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[Prognostic value of nuclear morphometry in follicular carcinoma of the thyroid gland].

Histological material from 60 cases of follicular carcinoma of the thyroid operated between 1962 and 1987 was examined morphometrically to see whether this would produce data that could be correlated with survival. Nuclear parameters (area, perimeter, minimum and maximum diameter and their ratio, form factor) and the mitotic index were investigated. At the same time, account was taken of certain clinical parameters (sex, age, degree of differentiation, size of the primary lesion, extension of the tumour) potentially correlated with prognosis. Survival in relation to all these variables was examined by means of an actuarial method and subjected to both uni- and multivariate analysis. The results, although suggesting the existence of a relationship between nuclear size and the aggressiveness of this type of tumour, failed to demonstrate a significant correlation between these morphometric parameters and survival after treatment. By contrast, survival was significantly influenced by some of the clinical variables, particularly loco-regional extension of the disease and the patient's age. The prognostic significance of nuclear size was recently demonstrated in breast cancer and in a series of thyroid carcinomas including tumours with different morphologies and progression patterns. In follicular thyroid carcinoma the degree of cellular pleomorphism is usually low. So, morphometry does not seem able to provide information regarding prognosis more valuable than those obtained by the clinical data.

Adenocarcinoma, Follicular↗

[Relationship between refractive elements and morphometry of corneal endothelial cells in normal eyes of young Japanese].

We analyzed corneal endothelial cells in 1,026 eyes from 12 to 29-year-old patients who had no eye disease except refractive error. Morphometric parameters were examined for their distribution and correlation with refractive elements. The distribution of cell density and hexagonal cells in percentage was normal. The logarithmic value of mean cell area and coefficient of variation (CV) also had normal distribution. There was also significant correlation between aging and morphometric parameters, i.e., positive correlation between the mean cell area and the CV, and negative correlation between the cell density and the hexagonality. There was significant correlation between corneal refraction and morphometric parameters, i.e., negative correlation with mean cell area, and positive correlation with cell density. There was also significant negative correlation between the corneal astigmatism and the hexagonality. Consequently, we suggest that the distribution of each morphometric parameter and the difference in age and refractive elements should be considered when discussing morphometry of the corneal endothelial cells.

Adolescent↗

Varying grades of epithelial atypia in the pancreatic ducts of humans. Classification based on morphometry and multivariate analysis and correlated with positive reactions of carcinoembryonic antigen.

To establish an adequate statistical classification of epithelial atypia in the pancreatic duct, a total of 78 areas of duct epithelia with varying grades of atypia were subjected to nine-parameter morphometry and nine-dimensional multivariate cluster analysis. The material was derived from 53 pancreases resected for various epithelial tumors or acute or chronic pancreatitis. The result was correlated with immunohistochemical findings in which the pattern of intraepithelial distribution of carcinoembryonic antigen changed with the degree of ductal atypia. Finally, atypical cells classified by cluster analysis and immunohistochemistry were subjected to computer-aided three-dimensional mapping to visualize their distribution in the ductal tree. Cluster analysis demonstrated that the various epithelial forms were classifiable into Clusters 1, 2, and 3, representing ordinary epithelia and mild and severe dysplasias, respectively. The last category was created so as to include not only in situ and invasive carcinoma but the so-called borderline atypical lesions. The reproducibility of this classification was proved by two sorts of discriminant analyses. Also, the grades of atypia shown by the clustering proved to correlate with the reaction patterns for carcinoembryonic antigen. In the computer-aided three-dimensional mapping, severely dysplastic areas were shown surrounded by zones of mild dysplasia, justifying the assumption of a stepwise carcinogenesis in the pancreatic ducts.

Carcinoembryonic Antigen↗

Nuclear shape and axillary metastases in breast cancer. Analytic morphometry of aspiration smears.

The aim of this work was to seek quantitative parameters other than dimensions to describe nuclear shape and, by this means, to determine the sum of contour irregularities and large asymmetries and seek a connection with the biologic behavior of the tumor. Nuclei of the cells obtained from 57 aspiration smears of breast cancers were studied. Dimensional parameters (area, perimeter, maximum diameter and roundness factor) and analytic parameters were computed by the Shape Analytical Morphometry software system to evaluate both contour irregularities and asymmetry of nuclear shape. All the tumors were subdivided according to their diameters into two groups: T1 tumors, the maximum diameter of which was < 2 cm (18 cases), and T2 tumors, the maximum diameter of which was > 2 cm and < 5 cm (39 cases). Among T1 tumors, both dimensional and analytic parameters were highly significant (P < .001) in distinguishing tumors with (N+) and tumors without (N-) axillary metastases, while among larger tumors (T2) only the analytic parameters showed degrees of significance, albeit variable. It could be inferred that in smaller tumors, aggressiveness is related to an increase in nuclear dimensions and shape distortions more so than in larger tumors.

Biopsy, Needle↗

Assessment of infarct volume in the mouse brain: correlation of magnetic resonance imaging with morphometry.

In the mouse brain, focal necrotic lesion was induced by occlusion of the left middle cerebral artery. The volume of cerebral edema was quantified two days later by MRI in vivo. Histological examination after 2 to 3 months of survival revealed a loss of tissue in the affected brain hemisphere predominantly involving the cortex. The extent of brain atrophy as determined by morphometry correlated well with the volume of edema as measured by MRI. There was a cerebroprotective effect of the N-methyl-D-aspartate receptor antagonist MK 801 on the extent of brain damage as determined by both analytical methods.

Animals↗

Computerized nuclear morphometry as an objective method for characterizing human cancer cell populations.

A new method for measuring differences in nuclear detail in chrome alum gallocyanin-stained nuclei of cells from human breast cancers was compared with conventional subjective grading and classification systems. The new method, termed computerized nuclear morphometry (CNM), gives a multivariate numerical score that correlates well with nuclear atypia and gives a higher reproducibility of classification than do subjective observations with conventional histological preparations. When 100 individual nuclei from each of 137 breast cancers were examined by CNM, there was a broad CNM score variation between patients but a good reproducibility for each tumor. When different parts of the same tumor were sampled, there was good reproducibility between samples, indicating that some breast cancers at least are "geometrically monoclonal." When these cancers were compared by the grading systems of WHO and Black, correlations of 0.43 and 0.48, respectively, were found. There was a poor correlation between CNM and classifications of tumor type, but in general there were high values for CNM in medullary tumors and low values in mucous tumors. Correlations between CNM and tumor progression and prognosis await future study of patients participating in the study.

Breast Neoplasms↗

Nuclear morphometry lacks prognostic value in squamous cell carcinoma of the oesophagus.

In order to determine the possible influence in oesophageal squamous cell carcinoma of nuclear measurements on patients' postoperative survival and on various histological tumour features, we performed a nuclear morphometry study on 53 patients (50 males, 3 females) with a mean age of 57.4 years (37-79). A statistical correlation was revealed between area, perimeter and diameter and the analysis was, therefore, performed only in terms of nuclear area. No influence of nuclear area on postoperative survival was observed. Nor was a relationship found between mean nuclear area and either involvement of the oesophageal wall or degree of histological differentiation. The tumours showing expansive growth had a larger mean nuclear area than those of the infiltrative growth type, although differences did not reach statistical significance. The nuclear area standard deviation (reflecting anisocytosis of the tumour) showed no correlation with survival. In conclusion, our data do not support that measurement of nuclear parameters by static methods is of any prognostic value in surgically-treated squamous cell carcinoma of the oesophagus.

Adult↗

Morphometry of human thigh muscles. Determination of fascicle architecture by magnetic resonance imaging.

A previous investigation suggested that striation patterns spanning individual muscles in longitudinally oriented MR images may represent the orientation of its fascicles. In this study, we confirmed that these striation patterns could be used to infer fascicle orientation and to compute other architectural features of muscles from MR images. The volumes of 14 muscles within a cadaveric thigh were shown to be estimated accurately from cross-sectional MR images by comparison with direct measures from muscle mass. The angles of striations were measured at several positions within vastus medialis and semimembranosus from sagittal and frontal-plane MR images. Mathematical techniques were developed to infer the 3-dimensional orientation of fascicles based on these striation angles. The angle of striations in a 3rd oblique plane was shown to agree with mathematical predictions based on these computed orientations. The pennation angle, defined as the angle between the fascicles and the line of action of the muscle, predicted from the MR images, was similar to directly measured values. Interestingly, the pennation angle of these fascicles varied along the length of the muscle; in vastus medialis, pennation angle ranged from 5 degrees to 50 degrees in a proximodistal direction. Procedures were developed and validated to compute fascicle length by projection of fascicle orientation across the 3D shape of the muscles. The use of MR images to estimate muscle morphometry could improve greatly the predictive capabilities of musculoskeletal modelling by reducing the number of unknown model parameters.

Aged↗

Sequential analysis of the pathogenesis of plutonium-induced pulmonary neoplasms in the rat: morphology, morphometry, and cytokinetics.

Light microscopy, morphometry, and cytokinetic techniques were used to examine the dynamics of plutonium-induced pulmonary proliferative lesions and neoplasms in rats at several intervals to 450 days after inhalation exposure to aerosols of 239PuO2. Maximal increases in alveolar and bronchiolar epithelial cell labeling were seen at 30 days; decreasing subsequently, the levels remained elevated above control indices. Focal proliferative epithelial lesions developed in the lung by 180 days and before the onset of pulmonary neoplasms. Pulmonary neoplasms, predominantly adenocarcinomas and squamous cell carcinomas, were initially observed at 308 days. The proliferative lesions progressed through a succession of morphological changes leading to the development of neoplasms. The volume density (fraction) and epithelial surface area of foci of alveolar epithelial hyperplasia increased progressively between 180 and 450 days after exposure, in contrast to the other proliferative lesions. We conclude that plutonium-induced pulmonary neoplasms develop through a succession of focal proliferative lesions that represent developmental preneoplastic lesions. Progressive increases in volume and epithelial surface area of the alveolar epithelial hyperplasias suggest that they may be more at risk for neoplastic transformation than the other histological types of proliferative foci.

Adenocarcinoma↗

[Small bowel morphometry in acute and persistent diarrhea due to classic enteropathogenic Escherichia coli].

Enteropathogenic E.coli infection may cause different ranges of abnormalities in the small bowel villi, but there are no morphometric studies about it. Thirty specimens of small intestinal mucosa obtained from children having acute or persistent diarrhea by enteropathogenic E.coli were analysed and then compared to the specimens of the small intestinal biopsy of thirteen patients of the control group. We had the following target in this paper: evaluate the morphological changes of intestinal mucosa using linear morphometry and to verify the number of intra-epithelial lymphocytes/100 enterocytes; search the presence of Gram negative bacteria adhered to the small intestinal mucosa. Gram negative bacteria were present in three patients with acute diarrhea. The morphometric changes were more remarkable in the villosites which were shorter, in the enteropathogenic E.coli group. The total mucosa thickness as well as the villous height and the relation villous/crypt were significantly shorter in the enteropathogenic E.coli group when compared to the control Group. There were no differences between the two groups for the crypt length and for de number of intraepithelial lymphocytes/100 enterocytes.

Acute Disease↗

Vitamin E deficiency as a model of precocious brain aging: assessment by X-ray microanalysis and morphometry.

Vitamin E (alpha-tocopherol) is a known biological antioxidant able to quench the lipid peroxidation chain and to protect the cellular structures (e.g., plasma membranes) from the attack of free radicals which are reported to play a primary role in aging. To assess whether the absence of alpha-tocopherol from the diet of young laboratory animals may be considered a reliable model of precocious brain aging, intracellular ionic content of brain cortex pyramidal cells, ultrastructural features of synaptic contact zones, synaptic mitochondria and perykarial mitochondria positive to the succinic dehydrogenase (SDH) histochemical reaction with copper ferrocyanide have been investigated by X-ray microanalysis and computer-assisted morphometry in young, adult, old and 11-month-old vitamin E deficient rats. Our data document significant alterations of intracellular ionic content, synaptic contact areas and synaptic and perykarial mitochondria in aging. Vitamin E deficiency caused similar alterations in adult animals. Taking into account the known role of alpha-tocopherol in protecting the cellular membrane structure, we support that the common process underlying the changes found in aging and vitamin E deficiency is an excessive deterioration of the neuronal membrane.

Aging↗

Classification of colorectal adenomas with quantitative pathology. Evaluation of morphometry, stereology, mitotic counts and syntactic structure analysis.

In search for an objective classification rule for the morphologic changes in colorectal adenomas, the results of nuclear morphometry for assessing geometric characteristics of tumour nuclei, syntactic structure analysis for assessing the arrangement of nuclei in the epithelium, stereological assessment of glandular changes, and area weighted mitotic counts were evaluated in a multivariate analysis. The H&E stained tissue sections of 59 colorectal adenomas were studied, of which 20 showed mild, 20 moderate and 19 severe dysplasia, according to blind duplicate assessments by two pathologists. In a stepwise jackknifed discriminant analysis, the combination of variables was selected that could best discriminate the cases into the previously assessed grade of dysplasia. With the combination of two variables (minimum line length and inner gland surface density), 71% of the cases could be correctly classified according to the previously assessed grade. No cases with mild dysplasia were classified as severe dysplasia and vice versa. However, since the reproduction of subjectively assessed grade was not the ultimate goal, we aimed to discriminate the cases into two groups on the basis of measurements results alone, by means of a cluster analysis. These two groups would merely reflect the cases with major versus minor morphologic changes. The results of the cluster analysis showed that all mild dysplasia cases were allocated into the low grade cluster, and that the moderate dysplasia cases were divided over both the low grade and high grade cluster. Two severe dysplasia cases with borderline morphometric results were allocated into the low grade cluster, and the remaining 16 into the high grade cluster. It is concluded that objective evaluation of dysplasia in colorectal adenomas is possible by a combination of morphometric techniques. The results of the morphometric analyses seem to favor a two-grade classification system rather than a three-grade system.

Adenoma↗

Cellobiose/mannitol sugar permeability test in children in relation to jejunal morphometry.

The ability of the sugar permeability test to detect minor degrees of mucosal damage is uncertain, particularly in children. This paper reviews experience with the cellobiose/mannitol test at a referral centre of paediatric gastroenterology, relating the results of intestinal permeability to the jejunal morphometry. Two hundred patients underwent the cellobiose/mannitol test at the same time as jejunal biopsy; morphometric analysis of the biopsy specimens was performed by a computerized image analysis system. Increased sugar permeability was revealed in 89%, 80%, 67% and 18% of subjects with subtotal villous atrophy, severe partial villous atrophy, mild partial villous atrophy and normal histological picture, respectively. Nevertheless, once the patients with the most severe changes in their mucosal architecture had been excluded, there was no statistically significant correlation between cellobiose/mannitol ratio and villous and crypt length, villous/crypt ratio and intraepithelial lymphocytes density. The cellobiose/mannitol test is a good indicator of severe mucosal damage; it does not discriminate subjects with minor degrees of mucosal abnormalities, but may give useful indications on the functional state of the jejunal mucosa.

Adolescent↗

Computerized nuclear morphometry of renal cell carcinomas.

The aim of this study was the evaluation of the usefulness of nuclear morphometry in the pathology of renal cell carcinoma by computer-aided image analysis and the statistical comparison of nuclear morphometric parameters with the histologic grade of the tumors. 44 cases of renal cell carcinoma, classified by two independent pathologists into 4 histologic grades (I-IV), were examined. The following 5 nuclear morphometric parameters were measured in a large number of randomly selected nuclei of each case: Major axis length, area, elongation, roundness and compactness. The statistical evaluation was performed using one-way analysis of variance between the four groups of the histologic grades (I-IV). Between them, there was a statistically very significant difference of the mean value of all the evaluated parameters. The values of the estimated parameters, with the exception of roundness and compactness, showed a strong tendency to increase in proportion to histologic grade. Our results suggest that image analysis is a reproducible and objective method for the grading of renal cell carcinoma, and it can be helpful in the unbiased evaluation of such tumors.

Adult↗

Histomorphology and bone morphometry of the bone marrow edema syndrome of the hip.

From a prospective study of patients with MR imaging proven bone marrow edema syndrome of the hip, bone biopsies that were retrieved at core decompression treatment of 32 femoral heads (from 28 men and 3 women; age range, 25-63 years) were evaluated microscopically. The undecalcified microtome sections showed diffuse or spotty areas of interstitial and intrasinusoidal fluid in the marrow cavities, together with fat cell destruction or fibrovascular regeneration or both in exactly the regions exhibiting the magnetic resonance signals for bone marrow edema. The vital bone trabeculae in these edematous regions showed more or less continuous, partly osteoblast covered osteoid seams, and often, formation of irregular woven bone (microcallus), pointing to increased bone formation activity. Preceding or active osteoclastic resorption was rarely seen. Computer assisted bone morphometry revealed age related normal to elevated bone volume densities (above 20% bone volume of tissue volume); thus, no evidence for osteoporosis was present. In addition to increased osteoid volumes, a decreased maximal hydroxyapatite content and a shift to undermineralized bone was found by mineral densitometry of corresponding microradiographs, when compared with age matched femoral heads without bone pathology. These bone mineral changes, but not transient bone loss, could be the explanation for the more or less subtle and transient radiolucency in hips affected by bone marrow edema syndrome. Live trabeculae and active bone formation, however, point to increased repair capacity, which seems the key for the spontaneously reversible course of this syndrome. There is still controversy whether the bone marrow edema syndrome represents a distinct transient disease or an early reversible phase of avascular necrosis, but because of the similarities in histopathology reported for early classic avascular necrosis and bone marrow edema in the literature and in the authors' own material, a common pathophysiology is discussed for these seemingly different diseases.

Adult↗

Morphometry and densitometry of alveolar macrophage cytoplasmic particles in Chernobyl, Ukraine, liquidators.

OBJECTIVE: To characterize intracytoplasmic particles found in alveolar macrophages (AMs) sampled by bronchial alveolar lavage (BAL) performed on Chernobyl, Ukraine, liquidators suffering form chronic obstructive lung disease. STUDY DESIGN: Eight BALs were assessed. BAL products containing AMs were cytocentrifuged, and appropriate fixation and epoxy embedding were performed for ultrastructural study. Morphometry of cells (AMs) and of cytoplasmic particles was then obtained by processing, using dedicated software, digitized ultrastructural images. RESULTS: AM cytoplasm contained crowded phagolysozomes, varying in size, shape and density and enclosing dense particles rich in radionuclides, with particular morphometric features: surface, 387 +/- 543 pixels (mean +/- SD); number, 77 +/- 34; phagozome/cell surface ratio, 23.7%; shape factor, 1.32 +/- 0.23; and mean optical density, 171 +/- 31. CONCLUSION: Processing of digitized ultrastructural images of AMs provides accurate morphometric data that can be used further for clinical purposes, in particular to evaluate BAL performed either for diagnosis or treatment.

Adult↗

Automated identification and quantitative morphometry of the senile plaques of Alzheimer's disease.

OBJECTIVE: Senile plaques (SP) are one of the characteristic neuropathologic lesions of Alzheimer's Disease (AD), and studies of SP cortical distribution, density and morphology may lead to new information about the mechanism and pathogenesis of AD. We used an automated, digital image analysis program to detect and measure SP size, shape and total fractional area in digital images of silver-stained tissue sections. STUDY DESIGN: The program observed 94,000 SP in 2,800 digitized microscope fields from tissue sections from 42 postmortem cases ranging from healthy aged to severely demented subjects, studied prospectively before death. RESULTS: Automated pattern recognition can measure SP densities in excellent agreement with an expert and can generate morphometric information not obtainable by conventional microscopy. SP densities (number of SPs/mm2) strongly correlate with tissue load (fraction of tissue area occupied by lesions). SP densities strongly correlate between cortical regions within the same subjects. SP densities, while correlating with the occurrence of AD, do not display a significant trend with respect to dementia severity; likewise, mean SP area and shape properties do not vary significantly with dementia severity. Finally, all the computed SP densities would have produced the same diagnoses of AD in these subjects as the manual SP densities according to the consensus criteria. CONCLUSION: This is the first fully automated program to identify SPs and measure SP morphometry; it uses well-established digital image analysis and statistical pattern recognition methods. The computed SP densities correlate highly with expert results, and the systematic differences are smaller than the interrater differences reported in several multicenter Alzheimer's disease neuropathology studies. The program measures morphometric properties that would be impractical to measure by manual means and, with program-controlled, scanning stage microscopy, can measure lesion densities exhaustively across large cortical areas without stereologic sampling. SP densities rise from near zero to significant values at the mildest diagnosed stage of AD, but beyond this point, there is no demonstrable correlation of density, or any other SP property, with dementia severity. Computed SP densities for even the mildest dementia satisfy the consensus diagnostic criteria.

Aged↗

Morphometry of the kidneys of fresh water percoid and ostariophysian teleosts.

Kidneys of four fresh water teleost species representing percormorpha (Oreochromis niloticus and Micropterus salmoides) and Ostariophysi (Cyprinus carpio and Clarias mossambicus) were studied for quantitative structural characteristics using tissues fixed by perfusion. The renosomatic index (weight of kidney/weight of fish) was higher in the ostariophysian than percoid fish (p < 0.05) but values of volume of nephronic tissue/body weight were not significantly different. Results obtained by point counting morphometry showed that the kidneys of the percoid species were made up of 56.85-64.4% nephronic tissue, 30.45-32.47% blood vessels, 2.84-8.20% ureter and ureteral ducts and 2.07-2.48% connective tissue. The kidneys of the osariophysian species comprised of 35.27-36.71% nephronic tissue, 27.86-29.29% blood vessels, 1.59-4.20% ureter and its ducts, 29.07-29.51% interstitial cells and 2.70-3.60% connective tissue. The mean values for the volume proportions of the components of nephronic tissue were not significantly different in the percoids and ostariophysians and they were; renal corpuscles 3.84-6.54%, neck segments 0.50-1.11%, proximal segments 67.17-69.72%, distal segments 18.16-20.55%, and collecting tubule-collecting duct (CT-CD) system 5.66-7.41%. These results show that the quantitative structural characteristics of the kidneys of fresh water species from different orders are quite similar and emphasise the all persuasive influence of the environment on renal structure and function in teleosts.

Adaptation, Physiological↗