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Detecting bilateral abnormalities with voxel-based morphometry.

In this article we describe a new method, using SPM99, that searches explicitly for bilateral structural abnormalities. Children with bilateral pathology have a poorer prognosis than children with unilateral damage. After brain injury or disease in childhood, it is thought that rescue of function is only possible if the neuronal substrates of that function are preserved and operational in at least one hemisphere [Vargha-Khadem and Mishkin, 1997]. If this is the case, the detection of bilateral abnormalities would greatly facilitate more accurate prognosis in children with brain injury or developmental disorders. We have therefore developed a technique to detect bilateral abnormalities that uses conjunction analysis with voxel based morphometry. It is illustrated using a group of patients with bilateral hypoxic-ischaemic damage to the hippocampus. The approach is shown to have enhanced specificity and sensitivity relative to conventional unilateral characterisations.

Amnesia↗

Effect of nebracetam on content of high-energy phosphates and morphometry of rat astrocytes in vitro. Comparison with piracetam.

The present study was initiated to examine the effect of nebracetam, a nootropic drug, on various biochemical and morphometric parameters in order to gain some insight into the mechanism of this agent action. The content of adenosine triphosphate (ATP) and phosphocreatine (PCr) and 3H-valine incorporation into proteins was measured and the morphometry was performed after nebracetam and piracetam treatment of rat astrocytes cultured in vitro with or without dibutyryl 3',5'-cyclic adenosine monophosphate (dBcAMP). Nootropics were added into the culture medium for 2 weeks at the final concentration of 10(-7) M. Cultured astrocytes treated with either nebracetam or piracetam showed decreased intracellular ATP and PCr levels. The addition of nebracetam and dBcAMP to cultures caused an increase of PCr content in astrocytes. The astrocytes treated with nebracetam showed a decrease in 3H-valine incorporation. The increase of 3H-valine incorporation into astrocytes after piracetam with dBcAMP treatment was found. Nootropic drugs change morphometric parameters (cell area, perimeter and form factor) of cultured astrocytes. It can be concluded that nootropics have differentiated influence on both the energetic metabolism and morphology of rat astrocytes in vitro.

Adenosine Triphosphate↗

Comparative morphometry, morphology of egg and adult surface topography under light and scanning electron microscopies, and metaphase karyotype among three size-races of Fasciola gigantica in Thailand.

Comparative morphometry of eggs and adults under light microscope, and morphology of adults under scanning electron microscope (SEM) were undertaken in the three size-races (< 25 mm, 25-35 mm, > 35 mm) of Fasciola gigantica (Thailand strain). Morphometric examination revealed intraspecific variation with respects to the dimensions of eggs and adults, whereas surface topography of the three size-race adults under SEM was morphologically similar. The observations on mitotic metaphase chromosomes of spermatogonial cells from testes of the three size-races revealed 2n=20 (diploid type), and no karyotypic difference was observed among them. The meiotic metaphase chromosome was 10 bivalents in primary spermatocyte in diplotene to diakinesis, and many mature spermatozoa were seen in the testicular preparations.

Animals↗

Quantitative morphometry of glomerulonephritis with crescents. Diagnostic and predictive value.

Histologic patterns in the glomerular tufts in "Glomerulonephritis with many crescents" take three main forms: (1) compression and sclerosis of glomeruli, (2) necrotizing glomerulitis, and (3) proliferation with or without exudation. In the third group, histologic differentiation between patients with poststreptococcal glomerulonephritis with many crescents (AGN) and those with nonstreptococcal rapidly progressive glomerulonephritis (RPGN) may be impossible. In a retrospective study, quantitative morphometry of glomeruli effectively separated three patients with AGN from two patients with RPGN after the usual histologic and electron microscopic observations had failed. Parameters studied were areas of tufts and crescents and total number of cells and granulocytes in tufts and crescents. Surface areas of tufts and crescents were separately determined by photographing glomeruli, projecting and tracing outlines of tufts and crescents, and cutting out and weighing the tracings. The cell density of glomerular tufts (cell per 1000-sq. mum. area) was significantly greater in AGN than in RPGN when either total cell densities (17.64 plus or minus 0.41 versus 13.63 plus or minus 0.30) or total cells minus granulocytes (16.39 plus or minus 0.50 versus 12.99 plus or minus 0.52) were compared. The cell density in the tufts was 120 and 70 per cent greater than controls in AGN and RPGN, respectively. Exudation of inflammatory cells is contributory but not the major cause of hypercellularity in AGN. Follow-up studies with biopsies showed marked resolution in two of three patients with AGN, with normal blood urea nitrogen levels and focal scarring in the third, whereas the two patients with RPGN had either extensive scarring and reduced renal function or required chronic hemodialysis.

Adolescent↗

Objectively measured sperm motility and sperm head morphometry in boars (Sus scrofa): relation to fertility and seminal plasma growth factors.

This study was conducted to investigate the relationships between results of computer-assisted semen analysis (spermatozoal motility and sperm head morphometry) and fertility of boars. In addition, concentrations of insulin-like growth factor (IGF)-I and IGF-II in seminal plasma were determined. The nonreturn rate (NRR) and the number of live-born piglets were compatible with the requirements of artificial insemination for all boars included in this study. Semen samples of 12 boars (Pietrain; 3 ejaculates each) were evaluated for spermatozoal motility and sperm head dimensions using computer-assisted methods. Native semen samples were centrifuged, and seminal plasma was frozen at -20 degrees C until assayed for IGF-I and IGF-II by specific radioimmunoassays. Spermatozoa of boars with a higher NRR (>86%) had a significantly slower average velocity of motile spermatozoa when compared with that of boars with an NRR below 86%. High-fertility boars (NRR > 86%) had significantly smaller sperm heads than did boars with an NRR below 86%, and their sperm heads were less elongated. Substantial concentrations of IGF-I (8.4-22.2 ng/mL) and IGF-II (12.1-19.8 ng/mL) could be measured in porcine seminal plasma; however, there was no correlation between IGF levels and semen parameters or individual fertility.

Animals↗

Nucleolar morphometry in fine needle aspiration biopsies of the prostate.

OBJECTIVE: To find efficient morphometric nucleolar features for distinguishing different prostatic atypia groups in fine needle aspiration biopsies. STUDY DESIGN: A computerized interactive morphometry program was used to outline nucleoli of prostate cells. The samples were divided into three groups: group 1 (definitely benign [n = 10] and atypical but benign [n = 13]), group 2 (moderately atypical [n = 11] or highly suspicious [n = 13]) and group 3 (definitely malignant [n = 17]). RESULTS: The analysis revealed a difference in the number of nucleoli between definitely benign samples and other atypia groups but not between the latter. Nucleolar size features were best in distinguishing between atypia groups. The sample-associated mean size features were more powerful than cell group-associated size features. CONCLUSION: The sample-associated mean area, defined from cells selected by an experienced cytologist, if larger than 2 micron 2, was strongly associated with definitely malignant samples. The same was true for the largest nucleolar area if larger than 5.0 micron 2. Morphometric nucleolar size features appeared efficient in distinguishing between definitely malignant and other samples.

Adenocarcinoma↗

[Method for the functional evaluation of contrasted vessels of the lungs with the aid of stereoroentgenogrammetry and morphometry].

A complex method for measuring vessels of the lungs is suggested; the method includes a number of successive procedures: contrasting of vessels under physiological pressure, stereoscopy of the preparation of the lung in a non-atelectatic and non-fixed state and obtaining of stereopaired angiograms, marking the levels of branching of vessels and determination of their lumen by means of stereocomparator, fixation of the lung, spot cutting and morphometry of the wall of the same segments of the lung vessels. The size of the lumen of the vessel approximating the intravital one, was combined with morphometric parametres of its wall and indices were calculated characterizing a morpho-functional state of the blood flow bed of the lungs.

Angiography↗

The expression of PDGF, its receptors and capillary morphometry in the developing lung: quantitative studies.

The aim of the present study was the evaluation of the expression levels of PDGF-A and B, and PDGFR-alpha, andchanges of capillary cross-sectional areas during terminal vascular network formation in the developing lung. Pathogen-free fetuses and newborns used for rats were used. Lungs were processed for frozen section immunohistochemical staining and parallel tissue specimens were prepared for transmission electron microscopy. The expression levels of PDGF-A and B, and PDGFR-alpha were obtained using quantitative image analysis. Additionally. the morphometry of capillary cross-sectional area was performed. We found that the expression levels of the studied antigens fluctuated, and the highest values were found in21-day old fetuses (p < 0.0001). Although there were no significant differences of the area of "a single" capillary, the area of the endothelium decreased significantly in perinatal period (p <0.0001). We conclude that the statistically significant changes of the studied antigens' expression as well as the of capillary cross-sectional area occur in the perinatal period,

Animals↗

Patterns of cerebral atrophy in dementia with Lewy bodies using voxel-based morphometry.

Previous cross-sectional MRI studies based on region-of-interest analyses have shown that increased cerebral atrophy is a feature of both Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Relative preservation of the hippocampus and temporal lobe structures in DLB compared to AD has been reported in region-of-interest-based studies. Recently, image processing techniques such as voxel-based morphometry (VBM) have been developed to provide an unbiased, visually informative, and comprehensive means of studying patterns of cerebral atrophy. We report the first study to use the voxel-based approach to assess patterns of cerebral atrophy in DLB compared to control subjects and AD. Regional gray matter volume loss was observed bilaterally in the temporal and frontal lobes and insular cortex of patients with DLB compared to control subjects. Comparison of dementia groups showed preservation of the medial temporal lobe, hippocampus, and amygdala in DLB relative to AD. Significant gray matter loss was also observed in the thalamus of AD patients compared to DLB.

Aged↗

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

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

Adult↗

Structural gray matter differences between first-episode schizophrenics and normal controls using voxel-based morphometry.

The aim of this study was to compare the gray matter segments from T1 structural MR images of the brain in first-episode schizophrenic subjects (n = 34) and normal control subjects (n = 36) using automated voxel-based morphometry (VBM). This study is novel in that few studies have examined subjects in their first episode of schizophrenia. The subjects were recruited for the Edinburgh High Risk project and regional brain volumes were previously measured using a semi-automated volumetric region of interest (ROI) method of analysis. The primary interest was to compare the results from the compatible parts of the ROI study and the primary VBM approach. Our secondary interest was to compare the results of a study-specific template that was constructed from the control group to those using the generic T1 template (152 Montreal Neurological Institute brains) supplied with SPM99 (statistical parametric mapping). The images were processed and statistically analyzed using the SPM99 program. VBM analysis identified significant decreases in gray matter in the schizophrenics relative to the normal control group at the corrected voxel level (P < 0.05) in the right anterior cingulate, right medial frontal lobe, left middle temporal gyrus, left postcentral gyrus, and the left limbic lobe. There were no increases in gray matter in the schizophrenics relative to the control group. The construction of a customized template appeared to improve the detection of structural abnormalities. The analyses were subsequently restricted to voxels within the amygdala-hippocampal complex using the SPM small-volume correction. This identified gray matter decreases in the schizophrenics, at the corrected voxel level (P < 0.05), in the left and right uncus and parahippocampal gyri and the right amygdala. These results are compatible with and extend the relevant findings of the previous volumetric ROI analysis, when allowing for the differences between the methods and interpretation of their results.

Adult↗

Voxel-based morphometry in hypocretin-deficient narcolepsy.

STUDY OBJECTIVES: Recent studies suggest that narcolepsy is caused by degeneration of hypocretin (orexin) producing neurons. To find evidence for this hypothesis, we aimed to detect structural changes in the hypothalamus and/or hypocretin projection areas of patients with narcolepsy. DESIGN: We used voxel-based morphometry (VBM), an unbiased MRI morphometric method with a high sensitivity for subtle changes in gray and white matter volumes. SETTING: Image acquisition was carried out in the department of Radiology at Leiden University Medical Center; image post-processing was performed in the Wellcome Department of Cognitive Neurology, London. PARTICIPANTS: Fifteen narcoleptic patients were studied, all having cataplexy and typical findings on Multiple Sleep Latency Testing. All patients were HLA-DQB1*0602 positive and hypocretin-1 deficient. The control group consisted of 15 age and sex matched healthy subjects. MEASUREMENTS AND RESULTS: We found no differences in global gray or white matter volumes between patients and controls. Furthermore, regional gray or white matter volumes in the hypothalamus and hypocretin projection areas did not differ between patients and controls. CONCLUSIONS: VBM failed to show structural changes in the brains of patients with narcolepsy. This suggests that narcolepsy either is associated with microscopic changes undetectable by VBM or that functional abnormalities of hypocretin neurons are not associated with structural correlates.

Adult↗

Comparison between morphometry and immunostaining of malignant cells in non-small cell lung cancer.

OBJECTIVE: To investigate the morphometric properties of tumor cells in combination with the expression of 5 immunomarkers, quantitatively evaluated by image analysis, in a series of 60 non-small cell lung carcinomas (NSCLCs) and to assess their prognostic significance. STUDY DESIGN: Tissue sections from 60 NSCLCs were assessed for the expression of p53, Ki-67, bcl-2, bax and FasL using immunohistochemistry and antibodies. Correlations between morphometric features and clinicopathologic variables, including overall survival and the expression of the above markers, were statistically investigated. RESULTS: Major and minor axis nuclear values, as well as nuclear area and perimeter values, were positively interrelated. No statistically significant correlations were observed between nuclear morphometry and any of the clinicopathologic parameters. p53 Accumulation, when quantitatively estimated, displayed a positive correlation with major axis (P = .008), minor axis (P = .06), nuclear perimeter (P = .006) and mainly nuclear area values (P = .003). Bcl-2- and bax-quantified immunostaining demonstrated a weak negative correlation with shape factor values (P = .039 and P = .025, respectively). Univariate and multivariate analysis showed that stage was the only significant predictor of survival in all patients. In univariate statistical analysis there was a trend between worse survival and shape factor values < 0.8 (P = .0791); this trend almost reached statistical significance in the subgroup of squamous cell carcinomas (P = .0570). CONCLUSION: p53 Accumulation, when quantified, appears to be positively linked with nuclear morphometric values. The prognostic significance of shape factor in NSCLC warrants further investigation.

Biomarkers, Tumor↗

The role of flow cytometry and morphometry in discriminating benign from malignant nonfunctioning pancreatic endocrine tumors.

Nonfunctioning pancreatic endocrine tumor (NFPET) is a kind of tumor with high malignancy but bland in morphological features. It is impossible to predict the malignancy solely by gross and light microscopic pictures of the tumor. For the purpose of assessing the value of flow cytometry and morphometry in predicting the prognosis of NFPET, the DNA content and several morphological parameters of 26 NFPETs were determined by appropriate techniques. The results show that abnormal DNA content has no practical value in discriminating benign from malignant NFPETs; whereas the "score" obtained by combining the morphological measurements of the number of nuclei/mm2 and N/C, is of certain referential significance in predicting the malignancy of NFPET.

Adenoma, Islet Cell↗

Nuclear morphometry and DNA flow cytometry as prognostic factors in female breast cancer.

OBJECTIVE: To evaluate the predictive value of traditional prognostic factors, nuclear morphometry, and flow cytometric data in invasive breast cancer. DESIGN: Open study. SETTING: One university hospital in Finland. SUBJECTS: 248 women with invasive breast cancer followed up for more than 11 years. MAIN OUTCOME MEASURES: Univariate and multivariate analysis of factors thought to indicate prognosis. RESULTS: Diameter of the tumour, lymph node status, S phase fraction. DNA index, the age of the patient, and the SD of nuclear perimeter were significant independent predictors in the whole series in a multivariate analysis. In node negative patients the SED of the nuclear perimeter and diameter of the tumour had independent prognostic value, whereas in node positive patients diameter of the tumour and the S phase fraction were independently related to survival. CONCLUSIONS: Diameter of the tumour is an important prognostic factor in breast carcinomas. Histoquantitative methods are superior to conventional histological techniques for the prediction of outcome in women with breast cancer.

Adult↗

Morphometry and discriminant analysis of the endometrium.

The authors dated 100 normal endometrial biopsies. Only endometrial specimens with histologically confirmed subphases and no evidence of organic disease were accepted for study. The morphometry and stereologic measures of the glands, lumina and endometrial epithelium were assessed. Quantitative assessment of the normal endometrium supported the histologic events that occur in the endometrial cycle (proliferative and secretory phases). There was a progressive increase in morphometric and stereologic values of the glands, epithelium and lumina during the endometrial cycle. Using stepwise discriminant analysis, 94% of the specimens were correctly classified into the categories of proliferative and secretory phase; two quantitative parameters were required, the epithelial volume density and longest luminal diameter. When three subphases within proliferative and secretory endometrium were considered, the overall accuracy was 90% and 78%, respectively.

Biopsy↗

[Nuclear morphometry and DNA cytometry in the grading of malignant tumors of the salivary gland].

Nuclear morphometry and DNA cytometry were performed in 6 normal salivary glands and 37 malignant tumors of the salivary gland. Multivariate discrimination analysis was used to grade the malignant salivary gland tumors. The discrimination rate was 100% for normal salivary gland, benign tumor, high malignant carcinoma and low malignant carcinoma. It was 66.7% for borderline malignancies. These results indicate that quantitative cytological analysis is effective and reproducible in the grading of salivary gland tumors. Stepwise multivariate regression analysis showed that there was a very complicated correlation between DNA content and nuclear morphometric parameters of salivary gland tumors.

Adenocarcinoma↗

DNA ploidy and nuclear morphometry in adult intracranial ependymomas.

The identification of prognostic parameters in ependymomas remains an important but controversial issue in particular to the significance of histopathological features. Intracranial location is a rare presentation for adult ependymomas. DNA ploidy status and nuclear morphometric features of ependymomas are not well-established. We retrospectively studied the clinicopathologic features of 12 adult intracranial ependymomas and performed image cytometric DNA analysis with nuclear morphometry. The overall survival rate was 75%. Two cases were anaplastic ependymomas. Statistically, histology failed to demonstrate a correlation with clinical outcome or overall survival. DNA ploidy (p = 0.033), DNA index (p = 0.016) and 5c exceeding rate (p = 0.017) were statistically correlated with clinical outcome, but not correlated with overall survival. Nuclear morphometric features measured using 3 different data selection methods were not correlated with clinical outcome or overall survival. It is difficult to identify prognostic factors in a series of cases with limited number. The problem is complicated by the fact that the common criteria used for recognizing malignancy in gliomas are not completely reliable in ependymomas. Nuclear morphometric findings support the general impression that ependymomas are morphologically highly variable tumors. In spite of the small sample size of our series and other factors influencing survival such as the extent of resection and malignant histology, aneuploidy can be suggested as a promising factor, which may reflect potential aggressiveness of the tumor in adult intracranial ependymomas.

Adolescent↗