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Biomedical subjects

Roger P Woods

Publications and source records attributed to Roger P Woods.

At least 19 recordsLinked to original sources

Asymmetries of cortical shape: Effects of handedness, sex and schizophrenia.

Some evidence suggests that sex, handedness and disease processes associated with schizophrenia affect the magnitude and/or direction of structural brain asymmetries. There are mixed findings, however, on how these factors influence cerebral torque, when torque is assessed with linear or volumetric measurements. We obtained MRI data from 67 healthy (30 males, 10 non-dextrals) and 84 schizophrenia subjects (60 males; 16 non-dextrals) and applied cortical pattern matching to spatially relate and compare differences in the surface morphology of the two cerebral hemispheres at high spatial resolution. Asymmetry indices, computed at thousands of matched hemispheric locations, were used to examine effects of sex, handedness and schizophrenia on hemispheric shape asymmetries while controlling for age and the other factors. Highly significant and discriminative right-frontal and left parietal-occipital surface expansions and protrusions (petalias) were mapped within groups. Although hemispheric shape asymmetries appeared less pronounced within female non-dextrals, asymmetry indices were not shown to differ significantly across sex, hand preference or diagnosis, or to reveal interactions of handedness with sex or diagnosis. Our 3D maps of spatially detailed anterior and posterior hemispheric shape asymmetries reflect subtle geometric distortions in hemispheric surface morphology that cannot be characterized with 2D or volumetric methods. Inter-individual variations in hemispheric torque appear minimally influenced by sex, dextrality or disease status. Biological factors driving language dominance or other lateralized brain functions dissociable from handedness, may more closely relate to hemispheric shape asymmetries, while the lateralization of other discrete brain regions may be more influenced by sexually dimorphic factors or by schizophrenia pathophysiology.

Cerebral Cortex↗

Automatic segmentation of left and right cerebral hemispheres from MRI brain volumes using the graph cuts algorithm.

An automated algorithm has been developed to segment stripped (non-brain tissue excluded) T1-weighted MRI brain volumes into left and right cerebral hemispheres and cerebellum+brainstem. The algorithm, which uses the Graph Cuts technique, performs a fully automated segmentation in approximately 30 s following pre-processing. It is robust and accurate and has been tested on datasets from two scanners using different field strengths and pulse sequences. We describe the Graph Cuts algorithm and compare the results of Graph Cuts segmentations against "gold standard" manual segmentations and segmentations produced by three popular software packages used by neuroimagers: BrainVisa, CLASP, and SurfRelax.

Adult↗

Relationships between IQ and regional cortical gray matter thickness in healthy adults.

Prior studies show positive correlations between full-scale intelligence quotient (FSIQ) and cerebral gray matter measures. Few imaging studies have addressed whether general intelligence is related to regional variations in brain tissue and the associated influences of sex. Cortical thickness may more closely reflect cytoarchitectural characteristics than gray matter density or volume estimates. To identify possible localized relationships, we examined FSIQ associations with cortical thickness at high spatial resolution across the cortex in healthy young adult (age 17-44 years) men (n = 30) and women (n = 35). Positive relationships were found between FSIQ and intracranial gray and white matter but not cerebrospinal fluid volumes. Significant associations with cortical thickness were evident bilaterally in prefrontal (Brodmann's areas [BAs] 10/11, 47) and posterior temporal cortices (BA 36/37) and proximal regions. Sex influenced regional relationships; women showed correlations in prefrontal and temporal association cortices, whereas men exhibited correlations primarily in temporal-occipital association cortices. In healthy adults, greater intelligence is associated with larger intracranial gray matter and to a lesser extent with white matter. Variations in prefrontal and posterior temporal cortical thickness are particularly linked with intellectual ability. Sex moderates regional relationships that may index dimorphisms in cognitive abilities, overall processing strategies, or differences in structural organization.

Adolescent↗

Sex differences in cortical thickness mapped in 176 healthy individuals between 7 and 87 years of age.

Findings from previous magnetic resonance imaging studies of sex differences in gray matter have been inconsistent, with some showing proportionally increased gray matter in women and some showing no differences between the sexes. Regional sex differences in gray matter thickness have not yet been mapped over the entire cortical surface in a large sample of subjects spanning the age range from early childhood to old age. We applied algorithms for cortical pattern matching and techniques for measuring cortical thickness to the structural magnetic resonance images of 176 healthy individuals between the ages of 7 and 87 years. We also mapped localized differences in brain size. Maps of sex differences in cortical thickness revealed thicker cortices in women in right inferior parietal and posterior temporal regions even without correcting for total brain volume. In these regions, the cortical mantle is up to 0.45 mm thicker, on average, in women than in men. Analysis of a subset of 18 female and 18 male subjects matched for age and brain volume confirmed the significance of thicker gray matter in temporal and parietal cortices in females, independent of brain size differences. Further analyses were conducted in the adult subjects where gender differences were evaluated using height as a covariate, and similar sex differences were observed even when body size differences between the sexes were controlled. Together, these results suggest that greater cortical thickness in posterior temporal inferior parietal regions in females relative to males are independent of differences in brain or body size. Age-by-sex interactions were not significant in the temporoparietal region, suggesting that sex differences in these regions are present from at least late childhood and then are maintained throughout life. Male brains were larger than female brains in all locations, though male enlargement was most prominent in the frontal and occipital poles, bilaterally. Given the large sample and the large range of ages studied, these results help to address controversies in the study of central nervous system sexual dimorphisms.

Adolescent↗

Normal variants of Microcephalin and ASPM do not account for brain size variability.

Normal human brain volume is heritable. The genes responsible for variation in brain volume are not known. Microcephalin (MCPH1) and ASPM (abnormal spindle-like microcephaly associated) have been proposed as candidate genes as mutations in both genes are associated with microcephaly, and common variants of each gene are apparently under strong positive selective pressure. In 120 normal subjects, we genotyped these variants and measured brain volumes using magnetic resonance imaging. We found no evidence that the selected alleles were associated with increases or decreases in brain volume. This result suggests that the selective pressure on these genes may be related to subtle neurobiological effects or to their expression outside the brain.

Adolescent↗

Regional specificity of cerebrospinal fluid abnormalities in first episode schizophrenia.

The timing and regional specificity of cerebrospinal fluid (CSF) enlargements have not been well described in schizophrenia. High-resolution magnetic resonance images and computational image analysis methods were used to localize cross-sectional changes in lateral ventricle and sulcal and subarachnoid CSF in first episode schizophrenia patients (51 males/21 females) and healthy subjects (37 males/41 females). Volumes were obtained for each lateral ventricle horn and regional differences identified by comparing the distances from the ventricular surfaces to the central core at anatomically matched locations. Extra-cortical CSF differences were compared by measuring the proportion of CSF voxels sampled from spatially homologous cortical surface points. Significant extra-cortical CSF enlargements were observed in first episode patients, where regional differences surrounded the temporal, anterior frontal and parietal cortices. Volume and ventricular surface analyses failed to show significant effects of diagnosis. However, interactions indicated dorsal superior horn expansions in female patients compared with same-sex controls. Since ventricular enlargements are widely reported in chronic patients, our observations at first episode suggest ventricular enlargement may progress after disease onset with early changes occurring around the dorsal superior horn. In contrast, sulcal and subarachnoid CSF increases may be manifest near or before the first episode but after brain development is complete, reflecting pronounced reductions in proximal brain tissue.

Adult↗

Impact of acquisition protocols and processing streams on tissue segmentation of T1 weighted MR images.

The segmentation of T1-weighted images into gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) is a fundamental processing step in neuroimaging, the results of which affect many other structural imaging analyses. Variability in the segmentation process can decrease the power of a study to detect anatomical differences, and minimizing such variability can lead to more robust results. This paper outlines a straightforward strategy that can be used (1) to select more optimal data acquisition and processing protocols and (2) to quantify the impact of such optimization. Using this approach with multiple scans of a single subject, we found that the choice of a segmentation algorithm had the largest impact on variability, while the choice of a pulse sequence had the second largest impact. The data indicate that the classification of GM is the most variable, and that the optimal protocol may differ across tissue types. Therefore, the intended use of segmentation data should play a role in optimization. Examples are provided to demonstrate that the minimization of variability is not sufficient for optimization; the overall accuracy of the approach must also be considered. Simple volumetric computations are included to illustrate the potential gain of optimization; these results show that volume estimates from optimal pathways were on average three times less variable than estimates from suboptimal pathways. Therefore, the simple strategy illustrated here can be applied to many studies to optimize tissue segmentation, which should lead to a net increase in the power of structural neuroimaging studies.

Adult↗

Automated brain tissue assessment in the elderly and demented population: construction and validation of a sub-volume probabilistic brain atlas.

OBJECTIVES: To develop an automated imaging assessment tool that accommodates the anatomic variability of the elderly and demented population as well as the registration errors occurring during spatial normalization. METHODS: 20 subjects with Alzheimer's disease (AD), mild cognitive impairment, or normal cognition underwent MRI brain imaging and had their 3D volumetric datasets manually partitioned into 68 regions of interest (ROI) termed sub-volumes. Gray matter (GM), white matter (WM), and cerebral spinal fluid (CSF) voxel counts were then made in the subject's native space for comparison against automated volumetric measures within three sub-volume probabilistic atlas (SVPA) models. The three SVPAs were constructed using 12 parameter affine (12 p), 2nd order (2nd), and 6th order (6th) transforms derived from registering the manually partitioned scans into a Talairach compatible AD population-based target. The three SVPA automated measures were compared to the manually derived measures in the 20 subjects' native space with a "jack-knife" procedure in which each subject was assessed by an SVPA they did not contribute toward constructing. RESULTS: The mean left and right GM ratio (GM ratio = [GM + CSF] / CSF) "r values" for the 3 SVPAs compared to the manually derived ratios across the 68 ROIs were 0.85 for the 12p SVPA, 0.88 for the 2nd SVPA, and 0.89 for the 6th SVPA. The mean left and right WM ratio (WM ratio = [WM + CSF] / CSF) "r values" for the 3 SVPAs being 0.84 for the 12p SVPA, 0.86 for the 2nd SVPA, and 0.88 for the 6th SVPA. CONCLUSION: We have constructed, from an elderly and demented cohort, an automated brain volumetric tool that has excellent accuracy compared to a manual gold standard and is capable of regional hypothesis testing and individual patient assessment compared to a population.

Aged↗

Cortical thinning in cingulate and occipital cortices in first episode schizophrenia.

BACKGROUND: Postmortem studies examining discrete regions show reduced cortical thickness in schizophrenia. Computational image analysis methods allow spatially detailed cortical thickness measurements across the entire cortex in 3D, but have not addressed thickness changes in cingulate or other cortices bordering the medial walls of the cerebral hemispheres in first episode schizophrenia. METHODS: Magnetic resonance images and cortical pattern matching methods were used to compare gray matter thickness, measured at sub-voxel resolution at thousands of spatially equivalent locations on the medial hemispheric surfaces, between 72 (51m/21f) first episode schizophrenia patients and 78 (37m/41f) healthy controls similar in age. Group differences were mapped in 3D, and their overall significance was confirmed by permutation testing. RESULTS: Patients with little or no prior antipsychotic medication treatment showed significant cortical thinning within cingulate, occipital and frontopolar cortices with no significant increases in any cortical location. Regional sex differences were observed with pronounced thinning in the left paracentral lobule and right posterior cingulate in male and female patients respectively compared to same sex controls. CONCLUSIONS: Cortical thinning may correspond to cytoarchitectural and neurochemical abnormalities observed in similar anatomic locations and may underlie systems-wise disturbances that include heteromodal association cortices, where cortical thinning has been previously observed in first episode schizophrenia.

Adult↗

Mapping structural differences of the corpus callosum in individuals with 18q deletions using targetless regional spatial normalization.

Individuals with a constitutional chromosome abnormality consisting of a deletion of a portion of the long arm of chromosome 18 (18q-) have a high incidence ( approximately 95%) of dysmyelination. Neuroradiologic findings in affected children report a smaller corpus callosum, but this finding has not been quantified. This is in part due to the large intersubject variability of the corpus callosum size and shape and the small number of subjects with 18q-, which leads to low statistical power for comparison with typically developing children. An analysis method called targetless spatial normalization (TSN) was used to improve the sensitivity of statistical testing. TSN converges all images in a group into what is referred as group common space. The group common space conserves common shape, size, and orientation while reducing intragroup variability. TSN in conjunction with a Witelson vertical partitioning scheme was used to assess differences in corpus callosum size between 12 children with 18q- and 12 age-matched normal controls. Significant global and regional differences in corpus callosum size were seen. The 18q- group showed an overall smaller (25%) corpus callosum (P < 10(-7)), even after correction for differences in brain size. Regionally, the posterior portions of corpus callosum (posterior midbody, isthmus, and splenium), which contain heavily myelinated fibers, were found to be 25% smaller in the population with 18q-.

Agenesis of Corpus Callosum↗

Mapping cortical thickness and gray matter concentration in first episode schizophrenia.

We mapped regional changes in cortical thickness and intensity-based cortical gray matter concentration in first episode schizophrenia. High-resolution magnetic resonance images were obtained from 72 (51 male, 21 female) first episode patients and 78 (37 male, 41 female) healthy subjects similar in age. Cortical pattern matching methods allowed comparisons of cortical thickness and gray matter concentration at thousands of homologous cortical locations between subjects in three dimensions. Principal components analyses reduced measures obtained across the cortex to identify global differences in cortical thickness/gray matter concentration. First principal component factor scores showed significant effects of diagnosis, sex and age for both cortical measures. Diagnosis and age effects remained significant after brain size correction. Cortical thickness and gray matter concentration values were highly correlated. Statistical maps showed significant regional gray matter thinning in frontal, temporal and parietal heteromodal association cortices bilaterally in first episode patients. Regional reductions in cortical gray matter concentration were similar but pronounced in the superior temporal lobe. Regional reductions in cortical thickness and gray matter concentration are present at disease onset in brain regions linked with functional disturbances in schizophrenia. Cortical thickness and gray matter concentration mapping produce similar results, although the concentration metric may be influenced by diagnostic differences in extra-cortical cerebrospinal fluid and surface curvature/complexity.

Adult↗

Regional specificity of hippocampal volume reductions in first-episode schizophrenia.

Hippocampal volume reductions are widely observed in schizophrenia. Some studies suggest anterior hippocampal regions are more susceptible and associated with frontal lobe dysfunctions, while others implicate posterior regions. Using high-resolution MR images and novel computational image analysis methods, we identified the hippocampal subregions most vulnerable to disease processes in 62 (45 m/17 f) first-episode schizophrenia patients compared to 60 (30 m/30 f) healthy controls, similar in age. The hippocampi were traced on coronal brain slices and hemispheric volumes were compared between diagnostic groups. Regional structural abnormalities were identified by comparing distances, measured from homologous hippocampal surface points to the central core of each individual's hippocampal surface model, between groups in 3D. CSF concentrations were also compared statistically at homologous hippocampal surface points to localize corresponding gray matter reductions. Significant bilateral hippocampal volume reductions were observed in schizophrenia irrespective of brain size corrections. Statistical mapping results, confirmed by permutation testing, showed pronounced left hemisphere shape differences in anterior and midbody CA1 and CA2 regions in patients. Significant CSF increases surrounding the hippocampus were observed in a similar spatial pattern in schizophrenia. Results confirm that hippocampal volume reductions are a robust neuroanatomical correlate of schizophrenia and are present by first episode. Mid- to antero-lateral hippocampal regions show pronounced volume changes and complementary increases in peri-hippocampal CSF, suggesting that these hippocampal regions are more susceptible to disease processes in schizophrenia. Targeting regional hippocampal abnormalities may help dissociate schizophrenia patients from other groups exhibiting global hippocampal volume changes, and better focus systems-level pathophysiological hypotheses.

Adolescent↗

A meta-algorithm for brain extraction in MRI.

Accurate identification of brain tissue and cerebrospinal fluid (CSF) in a whole-head MRI is a critical first step in many neuroimaging studies. Automating this procedure can eliminate intra- and interrater variance and greatly increase throughput for a labor-intensive step. Many available procedures perform differently across anatomy and under different acquisition protocols. We developed the Brain Extraction Meta-Algorithm (BEMA) to address these concerns. It executes many extraction algorithms and a registration procedure in parallel to combine the results in an intelligent fashion and obtain improved results over any of the individual algorithms. Using an atlas space, BEMA performs a voxelwise analysis of training data to determine the optimal Boolean combination of extraction algorithms to produce the most accurate result for a given voxel. This allows the provided extractors to be used differentially across anatomy, increasing both the accuracy and robustness of the procedure. We tested BEMA using modified forms of BrainSuite's Brain Surface Extractor (BSE), FSL's Brain Extraction Tool (BET), AFNI's 3dIntracranial, and FreeSurfer's MRI Watershed as well as FSL's FLIRT for the registration procedure. Training was performed on T1-weighted scans of 136 subjects from five separate data sets with different acquisition parameters on separate scanners. Testing was performed on 135 separate subjects from the same data sets. BEMA outperformed the individual algorithms, as well as interrater results from a subset of the scans, when compared for the mean Dice coefficient, a rating of the similarity of output masks to the manually defined gold standards.

Adult↗

Characterizing volume and surface deformations in an atlas framework: theory, applications, and implementation.

Given deformations for mapping images or surfaces into an atlas configuration, methods are described for characterizing the mean deformation and deviations from this mean. Jacobian matrices are used to characterize the deformations locally, and the method can be applied to any image warping method for which Jacobian matrices can be computed. The method makes use of the fact that each matrix descriptor of the local deformation required to match an image to the atlas corresponds to a point on a semi-Riemannian manifold. By assuring that the mean matrix lies within this manifold, fundamental geometric properties common to all of the images can be preserved. Local deviations from the mean can be characterized in a euclidean space tangent to the semi-Riemannian manifold at the mean and can be accumulated globally across multiple sampling locations within the atlas to generate a global multivariate characterization of how each image deviates from the mean.

Algorithms↗

Multitracer: a Java-based tool for anatomic delineation of grayscale volumetric images.

A Java-based tool for delineating anatomic boundaries in 8- and 16- bit grayscale volumetric images is described. Modern features implemented by the tool include the ability to simultaneously view the current cursor position and the previously delineated boundaries on three orthogonal planes, the ability to magnify images during delineation using high-quality interpolation, the ability to encode and save boundaries with subvoxel resolution, and the ability to utilize coregistered images interchangeably during delineation. Additional features facilitate use of the tool in a multiuser, multiplatform environment and provide support for the documentation of anatomic delineation protocols. In addition to providing direct estimates of structure volumes, areas, and lengths, the tool allows contoured boundaries to be exported for more sophisticated analyses. The tool also provides support for manual editing of image volumes to remove confounding structures and for manual correction of image volumes that have been inaccurately edited. In addition to its research utility, the tool also has potential value in education, allowing students to interact with volumetric data and structural boundaries in three dimensions.

Artifacts↗

Modulation of cortical activity during different imitative behaviors.

Imitation is a basic form of motor learning during development. We have a preference to imitate the actions of others as if looking in a mirror (specular imitation: i.e., when the actor moves the left hand, the imitator moves the right hand) rather than with the anatomically congruent hand (anatomic imitation: i.e., actor and imitator both moving the right hand). We hypothesized that this preference reflects changes in activity in previously described frontoparietal cortical areas involved in directly matching observed and executed actions (mirror neuron areas). We used functional magnetic resonance imaging to study brain activity in normal volunteers imitating left and right hand movements with their right hand. Bilateral inferior frontal and right posterior parietal cortex were more active during specular imitation compared with anatomic imitation and control motor tasks. Furthermore this same pattern of activity was also observed in the rostral part of the supplementary motor area (SMA-proper) of the right hemisphere. These findings suggest that the degree of involvement of frontoparietal mirror areas in imitation depends on the nature of the imitative behavior, ruling out a linguistic mediation of these areas in imitation. Moreover, activity in the SMA appears to be tightly coupled to frontoparietal mirror areas when subjects copy the actions of others.

Adult↗

Increases in regional subarachnoid CSF without apparent cortical gray matter deficits in schizophrenia: modulating effects of sex and age.

OBJECTIVE: The authors investigated the modulating effects of biological sex and age on regional decreases in cortical gray matter and increases in subarachnoid CSF in 25 patients with chronic schizophrenia and 28 group-matched healthy comparison subjects. METHOD: Computational cortical pattern-matching methods were employed to measure the local proportions of gray matter and subarachnoid CSF at thousands of homologous cortical surface locations in each subject using high-resolution magnetic resonance images. Principal-component analysis reduced tissue proportion values obtained at each cortical surface point into component scores for each subject. Principal-component analysis scores were used as dependent variables in statistical analyses that included diagnosis, age, and sex as predictor variables. To reveal more regional changes in tissue proportions, statistical differences in gray matter and CSF were compared at each cortical surface location and mapped in three dimensions. RESULTS: Principal-component analyses revealed main effects of diagnosis, sex, and age for the CSF increases seen in the schizophrenia patients, in male subjects, and in association with age. Significant diagnosis-by-age, diagnosis-by-sex, and diagnosis-by-sex-by-age interactions were also observed, revealing CSF increases in male patients at younger ages. Statistical maps showed regional increases in subarachnoid CSF in association with the above effects. For cortical gray matter measurements, only main effects of age were observed. CONCLUSIONS: Regionally specific increases in sulcal and subarachnoid CSF occur during adulthood and appear prematurely in male schizophrenia patients. Cortical gray matter reductions show aging effects but are below the threshold of significance in schizophrenia.

Adult↗

Genetic contributions to altered callosal morphology in schizophrenia.

Patients with schizophrenia exhibit abnormalities in midsagittal corpus callosum area, shape, and/or displacement. Our goal was to confirm these findings and to establish the genetic and nongenetic contributions to altered callosal morphology in schizophrenia. Relationships between ventricular enlargements potentially contributing to callosal displacements were assessed as a secondary goal. High-resolution magnetic resonance images were obtained from co-twins of monozygotic and dizygotic pairs discordant for schizophrenia and healthy control twins (N = 40 pairs). Investigators blind to group status segmented the corpus callosum and ventricles in native brain volumes aligned using a rigid-body transformation with no scaling. Total and parcellated midsagittal callosal areas and measures indexing vertical displacements of the corpus callosum were used in statistical tests to identify schizophrenia and sex effects and to dissociate genetic and nongenetic influences on morphology. Anatomical mesh modeling methods provided group average and surface variability maps of the callosum. Callosal areas did not differ between groups defined by sex or biological risk. Vertical displacements of the callosum, pronounced in male patients, were confirmed in schizophrenia and observed between dizygotic, but not monozygotic co-twins discordant for schizophrenia. Like their affected twins, however, unaffected monozygotic co-twins of the schizophrenia probands exhibited significant callosal displacements. Lateral and third ventricle enlargements were related to callosal displacements. Results clearly support that genetic rather than disease-specific or shared environmental influences contribute to altered callosal morphology in schizophrenia. An upward bowing of the callosum may thus provide an easily identifiable neuroanatomic marker to screen individuals possessing a biological vulnerability for schizophrenia.

Brain Mapping↗