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Using wavelets, we computed the entropy of the signal at various frequency levels (wavelet time entropy) and, thus, find an optimal measure to differentiate normal states from ischemic ones. This new indicator is independent from the ST segment and yet provide a conclusive detection of the ischemic states.
An estimated 300,000 Americans die each year from cardiac arrhythmias. Historically, drug therapy or surgery were the only treatment options available for patients suffering from arrhythmias. Recently, implantable arrhythmia management devices have been developed. These devices allow abnormal cardiac rhythms to be sensed and corrected in vivo. Proper arrhythmia classification is critical to selecting the appropriate therapeutic intervention. The classification problem is made more challenging by the power/computation constraints imposed by the short battery life of implantable devices. Current devices utilize heart rate-based classification algorithms. Although easy to implement, rate-based approaches have unacceptably high error rates in distinguishing supraventricular tachycardia (SVT) from ventricular tachycardia (VT). Conventional morphology assessment techniques used in ECG analysis often require too much computation to be practical for implantable devices. In this paper, a computationally-efficient, arrhythmia classification architecture using correlation-based morphology assessment is presented. The architecture classifies individuals heart beats by assessing similarity between an incoming cardiac signal vector and a series of prestored class templates. A series of these beat classifications are used to make an overall rhythm assessment. The system makes use of several new results in the field of pattern recognition. The resulting system achieved excellent accuracy in discriminating SVT and VT.
This article reviews the 21 studies that investigated possible relationships between structural brain abnormalities and outcome in schizophrenia. Fifteen studies used computer tomography to visualize brain morphology. In these studies, images were obtained of the ventricles but not of specific brain regions. The remaining six studies used magnetic resonance imaging, examining possible relationships between outcome, ventricular size, and specific brain regions. One out of two studies found relationships between brain structure and outcome. The data suggest that the extent of ventricular enlargement in patients with schizophrenia may be related to outcome. No clear relationship between outcome and changes in specific brain regions was found. Apart from considerations about the methodology of measuring different brain regions, the procedure used to measure outcome is important. Outcome, as it is assessed at various points during the course of illness, may be variable and seems to fluctuate during the first 10 to 15 years of disease. Significantly, to date no studies relating outcome to brain structure have used patient samples with a duration of illness longer than 15 years.
To date, only one published study has directly compared 67Ga scintigraphy (low dose, planar) with planar dual-head gamma camera 18F-fluorodeoxyglucose (18FDG) imaging for the purpose of treatment follow-up monitoring in lymphoma patients, and no data on restaging are available. The present study reports the direct comparison of high-dose (297-370 MBq) 67Ga planar and single photon emission computed tomography (SPECT) imaging and conventional 18FDG positron emission tomography (PET) for restaging and treatment follow-up of lymphoma patients versus a gold standard consisting of morphological imaging, including plain radiography and computed tomography (CT) scanning, bone marrow examination and long-term follow-up (<12 months). Sixteen patients, 10 with non-Hodgkin's lymphoma and six with Hodgkin's disease, were included (10 men, six women; median age, 43 years; range, 16-64 years). The median follow-up time was 27 months (range, 12-34 months). In two patients, 67Ga and 18FDG PET (370 MBq) were performed twice, resulting in 18 cross-sectional episodes. In 11 episodes, the results obtained by both imaging modalities were in agreement with regard to the presence or absence of disease when compared with the gold standard. However, the abnormalities found on 18FDG PET were always more extensive. In two episodes, 67Ga imaging normalized after treatment, whereas PET showed significant regression followed by subsequent normalization. In four additional episodes, 67Ga images were negative, whereas 18FDG PET visualized non-tumour-related pathology, such as lung infection, rib fracture or dense thymic tissue. In one gold standard-negative patient, the underlying cause of sternal FDG uptake remained undetermined. The data presented, although limited in number, suggest that 18FDG PET performs better than Ga imaging in monitoring lymphoma disease status. However, a correlation with clinical history and a knowledge of the characteristics of benign lesions are mandatory. Further studies are recommended.
Quantitative analysis of vascular generational branching demonstrated that transforming growth factor-beta1 (TGF-beta1), a multifunctional cytokine and angiogenic regulator, strongly inhibited angiogenesis in the arterial tree of the developing quail chorioallantoic membrane (CAM) by inhibition of the normal increase in the number of new, small vessels. The cytokine was applied uniformly in solution at embryonic day 7 (E7) to the CAMs of quail embryos cultured in petri dishes. After 24 h the rate of arterial growth was inhibited by as much as 105% as a function of increasing TGF-beta1 concentration. Inhibition of the rate of angiogenesis in the arterial tree by TGF-beta1 relative to controls was measured in digital images by three well-correlated, computerized methods. The first computerized method, direct measurement by the computer code VESGEN of vascular morphological parameters according to branching generations G(1) through G(>/=5), revealed that TGF-beta1 selectively inhibited the increase in the number density of small vessels, N(v>/=5) (382 +/- 85 cm(-2) for specimens treated with 1 microg TGF-beta1/CAM for 24 h, compared to 583 +/- 99 cm(-2) for controls), but did not significantly affect other parameters such as average vessel length or vessel diameter. The second and third methods, the fractal dimension (D(f)) and grid intersection (rho(v)), are statistical descriptors of spatial pattern and density. According to D(f) and rho(v), arterial density increased in control specimens from 1.382 +/- 0.007 and 662 +/- 52 cm(-2) at E7 (0 h) to 1.439 +/- 0.013 and 884 +/- 55 cm(-2) at E8 (24 h), compared to 1. 379 +/- 0.039 and 650 +/- 111 cm(-2) for specimens treated with 1 microg TGF-beta1/CAM for 24 h. TGF-beta1 therefore regulates vascular pattern and the rate of angiogenesis in a unique "fingerprint" manner, as do other major angiogenic regulators that include VEGF, FGF-2 (bFGF), and angiostatin. TGF-beta1 did not stimulate angiogenesis significantly at low cytokine concentrations, which suggests that this quail CAM model of angiogenesis is not associated with an inflammatory response.
New neuromagnetic imaging methods provide spatial information about the functional electrical properties of complex current distributions in the human brain. For practical use in medical diagnosis a combination of the abstract neuromagnetic imaging results with magnetic resonance (MR) or computed tomography (CT) images of the morphology is required. The biomagnetic images can be overlayed onto three-dimensional morphological images with spatially arbitrary selectable slices, calculated from conventional 2D data. For the current reconstruction the 3D images furthermore provide a priori information about the conductor geometry. A combination of current source density calculations and linear estimation methods for handling the inverse magnetic problem allows quick imaging of impressed current source density in arbitrary volume conductors.
We studied lectin histochemical properties of structures of caudal ganglia of the vagus nerve and ganglion of the trigeminal nerve in white rats using fucose-specific conjugates to peroxidase. Morphological samples were processed on a computer video analyzer. Metrical and optical indices of the afferent neurons were analyzed. The obtained data demonstrate different topography of glycoconjugates in the afferent ganglia. Application of recent image processing techniques allows revealing neuron populations in afferent ganglia of rats undetectable by standard morphological techniques.
In bronchiectasis the morphological determinants of (marginal) fluctuations in pulmonary function tests are uncertain. The aim of the present study was to evaluate serial computed tomography (CT) changes in relation to pulmonary function trends in patients with bronchiectasis. The relationships between pulmonary function indices and CT scans in 48 adult patients with bronchiectasis were evaluated at baseline and at follow-up, at a median interval of 28 months (range 6-74 months). Two independent observers semiquantitatively scored CT features of bronchial and small airways disease. At initial assessment, the severity of airflow obstruction was linked primarily to the extent of mosaic attenuation. However, serial changes in pulmonary function indices were only associated with serial changes in mucous plugging scores. Alterations in mucous plugging on serial CT were associated with changes in the severity of bronchiectasis and bronchial wall thickness. Greater severity of all three morphological abnormalities at baseline CT were predictive of significant declines in forced expiratory volume in one second, with severe bronchial wall thickness being the most adverse prognostic determinant. Variations in mucous plugging on computed tomography correlate with minor fluctuations in pulmonary function tests in bronchiectasis. However, the severity of bronchial wall thickness is the primary determinant of subsequent major functional decline.
Rat, hamster, and rabbit renal cortical lymphatics were examined by light and electron microscopy. Rat and hamster kidneys possessed both intra- and interlobular lymphatics that were structurally similar at the light microscopic level. Ultrastructural examination of the hamster lymphatic endothelium, however, revealed an unusual arrangement of cytoplasmic extensions not seen in the other two species. The intralobular lymphatics were related primarily to tubules, afferent arterioles, and renal corpuscles and were consistent with lymph formation from both plasma filtrate and tubular reabsorbate. Interlobular lymphatics were seen in connective tissue associated with the interlobular blood vessels. Rabbit cortex contained only interlobular lymphatics. Cross-sectional area, maximum diameter, volume density, and profile density were determined by stereological measurements using a computer-based image analyzer. The morphological data from the rat were used, in combination with published values for lymph flow, to calculate the rate of lymph formation per unit area of endothelium in lymphatics of the renal cortex. Among kidneys fixed by retrograde perfusion, the cortical lymphatic system was most extensive in maximum diameter, volume density, and profile density. It was smallest in the rabbit and intermediate in the rat. Lower volume and profile density were found for rat kidneys fixed by the dripping technique. It was concluded that: tubular reabsorbate probably contributes to renal lymph in the rat and hamster, but not in the rabbit; significant differences exist in the extent of the renal lymphatic systems among the three species, with the hamster kidney having the richest network and the rabbit the poorest; the method of fixation influences the measured size and density of renal cortical lymphatics; and the estimated rate of lymph formation in the kidney of the rat is roughly comparable to that in the dog.
We have quantified the influence of lens sutural anatomy on optical quality (focal length variability, i.e. spherical aberration) in adult monkeys (Macaque nemestrina). Adult lenses (n = 6) were initially scanned by a low-power helium-neon laser beam that was passed at a series of acute angles to, and/or directly through, lens sutures. Optical analysis showed that while the 'star' sutures of primate lenses exerted a quantifiable negative effect on focal length variability, this detrimental effect was far less significant than that attributable to 'line' and 'Y' sutures in non-primate lenses. Correlative morphological and 3-D computer-assisted drawing (CAD) analysis of the laser-scanned lenses areas, as well as of variably aged lenses (n = 30), revealed that primates have a more complex lens architecture than non-primates. Non-primate lenses feature suture planes, aligned along the visual axis that are responsible for a significant quantifiable increase in spherical aberration. Primate lenses are characterized by an absence of continuous suture planes aligned along the visual axis. Rather, 3-D-CADs of primate lenses demonstrate that distinct generations of progressively more complex sutures are produced as a function of development, growth, and age. In succession, 'Y' sutures (three branches) are formed throughout embryonic development, 'simple star' sutures (three-six branches) evolve after birth and through infancy, 'star' sutures (six-nine branches) are made in young adult lenses and, finally, 'complex star' sutures (nine-15 branches) are laid down from middle through old age. In view of the fact that slit-lamp evaluation of cataractous lenses often reveals abnormally thin zones of discontinuity, it is significant to note that the temporal development of the zones of discontinuity in normal human lenses is essentially identical to the progressive iteration of offset monkey lens sutures. In conclusion, these studies describe a specific structural aspect of lenses that adversely influences optical quality, and relates it to the most commonly employed clinical technique to identify and monitor the progress of cataracts.
Macroscopic and histologic evaluation of animal studies for general toxicity and carcinogenicity are cornerstones of the risk assessment of new chemical entities. Standard toxicopathologic evaluation is mainly based on the study of paraffin sections stained with hematoxylin and eosin. There are, however, a number of new approaches and techniques which have improved the objectivity of evaluation and the accuracy of cell identification, and provided deeper insight into the molecular biological mechanisms of toxicity and carcinogenicity. Such approaches include the standardization of the nomenclature, the creation of data banks for morphological alterations, the use of computers to register pathological findings in toxicity studies and to statistically evaluate incidences, and the use of morphometry. Other modern techniques are immunohistochemistry, in situ hybridization, and the assessment of cell kinetics.
Cystic fibrosis is the most common autosomal recessive metabolic disease in Europe with an incidence of 1:2500. The severity of the lung disease is the most important factor of morbidity and mortality in CF-patients. Because of the better diagnostic and therapeutic modalities life expectancy has increased significantly. The underlying pathology is a defect of chromosome 7, which encodes the regulation of the fluid balance across the cell membrane which effects chloride as well as sodium. The exocrine glands produce a viscous mucus which obstructs the airways and promotes infections. The result is the destruction of lung parenchyma. In daily routine, chest x-ray is still the most important radiological tool, although computed tomography depicts changes in morphology earlier and more exactly. Recent research studies show that MRI has-because of its additional functional options-interesting aspects for the future.
The purpose of this study was to compare positron emission tomography using fluorine-18 fluorodeoxyglucose (FDG-PET) and technetium-99m methylene diphosphonate (MDP) bone scintigraphy in the detection of osseous metastases from malignant primary osseous tumours. In 70 patients with histologically proven malignant primary bone tumours (32 osteosarcomas, 38 Ewing's sarcomas), 118 FDG-PET examinations were evaluated. FDG-PET scans were analysed with regard to osseous metastases in comparison with bone scintigraphy. The reference methods for both imaging modalities were histopathological analysis, morphological imaging [additional conventional radiography, computed tomography (CT) or magnetic resonance imaging (MRI)] and/or clinical follow-up over 6-64 months (median 20 months). In 21 examinations (18%) reference methods revealed 54 osseous metastases (49 from Ewing's sarcomas, five from osteosarcomas). FDG-PET had a sensitivity of 0.90, a specificity of 0.96 and an accuracy of 0.95 on an examination-based analysis. Comparable values for bone scintigraphy were 0.71, 0.92 and 0.88. On a lesion-based analysis the sensitivity of FDG-PET and bone scintigraphy was 0.80 and 0.72, respectively. Analysing only Ewing's sarcoma patients, the sensitivity, specificity and accuracy of FDG-PET and bone scan were 1.00, 0.96 and 0.97 and 0.68, 0.87 and 0.82, respectively (examination-based analysis). None of the five osseous metastases from osteosarcoma were detected by FDG-PET, but all of them were true-positive using bone scintigraphy. In conclusion, the sensitivity, specificity and accuracy of FDG-PET in the detection of osseous metastases from Ewing's sarcomas are superior to those of bone scintigraphy. However, in the detection of osseous metastases from osteosarcoma, FDG-PET seems to be less sensitive than bone scintigraphy.
It is well accepted that natural tissue regeneration is unlikely to occur if the cells are not supplied with an extracellular matrix (ECM) substitute. With this goal, several different methodologies have been used to produce a variety of 3D scaffolds as artificial ECM substitutes suitable for bone and cartilage tissue engineering. Furthermore, osteochondral tissue engineering presents new challenges since the combination of scaffolding and co-culture requirements from both bone and cartilage applications is required in order to achieve a successful osteochondral construct. In this paper, an innovative processing route based on a chitosan particles aggregation methodology for the production of cartilage and osteochondral tissue engineering scaffolds is reported. An extensive characterization is presented including a morphological evaluation using Micro-Computed Tomography (microCT) and 3D virtual models built with an image processing software. Mechanical and water uptake characterizations were also carried out, evidencing the potential of the developed scaffolds for the proposed applications. Cytotoxicity tests show that the developed chitosan particles agglomerated scaffolds do not exert toxic effects on cells. Furthermore, osteochondral bilayered scaffolds could also be developed. Preliminary seeding of mesenchymal stem cells isolated from human adipose tissue was performed aiming at developing solutions for chondrogenic and osteogenic differentiation for osteochondral tissue engineering applications.
Alterations in sleep organization were studied during the clinical phase of experimental Creutzfeldt-Jakob disease (CJD) in cats. Twenty months after intracerebral inoculation of a CJD agent, cats developed clinical signs including behavioral changes, diminished grooming activity, dysmetria, startle reflex, myoclonus, and unusual sleep abnormalities. Rapid eye movement (REM) sleep displayed a new and irreversible organization, with a continuous and constant pseudoperiodic pattern of rapid eye movements, synchronous with diffuse bursts of cortical abnormalities and with ponto-geniculo-occipital (PGO) wave activity. Computer analysis revealed a constant morphology of cortical bursts and their temporal relationship with ocular episodes. Induction of PGO wave activity with benzoquinolizine derivative Ro 4-1284 demonstrated the PGO-dependent nature of the cortical alterations. Abnormal unresponsive states were observed during REM sleep phases and arousal thresholds were increased in CJD cats during REM sleep. The percentages of wakefulness and slow-wave sleep were reversed in these animals. Preliminary neuropathological observations included discrete to minimal spongiosis of cerebral gray matter and a remarkably focalized intracytoplasmic vacuolation in neurons of the raphé system. Our findings suggest that particular neuronal systems involved in sleep regulation are impaired in CJD cats.
Dihydronicotinamide adenine-dinucleotide phosphate diaphorase (NADPH-d) positive neurons in the superficial layers of superior colliculus (SC) were studied in the adult rat after eye enucleation at postnatal day 5 (P5). Bilaterally, NADPH-d histochemistry revealed either weakly or intensely labeled neurons. In the SC contralateral to the enucleation, the volume of superficial layers decreased significantly, whereas the total number of NADPH-d positive neurons was only slightly reduced, thus resulting in an increased cell density. Bilaterally, the number of NADPH-d positive neurons was around 20% of Nissl-stained neurons. While the number of neurons which were weakly positive for NADPH-d was unchanged contralateral to the enucleation (thus resulting in a significant increase in their percentage on the overall NADPH-d population), the number of intensely labeled neurons decreased by 30%. Intensely labeled neurons were classified with respect to cell size and dendritic distribution. Some (126) were reconstructed and analyzed on the computer, in order to quantitate morphological differences in dendritic distribution in the denervated and control SC. The percent of neurons which could be assigned to some classes (marginal, stellate, narrow field vertical and wide field vertical) was reduced contralateral to the enucleation. In addition, vertically-oriented neurons (narrow field vertical, wide field vertical and pyriform) showed a significant decrease in soma size, dendritic length and number of branch points. And finally, the overall orientation of dendrites on narrow and wide field vertical neurons was more dispersed, when compared to the control colliculus. Thus, P5 eye enucleation affects the adult morphology of NADPH-d positive neurons in the superficial layers of the rat SC, resulting in increased cell density, changed relative number of cells in each morphological type, and altered soma size, dendritic length and orientation in specific neurons.
Spontaneous hepatocellular neoplasms of B6C3F1 mice (basophilic neoplasms) as well as those induced with the herbicide Nitrofen (eosinophilic neoplasms) were observed with an image analyzing computer to determine if quantifiable morphologic differences existed between them. Several morphologic parameters were measured on 5 liver sections from each of the following groups: (a) unexposed control liver; (b) non-trabecular basophilic neoplasms; (c) trabecular basophilic neoplasms; (d) small well circumscribed eosinophilic neoplasms; and large irregular eosinophilic neoplasms without (e) and with (f) pulmonary metastases. The total number of hepatocytes per unit area was significantly smaller in the eosinophilic neoplasms than in the basophilic neoplasms or the controls. This was the result of a greatly increased cell cross-sectional area in the eosinophilic neoplasms, caused predominantly by a larger cytoplasmic cross-sectional area. Nuclear cytoplasmic ratios of cells in eosinophilic neoplasms were lower than in the other groups for this reason. This demonstrates that quantitative morphologic differences exist between the spontaneous and induced neoplasms, which supports the conclusion that Nitrofen is a true carcinogen, and not a promoting agent.
The objective of this study was to test the hypothesis that chronic occupational exposure to high temperatures may be detrimental to male reproduction. The study was based on 92 healthy ceramics oven operators with a long exposure to high temperatures, and 87 controls, recruited from the shipment department of the same industry. Interviews with all subjects provided data on sociodemographic characteristics, health status, and fertility problems. Semen analysis was carried out on 46 of the workers exposed to high temperatures, and 14 of the controls, and included evaluation of the sperm concentration, morphology, and motility, including computer-assisted sperm motion analysis (velocity, linearity, ALH, BCF). The results of the questionnaire showed that exposed individuals had a higher incidence of childlessness and of self-reported difficulty in conceiving than controls. The semen analysis showed no significant differences except in sperm velocity. Although differences in semen parameters, taken singly, were not statistically significant, the overall evaluation of the sperm parameters indicated a higher prevalence of pathologic sperm profiles among the exposed compared to the controls.