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PubMed2004

Voxel-based morphometry of patients with schizophrenia or bipolar disorder and their unaffected relatives.

BACKGROUND: Structural brain abnormalities in schizophrenia are well replicated; many emerge before the onset of illness and are present in relatives who remain well. Structural changes in bipolar disorder are less clearly established. The possibility that structural abnormalities might provide a means by which the disorders might be separated is one that has attracted limited research effort. This study sought to examine these issues and clarify the associations of phenotypic expression and genetic liability. METHODS: Forty-nine control subjects, 71 patients, and 72 unaffected relatives were recruited for the study. Patients included those with schizophrenia from families affected by schizophrenia alone, those with bipolar disorder from families affected by bipolar disorder alone, and those with bipolar disorder from families affected by both bipolar disorder and schizophrenia. Unaffected relatives were recruited from the families of the three patient groups. Subjects underwent a magnetic resonance imaging scan of the brain, which was analyzed with a grey-matter-optimized, voxel-based morphometry technique. RESULTS: Compared with control subjects, all patient and relative groups showed evidence of reduced anterior thalamic gray matter. Reductions in middle prefrontal gyrus and dorsomedial thalamus were specific to participants with schizophrenia. CONCLUSIONS: Whereas prefrontal and dorsomedial thalamic gray matter reductions seem to be specific to schizophrenia, anterior thalamic reductions seem to be a marker of liability to psychosis in general. These results are discussed in the context of their functional role and in terms of their connections with other cortical and subcortical structures.

Adult↗

PubMed2005

Selective reduction in amygdala volume in pediatric anxiety disorders: a voxel-based morphometry investigation.

BACKGROUND: Significant controversy has emerged concerning pediatric anxiety disorders. Some researchers question the justification for diagnosing and treating pediatric anxiety disorders, owing to concerns about the inappropriate medicalization of social problems. Others note the importance of diagnosis and treatment, given that pediatric anxiety disorders represent a strong risk factor for serious adult mental disorders. We examine the neural correlates of pediatric anxiety disorders, to consider the validity of the categorization scheme used in recent treatment studies. METHODS: Using inclusion criteria derived from recent treatment trials, we compared gray matter volume throughout the brain in children with and without anxiety. Morphometric analyses used optimized voxel-based morphometry, an automated method for examining structural changes throughout the brain. RESULTS: Reductions in left amygdala gray matter volume were noted for patients with anxiety disorders relative to comparison subjects. CONCLUSIONS: We discuss implications of these findings for current controversies.

Adolescent↗

PubMed2005

Regional gray matter abnormalities in obsessive-compulsive disorder: a voxel-based morphometry study.

BACKGROUND: Several structural magnetic resonance imaging (MRI) studies have investigated the presence of brain abnormalities in obsessive-compulsive disorder (OCD) but have not produced consistent findings. This might be partly related to their use of a regions-of-interest approach. We assessed gray matter volumes in 19 OCD subjects and 15 healthy volunteers, using voxel-based morphometry (VBM). METHODS: Images were acquired with a 1.5-T MRI scanner, spatially normalized, and segmented with optimized VBM. Statistical comparisons were performed with the general linear model. RESULTS: Significant findings were detected in regions predicted a priori to be implicated in OCD, including increased gray matter in OCD subjects relative to control subjects in posterior orbitofrontal and parahippocampal regions; decreased gray matter in OCD patients in the left anterior cingulate cortex; and inverse correlations between obsessive-compulsive symptom severity and gray matter in the medial thalamus (p < .001, uncorrected for multiple comparisons). Also, an unpredicted site of gray matter reduction in OCD patients in the right parietal associative cortex approached significance (p = .052, corrected for multiple comparisons). CONCLUSIONS: Our findings are consistent with previous studies implicating dysfunction of orbitofrontal, cingulate, thalamic, and temporolimbic regions in OCD and suggest that the involvement of the parietal cortex in the pathophysiology of OCD warrants further investigation.

Adult↗

PubMed2005

The relationship of structural alterations to cognitive deficits in schizophrenia: a voxel-based morphometry study.

BACKGROUND: Region of interest studies have identified a number of structure-cognition associations in schizophrenia and revealed alterations in structure-cognition relationship in this population. METHODS: We examined the relationship of structural brain alterations, identified using voxel-based morphometry, to cognitive deficits in 45 schizophrenia patients relative to 43 healthy control subjects and tested the hypothesis that structure-cognition relationship is altered in schizophrenia. RESULTS: Patients had smaller total brain, gray matter, and white matter volumes. Regional alterations were left-hemisphere specific, including: gray matter reduction of inferior frontal, lingual, and anterior superior temporal gyri; white matter reduction of posterior and occipital lobes; and gray matter increase of the putamen and the precuneus. Smaller whole brain and gray matter volumes were associated with lower premorbid intelligence quotient (IQ) and poorer performance on IQ-dependent cognitive measures in patients and to a similar extent in control subjects. Larger precuneus was associated with better immediate verbal memory in patients, whereas verbal and nonverbal memory were positively associated with inferior frontal gyrus volume in control subjects. Smaller occipital white matter volume was associated with slower information processing speed in patients but not in control subjects. CONCLUSIONS: Regional volume alterations are associated with specific cognitive deficits in schizophrenia. Some structure-cognition relationships differentiate this population from healthy control subjects.

Adolescent↗

PubMed2006

Vertebral morphometry in children and adolescents with osteogenesis imperfecta: effect of intravenous pamidronate treatment.

Results in small patient series suggest that cyclical intravenous treatment with pamidronate can lead to reshaping of compressed vertebral bodies in children and adolescents with osteogenesis imperfecta (OI), but more detailed analyses are lacking. In this study of patients with moderate to severe OI (age range 0.1 to 16.7 years), we used vertebral morphometry to longitudinally assess changes in lumbar vertebral shape before (n = 17 patients) and during 2 to 4 years of pamidronate treatment (n = 72 patients). Anterior, posterior and midpoint vertebral heights of lumbar vertebrae L1 to L4 were determined on lateral lumbar spine X-rays and were related to vertebral body length in the antero-posterior direction. Before pamidronate treatment, vertebral body height ratios did not change significantly, but the mean concavity index (defined as the ratio between midpoint and posterior vertebral body heights) decreased by 22% (P = 0.002). Pamidronate treatment was associated with an increase in vertebral height ratio at each of the 12 sites that were analyzed. Consequently, patients who had received pamidronate for an average of 3 years had less compressed vertebrae than a historical control group of patients who had the same OI type, age and sex but who had not received pamidronate. Multiple regression analysis revealed that age was negatively and lumbar spine areal bone mineral density z score was positively associated with vertebral shape at baseline. The main determinant of treatment response was the severity of vertebral deformities at baseline. These results suggest that vertebral deformations worsen in patients with moderate to severe OI who do not receive medical treatment and that pamidronate helps to reverse this trend. In moderate to severe forms of OI, pamidronate should be started as early as possible to treat or to prevent vertebral deformations.

Absorptiometry, Photon↗

PubMed2006

Volume of left amygdala subregion predicted temperamental trait of harm avoidance in female young subjects. A voxel-based morphometry study.

We investigated the relationship between temperamental predisposition and brain structure by using a standard questionnaire and high-resolution T1-weighted magnetic resonance image (MRI) in normal young volunteers. Fifty-six subjects completed the Japanese version of the Temperament and Character Inventory (TCI, 125 items) and underwent an MRI acquisition of the brain. The gray matter (GM) was extracted from the whole brain image of the subjects and normalized to the standard brain template using statistical parametric mapping and the optimized voxel-based morphometry (VBM) method. When the score on the harm avoidance (HA) subscale was used as a dependent variable, the multiple regression analysis revealed that the HA score positively correlated with the volume of the part of left amygdala. The region-of-interest analysis showed that the correlation was significant in the female subjects but not in the male subjects. The correlation was significant even after the effects of age, depression score, and total GM volume were taken into account. The differential correlation between the sexes may be caused by differences in hormonal condition and the vulnerability of women to socio-psychological stress. In addition, the novelty seeking (NS) score positively correlated with the GM of the left middle frontal gyrus. The volume of the tail of the right caudate nucleus positively correlated with the reward dependence (RD) score. With regard to the NS and RD scores, no significant sex difference was observed in the correlation. These results indicate that the temperamental traits measured using the questionnaire may have a morphological basis in the human brain.

Adult↗

PubMed2003

Predictability of lymph node metastases by preoperative nuclear morphometry in squamous cell carcinoma of the tongue.

AIM: This study was undertaken to assess the predictability of lymph node metastases by analyzing preoperative nuclear morphometry of squamous cell carcinoma of the tongue. METHODS: Twenty-eight cases of well-differentiated squamous cell carcinoma (13 cases with metastasized lymph nodes, 15 node-negative cases) were examined. Using a computerized image system, the mean nuclear area, the nuclear perimeter, the circular rate, the largest to the smallest dimension ratio (LS ratio) of the nuclei, and the coefficient of variation of the nuclear area (NACV) were measured. The relationship between these results and the lymph node involved was evaluated retrospectively. RESULTS: The nuclear area and perimeter were significantly higher in cases with metastasized lymph nodes than in node-negative cases (P<0.05). The circular rate was also higher in cases with no metastasized lymph nodes than in node-positive cases (P<0.05). The LS ratio was higher in cases with metastasized lymph nodes than in node-negative cases (P=0.072). The NACV value was also higher in cases with metastasized lymph nodes than in node-positive cases, which showed no significant differences (P=0.322). CONCLUSIONS: Preoperative quantitative estimations of nuclear features could provide a feasible criterion for the prediction of lymph node metastases in squamous cell carcinoma of the tongue.

Adult↗

PubMed2005

Ankle morphometry evaluated using a new semi-automated technique based on X-ray pictures.

BACKGROUND: The study of bone morphometry is important in anatomy, biomechanics and the design of joint arthroplasty, because the design of prostheses depends also on the knowledge of joint geometry, both for the replication of function and for the proper sizing of the components. Relevant information for the human ankle joint bones is particularly scarce. METHODS: A large number of morphological measurements of the ankle joint were collected in 36 normal subjects by means of a new semi-automated radiographic measurement method based on standard frontal and sagittal X-ray projections. Lengths, heights and widths of the main parts of this articulation together with the radii of curvature of the talar dome and of the trochlea tali in the sagittal plane were worked out. Statistical analysis was performed on these measurements. FINDINGS: A large spectrum for the values of these measures was found. Significant correlation was found among some of the measures, but not between any of these and the subject height. INTERPRETATION: Bones at the ankle joint have similar shapes, i.e. the three dimensions are in direct proportion to each other. No one of the internal dimensions is correlated with the only one possible external measurement, i.e. the malleolar width. Sizes of the current total ankle replacement designs may differ considerably from real corresponding joint dimensions.

Adult↗

PubMed2003

Reduced cortical gray matter density in human MDMA (Ecstasy) users: a voxel-based morphometry study.

The popular recreational drug, 3,4-methylenedioxymethamphetamine (MDMA) exerts its actions in part via blockade of serotonin and dopamine reuptake. Many animal and human studies have demonstrated long-lasting reductions in measures of central nervous system (CNS) serotonin function following MDMA administration. One emerging role of serotonin function in the CNS is a positive trophic effect via stimulation of intracellular signaling pathways and trophic factors. We hypothesized that human MDMA users might display neocortical gray matter reductions due to loss of serotonergically mediated trophic effects on cortical cells. However, unlike animal models, most human MDMA users worldwide are polydrug users, thereby complicating the assessment of MDMA toxicity in this group. Structural magnetic resonance imaging (MRI) scans of 31 MDMA polydrug users versus 29 non-MDMA users were compared using voxel-based morphometry (VBM) to assess regional brain gray and white matter concentration. VBM employs gray/white matter segmentation and statistical parametric mapping (SPM) analysis to calculate a voxel-wise comparison of regional gray or white matter concentration. Using this method, we consistently found several brain regions having decreased gray matter concentration in MDMA polydrug users. These regions were localized to neocortex in bilateral Brodmann area (BA) 18, left BA 21, and left BA 45, as well as bilateral cerebellum, and midline brainstem. Overall, these preliminary findings suggest that MDMA polydrug users have multiple regions of gray matter reduction, potentially accounting for previously reported neuropsychiatric impairments in MDMA users. Additional animal model and human studies of the CNS effects of MDMA and combined MDMA-polydrug toxicity are needed to further explain these findings. Potential explanations for our results including pre-existing brain differences predisposing to MDMA polydrug use, direct MDMA and polydrug toxicity, indirect changes due to MDMA and polydrug toxicity, or combinations of all these factors.

Adolescent↗

PubMed2006

Assessment of renal maturity by assisted morphometry in autopsied fetuses.

BACKGROUND: The kidney is one organ which presents distinct morphology depending on GA; the classic references for kidney measurements were established several years ago and it is not certain if they are still accurate. AIM: To evaluate the renal maturity using a computer-assisted morphometry in autopsied fetuses within 20 to 40 weeks of GA. STUDY DESIGN: Microscopic hematoxylin and eosin stained renal sections from 67 stillborns were utilized for the morphometric analyses. RESULTS: It was possible to promote an adjustment in the formula used to calculate the number of mature glomeruli layers to the GA (GLN = 0.212GA + 0.0169) in autopsy material and it was different from the literature (Sr = 0.709; p < 0.001). Regarding the nephrogenic zone, it decreases with the GA as confirmed by the regression equation NZ = 490.7-(11.9 x GA) (p < 0.001; Sr = -0.685). CONCLUSION: In conclusion, our data contribute to the evaluation of renal maturity and GA in autopsied fetuses, showing particular importance in autolyzed fetuses, in which the parameters used in the present study can still be applied. The correction of the formula for counting mature glomeruli layers for each GA and the addition of new morphometric parameters for the evaluation of renal maturity increase the precision for the analysis of spontaneous abortion and autopsy material, improving the correlation with pathological processes in clinical findings and in the other organs.

Autopsy↗

PubMed2006

Comparing the Multi-ZSC one-step standardized swim-up method to the double-wash swim-up method with regard to the effects of sperm separation on morphology, head morphometry, and acrosome reaction inducibility.

The objective of this study was to test the efficacy of the new Multi-ZSC system on human sperm separation compared with the commonly used double-wash swim-up method. It was found that the double-wash swim-up method selects sperm with better head morphometry and acrosome reaction inducibility than the upper fractions of the Multi-ZSC.

Cell Culture Techniques↗

PubMed2005

Male elderly subthreshold depression patients have smaller volume of medial part of prefrontal cortex and precentral gyrus compared with age-matched normal subjects: a voxel-based morphometry.

BACKGROUND: The brain morphological changes in subthreshold depression (sD) have not been clarified. We examined the structural difference in regional gray matter volume between community-dwelling elderly subjects with sD and age-matched nondepressed normal subjects by voxel-based morphometry (VBM) based on magnetic resonance imaging (MRI). METHODS: Thirty-four community-dwelling elderly subjects with sD and 109 age-matched nondepressed normal subjects were studied by MRI. We defined subjects with sD as those who showed a Geriatric Depression Scale score of 15 or higher and a Mini Mental State Examination score of 22 or higher, and do not fulfill the criteria of major depressive disorder (MDD) in the Diagnostic and Statistical Manual for Mental Disorders IV. We collected brain magnetic resonance images of 34 subjects with sD and 109 age-matched normal subjects, and analyzed the difference in regional gray matter volume between these two groups by VBM. RESULTS: Male subjects with sD had significantly smaller volumes of the medial part of the bilateral frontal lobes and the right precentral gyrus than normal male subjects. LIMITATIONS: We have not clarified the discrepancy in the results of gender difference. CONCLUSIONS: Our study revealed that even community-dwelling elderly male subjects with sD show bilateral prefrontal gray matter volume reduction, which was reported to be observed in elderly patients with MDD, although there is no significant volume reduction in the hippocampus, which was also reported to be observed in MDD. Our study may contribute to clarifying the mechanism underlying brain pathological changes in sD.

Age of Onset↗

PubMed2005

Automatic morphometry of synaptic boutons of cultured cells using granulometric analysis of digital images.

Numbers, linear density, and surface area of synaptic boutons can be important parameters in studies on synaptic plasticity in cultured neurons. We present a method for automatic identification and morphometry of boutons based on filtering of digital images using granulometric analysis. Cultures of cortical neurons (DIV8 and DIV21) were fixed and marked with fluorescently labeled antibodies for synapsin I (a marker for synaptic boutons) and MAP-2 (a marker for dendrites). Images were acquired on a confocal microscope and automatically processed. Granulometry, a morphological operator sensitive to the geometry and size of objects, was used to construct a filter passing fuzzy fluorescent grains of a certain size. Next, the filter was overlaid with the original image (masking) and the positive pixels were identified by an integral intensity threshold (thresholding). Disjoint grains, representing individual boutons, were reconstructed from the connected pixels above the threshold, numbered and their area was measured. In total, 1498 boutons with a mean diameter of 1.63 +/- 0.49 microm (S.D.) were measured. Comparisons with manual counts showed that the proposed method was capable of identifying boutons in a systematic manner at the light microscopic level and was a viable alternative to manual bouton counting.

Algorithms↗

PubMed2006

Vertebral morphometry by DXA: a comparison of supine lateral and decubitus lateral densitometers.

Identification of vertebral fracture has become increasingly important in the diagnosis and management of osteoporosis. This study compares the morphometric techniques on a fan beam dual-energy X-ray absorptiometry (DXA) GE-Lunar Expert system (Expert) using a supine lateral position and a narrow fan beam GE-Lunar Prodigy system (Prodigy; GE Lunar, Madison, WI) that requires lateral decubitus positioning. Patient acceptability, image quality, observer, and equipment variability were determined. Study subjects were recruited from clinical referrals sent for a routine DXA study that included vertebral morphometry. Twenty-five patients underwent lateral vertebral assessment on both machines and completed a questionnaire on comfort and tolerability. Analysis was undertaken by two trained observers. Vertebral height, anterior/posterior height (A/P) and mid/posterior height (M/P) ratios, image quality, and prevalent fractures were assessed. There were no significant differences in patient comfort or image quality scores. More upper thoracic vertebrae could be assessed on the Expert, and good radiographic positioning was easier to achieve on the Expert. Inter-observer coefficients of variance percentage (CV%) of vertebral height was lower on the Prodigy (3.5% in the lumbar spine rising to 12.8% in the thoracic spine) than the Expert (4.2% to 16.9%). Inter-observer CV% for A/P and M/P ratios varied from 2.5% to 10.5% on the Prodigy compared with 3.5% to 12.3% on the Expert, depending on vertebral level. The variation between instruments was similar to the inter-observer CV% (anterior height: -0.11+/-1.65 mm; mid height: 0.54+/-1.51 mm; posterior height: 0.43+/-1.46 mm). There was good agreement between observers and between the Expert and Prodigy in identifying severe fractures, but lack of agreement in identifying moderate fractures. In conclusion, there was no clinically significant difference in patient comfort and image quality between the Expert and the Prodigy. The inter-observer variations in vertebral height and A/P and M/P ratios are similar to the variations between instruments. In making the change from the supine lateral to the decubitus lateral positioning, measurements of vertebral height are reproducible and patient comfort is not compromised.

Absorptiometry, Photon↗

PubMed2004

Analysis of magnetic resonance imaging (MRI) morphometry and cerebral blood flow in patients with hypoxic-ischemic encephalopathy.

The aim of this study was to analyze magnetic resonance imaging (MRI) morphometry and cerebral blood flow (CBF) in patients with hypoxic-ischemic encephalopathy, and determine the viability of such measurements for predicting cerebral outcome. The subjects were 26 patients with histories of cardiopulmonary resuscitation who had subsequently developed encephalopathy. We examined the CBF using stable xenon-computed tomography (Xe-CT) and MR images in the subacute period (8-20 days). Three signal-change patterns in the basal ganglia emerged in the MRI study. The first pattern, isointense areas evident in both the T1-weighted image (T1WI) and the T2-weighted image (T2WI), was observed in four patients with favorable outcomes. The second pattern, iso- or hypointense areas evident in the T1WI and hyperintense areas evident in the T2WI, was observed in six patients with favorable outcomes and three patients with poor outcomes. The third pattern, hyperintense areas evident in both the T1WI and T2WI, was observed in 13 patients with poor outcomes. Hemispheric CBFs were 38.9+/-4.6 (mean (SD)) ml/100 g/min in patients with favorable outcomes and 25.3+/-4.3 ml/100 g/min in patients with poor outcomes (p < 0.01). The CBF increase after acetazolamide administration was 13.3+/-3.4 ml/100 g/min in patients with favorable outcomes and 6.8+/-5.6 ml/100 g/min in patients with poor outcomes ( p < 0.05). The presence of hyperintense lesions in the basal ganglia in T1WI, low hemispheric CBF ( < 30 ml/100 g/min), and low acetazolamide reactivity ( < 10 ml/100 g/min) are all factors associated with poor outcome in patients with hypoxic-ischemic encephalopathy.

Adolescent↗

PubMed2006

Detrusor quantitative morphometry in obstructed males and controls.

PURPOSE: We studied the usefulness of computer assisted morphometry for measuring detrusor muscle cell diameter and the connective tissue-to-smooth muscle ratio in patients with bladder outlet obstruction, acute urinary retention and a nonobstructed control group. MATERIALS AND METHODS: A prospective study was done in patients with bladder outlet obstruction undergoing transurethral prostate resection. Patients were divided into 33 with obstruction and 14 in acute urinary retention. A total of 15 males without obstruction undergoing transurethral prostate resection for bladder tumor formed the control group. Detrusor specimens were obtained during transurethral prostate resection. Detrusor muscle cell diameter was measured using light microscopy and a semiautomatic image analysis system. The connective tissue-to-smooth muscle ratio was automatically determined with computer assisted image analysis. Symptoms and urodynamic assessment were performed preoperatively and 6 months postoperatively. RESULTS: A total of 62 patients were included. The obstruction and acute urinary retention groups had a statistically higher detrusor muscle cell diameter and more fibrosis than the control group. Patients in acute urinary retention had more intrafascicular fibrosis (higher connective tissue-to-smooth muscle ratio at 40x magnification) than patients with obstruction. There were no differences in detrusor muscle cell diameter or interfascicular fibrosis (connective tissue-to-smooth muscle ratio at 10x magnification) between the obstruction and acute urinary retention groups. Detrusor muscle cell diameter correlated with symptom duration and functional recovery after transurethral prostate resection. Detrusor fibrosis correlated with preoperative detrusor pressure at maximum flow and postoperative compliance. Patients in acute urinary retention had fewer symptoms and higher residual volume. Other urodynamic parameters and their improvement after surgery were similar in the acute urinary retention and obstruction groups. CONCLUSIONS: Morphometric differences in detrusor muscle cell diameter and the connective tissue-to-smooth muscle ratio were observed between controls and patients with obstruction. There is an increase in detrusor muscle cell diameter and fibrosis in bladder outlet obstruction and more intense intrafascicular collagen deposition in patients in acute urinary retention.

Acute Disease↗

PubMed2004

Brain morphometry using 3D moment invariants.

This paper advocates the use of shape descriptors based on moments of 3D coordinates for morphometry of the cortical sulci. These descriptors, which have been introduced more than a decade ago, are invariant relatively to rotations, translations and scale and can be computed for any topology. A rapid insight into the derivation of these invariants is proposed first. Then, their potential to characterize shapes is shown from a principal component analysis of the 12 first invariants computed for 12 different deep brain structures manually drawn for 7 different brains. Finally, these invariants are used to find some correlates of handedness and sex among the shapes of 116 different cortical sulci automatically identified in each of 142 brains of the ICBM database.

Algorithms↗

PubMed2005

Voxel-based morphometry to discriminate early Alzheimer's disease from controls.

We assessed the accuracy of voxel-based morphometry (VBM) using a three-dimensional T1-weighted MRI in discriminating Alzheimer's disease (AD) in the very early stage of amnestic type of mild cognitive impairment and age-matched healthy controls. We randomly divided these subjects into two groups. The first group comprising 30 AD patients and 41 controls was used to identify the area with the most significant gray matter loss in patients compared to normal controls based on the voxel-based analysis of a group comparison. The second group comprising 31 patients and 41 controls was used to determine the discrimination accuracy of VBM. A Z-score map for a gray matter image of a subject was obtained by comparison with mean and standard deviation gray matter images of the controls for each voxel after anatomical standardization and voxel normalization to global mean using the following equation; Z-score=([control mean]-[individual value])/(control S.D.). Receiver operating characteristic curves for a Z-score in the bilateral medial temporal areas including the entorhinal cortex with the most significant loss in the first group showed a high discrimination accuracy of 87.8%. This result would open up a possibility for early diagnosis of AD using VBM.

Aged↗