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Normal asymmetry of the planum temporale in patients with schizophrenia. Three-dimensional cortical morphometry with MRI.

BACKGROUND: Abnormal cerebral anatomical lateralisation has been reported in schizophrenia and may implicate anomalous neurodevelopment in the aetiology of this disease. A popular recent hypothesis has predicted that such disturbances in normal lateralisation should be especially apparent in the morphology of the temporal lobes. METHOD: A temporal cortical region lying in the plane of the Sylvian fissure--known as the planum temporale--exhibits pronounced leftward asymmetry in normal right-handed males. We compared lateralisation of the planum temporale in schizophrenic and control males using MRI surface-rendering morphometry of the supratemporal cortex. RESULTS: Contrary to the lateralisation hypothesis, normal patterns of leftward planum asymmetry were detected in both the schizophrenic and control groups. Schizophrenics and controls also exhibited a predicted symmetry in the bilateral areas of Heschl's gyrus, a supratemporal cortical structure immediately anterior to the planum. CONCLUSION: These data do not support the notion that neurodevelopmental mechanisms of cerebral asymmetry are abnormal in schizophrenia.

Adult↗

Grey-matter abnormalities in boys with Tourette syndrome: magnetic resonance imaging study using optimised voxel-based morphometry.

The genesis of Tourette syndrome is still unknown, but a core role for the pathways of cortico-striatal-thalamic-cortical circuitry (CSTC) is supposed. Volume-rendering magnetic resonance imaging data-sets were analysed in 14 boys with Tourette syndrome and 15 age-matched controls using optimised voxel-based morphometry. Locally increased grey-matter volumes (corrected P < 0.001) were found bilaterally in the ventral putamen. Regional decreases in grey matter were observed in the left hippocampal gyrus. This unbiased analysis confirmed an association between striatal abnormalities and Tourette syndrome, and the hippocampal volume alterations indicate an involvement of temporolimbic pathways of the CSTC in the syndrome.

Adolescent↗

Lung morphometry and collagen and elastin content: changes during normal development and after prenatal hormone exposure in sheep.

This study examined whether the improvement in lung function after prenatal hormone exposure coincided with changes in lung morphometry or in collagen and elastin content. Fetal lambs received a single intramuscular injection of betamethasone (0.5 mg/kg) plus L-thyroxine (T4) (15 micrograms/kg) or vehicle control 48 h before delivery at 121, 128, or 135 d gestational age (d 121, d 128, d 135, term = 150 d). T4 was administered in conjunction with betamethasone in an attempt to enhance the maturational response. The right-upper lobes were instillation fixed at 30 cm H2O by Karnovsky's fixative after a 40-min period of mechanical ventilation. A number of significant changes occurred between d 121 and d 135 in control animals: alveolar airspace volume increased by 270%; despite a 40% reduction in alveolar septal thickness, alveolar septal volume did not change appreciably, suggesting a "redistribution" of septal tissue into the formation of secondary alveolar septa, which doubled in number; and both parenchymal collagen and elastin volume increased significantly, whereas pleural collagen and elastin volume did not change. In contrast to the changes seen in control animals, exposure to betamethasone plus T4 led to alveolar septal thinning at each gestational age without an associated increase in secondary septal number, a 40% decrease in alveolar septal volume, and a proportionate reduction in parenchymal elastin at d 121. Although attenuation of alveolar septa coincides with redistribution of septal tissue into the formation of secondary septa during normal maturation, exposure to betamethasone plus T4 promotes thinning of alveolar septa in the absence of secondary septal formation, which results in a loss of alveolar septal tissue.

Aging↗

Effects of maternal undernutrition during late gestation on the lung surfactant system and morphometry in rats.

Intrauterine growth restriction (IUGR) is associated with reduced lung function during infancy and throughout adulthood. We investigated the effects of maternal undernutrition (50% rations of the control food intake) during the last week of gestation on the pulmonary surfactant system and lung morphometry in postnatal rats. IUGR rats exhibited a significantly lower body weight, lower lung weight, lower lung/body weight ratio, lower lung volume, and lower lung volume/body weight ratio on some postnatal days. IUGR rats had a significantly lower lung saturated phosphatidylcholine and lower plasma corticosterone levels on postnatal d 1 only, and values were comparable between control and IUGR rats in the ensuing weeks. Lung surfactant protein (SP)-A, SP-B, SP-C, and SP-D mRNA expressions were similar between control and IUGR rats. Volume fractions of the alveolar airspace were significantly lower in IUGR rats on postnatal d 7, 14, and 42. Alveolar surface areas were significantly lower in IUGR rats during the study period. The alveolar surface area/body weight ratio reached a peak on postnatal d 7, and values were significantly lower in IUGR rats on postnatal d 1, 14, 28, and 42. We conclude that maternal undernutrition during late gestation decreases lung surfactant lipid levels in the immediate postnatal period and alters the development of lung structure during the postnatal period. Alteration of lung surfactant and structure may be important in the pathogenesis of impaired pulmonary function in IUGR infants and children.

Animals↗

Somatosensory cortical atrophy after spinal cord injury: a voxel-based morphometry study.

The authors used voxel-based morphometry to compare sensorimotor cortical gray and white matter volume on structural MR images of a group of 17 individuals with cervical spinal cord injury (SCI) and a group of 17 healthy subjects. SCI subjects had reduced gray matter volume bilaterally in primary somatosensory cortex (p < 0.001). These findings suggest that the somatosensory cortex of the human brain atrophies after SCI.

Adolescent↗

The contribution of voxel-based morphometry in staging patients with mild cognitive impairment.

OBJECTIVE: To assess whether different patterns of regional gray matter loss in patients with mild cognitive impairment (MCI) are associated with different risks of conversion to Alzheimer disease (AD), using MRI and voxel-based morphometry (VBM). METHODS: The authors recruited 22 patients with MCI, 22 patients with probable AD, and 20 healthy subjects (HS). T1 volumes from each subject were postprocessed according to an optimized VBM protocol. All patients were clinically followed up (mean [SD] time = 28.7 [5.7] months), and patients with MCI were reclassified into two groups (converters and nonconverters to AD). RESULTS: When comparing patients with AD to HS, widespread areas of reduced gray matter density were found predominantly in temporal, frontal, and parietal lobes and in the insula. Comparing MCI converters and nonconverters with HS, the converters showed more widespread areas of reduced gray matter density than nonconverters, with a pattern of abnormalities similar to that seen in patients with AD. Conversely, when comparing the same groups with patients with AD, MCI nonconverters showed a pattern of gray matter density similar to that of HS. Areas of decreased gray matter density were also found in MCI converters compared with nonconverters. CONCLUSIONS: Different patterns of gray matter density distribution in patients with mild cognitive impairment may be associated to different rates of conversion to Alzheimer disease.

Aged↗

Voxel-based morphometry shows no decreases in cerebellar gray matter volume in essential tremor.

OBJECTIVE: To investigate cerebellar gray matter volume in patients with essential tremor (ET). METHODS: We used voxel-based morphometry (VBM) based on high-resolution T1-weighted MRI to compare gray and white matter density between 27 patients with ET and 27 age- and sex-matched healthy control subjects. Fourteen patients had only postural tremor, whereas 13 patients showed additional intention tremor. RESULTS: VBM failed to demonstrate regional decreases in gray and white matter volume in patients with ET. There was, however, an expansion in gray matter depending on the type of tremor. Compared with age-matched control groups, patients with intention tremor showed a relative expansion of gray matter bilaterally in the region of the temporoparietal junction and the right middle occipital cortex. CONCLUSIONS: The lack of a consistent decrease in gray and white matter density argues against a progressive neurodegenerative process in essential tremor that leads to a substantial decrease in cerebellar gray matter volume. Patients with predominant intention tremor show a relative expansion of gray matter areas involved in higher order visuospatial processing, which might represent a long-term result of adaptive reorganization compensating the higher demands on the visuospatial control of skilled movements in case of trembling.

Adult↗

Neocortical morphometry, lesion counts, and choline acetyltransferase levels in the age spectrum of Alzheimer's disease.

We studied neocortical morphometry (cortical thickness, neurons, and glia), lesion counts (plaques and tangles), and choline acetyltransferase levels in up to 113 Alzheimer brains and 48 controls. Comparisons between young (under 65) and old (over 70) Alzheimer cases revealed more tangles in the former, but no other statistically significant differences in the measured variables. Differences in these parameters between young Alzheimer cases and young controls were similar to the differences found between old Alzheimer cases and old controls. Linear regression analyses correlating some of these variables with age in Alzheimer's disease, considered together with the effects of normal aging on the same parameters, reveal in Alzheimer's disease a spectrum of graded pathologic severity inversely proportional to age. Nevertheless, even in advanced old age (80 to 100), significant differences persist in these parameters between very elderly Alzheimer brains and controls.

Aged↗

Effect of aldose reductase inhibition on nerve conduction and morphometry in diabetic neuropathy. Zenarestat Study Group.

OBJECTIVE: To determine whether the aldose reductase inhibitor (ARI) zenarestat improves nerve conduction velocity (NCV) and nerve morphology in diabetic peripheral polyneuropathy (DPN). METHODS: A 52-week, randomized, placebo-controlled, double-blinded, multiple-dose, clinical trial with the ARI zenarestat was conducted in patients with mild to moderate DPN. NCV was measured at baseline and study end. Contralateral sural nerve biopsies were obtained at 6 weeks and at the study's end for nerve sorbitol measurement and computer-assisted light morphometry to determine myelinated nerve fiber density (number of fibers/mm2 cross-sectional area) in serial bilateral sural nerve biopsies. RESULTS: Dose-dependent increments in sural nerve zenarestat level and sorbitol suppression were accompanied by significant improvement in NCV. In a secondary analysis, zenarestat doses producing >80% sorbitol suppression were associated with a significant increase in the density of small-diameter (<5 microm) sural nerve myelinated fibers. CONCLUSIONS: Aldose reductase pathway inhibition improves NCV slowing and small myelinated nerve fiber loss in DPN in humans, but >80% suppression of nerve sorbitol content is required. Thus, even low residual levels of aldose reductase activity may be neurotoxic in diabetes, and potent ARIs such as zenarestat may be required to stop or reverse progression of DPN.

Action Potentials↗

Brain morphometry in reading-disabled twins.

OBJECTIVE: To test for brain structure differences in reading disability (RD) by means of MRI-based morphometry. BACKGROUND: Consensus is lacking on the brain structural correlates of RD. The current study reports on a wider set of structures in the largest sample yet studied, controlling for age, gender, IQ, and attention deficit hyperactivity disorder (ADHD). METHODS: A case-control study was performed that was comprised of 75 individuals with RD (mean age, 17.43+/-4.29 years) and 22 control subjects without RD (mean age, 18.69+/-3.75 years), each a single member of a twin pair. The two groups were similar in age, gender, and handedness, but differed in full-scale IQ (FSIQ), with the RD group having a lower mean FSIQ (101.8+/-9.9 versus 118.3+/-10.3). Using three group-by-structure analyses of covariance, groups were compared in terms of volume (in cubic centimeters) of major neocortical subdivisions, subcortical structures, and midsagittal areas (in square millimeters) of three subdivisions of the corpus callosum. RESULTS: Controlling for age, gender, and IQ, the authors found a significant group-by-structure interaction for the major neocortical subdivisions (p = 0.002), reflecting a different developmental pattern in the RD group, with the insula and anterior superior neocortex being smaller and the retrocallosal cortex being larger in the RD group. In contrast, they found no group main or interaction effects for the subcortical or callosal structures. The pattern of results was essentially the same in subjects without ADHD. CONCLUSIONS: Most brain structures do not differ in size in RD, but cortical development is altered subtly. This study replicates in a larger sample previous findings of insular differences in RD and demonstrates further that those differences are not attributable to comorbid ADHD.

Adolescent↗

Epidermal nerve fiber density and sural nerve morphometry in peripheral neuropathies.

OBJECTIVE: To study intraepidermal nerve fiber (IENF) density in distal leg skin biopsies, sural nerve morphometry, electrophysiology, and clinical features in patients with peripheral neuropathies. METHODS: We studied 26 patients with neuropathic complaints who had undergone clinical evaluation, nerve conduction studies, distal leg skin biopsy, and sural nerve biopsy. We quantified densities of IENF and of myelinated and unmyelinated fibers in the sural nerve. Associations among skin and sural nerve morphometric measures and sensory nerve action potential (SNAP) amplitudes were examined nonparametrically. Morphometric measures were examined with respect to diagnostic category of neuropathy. RESULTS: IENF density correlated with the densities of sural nerve total myelinated (r = 0.57, p = 0.0011), small myelinated (r = 0.53, p = 0.0029), and large myelinated fibers (r = 0.49, p = 0.0054). There was a trend toward an association between IENF and sural nerve unmyelinated fiber densities (r = 0.32, p = 0.054). Sural SNAP amplitude and large myelinated fiber densities were highly correlated (r = 0.87, p < 0.0001). IENF density and sural nerve small fiber measures were concordant in 73% of patients. Reduced IENF density was the only indicator of small fiber depletion in 23% of cases. It was usually normal in acquired demyelinating neuropathies and where clinical suspicion for neuropathy was low. CONCLUSIONS: Distal leg Intraepidermal nerve (IENF) density may be more sensitive than sural nerve biopsy in identifying small fiber sensory neuropathies. Assessments of IENF density and large fiber measures on biopsy and electrophysiology are both useful for characterizing sensory and sensorimotor neuropathies.

Action Potentials↗

Reduced cortical gray matter in narcolepsy: preliminary findings with voxel-based morphometry.

There is a selective loss of hypocretin/orexin-containing hypothalamic neurons in patients with narcolepsy. The authors compared MRI-derived gray matter maps of 12 patients with narcolepsy with matched controls using voxel-based morphometry to ascertain whether there are other structural brain abnormalities. Patients with narcolepsy showed bilateral cortical gray matter reductions predominantly in inferior temporal and inferior frontal brain regions. Relative global gray matter loss was independent of disease duration or medication history. No significant subcortical gray matter alterations were noted.

Adult↗

Relationships between metacarpal morphometry, forearm and vertebral bone density and fractures in post-menopausal women.

The relationships between metacarpal morphometric, vertebral and forearm density measurements and the prevalence of vertebral and peripheral fractures were examined in 239 postmenopausal women (median age 63, range 32-84 years). Metacarpal cortical area/total area ratio (CA/TA) was measured with needle calipers, forearm mineral density (FMD) by single photon absorptiometry and vertebral mineral density (VMD) by single energy quantitative computed tomography. Of the 239 subjects 97 had not suffered any fractures, 44 had at least one previous vertebral fracture but no peripheral fractures, 41 had a history of peripheral fracture but no vertebral fracture and 57 had suffered both peripheral and vertebral fractures. There were significant correlations between a single measurement of CA/TA and both FMD (r = 0.65, p < 0.001) and VMD (r = 0.41, p < 0.001). Similar correlations existed between the mean of multiple measurements of CA/TA and both FMD and VMD. CA/TA (p < 0.001), FMD (p < 0.001) and VMD (p < 0.001) were reduced in subjects who had suffered fractures, when compared with the no fracture group. The percentage of cases in each of the four fracture groups (vertebral fracture only, peripheral fracture only, peripheral and vertebral fracture, peripheral or vertebral fracture) misclassified with reference to the no fracture group were similar with CA/TA, FMD or VMD measurements. We suggest that metacarpal morphometry, which is widely available at relatively low cost, yields cross-sectional information about bone density and fracture risk, comparable with that obtained by forearm and vertebral densitometry.

Absorptiometry, Photon↗

Nuclear morphometry and stereology in nasopharyngeal carcinoma.

The prognostic value of nuclear morphometry in nasopharyngeal carcinoma (NPC) was investigated in 28 patients. Seven morphometric nuclear variables were measured on 100 randomly selected tumor cells in nasopharyngeal biopsies from 18 patients with NPC confined to the nasopharynx. The same variables were measured in 6 patients with metastatic NPC, as well as in lymph node biopsies from 4 patients with metastatic NPC. Nuclear area, nuclear perimeter, long and short nuclear axes, nuclear form factor, nucleolar area, and the ratio of nucleolar area to nuclear area were all measured. Volume-weighted mean nuclear volume was also obtained. Tumor cells from patients with NPC confined to the nasopharynx had significantly larger mean nuclear areas, perimeters, and volume-weighted mean nuclear volumes but significantly smaller nucleolar to nuclear area ratios than tumor cells from patients with nodal metastases. Assessment of nuclear form factor and diameters did not differentiate the two groups.

Carcinoma↗

Morphometry on lancet flukes found in Japanese sika deer (Cervus nippon centralis) captured in Iwate Prefecture, Japan.

Thirty-six flukes were collected from the livers of wild deer (Cervus nippon centralis) captured in Iwate Prefecture, Japan, and were served for morphometry. The length and/or the width of the body, suckers, testes, ovary, vitelline glands, cirrus pouch and eggs in the uterus of the flukes were measured. The distance between anterior end of the body and position of the maximal body-width or upper end of the testes were also determined. A remarked morphological characteristic was that the right and left testes did not lie tandem but lined bilaterally. Also the position of the maximal body-width did not always locate in the posterior part of the body of the fluke. The property was in accordance with those for Dicrocoelium chinensis.

Animals↗

Morphometry confirms the presence of considerable nuclear size overlap between "small cells" and "large cells" in high-grade pulmonary neuroendocrine neoplasms.

We morphometrically evaluated 5-micron H&E-stained sections from 28 surgically resected high-grade pulmonary neuroendocrine neoplasms, including 16 small cell lung carcinomas (SCLCs) and 12 large cell neuroendocrine carcinomas (LCNECs). For each case, 200 tumor nuclei and 20 to 100 normal lymphocytes were measured. The frequency distributions of tumor cell/lymphocyte (TC/L) size ratios were plotted in bins ranging from 1 to 6, classified into 6 histogram types with TC/L size ratio peaks ranging from 2 to 6 (A-E) and a histogram with a wide distribution (F). SCLCs fit histograms A through E; LCNECs, A through F. Morphometry demonstrated considerable nuclear size overlap in high-grade neoplasms. Approximately one third of SCLCs exhibited considerable numbers of neoplastic cells that were larger than 3 normal lymphocytes, while 4 of 12 LCNECs had a predominant number of small cells. Ten tumors exhibited a B histogram with a "borderline" peak TC/L of 3. The rule that a TC/L size ratio larger than 3 helps distinguish "large" from "small" neoplastic cells was confirmed in only 9 of 28 cases. The use of more generic terminology such as "high-grade neuroendocrine carcinoma" or "grade III neuroendocrine carcinoma" for SCLC and LCNEC is discussed.

Carcinoma, Neuroendocrine↗

Morphometry of canine cutaneous mast cell tumors.

Twenty-four canine cutaneous nodules, diagnosed as mast cell tumors by fine-needle aspiration biopsy and confirmed by histopathologic analysis by staining with hematoxylin and eosin (HE) and toluidine blue, were analyzed by computerized nuclear morphometry on panoptic- and HE-stained cytopathology slides. Two hundred nuclei per lesion were examined. The morphometric parameters investigated were nuclear area, mean diameter, perimeter, regularity factor, and ellipticity factor. Lesions were graded as I (well differentiated), II (intermediate differentiation), or III (poorly differentiated) according to the following morphologic features: invasiveness, cellularity and cellular morphology, mitotic index, and stromal reaction. Nuclear morphometric results were then compared with histopathologic grades. Values of nuclear area, mean diameter, and perimeter increased with increase in histopathologic grade, but statistical analysis revealed significant differences only between grades II and III and between grades I and III when HE was used (P < 0.01) and between grades I and III with panoptic stain (P < 0.05). The ellipticity factor and regularity factor did not reveal significant differences between histopathologic grades. The results indicate that nuclear morphometric analysis, in combination with the rapid and inexpensive cytopathology technique, can help in mast cell tumor grading, thus contributing to the establishment of a more precise prognosis and treatment.

Animals↗

Aerosol-derived airway morphometry and aerosol bolus dispersion in patients with lung fibrosis and lung emphysema.

OBJECTIVE: Patients with lung emphysema show increased aerosol-derived dimensions of peripheral airspaces and increased aerosol bolus dispersion (AD). To apply these tests in epidemiologic studies, the objective of this pilot study was to investigate whether morphometric changes caused by lung fibrosis can be distinguished from those caused by emphysema. DESIGN: This study was designed as a cross-sectional study in which airspace dimensions and AD in patients with emphysema and in patients with fibrosis were compared. Forty patients participated in the study: 20 patients had high-resolution CT (HRCT)-proved lung emphysema and 20 patients had HRCT-proved lung fibrosis. All patients underwent conventional lung function tests, aerosol-derived airway morphometry (ADAM), and AD measurements. RESULTS: Patients with lung emphysema showed normal dimensions of small airways but enlarged airspace dimensions in the lung periphery. Patients with fibrosis showed in all lung depths increased airspace dimensions. AD was increased in patients with emphysema but was normal in patients with fibrosis. CONCLUSIONS: These results show that when using ADAM and AD, morphometric changes caused by emphysema can be distinguished from those caused by fibrosis with high sensitivity and specificity.

Adult↗