Biomedical subjects

A W Toga

Publications and source records attributed to A W Toga.

At least 19 recordsLinked to original sources

PubMed2006

Acceleration of cerebral ventricular expansion in the Cardiovascular Health Study.

Interactions between prevalent late-life medical conditions and expansion of the cerebral ventricles are not well understood. Thirty elderly subjects received three magnetic resonance (MR) scans each, in 1997-1999, 2002-2004, and 2003-2005. A linear expansion model of MR-measured lateral ventricle volume was estimated for each subject by fitting a line to a plot of their 1997-1999 and 2002-2004 volumes as a function of time. Acceleration in ventricular expansion was defined as the deviation between the 2003-2005 volumes measured from MR and the 2003-2005 volumes predicted by the linear expansion model. Ventricular acceleration was analyzed in a multivariate model with age, race, history of heart disease, diabetes, and hypertension as fixed effects. Ventricular acceleration was significantly higher in non-whites, diabetics, and those without heart disease (p<0.05). Ventricular acceleration was higher in subjects with a history of hypertension, but the difference was not statistically significant (p=0.08). Acceleration of ventricular expansion in the elderly may be related to demographic and cardiovascular factors.

Aged↗

PubMed2006

In vivo neuropathology of the hippocampal formation in AD: a radial mapping MR-based study.

Early involvement of the hippocampal formation is the biological basis of the typical learning deficit in Alzheimer's disease (AD). However, the hippocampal formation is unevenly affected by AD pathology, deposits of plaques and tangles being particularly dense in the CA1 field and subiculum. The aim of the study was to locate in vivo the structural changes within the hippocampal formation in AD patients of mild to moderate severity. A group of 28 AD patients and 40 cognitively intact persons (age 74 +/- 9 and 71 +/- 7 years) underwent T1-weighted high-resolution MR scans. The hippocampal formation was isolated by manually tracing on 35 coronal slices the outlines of the hippocampus proper and subiculum after registration to a common stereotactic space. Group differences were assessed with algorithms developed ad hoc that make use of three-dimensional parametric surface mesh models. In AD patients, significant atrophic changes amounting to tissue loss of 20% or more were found in regions of the hippocampal formation corresponding to the CA1 field and part of the subiculum. Regions corresponding to the CA2-3 fields were remarkably spared. We conclude that the regions of the hippocampal formation that we found atrophic in AD patients are those known to be affected from pathological studies. This study supports the possibility of carrying out in vivo macroscopic neuropathology of the hippocampus with MR imaging in the neurodegenerative dementias.

Age of Onset↗

PubMed2006

Pontine and cerebellar atrophy correlate with clinical disability in SCA2.

Spinocerebellar ataxia type 2 (SCA2) has protean manifestations, and a clinical marker of progression is needed. Although MRI is a promising tool, it is unclear whether the degree of atrophy shown on MRI is correlated with clinical dysfunction. Here the authors used high-resolution volumetric MRI analysis to show that cerebellar and pontine volumes specifically and closely correlate with functional staging scores.

Adult↗

PubMed2006

Postmortem high-resolution 3-dimensional imaging of the primate brain: blockface imaging of perfusion stained tissue.

Modern anatomy of the brain is primarily concerned with visualizing contrast between tissue elements and with 3-dimensional (3-D) reconstruction. The first objective relies on specific neuroanatomical and imaging protocols, the latter on proper alignment of serial cross-sectional anatomy. We present a method that meets these goals at a resolution that allows for the structural delineation in the primate central nervous system. Methylene blue was administered by perfusion to the intact brain of three rhesus macaques thereby staining the neuropil in the cortex and gray nuclei of the brain in situ. Subsequent dissection and serial sectioning revealed excellent contrast in the tissue and showed clear boundaries between anatomical structures. We captured sequential images of the block surface of the brain before each serial section was cut from the specimen by means of a digital camera mounted directly over the microtome stage and the brain. We developed a suite of algorithms to automate the alignment, segmentation, normalization, and intensity correction for the series of blockface images. These digital images were the basis for 3-D reconstruction of the brains.

Age Factors↗

PubMed2006

Gender effects on cortical thickness and the influence of scaling.

Using magnetic resonance imaging and well-validated computational cortical pattern matching methods in a large and well-matched sample of healthy subjects (n = 60), we analyzed the regional specificity of gender-related cortical thickness differences across the lateral and medial cortices at submillimeter resolution. To establish the influences of brain size correction on gender effects, comparisons were performed with and without applying affine transformations to scale each image volume to a template. We revealed significantly greater cortical thickness in women compared to men, after correcting for individual differences in brain size, while no significant regional thickness increases were observed in males. The pattern and direction of the results were similar without brain size correction, although effects were less pronounced and a small cortical region in the lateral temporal lobes showed greater thickness in males. Our gender-specific findings support a dimorphic organization in male and female brains that appears to involve the architecture of the cortical mantle and that manifests as increased thickness in female brains. This sexual dimorphism favoring women, even without correcting for brain size, may have functional significance and possibly account for gender-specific abilities and/or behavioral differences between sexes.

Adult↗

PubMed2005

Hemispheric asymmetries in cortical thickness.

Using magnetic resonance imaging and computational cortical pattern matching methods, we analyzed hemispheric differences in regional gray matter thickness across the lateral and medial cortices in young, healthy adults (n = 60). In addition, we investigated the influence of gender on the degree of thickness asymmetry. Results revealed global and regionally specific differences between the two hemispheres, with generally thicker cortex in the left hemisphere. Regions with significant leftward asymmetry were identified in the precentral gyrus, middle frontal, anterior temporal and superior parietal lobes, while rightward asymmetry was prominent in the inferior posterior temporal lobe and inferior frontal lobe. On the medial surface, significant rightward asymmetries were observed in posterior regions, while significant leftward asymmetries were evident from the vicinity of the paracentral gyrus extending anteriorly. Asymmetry profiles were similar in both sexes, but hemispheric differences appeared slightly pronounced in males compared with females, albeit a few regions also indicated greater asymmetry in females compared with males. Hemispheric differences in the thickness of the cortex might be related to hemisphere-specific functional specializations that are possibly related to behavioral asymmetries.

Adult↗

PubMed2005

A curvature-based approach to estimate local gyrification on the cortical surface.

Using magnetic resonance imaging and a new method to analyze local surface shape, we examined the effects of gender on gyrification in a large and well-matched sample of healthy subjects. Unlike traditional 2D methods that produce whole-brain measurements of cortical complexity or more sophisticated 3D parametric mesh-based techniques that allow only different sections (lobes) of the cortex to be investigated, we employed a novel approach with increased spatial resolution. Although our method is sensitive to similar cortical features like the classic whole-brain gyrification index (depths of sulci and heights of gyri), we are now able to provide detailed and regionally specific estimates of cortical convolution at thousands of points across the cortical surface without introducing any bias through the rater or the selected orientation of the slices. We revealed pronounced gender differences, showing increased gyrification in frontal and parietal regions in females compared to males that agree with recent regions-of-interest findings. In addition, we detected higher female gyrification in temporal and occipital cortices that was not previously identified in studies using more global measures. No cortical area was significantly more convoluted in males compared to females. Our results demonstrate the sensitivity of this automated approach for identifying very local changes in gyrification. This technique may serve to isolate regionally specific changes in fissuration/gyrification in neurodevelopmental or neuropsychiatric disorders.

Adult↗

PubMed2005

Three-dimensional preoperative maps of hippocampal atrophy predict surgical outcomes in temporal lobe epilepsy.

The authors used surface-based anatomic mapping to detect features of hippocampal anatomy that correlated with surgical outcomes in patients undergoing surgery for mesial temporal lobe epilepsy with hippocampal sclerosis. Compared with a seizure-free group, hippocampal profiles for the non-seizure-free group had greater diffuse ipsilateral atrophy and more region-specific contralateral atrophy in the anterior, lateral hippocampus. These atrophic regions may indicate areas of increased epileptogenicity, contributing to poorer surgical outcomes.

Adult↗

PubMed2005

Parasagittal asymmetries of the corpus callosum.

Significant relationships have been reported between midsagittal areas of the corpus callosum and the degree of interhemispheric transfer, functional lateralization and structural brain asymmetries. No study, however, has examined whether parasagittal callosal asymmetries (i.e. those close to the midline of the brain), which may be of specific functional consequence, are present in the human brain. Thus, we applied magnetic resonance imaging and novel computational surface-based methods to encode hemispheric differences in callosal thickness at a very high resolution. Discrete callosal areas were also compared between the hemispheres. Furthermore, acknowledging the frequently reported sex differences in callosal morphology, parasagittal callosal asymmetries were examined within each gender. Results showed significant rightward asymmetries of callosal thickness predominantly in the anterior body and anterior third of the callosum, suggesting a more diffuse functional organization of callosal projections in the right hemisphere. Asymmetries were increased in men, supporting the assumption of a sexually dimorphic organization of male and female brains that involves hemispheric relations and is reflected in the organization and distribution of callosal fibers.

Adult↗

PubMed2005

Mapping cortical gray matter in the young adult brain: effects of gender.

Using magnetic resonance imaging and well-validated computational cortical pattern matching methods in a large and well-matched sample of healthy subjects, we analyzed the effects of gender on regional gray matter (GM) concentration across the cortex. To clarify discrepancies in previous reports, we also examined sexual dimorphisms for whole-brain tissue volumes with and without controlling for brain size differences. In addition, we generated spatially detailed maps of average GM distributions and variability across the entire cortex given that these descriptors are not well characterized in the normative literature. After brain size correction, we detected numerous cortical regions showing significantly increased GM concentration in females compared to males, but no regionally increased GM concentration in males. Permutation testing confirmed the statistical significance of these findings. Locally increased concentration of cortical GM in females corroborates findings of larger global GM volumes in females after correcting for individual brain sizes. Larger global volumes of GM, white matter and CSF, however, are observed in males when individual brain volumes are not taken into account. Our results show that gender is a major contributor to regional and global GM differences between individuals, although the nature of these effects depend on whether brain size is taken into account.

Adult↗

PubMed2005

Brain structural mapping using a novel hybrid implicit/explicit framework based on the level-set method.

This paper presents a novel approach to feature-based brain image warping, by using a hybrid implicit/explicit framework, which unifies many prior approaches in a common framework. In the first step, we develop links between image warping and the level-set method, and we formulate the fundamental mathematics required for this hybrid implicit/explicit approach. In the second step, we incorporate the large-deformation models into these formulations, leading to a complete and elegant treatment of anatomical structure matching. In this latest approach, exact matching of anatomy is achieved by comparing the target to the warped source structure under the forward mapping and the source to the warped target structure under the backward mapping. Because anatomy is represented nonparametrically, a path is constructed linking the source to the target structure without prior knowledge of their point correspondence. The final point correspondence is constructed based on the linking path with the minimal energy. Intensity-similarity measures can be naturally incorporated in the same framework as landmark constraints by combining them in the gradient descent body forces. We illustrate the approach with two applications: (1) tensor-based morphometry of the corpus callosum in autistic children; and (2) matching cortical surfaces to measure the profile of cortical anatomic variation. In summary, the new mathematical techniques introduced here contribute fundamentally to the mapping of brain structure and its variation and provide a framework that unites feature and intensity-based image registration techniques.

Algorithms↗

PubMed2005

Relative atrophy of the flocculus and ocular motor dysfunction in SCA2 and SCA6.

Two hereditary ataxia syndromes show distinct profiles of region-specific atrophy and ocular motor deficits. Selective pontine atrophy is associated with slowed saccades in ataxin-2 mutations, and selective floccular atrophy is associated with impaired pursuit and gaze-holding abnormalities in Ca(V)2.1 mutations. Although the flocculus seems to be spared relative to the pons in ataxin-2 mutations, and pursuit and gaze-holding appear to be relatively normal, these can be difficult to assess at the bedside, as corrective saccades are also slow and hard to discern. Here, we show the presence of significant floccular atrophy compared with controls in both ataxin-2 and Ca(V)2.1 mutations, which raises the possibility that abnormalities of smooth pursuit or gaze-holding are present in both conditions.

Adult↗

PubMed2004

Localization of the human cortical visual area MT based on computer aided histological analysis.

We describe human area MT histologically based on the observer independent analysis of cortical myeloarchiteture, multiple complementary staining techniques and 3-D reconstruction. The topography of an architectonic field that presented constant structural characteristics across specimens was studied in relation to the sulcal geography of the occipito-temporal region. Objective and semi-automated analysis of local microstructure revealed a distinct cortical architecture and matched topographically the localization of MT derived from functional imaging. MT was localized by the histotopographic method in relation to definite macroscopic landmarks. This study demonstrates a new set of distinguishing architectonic features of human MT that permit localization on structural grounds and suggests that the characteristic laminar structure of this area may be related to its unique pattern of connections and to its role in visual perception.

Cell Shape↗

PubMed2004

In vitro autoradiographic localization of calcitonin and amylin binding sites in monkey brain.

Calcitonin (CT) and amylin are related peptides with potent central actions, including suppression of appetite and gastric acid secretion. Little is known about the distribution and binding characteristics of amylin receptors in species other than rat; therefore, in this study, by using in vitro autoradiography, we have mapped the distribution of 125I-rat amylin binding sites in the monkey brain and compared this distribution to that of binding sites for 125I-salmon CT (125I-sCT). Highest densities of 125I-amylin binding were in the hypothalamus, including the arcuate nucleus and parts of the ventromedial hypothalamic nuclei, and the solitary nucleus. Rostrally, moderate to high density binding was present in parts of the preoptic area, bed nucleus of the stria terminalis, amygdala and accumbens nucleus (Acb). Caudally, binding of amylin was more restricted, with moderate to high density binding present only in dorsal raphe, and area postrema. The primary visual cortex displayed strong and periodic CT binding in layer 4. The subcortical pattern of distribution of amylin and CT receptors in the monkey was similar to that seen previously in the rat, although the relative densities of binding to different brain structures were not always conserved. As with rat, monkey amylin receptors were a subset of the sites labeled with 125I-sCT. Analysis of receptor specificity indicated a greater relative potency of CT peptides in competing for 125I-amylin binding in monkey, when compared to rat, while, there was a decrease in the relative potency of CT gene-related peptides, potentially due to differences the level of receptor activity modifying proteins (RAMPs) in monkey versus rat brain. Amylin receptors in primates are likely to perform a similar role to those in rats; however, the interaction of the receptors with related peptides may differ.

Amyloid↗

PubMed2004

A myelo-architectonic method for the structural classification of cortical areas.

We describe an automatic and reproducible method to analyze the histological design of the cerebral cortex as applied to brain sections stained to reveal myelinated fibers. The technique provides an evaluation of the distribution of myelination across the width of the cortical mantle in accordance with a model of its curvature and its intrinsic geometry. The profile lines along which the density of staining is measured are generated from the solution of a partial differential equation (PDE) that models the intermediate layers of the cortex. Cortical profiles are classified according to significant components that emerge from wavelet analysis. Intensity profiles belonging to each distinct class are normalized and averaged to produce area-specific templates of cortical myelo-architecture.

Brain Mapping↗

PubMed2003

Relationships between sulcal asymmetries and corpus callosum size: gender and handedness effects.

Magnetic resonance imaging was used to establish the presence and nature of relationships between sulcal asymmetries and mid-sagittal callosal size in neurologically intact subjects, and to determine the influences of sex and handedness. Against a background of long-standing disputes, effects of gender and handedness on callosal size, shape, and variability were additionally examined. Both positive and negative correlations between sulcal asymmetry and callosal size were observed, with effects influenced by sex and handedness. The direction of relationships, however, were dependent on the regional asymmetry measured and on whether real or absolute values were used to quantify sulcal asymmetries. Callosal measurements showed no significant effects of sex or handedness, although subtle differences in callosal shape were observed in anterior and posterior regions between males and females and surface variability was increased in males. Individual variations in callosal size appear to outrange any detectable divergences in size between groups. Relationships between sulcal asymmetries and callosal size, however, are influenced by both sex and handedness. Whether magnitudes of asymmetry are related to increases or decreases in callosal size appears dependent on the chosen indicators of asymmetry. It is an oversimplification, therefore, to assume a single relationship exists between cerebral asymmetries and callosal connections.

Adult↗

PubMed2002

An optimized individual target brain in the Talairach coordinate system.

The goal of regional spatial normalization is to remove anatomical differences between individual three-dimensional brain images by warping them to match features of a single target brain. Current target brains are either an average, suitable for low-resolution brain mapping studies, or a single brain. While a single high-resolution target brain is desirable to match anatomical detail, it can lead to bias in anatomical studies. An optimization method to reduce the individual anatomical bias of the ICBM high-resolution brain template (HRBT), a high-resolution MRI target brain image used in many laboratories, is presented. The HRBT was warped to all images in a group of 27 normal subjects. Displacement fields were averaged to calculate the "minimal deformation target" (MDT) transformation for optimization. The greatest anatomical changes in the HRBT, following optimization, were observed in the superior precentral and postcentral gyri on the right, the right inferior occipital, the right posterior temporal lobes, and the lateral ventricles. Compared with the original HRBT, the optimized HRBT showed better anatomical matching to the group of 27 brains. This was quantified by the improvements in spatial cross-correlation and between the group of brains and the optimized HRBT (P < 0.05). An intended use of this processing is to create a digital volumetric atlas that represents anatomy of a normal adult brain by optimizing the HRBT to the group consisting of 100+ normal subjects.

Adult↗

PubMed2001

Mapping continued brain growth and gray matter density reduction in dorsal frontal cortex: Inverse relationships during postadolescent brain maturation.

Recent in vivo structural imaging studies have shown spatial and temporal patterns of brain maturation between childhood, adolescence, and young adulthood that are generally consistent with postmortem studies of cellular maturational events such as increased myelination and synaptic pruning. In this study, we conducted detailed spatial and temporal analyses of growth and gray matter density at the cortical surface of the brain in a group of 35 normally developing children, adolescents, and young adults. To accomplish this, we used high-resolution magnetic resonance imaging and novel computational image analysis techniques. For the first time, in this report we have mapped the continued postadolescent brain growth that occurs primarily in the dorsal aspects of the frontal lobe bilaterally and in the posterior temporo-occipital junction bilaterally. Notably, maps of the spatial distribution of postadolescent cortical gray matter density reduction are highly consistent with maps of the spatial distribution of postadolescent brain growth, showing an inverse relationship between cortical gray matter density reduction and brain growth primarily in the superior frontal regions that control executive cognitive functioning. Inverse relationships are not as robust in the posterior temporo-occipital junction where gray matter density reduction is much less prominent despite late brain growth in these regions between adolescence and adulthood. Overall brain growth is not significant between childhood and adolescence, but close spatial relationships between gray matter density reduction and brain growth are observed in the dorsal parietal and frontal cortex. These results suggest that progressive cellular maturational events, such as increased myelination, may play as prominent a role during the postadolescent years as regressive events, such as synaptic pruning, in determining the ultimate density of mature frontal lobe cortical gray matter.

Adolescent↗