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Voxel-based morphometry detects cortical atrophy in the Parkinson variant of multiple system atrophy.

To determine magnetic resonance imaging (MRI) patterns of brain atrophy in parkinsonian syndromes, we applied voxel-based morphometry (VBM) to segmented gray matter, white matter, and cerebrospinal fluid compartments of T(1)-weighted brain volumes of 12 patients with probable multiple system atrophy-parkinson variant (MSA-P) and 12 Parkinson's disease patients, comparing them with 12 normal controls matched for age. In comparison to controls, a cortical atrophy pattern was observed in MSA-P patients with significant clusters of volume loss in primary sensorimotor cortices bilateral, supplementary motor areas bilateral, right premotor cortex, prefrontal cortex bilateral (middle frontal gyri) and insular cortices bilateral; subcortical atrophy occurred bilaterally in caudate nuclei and putamen as well as in the midbrain. Furthermore, an enlargement of the cerebrospinal fluid compartment was found in the lateral ventricles, third ventricle, perimesencephalic and cerebellomedullar cavities. In PD patients, significant atrophy only occurred in left caudate head with enlargement of left lateral ventricle. Comparing MSA-P to PD patients, MSA-P showed a similar cortical pattern of atrophy as compared to controls. We conclude that VBM reveals selective cortical atrophy in patients with MSA-P affecting primary and higher order motor areas as well as prefrontal and insular cortices. Further studies are required to determine clinical and/or subclinical correlates of cortical atrophy in MSA-P.

Aged↗

Fiber type morphometry and capillary geometry in free, vascularized muscle transfers.

In order to establish the relationship among intraoperative ischemia time, the recovery of contractile function, muscle fiber morphometry, and capillary geometry following free muscle transfer, 15 male dogs underwent unilateral, orthotopic free transfer of the left gracilis muscle with microneurovascular anastomosis. Intraoperative ischemia time varied from 0 to 4 hours. After a recovery period averaging 14 months, isometric contractile function was measured in the transfers and the contralateral, control muscles. Muscle fiber type composition, fiber size, and capillary geometry were quantified from histochemical sections. Transferred and control muscles had similar type I fiber percentages, type I fiber sizes, and capillary densities. Type II fiber sizes were reduced in transfers relative to controls. There was no significant effect of intraoperative ischemia on any morphometric variable. Although contractile function was generally reduced after free, vascularized transfer, there was only a weak correlation between the recovery of tetanic tension and type I fiber percentage (r = 0.53, P less than 0.05). It is concluded that free, vascularized muscle transfer results in minimal disturbance of muscle fiber type composition, fiber size, or capillary supply and that the diminished contractile function observed in this setting is still largely unexplained.

Analysis of Variance↗

The use of nuclear morphometry to predict prognosis in pediatric urologic malignancies: a review.

Wilms tumor, the most common pediatric urologic malignancy, and genitourinary rhabdomyosarcoma, the most common soft tissue sarcoma of childhood, represent two of the most commonly diagnosed pediatric urologic malignancies. The introduction and use of multimodal therapy (surgery, radiation, and chemotherapy) by the National Wilms Tumor Study (NWTS) and the Intergroup Rhabdomyosarcoma Study (IRS) groups have greatly improved the survival among children with these malignancies. Present survival rates for Wilms tumor exceed 85% and for rhabdomyosarcoma survival rates are approaching 80% as well. For Wilms tumor, current treatment trends suggest less intense therapy for those children with favorable histology tumors who are considered at relatively low risk for tumor recurrence. Likewise, the significant morbidity associated with the present therapy regimens for rhabdomyosarcomas has prompted investigators to search for individualized management schemes for children with a high probability of responding. The need for accurate criteria to separate these high and low risk groups becomes imperative. In this review we present our work using nuclear morphometry, as a prognostic indicator, to retrospectively predict response to therapy for children with Wilms tumors and genitourinary rhabdomyosarcomas.

Adolescent↗

Morphometry of dermal collagen orientation by Fourier analysis is superior to multi-observer assessment.

In human dermis, collagen bundle architecture appears randomly organized, whereas in pathological conditions, such as scar tissue and connective tissue disorders, collagen bundle architecture is arranged in a more parallel fashion. Histological examination by one or two observers using polarized light is the most common method to determine collagen orientation. The hypothesis on which this study is based is that an objective image analysis technique, Fourier analysis, would improve the reliability (are the measurements reproducible?) and the accuracy (does the method measure what it is supposed to measure?) of collagen orientation assessment, compared with observer ratings. Fourier analysis was applied to 271 images of scar tissue and normal skin that were acquired by confocal laser-scanning microscopy. Observers rated the same areas using polarized light as well as the confocal microscopy images. Computer images consisting of different types of ellipses were generated with a fixed orientation. Observers and Fourier analysis evaluated the images to evaluate accuracy. The inter-observer reliability was acceptable when at least three observers rated polarized light images (r > 0.69), whereas two observers were sufficient for rating confocal microscopy images (r > 0.71). Fourier analysis correlated better with observer ratings of confocal microscopy images (r = 0.69) than with polarized light microscopy images (r = 0.42). Fourier analysis was more accurate than four observers for the evaluation of the 'true' orientation for almost all types of computer-generated images. For the first time it is shown that Fourier image analysis is suitable for the morphometry of dermal collagen orientation and leads to a superior measurement of collagen orientation compared with subjective histological evaluation by several experts. If an evaluation is performed by conventional light microscopy, at least three observers are required to attain an acceptable inter-observer reliability.

Adult↗

Morphometry of bladder carcinoma: I. The automatic delineation of urothelial nuclei in tissue sections using an IBAS II image array processor.

Semi-automatic methods of morphometry require the boundaries of the objects under study to be drawn by hand. This is slow, tedious and does not guarantee accuracy. Complete automation, with recognition, detection and verification by computer is not yet feasible. Automatic detection of nuclear boundaries with observer verification provides a means of obtaining large amounts of data for analysis, quickly and with similar accuracy to manual tracing.

Cell Nucleus↗

Morphometry of gastric carcinoma: its association with patient survival, tumour stage, and DNA ploidy.

Morphometric image analysis of nuclear features was performed on tissue from 46 patients who had had curative resections for gastric cancer. Clinical, pathological, flow cytometric, and follow-up data were available for these patients, which were drawn from a larger, previously reported series. The morphometric data were compared with patient survival, clinico-pathological status, and DNA ploidy. Univariate survival analysis revealed that morphometric parameters were not significantly related to survival, but examination of clinico-pathological data showed lymph node involvement, involvement of the resection margin, and lymphatic invasion to be significantly associated (P < 0.01) with patient prognosis. Multivariate survival analysis using the Cox model found only lymph node and resection margin involvement to be independently related to survival. Comparison of morphometric results with the clinico-pathological parameters showed various features, relating to nuclear size, and its variation to be significantly associated (P < 0.01) with the presence of lymphatic invasion, resection margin involvement, and tumour pattern (intestinal/diffuse). A comparison of morphometry with flow cytometric analysis in these cases showed that nuclear size was not significantly related to either DNA aneuploidy or the DNA proliferative index.

Aged↗

Effect of melatonin on the anuran thyroid gland: follicle cell proliferation, morphometry, and subsequent thyroid hormone secretion in vitro after melatonin treatment in vivo.

The thyroid gland controls the progress of metamorphosis, although other hormones influence metamorphic rate, including melatonin, which may coordinate metamorphosis with seasonal and light conditions. Melatonin directly antagonized the action of thyroxine (T4) in promoting regression of tadpole tail tips in vitro, and this study sought to determine if it affects the thyroid axis of tadpoles as well. In an experiment sampling at 8-hr intervals for 24 hr, after melatonin treatment (15 micrograms/day for 12 days) of premetamorphic Rana pipiens tadpoles at approximately 1100 hr on 18L:6D, thyroid follicle cell height and lumen diameter were lowered by melatonin, but follicle cell proliferation was not significantly depressed. In a second experiment conducted under the same conditions, but sampling at 3-hr intervals for 24 hr, melatonin significantly lowered follicle cell labeling index and suppressed its ultradian (7.6 hr) rhythm, while shifting the peak of follicle lumen diameter to the dark instead of the light. Thus, melatonin tended to depress the thyroid of young tadpoles and suppress or shift its rhythms. Melatonin (10 micrograms/day for 5 days) injected into prometamorphic Rana catesbeiana tadpoles at 1930 hr on 18L:6D significantly altered subsequent in vitro thyroid function as determined by radioimmunoassay of media collected at intervals for 54 hr from cultured thyroids of injected control and melatonin groups, and a noninjected control group. Melatonin decreased T4 secretion during the first 30 hr, but not during the last 24 hr of culture, suppressed 3,5,3'-triidothyronine (T3) secretion for 12 hr, and then raised T3 output into the media above the control for the remainder of the culture period, increasing the T3:T4 ratio. Injection alone increased both T3 and T4 secretion for the first 30 hr, but did not change the T3:T4 ratio. The findings show that exogenous melatonin administered in vivo significantly modulated thyroid activity and morphometry directly and/or indirectly and comprise the first demonstration of an effect of melatonin on the amphibian thyroid gland.

Animals↗

The significance of histology and morphometry in predicting lymph node metastases in patients with squamous cell carcinoma of the vulva.

The material consists of a series of 73 patients with squamous cell carcinoma of the vulva. The site and the size of the primary tumor and the histological status of the lymph nodes of the groin were known. Two pathologists evaluated nuclear hyperchromatism, nuclear polymorphism, histological differentiation, number of mitoses, inflammatory response, and vascular invasion and graded these parameters from one to three. The reliability of the histopathological grades evaluated by the kappa coefficient showed considerable interobserver variation. Despite this a model which included the subjective parameter nuclear hyperchromatism could predict patients without lymph node metastases. The model consisted of patients with tumors which were not situated on the clitoris, were less than 40 mm in diameter, and exhibited only slight hyperchromatism. The model fitted 19 (26%) and 14 (19%) of the patients with two different pathologists evaluating the nuclear hyperchromatism and none of these patients had lymph node metastases. The quantitative parameter--mean nuclear volume--determined by morphometry was of no diagnostic value for the prediction of patients without groin node metastases at the time of operation.

Adult↗

Neural isolation of the jejunoileum. Effect on tissue morphometry, mucosal disaccharidase activity, and tissue peptide content.

The aim of this study was to determine the effects of a model of intestinal extrinsic denervation on mucosal structure and function. Six dogs underwent in situ neural isolation of the jejunoileum (Group 2); six other dogs served as operated controls (Group 1), and five nonoperated dogs were naive controls (Group 3). Thirty-centimeter segments of proximal jejunum and distal ileum were excised before (time zero) and at 2 weeks and 8 weeks postoperatively in Groups 1 and 2, while similar regions were removed at time zero in Group 3. Tissues were analyzed for morphology with quantitative morphometry, mucosal disaccharidase activities (sucrase, maltase, and lactase), and tissue content of selected regulatory peptides in transmural, mucosa/submucosa, and muscularis regions. In situ neural isolation had no significant or consistent effects on morphology/morphometry or on mucosal disaccharidase activities. Tissue content of neuropeptide Y decreased markedly (P < 0.002) in all layers of the jejunal and ileal walls, but tissue content of vasoactive inhibitory polypeptide, substance P, cholecystokinin, neurotensin, met-enkephalin, neurokinin A, somatostatin, and calcitonin gene-related peptide demonstrated only minor changes. The physiologic effects of intestinal transplantation (extrinsic denervation and disruption of intrinsic, enteric neural continuity, and lymphatic drainage) have little effect on morphology, mucosal disaccharidase activity, and tissue content of most regulatory peptides. How these minor alterations might affect enteric function, however, needs to be investigated.

Animals↗

Morphometry of the canine prostate vasculature.

Morphometric data of the tissue vasculature are fundamental to the development of models for blood perfused tissue mass and heat transfer. Vascular casts of six canine prostates were made and morphometry was performed on 14 transverse sections. The region sampled was restricted to the midsection within the parenchyma. General vascular features that were observed include the radially arranged arteries and veins within the parenchyma, the axially oriented periurethral venous plexae, and the parenchymal arteries ramifying less than the veins. The arterial and venous lumen diameters (mean +/- SD) are 84 +/- 31 (N = 42) and 125 +/- 51 (N = 117), respectively. The lengths for a single vessel generation are 2147 +/- 1196 microm (N = 14) and 1265 +/- 693 microm (N = 39) for the arteries and veins, respectively. Intervessel distances are 4056 +/- 2350 microm (N = 33) between arteries, 1526 +/- 982 microm (N = 330) between veins, and 1498 +/- 874 microm (N = 108) between arteries and veins. A simple vasculature model of evenly distributed vessels imbedded in tissue for heat transfer analysis was developed. The artery-artery distance being about three times that of the vein-vein distance suggested a rete-like configuration of arteries surrounded by veins. An effective distance of 1519 microm between vessels was used. Based upon this vasculature model, the vessel density was calculated to be 5.6 arteries/cm(2) and 44.5 veins/cm(2).

Animals↗

Voxel-based morphometry--the methods.

At its simplest, voxel-based morphometry (VBM) involves a voxel-wise comparison of the local concentration of gray matter between two groups of subjects. The procedure is relatively straightforward and involves spatially normalizing high-resolution images from all the subjects in the study into the same stereotactic space. This is followed by segmenting the gray matter from the spatially normalized images and smoothing the gray-matter segments. Voxel-wise parametric statistical tests which compare the smoothed gray-matter images from the two groups are performed. Corrections for multiple comparisons are made using the theory of Gaussian random fields. This paper describes the steps involved in VBM, with particular emphasis on segmenting gray matter from MR images with nonuniformity artifact. We provide evaluations of the assumptions that underpin the method, including the accuracy of the segmentation and the assumptions made about the statistical distribution of the data.

Brain↗

Voxel-based morphometry of herpes simplex encephalitis.

Voxel-based morphometry (VBM) is a powerful tool for analyzing changes in gray or white matter density of the brain. By using an automated segmentation procedure and standardized parametric statistics it avoids biases inherent in operator-dependent morphological operations (J. Ashburner and K. J. Friston, 2000, NeuroImage 11, 805-821). Since its introduction in 1995, VBM has been used to examine anatomical changes in a variety of diseases associated with neurologic and psychiatric dysfunction. Given the power of this technique for discerning subtle anatomical changes, we wanted to assess its performance on brains with gross structural abnormalities. Such results could have implications regarding the difficulties to be faced when examining other types of distorted brains (e.g., brains with changes due to degenerative disease). This report describes the use of VBM for examining individual and group changes in gray matter concentration in five patients who had recovered from herpes simplex encephalitis (HSE) compared with age- and sex-matched controls. Because HSE tends to affect a specific set of brain regions we thought that this would (1) provide an opportunity to assess the anatomical face validity of VBM, (2) allow us to assess the problems of this technique when used on distorted brains, and (3) provide an in vivo demonstration of the gray matter changes due to HSE. We found that, despite problems in normalizing and segmenting these severely distorted brains, VBM was able to identify correctly a number of the regional gray matter abnormalities in HSE. The results, while consistent with the well-known histopathology of the disease, also demonstrate potential difficulties with this method.

Adult↗

"Voxel-based morphometry" should not be used with imperfectly registered images.

John Ashburner and Karl Friston (2000) introduced a standardized method of "voxel-based morphometry" (VBM) for comparisons of local concentrations of gray matter between two groups of subjects. Segmented images of gray matter from grossly normalized high-resolution images are smoothed and their group differences analyzed by the now-conventional voxelwise Worsley approach to Gaussian random fields of differences. This comment concerns an unfortunate interaction between the algorithm's spatial normalization and voxelwise comparison steps, whereby several obvious quantitative confounds are injected at the core of the inference engine the authors put forward. Specifically, the statistics of the resulting voxelwise comparisons are uninformative about group differences wherever the spatial normalization algorithm has failed to register on any robustly appearing image gradient. The method of Ashburner and Friston is defensible only far from all image gradients.

Artifacts↗

Deformation-based morphometry and its relation to conventional volumetry of brain lateral ventricles in MRI.

Deformation-based morphometry (DBM) is a useful technique to detect morphological differences over the entire brain since it analyses positional differences between every voxel and a standard brain. In this report we compare DBM to semimanual tracing of brain ventricles in a population of 39 patients with schizophrenia. High-resolution T(1)-weighted magnetic resonance images were obtained and processed with DBM and interactive tracing software. We evaluate the validity of the DBM in two different approaches. First, we divide subjects into two groups based on the mean ventricular/brain ratios and compute statistical maps of displacement vectors and their spatial derivatives. This analysis demonstrates a striking consistency of the DBM and visual tracing results. We show that restricting the information about the deformation fields by computing the local Jacobian determinant (as a measure of volume change) provides evidence of the shape of ventricular deformation which is unavailable from ventricular volume measures alone. Second, we compute a mean measure of the Jacobian values over the entire ventricles and observe a correlation of r = 0.962 with visual tracing based ventricular/brain ratios. The results support the usefulness and validity of DBM for the local and global examination of brain morphology.

Adolescent↗

Sexual dimorphism in the corpus callosum: a characterization of local size variations and a classification driven approach to morphometry.

We present two complementary quantitative approaches to the problem of characterizing morphometric variations between two distinct populations. The case presented focuses solely on local size variations, but the general method can easily be applied to other scalar morphometric quantities. The first method uses a statistical parametric map (SPM) to ascertain a P value, which indicates whether any statistically significant differences exist between the populations. The second method focuses on finding the best single measurement which can be used for classifying the two populations. For our case study midsagittal cross sections of the corpora callosa from a population of normal males and females are nonrigidly registered (spatially normalized) to an atlas. The resulting deformations are then used to ascertain (i) whether there are any statistically significant differences between the populations and (ii) whether these differences allow one to perform classification. We make use of the Jacobian of the deformation field and normalize it to account for overall volume changes allowing us to focus on differences which are more related to morphometry than scale. From the (SPM) approach to the problem we find evidence of statistically significant differences in the morphology between the populations. Using a linear discriminant function we find that these differences do not appear to be useful for classification. Thus, this dataset provides an example of how statistically significant effects may not be of much diagnostic value. They may be of interest to the research community, but of little value to the clinician.

Adult↗

Voxel-based morphometry reveals increased gray matter density in Broca's area in male symphony orchestra musicians.

Broca's area is a major neuroanatomical substrate for spoken language and various musically relevant abilities, including visuospatial and audiospatial localization. Sight reading is a musician-specific visuospatial analysis task, and spatial ability is known to be amenable to training effects. Musicians have been reported to perform significantly better than nonmusicians on spatial ability tests, which is supported by our findings with the Benton judgement of line orientation (JOL) test (P < 0.001). We hypothesised that use-dependent adaptation would lead to increased gray matter density in Broca's area in musicians. Voxel-based morphometry (VBM) and stereological analyses were applied to high-resolution 3D MR images in male orchestral musicians (n = 26) and sex, handedness, and IQ-matched nonmusicians (n = 26). The wide age range (26 to 66 years) of volunteers permitted a secondary analysis of age-related effects. VBM with small volume correction (SVC) revealed a significant (P = 0.002) region of increased gray matter in Broca's area in the left inferior frontal gyrus in musicians. We observed significant age-related volume reductions in cerebral hemispheres, dorsolateral prefrontal cortex subfields bilaterally and gray matter density in the left inferior frontal gyrus in controls but not musicians; a positive correlation between JOL test score and age in musicians but not controls; a positive correlation between years of playing and the volume of gray matter in a significant region identified by VBM in under-50-year-old musicians. We suggest that orchestral musical performance promotes use-dependent retention, and possibly expansion, of gray matter involving Broca's area and that this provides further support for shared neural substrates underpinning expressive output in music and language.

Adult↗

Morphometry of right ventricular papillary muscle in rat during development and regression of hypoxia-induced hypertension.

Morphometric analyses of the right ventricular papillary muscle, as well as measurements of right ventricular pressure and weight, were carried out in the rat during the development and recovery of hypoxic pulmonary hypertension. Animals were divided into hypoxic and normobaric control groups. The hypoxic rats were placed in hypobaric chambers for 1, 2, and 3 wks; and after 3 wks exposure, subgroups of hypoxic rats were allowed to recover in normoxia for 1 to 9 wks. Hematocrit (HCT) and right ventricular systolic pressure (RVSP) were measured prior to sacrifice. The heart was perfused, and the right ventricle (RV) was separated from the left ventricle and septum (LV+S) and weighed. The papillary muscles were dissected and processed for ultrastructural morphometry. Results showed that HCT, RVSP, and RV weight increased in the rats during the hypoxic exposure and then gradually returned to control levels after 3 to 4 wks of normobaric recovery. The papillary muscle of the hypoxic rats showed increased volume density of interstitium, increased diameter and cross sectional area of the cardiac myocytes, reduced volume density of mitochondria, and reduced mitochondria to myofilament ratio. During normoxic recovery, these morphometric indices returned toward control values at various periods of time ranging from less than 3 wks to 9 wks. The results indicate that the adaptive ultrastructural changes of the papillary muscle in RV hypertrophy paralleled the RVSP changes, and also demonstrate the reversibility of these changes in ambient oxygen.

Animals↗

Morphometry of the corpus callosum in normal aging and Alzheimer's disease.

Changes of the human corpus callosum in normal aging and Alzheimer's disease were analysed by means of morphometry. A standardized computerized evaluation program was implemented allowing objective, quantitative and reproducible data. The various parts of the corpus callosum showed a different pattern of changes in normal aging as compared to Alzheimer's disease. In conclusion, in normal aging affects mostly the front-temporal interhemispheric fiber systems, whereas in Alzheimer's disease the parietotemporal commissural fibers are altered.

Aging↗