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Quantitative human in vivo evaluation of high resolution MRI for vessel wall morphometry after percutaneous transluminal angioplasty.

Visualization of the vessel wall after transluminal angioplasty is important to monitor the restenosis progress. Intravascular ultrasound proved its capabilities as an invasive procedure in many studies. The aim of this study was to evaluate the feasibility of high-resolution MRI as a non-invasive tool for follow-up after PTA. High-resolution magnetic resonance images (pixel size: 0.49 * 0.49 mm(2)) were acquired on a 1.0 T clinical scanner. Morphometry was conducted after conversion of DICOM images into TIFF format using ScionImage on a PC. In-vitro studies using a polyvinylchloride tube were evaluated by two independent investigators. Goldstandard was a caliper rule and direct radiography. Five patients were monitored before and 24 h, six weeks, three months and six months after PTA. In vivo measurements promised a good concordance for both investigators for area as well as for diameter measurements. Area measurements showed correlations up to r = 0.86 (p < 0.001) whereas the correlations of diameters were slightly inferior (r between 0.58 and 0.84; p < 0.005). Relocation of the same slice position in the follow up studies could be guaranteed using anatomic landmarks in the images. As a non-invasive tool to assess restenosis after PTA high-resolution MRI promises to be a reproducible technique. It is easy to identify the same vascular region in different studies due to neighboring anatomic landmarks. Progression of disease as well as success of pharmacologic treatment to prevent restenosis may be monitored.

Aged↗

Facial three-dimensional morphometry.

Three-dimensional facial morphometry was investigated in a sample of 40 men and 40 women, with a new noninvasive computerized method. Subjects ranged in age between 19 and 32 years, had sound dentitions, and no craniocervical disorders. For each subject, 16 cutaneous facial landmarks were automatically collected by a system consisting of two infrared camera coupled device (CCD) cameras, real time hardware for the recognition of markers, and software for the three-dimensional reconstruction of landmarks' x, y, z coordinates. From these landmarks, 15 linear and 10 angular measurements, and four linear distance ratios were computed and averaged for sex. For all angular values, both samples showed a narrow variability and no significant gender differences were demonstrated. Conversely, all the linear measurements were significantly higher in men than in women. The highest intersample variability was observed for the measurements of facial height (prevalent vertical dimension), and the lowest for the measurements of facial depth (prevalent horizontal dimension). The proportions of upper and lower face height relative to the anterior face height showed a significant sex difference. Mean values were in good agreement with literature data collected with traditional methods. The described method allowed the direct and noninvasive calculation of three-dimensional linear and angular measurements that would be usefully applied in clinics as a supplement to the classic x-ray cephalometric analyses.

Adult↗

A three-dimensional computerized mesh diagram analysis and its application in soft tissue facial morphometry.

A modified computerized mesh diagram analysis that allows rapid and independent quantifications of soft tissue facial size and shape in the three-dimensional space is presented. Normal references are provided, and the application of the method is also exemplified by the analysis of two maxillofacial surgical patients. The Three-Dimensional Facial Morphometry method has been used for the collection of the x, y, z coordinates of 22 soft tissue landmarks in 50 men and 50 women (all healthy young white adults). The method detects the three-dimensional coordinates of retroreflective, wireless markers positioned on selected facial landmarks with two charge-coupled device cameras, working in the infrared field. The midpoint between the right and left tragus landmarks served as the origin of the coordinate axes, and the landmark coordinates were rotated, setting the intercantheal line horizontal on both the frontal and the horizontal planes, and the Camper's plane inclined at -7.5 degrees on the sagittal plane. A standardized mesh of equidistant horizontal (dimension: half the upper face width), vertical (half the vertical projection of upper face height), and anteroposterior (half the horizontal projection of upper face depth) lines was consequently constructed. The lattice was replicated on the entire face and comprised 84 parallelepipeds. Both male and female reference meshes had a harmonious and symmetric appearance, with gender differences in facial size but not in facial shape. The standard normal reference was superimposed on the patient's tracing, and the global (size plus shape) difference was then evaluated by the calculation of the relevant displacement vectors for each soft tissue landmark. A global difference factor was calculated as the sum of the modules of all the displacement vectors. Consequently, a size normalization was performed, and the shape difference (size-standardized) was then evaluated by the calculation of new relevant displacement vectors for each landmark, as well as a shape--global difference vectors.

Adult↗

Stereology, morphometry, and mapping: the whole is greater than the sum of its parts.

The latest developments in computer-based stereology build upon the similarities of classical stereology and computer microscopy to provide refined and effective spatial analyses that also permit mapping of anatomical regions. Classical stereology and computer microscopy have developed along independent pathways as methodologies to provide a quantitative understanding of the structure of the brain. They approach brain morphology and brain morphometry from different points of view. On one hand, stereology has concentrated upon the unbiased numerical estimation of parameters, such as length, area, volume, and population size that characterize entire regions of the brain, e.g. hippocampus, as well as individual elements within them, e.g. cell volume. On the other hand, computer microscopy has concentrated upon providing accurate three-dimensional maps of the morphology of entire regions of the brain as well as of individual elements within them, e.g. neuronal dendrite and axon systems. The differences in point of view are not so extensive as to keep the two methodologies separate. They share, after all, a similar manner of controlling microscope data input and analyzing the images the microscope provides. The incorporation of data archiving permits easier access to previous studies, as well as the sharing of stereological findings and their related maps throughout the scientific community. Some of the stereological systems now integrate spatial mapping with stereological analyses to provide more comprehensive methods to analyze brain tissue.

Animals↗

Chronic schizophrenia as a brain misconnection syndrome: a white matter voxel-based morphometry study.

It has been hypothesized that schizophrenia could be due to a defect of neural circuitry, that is a misconnection between different cerebral areas, particularly those involved in language processing and production. A group of 28 patients with chronic schizophrenia were investigated in order to detect differences in locations of white matter voxel signal intensity in comparison with a control group of 28 normal subjects matched for age, gender and educational level. Voxel-based morphometry was used to assess the white matter of the brain. Significant voxel signal hypointensity was identified in schizophrenic patients bilaterally (mainly in the left hemisphere) in the post-central gyrus and superior temporal gyrus and unilaterally (in the left hemisphere) in the inferior frontal gyrus-pars triangularis and pars pretriangularis, the medial orbital gyrus, the lateral orbital gyrus and the rectus gyrus. Thus, the white matters of these cerebral areas were structurally modified particularly in the left hemisphere and in those structures that control language and hearing processes.

Adult↗

Voxel-based morphometry of grey matter densities in subjects at high risk of schizophrenia.

The grey matter (GM) segments from T1 structural magnetic resonance (MR) images of the brain in subjects at high risk of schizophrenia (n=146) were compared with normal control subjects (n=36) and first episode schizophrenic subjects (n=34) using automated voxel-based morphometry (VBM). The subjects were recruited for the Edinburgh High Risk Study (EHRS) and regional brain volumes had previously been measured using a semi-automated volumetric region of interest (ROI) method of analysis. For the current report, the images were processed using a study specific template and statistically analysed using the SPM99 program. The small volume correction tool in SPM was also used to restrict the analyses to specific voxels. Reductions in the probability of grey matter (GM) density were seen bilaterally in the anterior cingulate, and as a trend in the left parahippocampal gyrus for the high-risk vs. control subjects. In contrast, first episode schizophrenia subjects had less GM than high-risk subjects in several frontal and temporal regions. These results are compatible with the findings of our previous volumetric ROI analysis.

Acute Disease↗

Supporting evidence for the model of cognitive dysmetria in schizophrenia--a structural magnetic resonance imaging study using deformation-based morphometry.

The aim of the study was to investigate whether there is any structural evidence for the model of 'cognitive dysmetria' in schizophrenia if an automatic whole-brain analysis method is used. High-resolution magnetic resonance scans were obtained for 75 schizophrenic patients and 75 controls. These data were analysed using the recently developed deformation-based morphometry allowing the assessment of volumetric differences without a priori definition of regions of interest. When compared with controls, we found reduced volumes in patients with schizophrenia in the frontal lobe (gyrus frontalis superior, medius and medialis), the temporal lobe (gyrus temporalis superior and inferior), the thalamus, the left cerebellar hemisphere and the right cerebellar vermis. There was an increase in volume in the right putamen. To date, this is the first structural magnetic resonance imaging study to demonstrate that the three key-elements of the model of cognitive dysmetria--frontal lobe, thalamus, and cerebellum--are reduced in volume in schizophrenic patients. This highlights the importance of this concept for future investigations.

Adult↗

Searching for a structural endophenotype in psychosis using computational morphometry.

Structural cerebral abnormalities are frequently observed in schizophrenia. These abnormalities may indicate vulnerability for the disorder, as evidenced by reports of familial clustering of measures identified through region-of-interest analyses using manual outlining procedures. We used computational morphometry to detect structural differences within the entire brain to further examine possible structural endophenotypes. Magnetic resonance imaging scans were obtained in 31 psychotic patients, 32 non-psychotic first-degree relatives of psychotic patients and 27 healthy controls. The images were processed using an automated procedure, yielding global grey matter, white matter, CSF and total brain volume. The relative distribution of grey matter was compared between groups on a clustered-voxel basis. Global grey matter and total brain volume did not differ between the groups. White matter volume was significantly higher and CSF volume significantly lower in relatives compared to both cases and controls. The clustered-voxel based group comparison yielded evidence for significant grey matter deficits in fronto-thalamic-cerebellar regions, in psychotic patients, whereas the most prominent deficits in relatives involved the cerebellum. Patients with psychosis and first-degree healthy relatives of patients with psychosis show cerebellar abnormalities, which may constitute a marker of genetic transmission.

Adolescent↗

Magnetic-resonance morphometry in patients with major depression.

Magnetic-resonance morphometry performed on 72 patients with major depression compared with 38 control subjects replicated previously reported, statistically significant reductions in the volumes of the caudate (P < 0.03) and putamen (P < 0.05) in depressed patients. Borderline statistical significance was observed for whole-brain (P < 0.07) and frontal volume (P < 0.10) in a subsample of 32 patients matched on age and sex with 32 control subjects, whereas statistical significance was observed for the full sample (P < 0.007 and P < 0.03, respectively). Chronological age was related to volume of the frontal lobes (P < 0.0002), caudate (P < 0.0001), putamen (P < 0.008), thalamus (P < 0.002), cerebellum (P < 0.007), lateral ventricles (P < 0.0001), and ratios of [whole brain]/[whole brain + cerebrospinal fluid (CSF)] (P < 0.0001) and [frontal]/[frontal + CSF] (P < 0.0001). Age of first depressive episode was related to putamen volume after accounting for chronological age (R2= 0.16, P < 0.005), and a correlation of 0.26 (P < 0.04) was observed between caudate volume and global mental status. Results are in accord with previous reports of basal-ganglia abnormalities in depressed patients and support the role of subcortical structures in mediating affective disorder.

Adult↗

Ultrastructural morphometry of parotid acinar cells following fractionated irradiation.

The aim of this study was to evaluate the long term effects on the ultrastructure of parotid glands after fractionated irradiation. The method implemented involved 5 x 6 Gy and 5 x 8 Gy, Monday to Friday 6 MV photons. By unilateral irradiation, the contralateral parotid gland served as a control. Although irradiation diminished the acinar cell density in light microscopic sections from 75 to 32% after 5 x 8 Gy of irradiation, ultrastructural morphometry could not detect any statistically significant differences in acinar cell size, nuclear size, nuclear density, granule area, mean granule size, or granule density. In general, greater differences were seen between rats receiving 30 or 40 Gy, on both the irradiated and the control size, than between the irradiated side and the control side. This was interpreted as due to differences in the nutritional state of the animals. This analysis concluded that individual acinar cells that survive irradiation seem not to be damaged in the long term when evaluated at the ultrastructural level. The study further stresses the importance of adequate sampling sizes and the use of adequate controls.

Analysis of Variance↗

Morphometry of E-PTA stained synapses at the periphery of pathological lesions.

We carried out a novel application of the disector sampling and counting method, in a biopsy material from the pathologic human brain, to estimate the synaptic structural dynamics, quantitatively. Parietal cortex biopsies of adult (mean age: 40.0 years) and old (mean age: 66.2 years) patients having undergone surgical intervention were investigated. The tissue samples were excised at the periphery of meningioma masses. Synaptic contact zones were stained en bloc by the ethanol phosphotungstic acid (E-PTA) preferential technique which selectively enhances both the pre- and post-synaptic paramembranous material separated by a sharp cleft against a very faint background, thus facilitating and objectifying synaptic morphometry. The disector method, associated with currently used morphometric formulas, enabled us to measure the number of synapses/m3 of tissue (numeric density: Nv); the total area of the synaptic contact zones/m3 of tissue (surface density: Sv) and the average synaptic size (S). In old vs. adult patients, Nv decreased by 7.5% (Mean (SEM): Adult 2.0040(0.0452); Old 1.6780(0.0623)), while S increased by 17.5% (Adult 0.0203(0.0026); Old 0.0246(0.0035)). Sv did not show any age-related difference. The same negative correlation between Nv and S has also been reported in physiological aging, and this suggests the active presence of age-related synaptic restructuring mechanisms in the nervous tissue surrounding a tumoral mass.

Adult↗

A morphological study of the effect of chlorambucil during the S and G2 phases of the cell cycle of synchronized HEp-2 cancer cell populations using computerized morphometry.

Chlorambucil, a bisalkylating agent, used extensively in the treatment of autoimmune and neoplastic diseases, is known to affect DNA synthesis. However recent studies have revealed that it also affects the synthesis of other nuclear protein constituents, especially histones. Since histones play a major role in both the structural and functional integrity of chromatin, we have analyzed the morphological effects of this agent, using low dose conditions and synchronized populations of HEp-2 cancer cells in the S and G2 phases of the cell cycle. Analyses at the light and electron microscopy levels were undertaken using synchronous image analysis techniques. Computerized morphometry was used so as to evaluate various nuclear and cytological morphological parameters. It was found that chlorambucil affects the organization of chromatin, as well as other cellular parameters in a manner characteristic of decreased tumor aggressiveness. A finding of significance in this study was that chlorambucil exerted its influence on all these morphological parameters only when treatment was initiated at the beginning of the S phase and not during the second half of the S phase or the G2 phase.

Antineoplastic Agents, Alkylating↗

Morphometry of the corneal endothelium in glassblowers compared to non-glassblowers.

Acute exposure to high levels of IR radiation (IRR) can damage the endothelial cell layer of the human cornea, but the impact of chronic lower-dose exposure has not been assessed objectively. The corneal endothelium of 10 individuals who had occupational exposure to IRR as glassblowers (average 16 years) was examined by photo-slitlamp biomicroscopy, the endothelial mosaic assessed by morphometry, and compared to 10 non-glassblowers (controls). The analyses reveal the glassblowers to have higher than expected endothelial cell density (ECD, average 3371+/-304 cells/mm(2) compared to a control value of 3072+/-198 cells/mm(2)), a higher variance in cell area, and a lower percentage of the most-prevalent cell type, i.e. the six-sided cells (average 52.0+/-12.2%, compared to controls of 64.1+/-6.6%). Analyses of the sizes of different cell types (four-, five-, six-sided, etc.) indicate that the cells in both groups are proportionately larger as the number of sides increases, but that this area-side relationship is different in the glassblowers, who had both smaller and larger cells compared to controls. Two other cases had even higher cell density values (>5000 cells/mm(2)) and <50% six-sided cells. Occupational exposure to a mixture of IRR, perhaps some UVR as well as thermal convection effects, can apparently result in morphological changes in the human corneal endothelium. These may be the result of IRR-stimulated cell division.

Endothelium, Corneal↗

A comprehensive study of gray matter loss in patients with Alzheimer's disease using optimized voxel-based morphometry.

Voxel-based morphometry (VBM) has already been applied to MRI scans of patients with Alzheimer's disease (AD). The results of these studies demonstrated atrophy of the hippocampus, temporal pole, and insula, but did not describe any global brain changes or atrophy of deep cerebral structures. We propose an optimized VBM method, which accounts for these shortcomings. Additional processing steps are incorporated in the method, to ensure that the whole spectrum of brain atrophy is visualized. A local group template was created to avoid registration bias, morphological opening was performed to eliminate cerebrospinal fluid voxel misclassifications, and volume preserving modulation was used to correct for local volume changes. Group differences were assessed and thresholded at P < 0.05 (corrected). Our results confirm earlier findings, but additionally we demonstrate global cortical atrophy with sparing of the sensorimotor cortex, occipital poles, and cerebellum. Moreover, we show atrophy of the caudate head nuclei and medial thalami. Our findings are in full agreement with the established neuropathological descriptions, offering a comprehensive view of atrophy patterns in AD.

Aged↗

The morphometry of auditory cortex in the congenitally deaf measured using MRI.

The study of congenitally deaf individuals provides a unique opportunity to understand the organization and potential for reorganization of human auditory cortex. We used magnetic resonance imaging (MRI) to examine the structural organization of two auditory cortical regions, Heschl's gyrus (HG) and the planum temporale (PT), in deaf and hearing subjects. The results show preservation of cortical volume in HG and PT of deaf subjects deprived of auditory input since birth. Measurements of grey and white matter, as well as the location and extent of these regions in the deaf showed complete overlap both with matched controls and with previous samples of hearing subjects. The results of the manual volume measures were supported by findings from voxel-based morphometry analyses that showed increased grey-matter density in the left motor hand area of the deaf, but no differences between the groups in any auditory cortical region. This increased cortical density in motor cortex may be related to more active use of the dominant hand in signed languages. Most importantly, expected interhemispheric asymmetries in HG and PT thought to be related to auditory language processing were preserved in these deaf subjects. These findings suggest a strong genetic component in the development and maintenance of auditory cortical asymmetries that does not depend on auditory language experience. Preservation of cortical volume in the deaf suggests plasticity in the input and output of auditory cortex that could include language-specific or more general-purpose information from other sensory modalities.

Adult↗

Evaluation of voxel-based morphometry for focal lesion detection in individuals.

Voxel-based morphometry (VBM) is an automated statistical technique used to detect regional differences in tissue density and tissue amount based on spatially standardized structural magnetic resonance (MR) images. Developed initially to discern differences between groups of subjects, VBM is now being used to characterize structural abnormalities in individual brains. While VBM performance has been qualitatively assessed for this purpose, to date no quantitative validation study has been performed. This study evaluated several commonly used variants of VBM for detecting structural differences at the individual level by assessing their performance in MR images of 10 subjects with stable focal brain lesions. Results were quantitatively compared to expert tracings of the lesions, the current gold standard for lesion detection and delineation. Additionally, analyses using two sets of simulated lesion data were performed to examine the relative impact of the underlying processing steps on VBM results. Performance metrics revealed that (1) for this application, VBM had low sensitivity; (2) detection sensitivity was altered by model parameterization; (3) underperformance was due to the adverse influence of lesions on the preprocessing steps and to insufficient statistical power; and (4) VBM could not satisfactorily delineate the spatial extent of lesions, even in simulations that avoided preprocessing artifacts. In its current form, VBM is not a suitable stand-alone technique for detecting or spatially characterizing focal lesions.

Adult↗

Morphometry and allometry of the postnatal lung development in the quokka wallaby (Setonix brachyurus): a light microscopic study.

The postnatally developing lungs of the quokka wallaby, Setonix brachyurus, were investigated macroscopically and by light microscopic morphometry. Lung, parenchymal and non-parenchymal volumes as well as the components of the latter two were analysed by regression analysis. The lungs comprised a single undivided left lung and a right lung with an adherent accessory lobe. Septal tissue growth was most remarkable in the canalicular and saccular stages. Between mid-canalicular stage and the saccular stage, the lung volume increased 2-fold, mainly due to airspace expansion, coupled with septal tissue thinning. The non-parenchymal vascular volume increase accelerated in the successive developmental stages while the airway and connective tissue volumes progressed in a decreasing order, being highest in the canalicular and saccular stages and lowest in the alveolar stage. Growth and remodelling of the alveolar septa occurred simultaneously with airspace subdivision. Airspace expansion accelerated during the stage of microvascular maturation, when most other parameters showed the least rate of increase.

Animals↗

Morphometry in schizophrenia revisited: height and its relationship to pre-morbid function.

BACKGROUND: Morphometry, the measurement of forms, is an ancient practice. In particular, schizophrenic somatology was popular early in this century, but has been essentially absent from the literature for over 30 years. More recently, evidence has grown to support the notion that aberrant neurodevelopment may play a role in the pathophysiology of schizophrenia. Is the body, like the brain, affected by abnormal development in these patients? METHODS: To evaluate global deficit in development and its relationship to pre-morbid function, height was compared in a large group (N = 226) of male schizophrenics and a group of healthy male controls (N = 142) equivalent in parental socio-economic status. Patients in the lower quartile of height were compared to those in the upper quartile of height. RESULTS: The patient group had a mean height of 177.1 cm, which was significantly shorter than the mean height of the control group of 179.4 (P < 0.003). Those in the lower quartile had significantly poorer pre-morbid function as measured by: (1) psychosocial adjustment using the pre-morbid adjustment scales for childhood and adolescence/young adulthood, and (2) cognitive function using measures of school performance such as grades and need for special education. In addition, these measures of pre-morbid function correlated significantly with height when analysed using the entire sample. CONCLUSIONS: These findings provide further support to the idea that abnormal development may play a key role in the pathophysiology of schizophrenia. Furthermore, this is manifested as a global deficit in growth and function resulting in smaller stature, poorer social skills, and deficits in cognitive abilities.

Adolescent↗