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Morphological analysis and classification of latent prostate cancer using a 3-dimensional computer algorithm: analysis of tumor volume, grade, tumor doubling time and life expectancy.

PURPOSE: We estimate the potential clinical significance of prostate cancers found at autopsy provided the individual had lived to the projected lifespan based on life expectancy tables. MATERIALS AND METHODS: We used 3-dimensional computer models of 59 autopsy prostates that contained clinically undetected carcinoma to determine tumor volumes. Using doubling times of 2, 3, 4 and 6 years, carcinoma volumes at autopsy were extrapolated through patient projected lifespans. The carcinomas were then classified as clinically insignificant or significant according to Mayo Clinic criteria. RESULTS: In 13 patients less than 60 years old, using doubling times of 2, 3, 4 and 6 years, clinically significant tumors were identified in 13 (100%), 10 (77%), 7 (54%) and 7 (54%), respectively. In 46 patients 60 years old or greater significant tumors were identified in 32 (70%), 22 (48%), 21 (46%) and 18 (39%), respectively. A statistical difference (p <0.0001) was found between the mean tumor volume (0.20 +/- 0.10 cc) of 43 organ confined carcinomas and the mean tumor volume (3.26 +/- 3.58 cc) of 16 extracapsular tumors. No capsule perforation was found in tumors with Gleason sums of 4 or less. However, capsule perforation was present in 8 of 31 tumors (25.8%) with Gleason sums of 5 or 6, and 8 of 11 tumors (72.7%) with Gleason scores of 7 or 8. CONCLUSIONS: Prostatic carcinomas that remain clinically insignificant throughout life are likely to have doubling times greater than 4 years. The subset of carcinomas that emerge as clinically significant are likely to have doubling times less than 3 years. Therefore, an accurate method to measure doubling time at diagnosis could, provide an objective indicator to guide clinical management.

Adult↗

Indicators to assess temporal genetic diversity in the French Catalogue: no losses for maize and peas.

The aim of this study, led by the GEVES (Research and Control Group for Varieties and Seeds), was to suggest indicators to assess the diversity available to farmers since the French Official Catalogue for Plant Varieties and Species was initiated. The largest datasets of 1990 inbred maize lines and 578 pea lines from the last 50 years were analysed using morphological and enzymatic parameters. Lines were grouped into three to five periods. Genetic diversity was estimated in each period from morphological and enzymatic markers by computing numerous indices, such as the number of classes of scores for each characteristic, allelic richness or genetic diversity index (H ( e )). Population differentiation parameters (G(ST), G(ST)', F(ST), Q(ST)) were also estimated between periods. While genetic diversity computed from distinction, uniformity, stability traits was more marked for maize (0.66) than for garden peas (0.35) or feed peas (0.29), the opposite trend was observed with enzymes, resulting in a genetic diversity of 0.43, 0.35 and 0.22 for garden peas, feed peas and maize, respectively. However, no significant changes in genetic diversity were observed over time, and genetic differentiation was slight between periods. All our results demonstrated that no significant reduction in the diversity available to farmers had been observed since initiation of the French Catalogue. The H ( e ) was a good indicator providing a quantitative estimate of genetic diversity, but it should be interpreted alongside a more precise indicator such as allelic richness or the number of classes for morphological characteristics.

Agriculture↗

Morphology of the turtle accessory optic system.

Neural signals of the moving visual world are detected by a subclass of retinal ganglion cells that project to the accessory optic system in the vertebrate brainstem. We studied the dendritic morphologies and direction tuning of these brainstem neurons in turtle (Pseudemys scripta elegans) to understand their role in visual processing. Full-field checkerboard patterns were drifted on the contralateral retina while whole-cell recordings were made in the basal optic nucleus in an intact brainstem preparation in vitro. Neurobiotin diffused into the neurons during the recording and was subsequently localized in brain sections. Neuronal morphologies were traced using appropriate computer software to analyze their position in the brainstem. Most labeled neurons were fusiform in shape and had numerous varicosities along their processes. The majority of dendritic trees spread out in a transverse plane perpendicular to the rostrocaudal axis of the nucleus. Neurons near the brainstem surface were often oriented tangential to that surface, whereas more cells at the dorsal side of the nucleus were oriented radial to the brainstem surface. Further analysis of Nissl-stained neurons revealed the largest neurons are located in the rostral and medial portions of the nucleus although neurons are most densely packed in the middle of the nucleus. The preferred directions of the visual responses of the neurons in this sample did not correlate with their morphology and position in the nucleus. Therefore, the morphology of the cells in the turtle accessory optic system appears dependent on its position within the nucleus while its visual responses may depend on the synaptic inputs that contact each cell.

Animals↗

Computer controlled bioreactor for large-scale production of cultured skin grafts.

KERATOR--an automated membrane bioreactor--was developed to produce Autologous Wound Dressing (AWD) at significantly reduced cost and time of transplantation down to two weeks time. At the same time, the risk of human error is largely eliminated. The computer-controlled reactor is modular, allowing the production of up to 0.5 m2 AWD at one time. A special feature of the reactor is a hydrophilic polymeric support membrane on which the human keratinocytes attach and proliferate. Recently developed serum-free medium is used to culture keratinocytes as a monolayer without a feeder layer of murine fibroblasts. The use of composite skin grafts consisting of a subconfluent keratinocyte layer on a polymeric support film is a very promising method for skin transplantation owing to the high activity of non-differentiated keratinocyte cells and reduction of the time needed to prepare the skin grafts. A microscopic video system with image analysis was developed for on-line monitoring of the cell growth and morphology in the KERATOR. The computer uses the obtained information to control medium change and to predict the end of cultivation.

Animals↗

Juvenile visual callosal axons in kittens display origin- and fate-related morphology and distribution of arbors.

In kittens, callosal axons originating either from medial area 17 (transient axons) or near the 17/18 border (mostly permanent axons) were labelled with anterogradely transported biocytin; they were reconstructed by computer from serial sections, and their morphologies compared at different ages. During the first and second postnatal weeks both sets of axons branched profusely in the white matter of the lateral gyrus and the number of branches increased with age. The most common type of axon ending was the growth cone; others may have been collapsing growth cones, branches in the process of elimination or early synaptic boutons. Axons from medial area 17 distributed over a broad territory, including the 17/18 border where callosal axons terminate in the adult cat, but without aiming specifically at any one area. The majority of axons and their branches terminated in the white matter or at the bottom of layer VI; exceptionally they extended further into the cortex. Most of the axons originating near the 17/18 border were different from those described above, and the difference increased with age. Although they also terminated profusely in the white matter of the lateral gyrus, most of the branches terminated near the contralateral 17/18 border; they frequently entered the grey matter up to the superficial layers and branched into it. During the third week, axons from medial area 17 were rarely found to extend beyond the corpus callosum, probably because they were in the process of being eliminated. In contrast, axons originating near the 17/18 border had increased their number of branches in the grey matter. In conclusion, during the first and second postnatal weeks axons grew and differentiated according to their origin, and this anticipated whether they would be maintained or eliminated. Neurotrophic signals, possibly from the white matter or the subplate, and growth-inhibiting signals from area 17 may be involved in this process.

Aging↗

Computerized methods of pace-mapping for topical diagnosis of ventricular arrhythmias.

Surgical treatment of ventricular arrhythmias (VAs) is an effective method of solving sudden cardiac death. The important problem of surgical treatment of VAs is the topical diagnosis of the origin of arrhythmia. The precise localization of this area is extremely important for effectiveness of operation. The method of epicardial mapping of the heart during the induced paroxysm of VA is widely used for solving this problem. This problem is difficult when it is impossible to induce tachycardia during the operation. The method of pace-mapping was developed for such cases. This method includes sequential electrical stimulation of ventricles with ECG recording and comparison between intraoperative and preoperative ECG. The goal is the identification of the area of ventricles closed to preoperative ECG with VA. Manual processing of these data is difficult and takes time. The results of such processing have a low precision. That is why we propose using computerized methods. The goal of this investigation is to develop computerized methods of topical ECG diagnosis of VA. We propose a method of computer comparative analysis of ECG morphology for spontaneous and stimulated ECG. The goal is the determination with stimulated ECG the point of ventricles with ECG closest to spontaneous ECG during ventricular tachycardia. Nine patients (15-57 years old) with VA were studied. The main result of this investigation is that computerized pace-mapping method is an effective tool for topical diagnostics of different forms of VAs, which is impossible to induce by electrical programmed stimulation.

Adolescent↗

Three-dimensional imaging diagnosis for cranial base lesions.

Diagnosis of neurological disease by imaging has greatly improved in recent years. Precise morphological information can be obtained by computed tomography and magnetic resonance imaging, and biochemical or electrophysiological dynamic changes can be assessed by positron emission tomography or magnetoencephalography. The transcription of such biochemical or electrophysiological data on computed tomographic scan or magnetic resonance imaging can precisely demonstrate the local dynamic information in the brain. Three-dimensional imaging also provides accurate intelligence on the morphological structure of lesions and facilitates the surgical management. In this article the recent technology of three-dimensional imaging diagnosis in skull base surgery is reported.

Brain Neoplasms↗

Glenoid rim morphology in recurrent anterior glenohumeral instability.

BACKGROUND: Knowledge regarding the morphology of the glenoid rim is important when patients with recurrent anterior glenohumeral instability are assessed. Ordinary imaging techniques are not always sensitive enough to demonstrate the morphology of the glenoid rim accurately. We developed a method of three-dimensionally reconstructed computed tomography with elimination of the humeral head to evaluate glenoid morphology. The purpose of the present study was to quantify glenoid osseous defects and to define their characteristics in patients with recurrent anterior instability. METHODS: The morphology of the glenoid rim in 100 consecutive shoulders with recurrent unilateral anterior glenohumeral instability was evaluated on three-dimensionally reconstructed computed tomography images with the humeral head eliminated. The configuration of the glenoid rim was evaluated on both en face and oblique views. Concurrently, we also investigated seventy-five normal glenoids, including both glenoids in ten normal volunteers. Shoulders without an osseous fragment at the anteroinferior portion of the glenoid were compared with the contralateral shoulder in the same patient to determine if the glenoid morphology was normal. In shoulders with an osseous fragment, the fragment was evaluated quantitatively and its size was classified as large (>20% of the glenoid fossa), medium (5% to 20%), or small (<5%). Finally, all 100 shoulders were evaluated arthroscopically to confirm the presence of the lesion at the glenoid rim that had been identified with three-dimensionally reconstructed computed tomography. RESULTS: Investigation of the normal glenoids revealed no side-to-side differences. Investigation of the affected glenoids revealed an abnormal configuration in ninety shoulders. Fifty glenoids had an osseous fragment. One fragment was large (26.9% of the glenoid fossa), twenty-seven fragments were medium (10.6% of the glenoid fossa, on the average), and twenty-two were small (2.9% of the glenoid fossa, on the average). In the forty shoulders without an osseous fragment, the anteroinferior portion of the glenoid appeared straight on the en face view and it appeared obtuse or slightly rounded, compared with the normally sharp contour of the normal glenoid rim, on the oblique view, suggesting erosion or a mild compression fracture at this site. Arthroscopic investigation revealed a Bankart lesion in ninety-seven of the 100 shoulders and an osseous fragment in forty-five of the fifty shoulders in which an osseous Bankart lesion had been identified with the three-dimensionally reconstructed computed tomography. In the shoulders with distinctly abnormal morphology on three-dimensionally reconstructed computed tomography, the arthroscopic appearance of the anteroinferior portion of the glenoid rim was compatible with the appearance demonstrated by the three-dimensionally reconstructed computed tomography. CONCLUSIONS: We introduced a method to evaluate the morphology of the glenoid rim and to quantify the osseous defect in a simple and practical manner with three-dimensionally reconstructed computed tomography with elimination of the humeral head. Fifty percent of the shoulders with recurrent anterior glenohumeral instability had an osseous Bankart lesion; 40% did not have an osseous fragment but demonstrated loss of the normal circular configuration on the en face view and an obtuse contour on the oblique view, suggesting erosion or compression of the glenoid rim.

Adolescent↗

Interactive classification of porcine Eimeria spp. by computer-assisted image analysis.

Digitalized pictures of oocysts of Eimeria scabra, E. polita, E. debliecki, E. suis, and E. porci were used to develop a program routine that allows semi-automatic interactive classification of porcine Eimeria spp. with a computer-assisted image analysis system. Morphological parameters (shape, color, length and width of oocysts and length and width of sporocysts) were assayed, transformed to color and shape factors and used to calculate classification indices (G1, SP). Thresholds were defined for these indices to allocate oocysts to groups of species and successively to single species. In more than 97% of cases the program routine allocated digitalized oocysts (n = 175) to the respective species. E. suis was always correctly classified. Interactive classification proved to be convenient, fast, precise and largely free of individual bias.

Animals↗

Computed tomography in the diagnosis of lymphangiomas in infants and children.

The computed tomographic features in 14 children (age range = 2 days to 10 years) with cystic hygromas of the neck and lymphangiomas of the chest, abdomen, and extremities were studied. Computed tomography can determine the morphology of these masses, their exact locations and their relationship to other organs. Most lymphangiomas appear as cystic masses of low attenuation value with or without septations. The septations may be thin or thick and result in a conglomerate of cysts of irregular borders, varying in size from a few millimeters to several centimeters. Some of the septae show enhancement after a bolus injection of contrast material. Contrary to what has been reported, lymphangiomas may invade nearby tissues and organs.

Abdominal Neoplasms↗

Three-dimensional reconstruction and surface rendering of the five different spectral types of cone pedicle in the turtle retina.

Pseudo-3-dimensional models and surface renderings of a small group of neighboring cone pedicles in the turtle retina, in which the 5 different spectral types are represented, have been made from scanned serial electron micrographs using a Macintosh personal computer, Autocad and Studio Pro software. The resultant computer generated images clarify the morphological differences between the spectral types and show how they are related to each other via telodendrial connections and different levels of ending in the neuropil of the outer plexiform layer (OPL). The double cone pedicles end highest in the neuropil and the single red and green pedicles lie slightly lower into the OPL with the single blue and ultraviolent (UV)-sensitive cone pedicles coming in from obliquely angled axons to assume positions between the others much more vitread in the OPL. Telodendria interconnect the double and single red and green cones but not the blue and UV-sensitive cones.

Animals↗

Relationship of tumor cell motility and morphologic patterns. Part 2. Analysis of tumor cell sublines with different motility in vitro.

We have previously demonstrated by computer simulation that the relationship of proliferation and motility is likely to influence the morphological pattern of a tumor. Our study of a set of melanocytic skin tumors provided evidence that the assumptions of the model were correct with respect to proliferation. In order to test the validity of the assumptions concerning motility, we injected a tumor cell line with low motility in vitro and a subline of the same tumor cell line with high motility in vitro into the thigh of syngeneic rats. When we evaluated the morphological patterns of the resulting tumors by image analysis and compared them with computer simulations, we found that the differences of the morphological patterns were the same as predicted by the computer model. This finding further supports the concept that estimates of tumor cell proliferation and motility can be derived from the analysis of static histological patterns.

Animals↗

Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition.

The finite-difference time-domain (FDTD) method provides a flexible approach to studying the scattering that arises from arbitrarily inhomogeneous structures. We implemented a three-dimensional FDTD program code to model light scattering from biological cells. The perfectly matched layer (PML) boundary condition has been used to terminate the FDTD computational grid. We investigated differences in angle-dependent scattering properties of normal and dysplastic cervical cells. Specifically, the scattering patterns and phase functions have been computed for normal and dysplastic cervical cells at three different epithelial depths, namely, basal/parabasal, intermediate, and superficial. Construction of cervical cells within the FDTD computational grid is based on morphological and chromatin texture features obtained from quantitative histopathology. The results show that angle-dependent scattering characteristics are different not only for normal and dysplastic cells but also for cells at different epithelial depths. The calculated scattering cross-sections are significantly greater for dysplastic cells. The scattering cross-sections of cells at different depths indicate that scattering decreases in going from the superficial layer to the intermediate layer, but then increases in the basal/parabasal layer. This trend for epithelial cell scattering has also been observed in confocal images of ex vivo cervical tissue.

Algorithms↗

Computer-controlled, multilevel, morphometric analysis of blastomere size as biomarker of fragmentation and multinuclearity in human embryos.

BACKGROUND: Little is known about blastomere size at different cleavage stages and its correlation with embryo quality in human embryos. Using a computer system for multilevel embryo morphology analysis we have analysed blastomeres of human embryos and correlated mean blastomere size with embryonic fragmentation and multinuclearity. METHODS: A consecutive cohort of 232 human 2-, 3- and 4-cell embryos from patients referred for ICSI treatment were included. Sequences of digital images were taken by focusing at 5- micro m intervals through the embryo. Blastomere sizes and number of nuclear structures were evaluated based on these sequences. The degree of embryonic fragmentation was evaluated by normal morphological assessment prior to transfer and correlated to the blastomere sizes. RESULTS: As a result of normal cell cleavage, mean blastomere size decreased significantly from a volume of 0.28 x 10(6) microm(3) at the 2-cell stage to 0.15 x 10(6) microm(3) at the 4-cell stage (P < 0.001). Mean blastomere size decreased significantly (P < 0.001) with increasing degree of embryonic fragmentation, where highly fragmented embryos showed a 43-67% reduction in blastomere volume compared with embryos with no fragmentation. Multinucleated blastomeres were significantly larger than non-multinucleated blastomeres (P < 0.001). On average, multinucleated blastomeres were 51.5, 67.8 and 73.1% larger than their non-multinucleated sibling blastomeres at the 2-, 3- and 4-cell stage, respectively. Furthermore, the average volume of non-multinucleated blastomeres originating from multinucleated embryos was significantly smaller than the average volume of the blastomeres from mononucleated embryos (P < 0.001). CONCLUSIONS: The results of this study show that the average blastomere size is significantly affected by degree of fragmentation and multinuclearity, and that computer-assisted, multilevel analysis of blastomere size may function as a biomarker for embryo quality.

Adult↗

Microtubular disarray in cortical dendrites and neurobehavioral failure. II. Computer reconstruction of perturbed microtubular arrays.

A previous report details morphological alterations in dendritic structure of cortical neurons in severe neurobehavioral retardation of unknown etiology. Using computer graphic techniques, the present study describes perturbations in the 3-dimensional character of the microtubular array, which correspond to degenerative change in dendritic geometry. In large proximal processes, two types of array have been reconstructed. Segmented microtubules may form a continuous helical swirl which underlies a bulge in the dendritic cylinder. Alternatively, small groups of microtubules, while maintaining orderly internal organization, may be disoriented with respect to the long axis of the process. In varicose regions of the dendrite the microtubular array is discontinuous. Microtubules course side by side through constructed regions, only to splay out and terminate within expanded regions. These pathological alterations in the microtubular array contrast sharply with the cortical dendritic microtubular array reconstructed from the normal adult mouse. Perturbation in those parameters which determine packing of microtubules within the dendritic process is also documented. In the pathological condition, microtubules lose the ability to exclude one another from close approach. The role of cross-linking molecules in maintaining the integrity of the microtubular array, and the role of microtubules in maintaining the geometry of the dendrite, are considered.

Cerebral Cortex↗

Morphologic alterations in the cilia of a cat.

Based upon ultrastructural findings and computed tomography, a presumptive diagnosis of feline primary ciliary dyskinesia was made in a 2.5-year-old cat. The cat demonstrated morphologic alterations in the ultrastructure of oviductal cilia. In the oviduct, axonemal abnormalities were detected in 132 (20%) of 660 cross-sectioned cilia. The main ultrastructural ciliary defects were a lack of central microtubules, transposition of peripheral doublets to the center of the axoneme, supernumerary microtubules, and morphologic abnormalities of peripheral doublets. Computed tomography of the chest was consistent with early lesions of bronchiectasis, suggesting chronic stagnation of respiratory secretions, attributed to abnormal function of respiratory cilia. Specifically, the cranial branches of the cat's bronchi were wider and thicker than those of five healthy controls. Foci of pleural thickening and interstitial enlargement were also observed.

Animals↗

Computer simulation system for orthognathic surgery.

OBJECTIVE: The system aimed to make a simulation model of an orthognathic patient without using his/her computed tomography data. DESIGN: The morphological data of the teeth and face were obtained by laser scanner. All the data were integrated in the reference coordinate system of frontal and lateral cephalograms using projection matching technique. SETTING: A case of mandibular prognathism was analyzed and presented. EXPERIMENTAL VARIABLE: About 7 mm (left side) to 6 mm (right side) of mandibular setback with a small rotation was performed on this case. RESULTS: Simulated osteotomies and bone movements help us to analyze the movement of bone and soft tissue. Collisions and gaps generated between bone segments and facial changes are shown. CONCLUSION: This simulation system will be particularly useful for the selection of an optimal operative method in cases in which the change in facial soft tissue shape should be carefully deliberated.

Cephalometry↗

Theoretical study of the morphologically originated noise associated with the transmittance of a precipitation system.

In this paper we present the results of a computational study that analyses the relationship between the noise associated with the optical transmittance of a system of particles and the morphology of such particles. Computational algorithms have been developed in order to represent the different morphologies within a wide range of sizes. By using this methodology, it has been possible to study the morphology of particles in a virtual system, therefore avoiding the distortions that would inevitably be present in a real system. As a consequence of this study, a classification of the morphologies observed has been made according to the amount of noise they would add to the transmittance of a system of particles. The theoretical results obtained are in good agreement with the available experimental data obtained in real systems.

Journal Article↗