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The modified Fontan procedure: morphometry and surgical implications.

BACKGROUND: The modified Fontan procedure for patients with only one well-formed ventricle is now widely regarded as palliative, not curative. METHODS: To improve the surgical management and postoperative follow-up of such patients, a morphometric study of 33 postmortem cases was done. RESULTS: The three main causes of death were congestive heart failure (82%), arrhythmias (12%), and central nervous system dysfunction (6%). The cross-sectional area of the Fontan anastomosis (FA) relative to the systemic venous area (SVA) and relative to the body surface area (BSA) revealed that the Fontan pathway was often obstructive. The mean FA/SVA index was 73% less than normal: 0.54 +/- 0.22, range 0.13 to 0.98. The mean FA/BSA index was 70% less than normal: 143.52 +/- 50.01 mm2/M2, range 55.09 to 261.67 mm2/M2. CONCLUSIONS: The main surgical challenge is to minimize or eliminate prepulmonary stenosis. Although significant postoperative obstruction was often not evident hemodynamically because of small or absent gradients, the presence of important obstruction of the Fontan pathway was clearly revealed by morphometry.

Adolescent↗

Hippocampal morphometry in depressed patients and control subjects: relations to anxiety symptoms.

BACKGROUND: Although it has been hypothesized that glucocorticoid hypersecretion in depressed patients leads to neuronal atrophy in the hippocampus, magnetic resonance imaging (MRI) -based morphometry studies of the hippocampus to date have produced mixed results. METHODS: In our MRI study, hippocampal volumes were measured in 25 depressed patients (13 with melancholia and 12 without melancholia) and 15 control subjects. RESULTS: No significant differences in hippocampus volumes were found between any of the subject groups, although within subjects right hippocampal volumes were found to be significantly larger than left hippocampal volumes. Additionally, right and total (left + right) hippocampal volumes in control and depressed subjects were found to be positively correlated with trait anxiety as measured by the state/trait anxiety inventory. CONCLUSIONS: Because our subject group is younger than those in studies reporting hippocampal atrophy, we conclude that longitudinal studies will be necessary for investigation of the lifelong course of hippocampal volumetry.

Adult↗

Quantitative cytochemistry of cytochrome oxidase and cellular morphometry of the human inferior colliculus in control and Alzheimer's patients.

Quantitative cytochemistry of cytochrome oxidase (C.O.) was implemented in human brains to measure C.O. activity in the 3 main divisions of the inferior colliculus (IC): central (ICC), dorsal (ICD), and external (ICE). Units of C.O. activity (micromol/min/g tissue wet weight) were quantified in cellular compartments (overall average, neuropil, perikaryon, and dendrites) at the light microscope level using microdensitometry calibrated with C.O. activity standards measured spectrophotometrically. In a non-AD (Alzheimer's disease) control group (mean age = 79.6 +/- 3.1 years, postmortem time = 6.9 +/- 1.6 h), the ICC and ICD demonstrated higher (p < 0.008) overall average activities (mean = 183.40 +/- 18.7 and 184.98 +/- 45.1 units, respectively) relative to the ICE (56.46 +/- 15.9 units). Comparison of cellular morphometry (soma and nucleus area, perimeter, and diameter) revealed that the ICC contained cells of significantly larger soma size than in both the ICD and ICE (p < 0.002). The distribution of soma diameters in the ICC of controls showed a clear bimodality, enabling the typing of the cells into larger and smaller than average soma diameter. Brains from patients with Alzheimer's disease (AD; mean age = 78.3 +/- 2.9 years, postmortem time = 6.5 +/- 1.3 h) were compared with the non-AD controls. Significant group differences were found only in the large cells of the ICC. The AD large cells showed a decrement in C.O. activity relative to the corresponding controls in overall average activity (p < 0.032) and in peak activity of neuropil near the soma (p < 0.012). These findings provide the first quantitative cytochemical data of C.O. activity in humans. They also suggest that cellular alterations in C.O. metabolism in AD affect predominantly specific groups of larger projection neurons while neighboring neurons are spared.

Aged↗

Anatomical signatures of dyslexia in children: unique information from manual and voxel based morphometry brain measures.

Thirteen male control and thirteen male dyslexic children (age, 121-152 months) were studied to determine if voxel based morphometry (VBM) could identify anatomical differences in the right cerebellar anterior lobe, and right and left pars triangularis that were identified with manual measures of the same children. VBM demonstrated significant gray and white matter differences in these three brain regions. In contrast to the manual results, these differences were not significant after controlling for brain volume, suggesting the manual measures captured additional important variance that distinguished the groups. Post-hoc VBM comparisons demonstrated white matter volume differences in a left temporal-parietal region that are consistent in location with results from diffusion tensor imaging studies of dyslexia. The VBM analyses also identified, gray matter volume differences in the left and right lingual gyrus, left inferior parietal lobule and cerebellum, areas that had not been examined with manual methods. We conclude that manual and automated methods provide valuable and complementary approaches to the search for functionally significant neurobiological characteristics of dyslexia.

Brain↗

Standardization of specimen preparation, staining, and sampling methods improves automated sperm-head morphometry analysis.

OBJECTIVES: To evaluate the accuracy and performance of the CellForm-Human automated sperm morphometry instrument (Motion Analysis Corp., Santa Rosa, CA) using different specimen preparation, staining, and analysis techniques. SETTING: Clinical and research andrology and in vitro fertilization laboratories. PATIENTS: Individuals who were undergoing semen evaluation and infertility work-up. RESULTS: The percentage of normal sperm detected by CellForm-Human was not different for washed specimens compared with nonwashed controls. Washing and resuspension to a standard concentration in medium significantly increased spermatozoan density and homogeneity on the slide. Comparison of digitization errors and morphometric measures of sperm stained by the Papanicolaou (PAP) method, the hematoxylin portion of the PAP method, and a new method developed by us, GZIN (pronounced Gee-ZIN), showed that GZIN produced larger measures for length, width, area, and perimeter, but not for width/length, and also produced less variability for most measures than PAP or hematoxylin. The number of digitization errors was significantly less for GZIN than for PAP. Visual inspection revealed that GZIN produced a more consistent stain over the entire sperm head than hematoxylin. The number of sperm analyzed affected the percentage of normal sperm detected. The % normal stabilized only after at least 200 sperm had been analyzed for each man. CONCLUSIONS: Technical variability arising from semen preparation and slide staining methods can be reduced when specimens are washed and resuspended to a standard concentration before smearing. At least 200 sperm should be analyzed to obtain a stable estimate of the percentage of normal sperm. More sperm should be analyzed if the % normal is < 50%. Morphometric measurements are more accurate and precise when sperm are stained with GZIN than when stained with PAP or hematoxylin.

Cytological Techniques↗

Histology and morphometry of Strongylus vulgaris-mediated equine mesenteric arteritis.

Histological and morphometric evaluation of equine cranial mesenteric arteries was performed on 239 and 89 arteries, respectively. Histological examination revealed that thrombosis and the severity of inflammation varied on a seasonal basis and were directly associated with larval presence. Intimal and adventitial fibrosis were generally of greater severity than medial fibrosis. Fibrosis of the vasa vasorum was less frequent than fibrosis of the artery itself. Morphometry revealed a significant increase in intimal, adventitial and, to a lesser extent, medial area in affected as compared with normal arteries. This change was due to the accumulation of collagen and was considered to result in decreased arterial elasticity. The luminal area varied widely among affected arteries.

Animals↗

Peripheral neuropathy associated with hereditary and sporadic inclusion body myositis: confirmation by electron microscopy and morphometry.

Inclusion body myositis (IBM) is a disabling myopathy affecting proximal and distal muscle groups. The involvement of peripheral nerves in IBM is still a controversial matter. In a previous morphometric study at the light microscopic level only, we described a peripheral neuropathy in sural nerve biopsies of eight patients with sporadic IBM (s-IBM). Here we present a larger series of 14 cases in which a combined muscle and nerve biopsy was available for additional electron microscopic investigation. In two of the new cases, the IBM had a hereditary background (h-IBM). The presence of neuropathy was confirmed in all 14 cases studied. Morphometry using an optic-electronic, digital evaluation system showed large variation of severity presumably due to age and coincidal factors such as diabetes mellitus or lymphoma. Ultrastructural analysis revealed a variety of changes considered to be non-specific. Signs of axonal damage predominated. In addition, there were numerous changes in Schwann cells and myelin sheaths. Neither inflammatory changes nor tubulofilamentous inclusions were detectable in the sural nerves. Peripheral neuropathy, although occasionally without apparent clinical manifestation, appears to be a common and aggravating feature in IBM; its pathogenesis, however, remains elusive.

Adolescent↗

Quantitative morphometry of the adult human bladder.

The primary objective of the present retrospective study was to characterize the effects of aging and BPH on bladder morphometry. Eighty-six bladder specimens were obtained from the autopsy archives of the Milwaukee County Medical Complex. The bladder specimens were divided into 4 groups based upon age and gender: Group I: males between the ages of 35-45 years; Group II: males between the ages of 65-75 years; Group III: females between the ages of 35-45 years; and Group IV: females between the ages of 65-75 years. The age groups were selected in order to identify a group of males with and without BPH. The area density of smooth muscle:connective tissue was determined in bladder specimens using color assisted computer image analysis. Masson-trichrome and double immunoenzymatic staining techniques were used to discriminate the smooth muscle and connective tissue elements of the bladder. The area density of smooth muscle:connective tissue in the Masson-trichrome stained sections was significantly greater in Group I vs. Group II (2.90 +/- 0.22 vs. 2.33 +/- 0.16) and in Group III vs. Group IV (2.85 +/- 0.13 vs. 2.03 +/- 0.20). Aging was associated with a decrease in the area density of smooth muscle:connective tissue ratio in both males and females. The area density of smooth muscle:connective tissue was not significantly different in younger males and females (Group I vs. Group III) and older males and females (Group II vs. Group IV). The present morphometric study suggests that aging and not BPH, is associated with a relative increase in detrusor fibrosis. Infravesical obstruction in BPH may effect bladder function via mechanisms unrelated to the histologic composition of the bladder.

Adult↗

Nuclear morphometry as a prognostic indicator for genitourinary rhabdomyosarcoma: a preliminary investigation.

Rhabdomyosarcoma of the urogenital tract is a malignant mesenchymal tumor seen primarily in childhood. Multimodal therapy, encompassing surgery, radiotherapy and chemotherapy, has dramatically improved the survival of patients with this disease. However, the quest for markers of tumor aggression is important to decrease the morbidity of treatment given to patients with good prognosis tumors, while at the same time intensifying treatment of tumors with poor prognosis. Using archival tumor specimens from 13 patients with genitourinary rhabdomyosarcoma, a multivariate analysis of multiple nuclear shape descriptors was done with the Hopkins Morphometry System. Three nuclear shape descriptors clearly separated patients with no evidence of disease recurrence or progression from those with recurrent disease, progressive disease or death of disease. These nuclear shape descriptors were standard error of the chain code standard deviation analysis (p = 0.010), range of the feret ellipticity distribution (p = 0.016) and standard error of the chain code range analysis (p = 0.037). With multivariate analysis these shape descriptors taken together separated patients with good and poor prognoses to a level of significance of p = 0.007. Thus, nuclear morphometric analysis may prove to be useful as an individual prognostic indicator in childhood genitourinary rhabdomyosarcoma and warrants further analysis in a much larger, blinded, controlled study.

Cell Nucleus↗

Relationship between attentional performance and corpus callosum morphometry in patients with Alzheimer's disease.

There has been considerable interest in cognitive deficits associated with Alzheimer's disease (AD) and relationships between these impairments and specific cortical atrophies. Two previous studies [Neuropsychologia 28 (1990) 1197; Dementia 3 (1992) 350] have found that AD patients exhibit significant impairments in the attentional ID/ED set-shifting tasks of the CANTAB battery which involved attentional shifting abilities. But, at present, no study has examined the neural bases of these abilities in AD patients. In the present study, the relationship between performances on this attentional test and morphometry of the anterior and posterior corpus callosum is examined in AD patients in the mild to moderate stages of the disease (n=30, mean age=74.1+/-4.9 years, mean MMSE score=23.9+/-2.6). A control group is constituted (n=20, mean age=73.15+/-5.5 years) for comparison of cerebral measurements. The stepwise multiple regression analysis indicates that the relative contribution for the total callosal and the anterior CC areas of the simple discrimination subtest is significantly positive whereas for the posterior callosal areas the relative contribution of the more complex subtest is significantly positive. AD patients from the subgroup "low", who failed to do the nine subtests of the attentional set-shifting tasks, exhibit smaller callosal areas than control subjects. There is no significant difference for all callosal measurements between AD patients from the subgroup "high", who completely succeeded the test, and control subjects. Our findings suggest that the anterior corpus callosum would be related to attentional shifting abilities in AD patients. Moreover, these patients with probable AD seem heterogeneous for performances in the attentional test of the CANTAB and for callosal atrophies.

Aged↗

Computerized microscope morphometry of umbilical vessels from pregnancies with intrauterine growth retardation and abnormal umbilical artery Doppler.

Computerized microscope morphometry was used to study cross sections from the vessels of the umbilical cord in placentas of patients with intrauterine growth retardation (IUGR) that displayed either normal or abnormal umbilical arteries (UA) Doppler flow velocity waveforms (FVW). Cords from 63 eutrophic fetuses with normal Doppler (controls), 47 IUGR fetuses with normal Doppler and 32 IUGR fetuses with abnormal Doppler underwent morphometric analysis using a highly optimized microscope environment (HOME) and "CordHOME" software. IUGR with an accompanying normal Doppler versus control showed a reduction of Wharton jelly and both the total and lumen vein areas. IUGR with an accompanying pathological Doppler showed a comparable reduction in wall thickness and areas of every vessel. These findings indicate that the hypoplastic umbilical vessels are associated with an increase in placental vascular resistance that may be the consequence of underdevelopment in response to a chronic reduction in placental blood flow.

Blood Flow Velocity↗

Prognostic value of proliferative activity and nuclear morphometry for progression in TaT1 urothelial cell carcinomas of the urinary bladder.

OBJECTIVES: To analyze the predictive power of Ki67 area% (Ki67), mitotic activity index (MAI), p53 area% (p53), and the mean area of the 10 largest nuclei (MNA10) for progression of stage in 195 primary consecutive TaT1 urothelial cell carcinomas of the urinary bladder. METHODS: Ki67- and p53-positive versus negative nuclei, MAI, and MNA10 using motorized systematic random sampling morphometry were determined. Kaplan-Meier curves and multivariate survival analysis (Cox model) were used to assess the prognostic value of the quantitative and classic clinicopathologic risk factors (age, sex, stage, grade, carcinoma in situ, multicentricity). RESULTS: Thirteen (6.7%) of the 195 patients had progression (0 [0%] of 36 low-risk, 1 [1.1%] of 85 intermediate-risk, and 12 [16.2%] of 74 high-risk patients). In univariate analysis (all variables), the strongest predictors with the highest hazard ratios were Ki67 (threshold 25.0%), MAI (threshold 30), and MNA10 (threshold 170 microm2). In multivariate analysis, the strongest independent combinations for progression--MNA10 (170 microm2) plus MAI (threshold 30) and MNA10 (threshold 170 microm2) plus Ki67 (threshold 25.0%)--overshadowed all other features. p53 was weaker but, combined with Ki67, still predicted progression fairly well. In the total group, the sensitivity, specificity, and positive and negative predictive values of MNA10-MAI and MNA10-Ki67 at the thresholds mentioned were 100%, 89%, 38%, and 100%, respectively. These feature combinations were also strongest prognostically in the high-risk treatment group. CONCLUSIONS: The combined biomarkers MNA10-MAI or MNA10-Ki67 are accurate, well reproducible, and easy to assess progression predictors in all patients with TaT1 urothelial cell carcinomas, as well as in high-risk (bacille Calmette-Guérin-treated) patients.

Adult↗

Mast cells and nerve fibers in interstitial cystitis (IC): an algorithm for histologic diagnosis via quantitative image analysis and morphometry (QIAM).

OBJECTIVE: To develop and evaluate a diagnostic algorithm based on the alteration of mast cell and nerve fiber observed in bladder tissue of patients with interstitial cystitis (IC). MATERIALS AND METHODS: Non-IC samples from 6 control groups (N = 10, 10, 13, 2, 11, and 3, respectively) and nonclassic interstitial cystitis (NC-IC, N = 20) were stained with Giemsa stain in order to calculate the detrusor to mucosa mast cell ratio (DMMCR) using quantitative image analysis and morphometry (QIAM). Immunohistochemical staining for S-100 protein was also performed to quantify nerve fiber proliferation in the detrusor muscle of the bladder. RESULTS: The average DMMCR of NC-IC was 1.19. Bacille Calmette-Guérin (BCG) cystitis was 0.84 and microscopically normal bladder tissue from patients with bladder or prostate cancer was 0.45. No case of IC that we examined had a DMMCR < 0.5. The number and percentage area of nerve fibers in the detrusor in IC were increased compared to controls and BCG (IC, 2.01%; BCG, 0.95%; control, 1.3%). CONCLUSION: A diagnostic algorithm is proposed for IC based on the findings that indicate that: 1) if the DMMCR > 0.75, then IC is present; 2) if the DMMCR < 0.5, then IC is negative; and 3) if the DMMCR is between 0.5 and 0.75, a quantitative S-100 protein staining analysis can be employed to evaluate nerve fiber proliferation to detect those marginal cases of NC-IC. The findings of the study also suggest that a neuroimmune process or mediation may be involved in the pathogenesis of IC.

Algorithms↗

Infection of Vero cells with Coxiella burnetii phase II: relative intracellular bacterial load and distribution estimated by confocal laser scanning microscopy and morphometry.

Coxiella burnetii, the agent of Q fever in man and of coxiellosis in other species, is an intracellular pathogen not yet grown axenically. Confocal laser fluorescence microscopy and morphometry were used to measure relative C. burnetii phase II loads and their intracellular distribution in aldehyde fixed and DAPI stained Vero cell monolayers. The fluorescence of single horizontal optical sections provided useful information on relative loads of bacteria in cells and vacuoles. The relative density of the bacteria in the vacuoles was inferred from ratios of fluorescence to vacuolar section areas. Relative bacterial loads, bacterial densities and section areas of large vacuoles increased exponentially between days 2 and 4 of the infection of gamma-irradiated host cells, stabilized between days 4 and 6, and decreased thereafter. Estimated minimum doubling times were higher for the overall complement of the intracellular organisms (about 12 h) than for bacteria that were confined to larger vacuoles (about 10 h).

Animals↗

A voxel-based morphometry study of temporal lobe gray matter reductions in Alzheimer's disease.

Several MRI studies have reported reductions in temporal lobe volumes in Alzheimer's disease (AD). Measures have been usually obtained with regions-of-interest (ROI) drawn manually on selected medial and lateral portions of the temporal lobes, with variable choices of anatomical borders across different studies. We used the fully automated voxel-based morphometry (VBM) approach to investigate gray matter abnormalities over the entire extension of the temporal lobe in 14 AD patients (MMSE 14-25) and 14 healthy controls. Foci of significantly reduced gray matter volume in AD patients were detected in both medial and lateral temporal regions, most significantly in the right and left posterior parahippocampal gyri and the left posterior inferior temporal gyrus/fusiform gyrus (P<0.05, corrected for multiple comparisons). At a more flexible statistical threshold (P<0.001, uncorrected for multiple comparisons), circumscribed foci of significant gray matter reduction were also detected in the right amygdala/enthorinal cortex, the anterior and posterior borders of the superior temporal gyrus bilaterally, and the anterior portion of the left middle temporal gyrus. These VBM results confirm previous findings of temporal lobe atrophic changes in AD, and suggest that these abnormalities may be confined to specific sites within that lobe, rather than showing a widespread distribution.

Aged↗

Ultrastructural morphometry of cultivated smooth muscle cells from normotensive and hypertensive rats.

Cultivated aortic smooth muscle cells (SMC) derived from normotensive and hypertensive rats were analyzed by transmission electron microscopy and ultrastructural morphometry. SMC cultures obtained from hypertensive rats showed an increase in cell size and a higher percentage of large, often polynuclear cells. The stereological data of mitochondria, rough endoplasmic reticulum (RER) and secondary lysosomes were determined by measuring area according to the "Delesse principle". The organelle contents of small and large cells of each group were only slightly different. Significant changes were found between SMC from normotensive and hypertensive rats: The volume density Vv of mitochondria per unit cytoplasm volume was increased up to 48% in small and 50% in large SMC from hypertensive rats compared to those of control animals. The numerical density Nv of secondary lysosomes per unit cytoplasm volume was increased up to 68% in small and 267% in large SMC from hypertensive rats. The content of rough endoplasmic reticulum varied tremendously between the individual cells. All these stereological data represent relative parameters of cell organelles relative to the unit cytoplasm volume. Therefore the differences between the absolute values would be even higher since SMC from hypertensive rats are shown to have a higher mean cell size and volume. We conclude that the effect of experimental hypertension, resulting in an activation of SMC, persists even when the cells are transferred to in vitro conditions.

Animals↗

Predictive variables for the biological behaviour of basal cell carcinoma of the face: relevance of morphometry of the nuclei.

We did a morphometric analysis of 130 histological sections of basal cell carcinoma (BCC) of the face to find out whether morphometric variables in the structure of the nuclei of BCC cells could serve as predictors of the biological behaviour. We considered the following variables: maximum and minimum diameters, perimeter, nuclear area and five form factors that characterise and quantify the shape of a structure (axis ratio, shape factor, nuclear contour index, nuclear roundness and circumference ratio). We did a statistical analysis of primary and recurring tumours and four histology-based groups (multifocal superficial BCCs, nodular BCCs, sclerosing BCCs and miscellaneous forms) using a two-sided t test for independent samples. Multifocal superficial BCCs showed significantly smaller values for the directly measured variables (maximum and minimum diameters, perimeter and nuclear area). Morphometry could not distinguish between primary and recurring tumours.

Adolescent↗

Magnetic resonance-based vertebral morphometry of the thoracic spine: age, gender and level-specific influences.

OBJECTIVE: The aim of this study was to examine age, gender, and segmental trends in thoracic vertebral body shape, utilising thoracic spine magnetic resonance images involving an age range spanning the life span. DESIGN: A quantitative, cross-sectional, retrospective study design involving a sample of convenience. BACKGROUND: Thoracic vertebral shape data are commonly derived from radiographic resources. The non-ionising properties of magnetic resonance imaging and availability of digital data for image analysis suggest potential for MR-based morphometric studies. For the thoracic spine, there is limited vertebral shape data on males, while few studies have examined the pattern of age-related changes across the life span. METHODS: Morphometry was performed on 220 mid sagittal T1-weighted MR images using image analysis software. Three indices of vertebral shape were utilised: the antero-posterior height ratio or anterior wedge index, mid-posterior height ratio or biconcavity index, and ratio of posterior vertebral height to mid antero-posterior diameter or compression index. RESULTS: Different segmental patterns were noted for the vertebral shape indices. Significantly lower mean values were noted in males for the compression index. Age trends were significant, with a linear age-related decline demonstrated for the anterior wedge and biconcavity indices, and a quadratic trend noted for the compression index. CONCLUSIONS: Thoracic vertebral body shape may be uniquely described using specific shape indices, for examining various segmental, gender and age-associated changes. RELEVANCE: These results suggest the importance of defining specific reference criteria for thoracic vertebral body shape indices, particularly age-related data encompassing a wide age range. Magnetic resonance studies enable interpretation of vertebral shape data in relation to the wide spectrum of pathologies afflicting the thoracic spine, without the concerns of ionising radiation.

Adolescent↗