition. This study demonstrates for the first time a relationship between the site of lesions and the type of disability in large scale MRI data set in MS.

Adult↗

PubMed2003

A fully automatic and robust brain MRI tissue classification method.

A novel, fully automatic, adaptive, robust procedure for brain tissue classification from 3D magnetic resonance head images (MRI) is described in this paper. The procedure is adaptive in that it customizes a training set, by using a 'pruning' strategy, such that the classification is robust against anatomical variability and pathology. Starting from a set of samples generated from prior tissue probability maps (a 'model') in a standard, brain-based coordinate system ('stereotaxic space'), the method first reduces the fraction of incorrectly labeled samples in this set by using a minimum spanning tree graph-theoretic approach. Then, the corrected set of samples is used by a supervised kNN classifier for classifying the entire 3D image. The classification procedure is robust against variability in the image quality through a non-parametric implementation: no assumptions are made about the tissue intensity distributions. The performance of this brain tissue classification procedure is demonstrated through quantitative and qualitative validation experiments on both simulated MRI data (10 subjects) and real MRI data (43 subjects). A significant improvement in output quality was observed on subjects who exhibit morphological deviations from the model due to aging and pathology.

Adult↗

PubMed2003

Cortical specialization for processing first- and second-order motion.

Distinct mechanisms underlying the visual perception of luminance- (first-order) and contrast-defined (second-order) motion have been proposed from electrophysiological, human psychophysical and neurological studies; however a cortical specialization for these mechanisms has proven elusive. Here human brain imaging combined with psychophysical methods was used to assess cortical specializations for processing these two kinds of motion. A common stimulus construction was employed, controlling for differences in spatial and temporal properties, psychophysical performance and attention. Distinct cortical regions have been found preferentially processing either first- or second-order motion, both in occipital and parietal lobes, producing the first physiological evidence in humans to support evidence from psychophysical studies, brain lesion sites and computational models. These results provide evidence for the idea that first-order motion is computed in V1 and second-order motion in later occipital visual areas, and additionally suggest a functional dissociation between these two kinds of motion beyond the occipital lobe.

Adult↗

PubMed2002

Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder.

CONTEXT: Various anatomic brain abnormalities have been reported for attention-deficit/hyperactivity disorder (ADHD), with varying methods, small samples, cross-sectional designs, and without accounting for stimulant drug exposure. OBJECTIVE: To compare regional brain volumes at initial scan and their change over time in medicated and previously unmedicated male and female patients with ADHD and healthy controls. DESIGN, SETTING, AND PARTICIPANTS: Case-control study conducted from 1991-2001 at the National Institute of Mental Health, Bethesda, Md, of 152 children and adolescents with ADHD (age range, 5-18 years) and 139 age- and sex-matched controls (age range, 4.5-19 years) recruited from the local community, who contributed 544 anatomic magnetic resonance images. MAIN OUTCOME MEASURES: Using completely automated methods, initial volumes and prospective age-related changes of total cerebrum, cerebellum, gray and white matter for the 4 major lobes, and caudate nucleus of the brain were compared in patients and controls. RESULTS: On initial scan, patients with ADHD had significantly smaller brain volumes in all regions, even after adjustment for significant covariates. This global difference was reflected in smaller total cerebral volumes (-3.2%, adjusted F(1,280) = 8.30, P =.004) and in significantly smaller cerebellar volumes (-3.5%, adjusted F(1,280) = 12.29, P =.001). Compared with controls, previously unmedicated children with ADHD demonstrated significantly smaller total cerebral volumes (overall F(2,288) = 6.65; all pairwise comparisons Bonferroni corrected, -5.8%; P =.002) and cerebellar volumes (-6.2%, F( 2,288) = 8.97, P<.001). Unmedicated children with ADHD also exhibited strikingly smaller total white matter volumes (F(2,288) = 11.65) compared with controls (-10.7%, P<.001) and with medicated children with ADHD (-8.9%, P<.001). Volumetric abnormalities persisted with age in total and regional cerebral measures (P =.002) and in the cerebellum (P =.003). Caudate nucleus volumes were initially abnormal for patients with ADHD (P =.05), but diagnostic differences disappeared as caudate volumes decreased for patients and controls during adolescence. Results were comparable for male and female patients on all measures. Frontal and temporal gray matter, caudate, and cerebellar volumes correlated significantly with parent- and clinician-rated severity measures within the ADHD sample (Pearson coefficients between -0.16 and -0.26; all P values were <.05). CONCLUSIONS: Developmental trajectories for all structures, except caudate, remain roughly parallel for patients and controls during childhood and adolescence, suggesting that genetic and/or early environmental influences on brain development in ADHD are fixed, nonprogressive, and unrelated to stimulant treatment.

Adolescent↗

PubMed2002

Motor learning produces parallel dynamic functional changes during the execution and imagination of sequential foot movements.

The aim of the present positron emission tomography study was to measure the dynamic changes in cerebral activity before and after practice of an explicitly known sequence of foot movements when executed physically and to compare them to those elicited during motor imagery of the same movements. Nine healthy volunteers were scanned while performing both types of movement at an early phase of learning and after a 1-h training period of a sequence of dorsiflexions and plantarflexions with the left foot. These experimental conditions were compared directly, as well as to a perceptual control condition. Changes in regional cerebral blood flow associated with physical execution of the sequence early in the learning process were observed bilaterally in the dorsal premotor cortex and cerebellum, as well as in the left inferior parietal lobule. After training, however, most of these brain regions were no longer significantly activated, suggesting that they are critical for establishing the cognitive strategies and motor routines involved in executing sequential foot movements. By contrast, after practice, an increased level of activity was seen bilaterally in the medial orbitofrontal cortex and striatum, as well as in the left rostral portion of the anterior cingulate and a different region of the inferior parietal lobule, suggesting that these structures play an important role in the development of a long lasting representation of the sequence. Finally, as predicted, a similar pattern of dynamic changes was observed in both phases of learning during the motor imagery conditions. This last finding suggests that the cerebral plasticity occurring during the incremental acquisition of a motor sequence executed physically is reflected by the covert production of this skilled behavior using motor imagery.

Adult↗

PubMed2002

Volumetry of temporopolar, perirhinal, entorhinal and parahippocampal cortex from high-resolution MR images: considering the variability of the collateral sulcus.

Researchers in clinical and basic neuroscience frequently target structures of the human medial temporal lobe (MTL) for volumetric analysis with magnetic resonance imaging (MRI). In neurodegenerative diseases, a precise volumetric analysis of MTL structures can assist in differential diagnosis and can be used in guiding early treatment. Also, in functional neuroimaging, exact localization is crucial for the correct interpretation of focal MTL activations with respect to specific memory functions. In presently available protocols, precise and consistent volumetric analysis of MTL structures is compromised in numerous ways. Most importantly, in order to cover all structures of the MTL, the researcher is presently forced to combine independently developed segmentation protocols for different structures from different laboratories. This approach limits anatomical precision because these protocols are based on different anatomical guidelines and descriptions that cannot easily be integrated. The segmentation approach presented in this paper was designed to address this issue by presenting segmentation guidelines for all major structures of the parahippocampal gyrus (PHG). It was developed directly to complement a volumetric protocol for hippocampus and amygdala (Pruessner et al., 2000, Cereb Cortex 10:433-442), thus allowing volumetric assessment of all major MTL structures in an integrated and consistent manner. Furthermore, it takes into consideration the neuroanatomical appearance of the collateral sulcus by presenting a method to correct the volumes of the surrounding cortices for the variability of this sulcus. The protocol was validated using MR images of 40 healthy normal control subjects (20 men and 20 women, age range 18-42 years). Intra- and interrater coefficients are presented, together with mean values for the volumes of all PHG structures, correlations with age and sex, and tests for hemispheric differences.

Adult↗

PubMed2002

Positron emission tomography partial volume correction: estimation and algorithms.

Partial volume effects in positron emission tomography (PET) lead to quantitative under- and over-estimations of the regional concentrations of radioactivity in reconstructed images and corresponding errors in derived functional or parametric images. The limited resolution of PET leads to "tissue-fraction" effects, reflecting underlying tissue heterogeneity, and "spillover" effects between regions. Addressing the former problem in general requires supplementary data, for example, coregistered high-resolution magnetic resonance images, whereas the latter effect can be corrected for with PET data alone if the point-spread function of the tomograph has been characterized. Analysis of otherwise homogeneous region-of-interest data ideally requires a combination of tissue classification and correction for the point-spread function. The formulation of appropriate algorithms for partial volume correction (PVC) is dependent on both the distribution of the signal and the distribution of the underlying noise. A mathematical framework has therefore been developed to accommodate both of these factors and to facilitate the development of new PVC algorithms based on the description of the problem. Several methodologies and algorithms have been proposed and implemented in the literature in order to address these problems. These methods do not, however, explicitly consider the noise model while differing in their underlying assumptions. The general theory for estimation of regional concentrations, associated error estimation, and inhomogeneity tests are presented in a weighted least squares framework. The analysis has been validated using both simulated and real PET data sets. The relations between the current algorithms and those published previously are formulated and compared. The incorporation of tensors into the formulation of the problem has led to the construction of computationally rapid algorithms taking into account both tissue-fraction and spillover effects. The suitability of their application to dynamic and static images is discussed.

Algorithms↗

PubMed2002

Automatic "pipeline" analysis of 3-D MRI data for clinical trials: application to multiple sclerosis.

The quantitative analysis of magnetic resonance imaging (MRI) data has become increasingly important in both research and clinical studies aiming at human brain development, function, and pathology. Inevitably, the role of quantitative image analysis in the evaluation of drug therapy will increase, driven in part by requirements imposed by regulatory agencies. However, the prohibitive length of time involved and the significant intraand inter-rater variability of the measurements obtained from manual analysis of large MRI databases represent major obstacles to the wider application of quantitative MRI analysis. We have developed a fully automatic "pipeline" image analysis framework and have successfully applied it to a number of large-scale, multicenter studies (more than 1,000 MRI scans). This pipeline system is based on robust image processing algorithms, executed in a parallel, distributed fashion. This paper describes the application of this system to the automatic quantification of multiple sclerosis lesion load in MRI, in the context of a phase III clinical trial. The pipeline results were evaluated through an extensive validation study, revealing that the obtained lesion measurements are statistically indistinguishable from those obtained by trained human observers. Given that intra- and inter-rater measurement variability is eliminated by automatic analysis, this system enhances the ability to detect small treatment effects not readily detectable through conventional analysis techniques. While useful for clinical trial analysis in multiple sclerosis, this system holds widespread potential for applications in other neurological disorders, as well as for the study of neurobiology in general.

Algorithms↗

PubMed2002

Regional frontal cortical volumes decrease differentially in aging: an MRI study to compare volumetric approaches and voxel-based morphometry.

Recent neuroimaging studies suggest that the frontal lobes are the part of the brain most profoundly affected by the aging process. The present study investigated whether subregions within the frontal cortex show different patterns of brain aging. Magnetic resonance images of 57 healthy participants between 21 and 81 years old were used to measure regional frontal gray matter volumes in three ways: a manual tracing method, a semiautomatic "Talairach boxes" volumetric method, and voxel-based morphometry. Seven regions within each hemisphere were manually traced: precentral gyrus, inferior frontal gyrus, dorsolateral frontal cortex, ventral medial region, lateral orbital region, anterior cingulate, and frontal pole. With the semiautomatic approach, four regions were measured: lateral, orbital, and medial frontal regions and frontal pole. Advancing age was strongly associated with decreases in the volume of the whole frontal cortex. Differential age effects on the volumes of frontal subregions were dependent on the method applied. According to the manual approach, age-related volume decreases were strongest in the lateral and orbital frontal gray matter. The semiautomatic and voxel-based analyses found that age effects were most prominent within the lateral frontal and cingulate regions. Overall, it was concluded that although semiautomated and voxel-based methods can provide a reasonable estimate of regional brain volume, they cannot serve as a substitute for manual volumetry.

Adult↗