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Biomedical subjects

A C Evans

Publications and source records attributed to A C Evans.

At least 19 recordsLinked to original sources

Cerebral atrophy and its relation to cognitive impairment in Parkinson disease.

OBJECTIVE: Voxel-based morphometry was used to compare the amounts of gray matter in the brains of patients with Parkinson disease (PD) and normal control subjects (NCs) and to identify the specific regions responsible for cognitive dysfunction in PD. METHODS: Patients were classified into nondemented (ND) and demented (D) groups according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.), and a group comparison was performed. In the ND patients, a correlation was also performed between local gray matter density and the score on Raven Colored Progressive Matrices (RCPM), a test of executive and visuospatial function. RESULTS: In patients with advanced ND-PD vs NCs, atrophic changes were observed in the limbic/paralimbic areas and the prefrontal cortex. In D vs ND patients, atrophic change was observed widely in the limbic/paralimbic system, including the anterior cingulate gyrus and hippocampus as well as the temporal lobe, dorsolateral prefrontal cortex, thalamus, and caudate nucleus. The RCPM score was positively correlated with the gray matter density in the dorsolateral prefrontal cortex and the parahippocampal gyrus. CONCLUSIONS: In patients with Parkinson disease (PD), atrophic changes occur mainly in the limbic/paralimbic and prefrontal areas. These atrophic changes may be related to the development of dementia in PD.

Aged↗

Large-scale morphometric analysis of neuroanatomy and neuropathology.

Brain imaging research with MRI spans a wide area, covering both structure and function, and ranging from basic research through clinical research to drug design and clinical trials. In recent years there has been a trend towards the collection of very large MRI databases which can allow for the detection of very small group-dependent effects. However, the logistical challenges of analysing such large datasets presents new challenges. This paper describes the "pipeline" framework developed at the Montreal Neurological Institute for the fully automated morphometric analysis of large brain imaging databases. The potential use of these techniques is illustrated by examples of their applications in multiple sclerosis, Alzheimer's disease, and pediatric development.

Alzheimer Disease↗

Atypical Papanicolaou smear in pregnancy.

Atypical glandular cells (AGC) in Papanicolaou (Pap) smears can be associated with premalignant and malignant cervical and endometrial lesions. AGC is difficult to diagnose in pregnancy due to confusion with normal cellular changes that accompany graviditas. While guidelines have been established for management of AGC cases in the non-pregnant patient, special considerations are required when this is discovered during a pregnancy. A routine Pap smear performed on a 29-year-old woman being seen for a history of infertility yielded AGC and a high-grade squamous intraepithelial lesion. The patient achieved pregnancy 1 month later. Satisfactory colposcopic exam was performed with cytobrush sampling of the endocervical canal, in addition to 2 exocervical biopsies at 11 weeks gestation. Positive diagnosis of endocervical adenocarcinoma in situ resulted in a risk-informed decision to proceed with a cold knife conization of the cervix. Final pathology showed complete resection of the lesion with negative margins and an additional area of squamous dysplasia (cervical intraepithelial neoplasia, grade II to III). Appropriate follow-up was recommended. AGC found upon Pap smear during a pregnancy can be associated with significant pathology for which an aggressive management approach is warranted.

Adult↗

A three-dimensional MRI atlas of the mouse brain with estimates of the average and variability.

Although there is growing interest in finding mouse models of human disease, no technique for quickly and quantitatively determining anatomical mutants currently exists. Magnetic resonance imaging (MRI) is ideally suited to probe fine structures in mice. This technology is three-dimensional, non-destructive and rapid compared to histopathology; hence MRI scientists have been able to create detailed three-dimensional images of 60 mum resolution or better. The data is digital which lends itself to sophisticated image processing algorithms. Here we show a variational MRI atlas constructed from nine excised brains of 8 week old 129S1/SvImJ male mice. This new type of atlas is comprised of an unbiased average brain--created from alignment of the individual brains--and the mathematical descriptors of anatomical variation across the individuals. We found that the majority of internal points in the individuals never varied more than 117 microm from equivalent points in the atlas. A three-dimensional annotation of the average image was performed and used to estimate the mean and standard deviation of volumes in a variety of structures across the individual brains; these volumes never differed by more than 5%. Our results indicate that variational atlases of inbred strains represent a well-defined basis against which mutant outliers can be readily compared.

Algorithms↗

Brain morphometry using 3D moment invariants.

This paper advocates the use of shape descriptors based on moments of 3D coordinates for morphometry of the cortical sulci. These descriptors, which have been introduced more than a decade ago, are invariant relatively to rotations, translations and scale and can be computed for any topology. A rapid insight into the derivation of these invariants is proposed first. Then, their potential to characterize shapes is shown from a principal component analysis of the 12 first invariants computed for 12 different deep brain structures manually drawn for 7 different brains. Finally, these invariants are used to find some correlates of handedness and sex among the shapes of 116 different cortical sulci automatically identified in each of 142 brains of the ICBM database.

Algorithms↗

Object-based morphometry of the cerebral cortex.

Most of the approaches dedicated to automatic morphometry rely on a point-by-point strategy based on warping each brain toward a reference coordinate system. In this paper, we describe an alternative object-based strategy dedicated to the cortex. This strategy relies on an artificial neuroanatomist performing automatic recognition of the main cortical sulci and parcellation of the cortical surface into gyral patches. A set of shape descriptors, which can be compared across subjects, is then attached to the sulcus and gyrus related objects segmented by this process. The framework is used to perform a study of 142 brains of the International Consortium for Brain Mapping (ICBM) database. This study reveals some correlates of handedness on the size of the sulci located in motor areas, which was not detected previously using standard voxel based morphometry.

Algorithms↗

Object-based strategy for morphometry of the cerebral cortex.

Most of the approaches dedicated to automatic morphometry rely on a point-by-point strategy based on warping each brain towards a reference coordinate system. In this paper, we describe an alternative object-based strategy dedicated to the cortex. This strategy relies on an artificial neuroanatomist performing automatic recognition of the main cortical sulci and parcellation of the cortical surface into gyral patches. A set of shape descriptors, which can be compared across subjects, is then attached to the sulcus and gyrus related objects segmented by this process. The framework is used to perform a study of 142 brains of the ICBM database. This study reveals some correlates of handedness on the size of the sulci located in motor areas, which seem to be beyond the scope of the standard voxel based morphometry.

Algorithms↗

A general statistical analysis for fMRI data.

We propose a method for the statistical analysis of fMRI data that seeks a compromise between efficiency, generality, validity, simplicity, and execution speed. The main differences between this analysis and previous ones are: a simple bias reduction and regularization for voxel-wise autoregressive model parameters; the combination of effects and their estimated standard deviations across different runs/sessions/subjects via a hierarchical random effects analysis using the EM algorithm; overcoming the problem of a small number of runs/session/subjects using a regularized variance ratio to increase the degrees of freedom.

Algorithms↗

Estimating the delay of the fMRI response.

We propose a fast, efficient, general, simple, valid, and robust method of estimating and making inference about the delay of the fMRI response modeled as a temporal shift of the hemodynamic response function (HRF). We estimate the shift unbiasedly using two optimally chosen basis functions for a spectrum of time shifted HRFs. This is done at every voxel, to create an image of estimated delays and their standard deviations. This can be used to compare delays for the same stimulus at different voxels, or for different stimuli at the same voxel. Our method is compared to other alternatives and validated on an fMRI data set from an experiment in pain perception.

Brain↗

Ovulation of aged follicles does not affect embryo quality or fertility after a 14-day progestagen estrus synchronization protocol in ewes.

The aim was to examine the effect of ovulation of aged follicles on embryo quality and fertility in ewes. In Experiment 1, ewes (n = 39) received a prostaglandin analogue on Day 6 of the cycle and then received either a progestagen sponge from Day 6 to 20 after estrus (Single sponge) or a progestagen sponge on Day 6 that was replaced on Day 11 and 16 and removed on Day 20 (Multiple sponges). In a subgroup of ewes, the growth of ovarian follicles was characterised using ultrasonography. Fertile rams were introduced 48 hours after sponge withdrawal; we slaughtered the ewes on Day 5 of pregnancy and recovered the embryos. The mean age of the ovulatory follicles was greater in ewes that received a single sponge compared with multiple sponges (8.7+/-0.8 days, range 4 to 14, versus 4.5+/-0.7 days, range 3 to 6; P<0.05). However, the groups did not differ (P>0.05) in ovulation rate (2.4+/-0.3 corporal lutea per ewe) or the proportion of good quality embryos recovered (71 to 82%; developed to the early morula stage or further). In Experiment 2, ewes (570 in total) received treatments similar to those in Experiment 1 but were kept until lambing. Ewes that received a single sponge came into heat earlier (P<0.05) than those that received multiple sponges, but > or = 97% of ewes in all groups (P>0.05) were bred by 48 to 72 hours after ram introduction. There was no difference (P>0.05) between groups for the proportion of ewes that lambed to first service (80 to 86%) or the number of lambs per ewe (1.94+/-0.08 lambs). We conclude that when luteolysis occurs at the beginning of progestagen synchronisation, ewes will ovulate aged follicles, but that compared to shorter duration follicles, these follicles produce oocytes that are equally competent to be fertilised and develop into good quality embryos and full-term lambs.

Administration, Intravaginal↗

Amygdala-hippocampal volume and verbal memory in first-degree relatives of schizophrenic patients.

Verbal memory deficits have been related to reduced volume of medial temporal structures in several neurological and psychiatric populations, including schizophrenic patients. Impairments in verbal memory have been proposed to be a marker of risk for schizophrenia. Recently, relatives of schizophrenic patients have been reported to have reduced volume of the amygdala-hippocampal complex. In this study, we evaluate the possibility that amygdala-hippocampal volume reductions may constitute one neural substrate of verbal memory deficits in first-degree relatives. Subjects were 20 healthy first-degree relatives of schizophrenic patients and 14 demographically similar controls. Verbal memory was assessed with the Logical Memory Test. Subjects were scanned with high-resolution MRI and the images were transformed into Talairach space. Volumes of interest were amygdala-anterior hippocampus and posterior hippocampus. Relatives of schizophrenic patients had intact immediate verbal memory but significantly poorer delayed verbal memory than controls. Relatives also had significantly reduced amygdala-anterior hippocampus volumes. Across all subjects, delayed verbal memory was significantly correlated with amygdala-anterior hippocampus volume. The magnitude of the correlation did not differ between the groups. These data provide an empirical link between memory performance and volumetric abnormalities in the amygdala-hippocampal complex in the relatives of schizophrenic patients.

Adolescent↗

Effect of diet quantity and urea supplementation on oocyte and embryo quality in sheep.

The objective was to investigate the effects of dietary energy and urea supplementation on oocyte and embryo quality in sheep using in vivo and in vitro experimental models. Sixty-three ewes were fed grass meal at 0.5 or 2.0 times maintenance energy requirements (MER). The diet was supplemented with feed grade urea (U) for half of the ewes on each energy treatment. Ewes were stimulated with 1000 IU eCG and either slaughtered on the day of pessary withdrawal, for in vitro embryo production, or mated and slaughtered on Day 5 for embryo recovery. Urea decreased cleavage rate (48.3 vs 39.7%) and consequently blastocyst rate (41.6 vs 36.8%) but the differences were not significant. Oocytes from animals on 2.0 MER had a lower cleavage rate (54.9 vs 36.0%) and blastocyst yield (49.3 vs 31.4%) than those on 0.5 MER. However, there was an interaction between urea and energy for cleavage (P = 0.04) and blastocyst yield (P = 0.03) indicating a variable response to urea in the presence of high energy. This was manifested by a decrease in cleavage rate in the presence of urea and high energy (22%, 8 of 36), and a reduction in blastocyst development (19%, 7 of 36). When blastocyst development rate was expressed as a proportion of cleaved oocytes there was no difference between groups; in addition, there was no difference between groups in terms of blastocyst hatching rate (overall mean 66.1%) or blastocyst cell number on Day 8 (overall mean +/- SEM, 138.4 +/- 9.0, n=61). The effect of urea on cleavage rate in vivo was more severe. Urea supplementation reduced (P<0.001) the cleavage rate (93 vs 62%). Despite this, the yield of blastocysts was unaffected. Oocytes from ewes on 0.5 MER exhibited a lower (P<0.05) cleavage rate than those on 2.0 MER (66 vs 87%). This effect was also apparent at the blastocyst stage (40.0 vs 50.9%), although the difference was no longer significant. There were no differences in hatching rate (overall mean 70.7%) or blastocyst cell numbers (overall mean +/- SEM, 166.3 +/- 15.6, n=40). Collectively, these results suggest that both high dietary energy and urea content influence subsequent embryo development in vitro, and the deleterious effects of urea are likely influenced by concomitant energy intake.

Animals↗

Age and gender predict volume decline in the anterior and posterior hippocampus in early adulthood.

Magnetic Resonance Imaging (MRI) provides a noninvasive method for investigating brain morphology. Within the medial temporal lobe, special attention has been paid to the hippocampus (HC) and amygdala (AG) because of their role in memory, depression, emotion, and learning. Volume changes in these areas have been observed in conjunction with certain disease states, e.g. Alzheimer's disease, post-traumatic stress disorder, and depression. Aging has also been shown to result in gray matter volume loss of the overall brain, including the HC. With regard to gender specificity, results suggest a larger shrinkage for men of brain gray matter, with controversial observations being made for the HC. With recently refined MRI acquisition and segmentation protocols, the HC and AG of 80 subjects in early adulthood (39 men and 41 women, age 18-42 years) were investigated. Whereas the volume of the AG appeared to be independent of age and gender, a significant negative correlation with age for both left and right HC was found in men (r = -0.47 and -0.44, respectively) but not in women (r = 0.01 and 0.02, respectively). The volume decline in men appeared to be linear, starting at the beginning of the third life decade and approximating 1.5% per annum. Using voxel-based regressional analysis, it was shown that changes with age occurred mostly in the head and tail of the HC. This finding underscores the need to include sociodemographic variables in functional and anatomical MRI designs.

Adolescent↗

Focal gray matter density changes in schizophrenia.

BACKGROUND: The view that schizophrenia is a brain disease particularly involving decrements in gray matter is supported by findings from many imaging studies. However, it is unknown whether the (progressive) loss of tissue affects the brain globally or whether tissue loss is more prominent in some areas than in others. METHODS: Magnetic resonance whole brain images were acquired from 159 patients with schizophrenia or a schizophreniform disorder and 158 healthy subjects across a 55-year age span. Gray matter density maps were made and analyzed using voxel-based morphometry. RESULTS: Compared with healthy subjects, decreases in gray matter density were found in the left amygdala; left hippocampus; right supramarginal gyrus; thalamus; (orbito) frontal, (superior) temporal, occipitotemporal, precuneate, posterior cingulate, and insular cortices bilaterally in patients with schizophrenia or schizophreniform disorder. Compared with healthy subjects, increases in gray matter density were exclusively found in the right caudate and globus pallidus in patients with schizophrenia or schizophreniform disorder. A group-by-age interaction for density was found in the left amygdala, owing to a negative regression slope of gray matter density on age in the left amygdala in patients compared with healthy subjects. CONCLUSIONS: Gray matter density is decreased in distinct focal areas in the brains of patients with schizophrenia or schizophreniform disorder. The decreased density in the left amygdala is more pronounced in older patients with schizophrenia.

Adolescent↗

Quantitative brain magnetic resonance imaging in girls with attention-deficit/hyperactivity disorder.

BACKGROUND: Anatomic studies of boys with attention-deficit/hyperactivity disorder (ADHD) have detected decreased volumes in total and frontal brain, basal ganglia, and cerebellar vermis. We tested these findings in a sample of girls with ADHD. METHODS: Anatomic brain magnetic resonance images from 50 girls with ADHD, of severity comparable with that in previously studied boys, and 50 healthy female control subjects, aged 5 to 15 years, were obtained with a 1.5-T scanner with contiguous 2-mm coronal slices and 1.5-mm axial slices. We measured volumes of total cerebrum, frontal lobes, caudate nucleus, globus pallidus, cerebellum, and cerebellar vermis. Behavioral measures included structured psychiatric interviews, parent and teacher ratings, and the Wechsler vocabulary and block design subtests. RESULTS: Total brain volume was smaller in girls with ADHD than in control subjects (effect size, 0.40; P =.05). As in our previous study in boys with ADHD, girls with ADHD had significantly smaller volumes in the posterior-inferior cerebellar vermis (lobules VIII-X; effect size, 0.54; P =.04), even when adjusted for total cerebral volume and vocabulary score. Patients and controls did not differ in asymmetry in any region. Morphometric differences correlated significantly with several ratings of ADHD severity and were not predicted by past or present stimulant drug exposure. CONCLUSIONS: These results confirm previous findings for boys in the posterior-inferior lobules of the cerebellar vermis. The influence of the cerebellar vermis on prefrontal and striatal circuitry should be explored.

Adolescent↗

Measurement of cortical thickness using an automated 3-D algorithm: a validation study.

A validation study was conducted to assess the accuracy of the algorithm developed by MacDonald et al. (1999) for measuring cortical thickness. This algorithm automatically determines the cortical thickness by 3-D extraction of the inner and outer surfaces of the cerebral cortex from an MRI scan. A manual method of tagging the grey-csf and grey-white interface was used on 20 regions (10 cortical areas found in each hemisphere) in 40 MRIs of the brain to validate the algorithm. The regions were chosen throughout the cortex to get broad assessment of the algorithm's performance. Accuracy was determined by an anatomist tagging the csf-grey and grey-white borders of selected gyri and by allowing the algorithm to determine the csf-grey and grey-white borders and the corresponding cortical thickness of the same region. Results from the manual and automatic methods were statistically compared using overall ANOVA and paired t tests for each region. The manual and automatic methods were in agreement for all but 4 of the 20 regions tested. The four regions where there were significant differences between the two methods were the insula left and right, the right cuneus, and the right parahippocampus. We conclude that the automatic algorithm is valid for most of the cortex and provides a viable alternative to manual methods of determining cortical thickness in vivo. However, caution should be taken when measuring the regions mentioned previously where the results of the algorithm can be biased by surrounding grey structures.

Adult↗

A unified statistical approach to deformation-based morphometry.

We present a unified statistical framework for analyzing temporally varying brain morphology using the 3D displacement vector field from a nonlinear deformation required to register a subject's brain to an atlas brain. The unification comes from a single model for structural change, rather than two separate models, one for displacement and one for volume changes. The displacement velocity field rather than the displacement itself is used to set up a linear model to account for temporal variations. By introducing the rate of the Jacobian change of the deformation, the local volume change at each voxel can be computed and used to measure possible brain tissue growth or loss. We have applied this method to detecting regions of a morphological change in a group of children and adolescents. Using structural magnetic resonance images for 28 children and adolescents taken at different time intervals, we demonstrate how this method works.

Adolescent↗

Working memory in another dimension: functional imaging of human olfactory working memory.

The majority of working memory research has been carried out within the visual and auditory modalities, leaving it unclear how other modalities would map onto currently proposed working memory models. In this study we examined the previously uninvestigated area of olfactory working memory. Our aim was to investigate if olfactory working memory would engage prefrontal regions known to be involved in working memory for other sensory modalities. Using positron emission tomography we measured cerebral blood flow changes in 12 volunteers during an olfactory working memory task and a comparison visual working memory task. Our findings indicate that both olfactory and face working memory engaged dorsolateral and ventrolateral frontal cortex when the task requirements were matched; a conjunction analysis indicated overlap in the distribution of activity in the two tasks. Similarities and differences in activity were noted in parietal lobe regions, with both tasks engaging inferior areas of 40/7, but only visual working memory showing increased activity within left superior parietal cortex. The findings support the idea that working memory processes engage frontal cortical areas independent of the modality of input, but do not rule out the possibility of modality-specific neural populations within dorsolateral or ventrolateral cortex.

Adult↗