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Time resolved 3-dimensional recording of redox ratio during spreading depression in gerbil brain.

Optical fluorescence and reflectance measurements have been used to map the distribution of metabolic states in three dimensions in the gerbil brain with a spatial resolution of 200 microns an a time resolution of 4-6 s. In Mongolian gerbils anesthetized with pentobarbital, the redox states of the nicotinamide adenine dinucleotide (NADH) and flavoprotein components of the electron transport chain exhibit two distinct phases during the wave of spreading depression: (1) a transient period of oxidation and (2) a prolonged period of reduction, during which the cytochromes are reduced, and the hemoglobin is predominantly in the deoxy form. These data are interpreted as indicating that the energy demand placed on the gerbil brain during such spreading depression wave is sufficient to drive the brain temporarily hypoxic.

Animals↗

Atlas-based automatic segmentation of MR images: validation study on the brainstem in radiotherapy context.

PURPOSE: Brain tumor radiotherapy requires the volume measurements and the localization of several individual brain structures. Any tool that can assist the physician to perform the delineation would then be of great help. Among segmentation methods, those that are atlas-based are appealing because they are able to segment several structures simultaneously, while preserving the anatomy topology. This study aims to evaluate such a method in a clinical context. METHODS AND MATERIALS: The brain atlas is made of two three-dimensional (3D) volumes: the first is an artificial 3D magnetic resonance imaging (MRI); the second consists of the segmented structures in this artificial MRI. The elastic registration of the artificial 3D MRI against a patient 3D MRI dataset yields an elastic transformation that can be applied to the labeled image. The elastic transformation is obtained by minimizing the sum of the square differences of the image intensities and derived from the optical flow principle. This automatic delineation (AD) enables the mapping of the segmented structures onto the patient MRI. Parameters of the AD have been optimized on a set of 20 patients. Results are obtained on a series of 6 patients' MRI. A comprehensive validation of the AD has been conducted on performance of atlas-based segmentation in a clinical context with volume, position, sensitivity, and specificity that are compared by a panel of seven experimented physicians for the brain tumor treatments. RESULTS: Expert interobserver volume variability ranged from 16.70 cm(3) to 41.26 cm(3). For patients, the ratio of minimal to maximal volume ranged from 48% to 70%. Median volume varied from 19.47 cm(3) to 27.66 cm(3) and volume of the brainstem calculated by AD varied from 17.75 cm(3) to 24.54 cm(3). Medians of experts ranged, respectively, for sensitivity and specificity, from 0.75 to 0.98 and from 0.85 to 0.99. Median of AD were, respectively, 0.77 and 0.97. Mean of experts ranged, respectively, from 0.78 to 0.97 and from 0.86 to 0.99. Mean of AD were, respectively, 0.76 and 0.97. CONCLUSIONS: Results demonstrate that the method is repeatable, provides a good trade-off between accuracy and robustness, and leads to reproducible segmentation and labeling. These results can be improved by enriching the atlas with the rough information of tumor or by using different laws of deformation for the different structures. Qualitative results also suggest that this method can be used for automatic segmentation of other organs such as neck, thorax, abdomen, pelvis, and limbs.

Algorithms↗

Expressions for aberration coefficients using nonlinear transforms.

A matrix method to do nonlinear calculations is described. This is possible only under the special condition when a transformation maps a zero vector onto a zero vector. Geometrical optics conform to this condition and hence matrix methods can be applied to calculate aberrations. Methods to reduce computational complexities using symmetry arguments are provided. The formalism is applied to study refraction by a conic surface. Aberration coefficients, up to fifth order, are obtained as functions of eccentricity and the latus rectum of the conic surface. The method can be used to model corneal aberrations.

Cornea↗

Induction of compression in the re-established visual projections on to a rotated tectal reimplant that retains its original topographic polarity within the halved optic tectum of adult goldfish.

1. The topographic pattern of re-established retinotectal projections following various surgical manipulations of the optic tectum was studied in adult goldfish with neurophysiological mapping methods. 2. Immediately following excision of the caudal half of the tectum, a piece of the tectal tissue was dissected from the remaining rostral half-tectum, and then reimplanted to the same half-tectum after either 180 or 90 degrees anticlockwise rotation around the dorsoventral axis in the first experimental group. 3. A majority (twenty-one out of twenty-three) of these operated fish, in which the reimplanted tectal tissue degenerated, showed no sign of a field compression: only the nasal half of the visual field (with a localized partial scotoma corresponding to the area of the degenerated reimplant) projected on to the remaining intact area of the rostral half-tectum. 4. In seven fish, the re-established visual projections on to the 180 or 90 degrees rotated reimplants showed a corresponding localized 180 or 90 degrees rotation with reference to the other projections on to the surrounding intact area of the same half-tectum. Only one of these seven fish showed also a compression in the re-established projections from the entire visual field on to the operated half-tectum with the 90 degrees rotated reimplant. 5. When a field compression was induced first in the intact rostral half-tectum following excision of the caudal half, and then a piece of the 90 degrees rotated tectal tissue was reimplanted later within the rostral half-tectum, the previously induced field compression persisted, regardless of whether the reimplanted tissue degenerated or survived. In the latter case, the compression in the re-established visual projections on to the surviving reimplant occurred according to the original topographic polarity of the 90 degrees rotated tectal tissue. 6. A field compression could also be induced within a rotated tectal reimplant, which retained its original polarity, as follows. A piece of the tectal tissue was dissected from the central area of the whole tectum, and then reimplanted after either 180 or 90 degrees rotation. When the reimplanted tectal tissue became reinnervated later, the caudal half of the operated tectum (including the posterior half of the reimplant) was excised. The re-established visual projections on to the remaining part of the halved reimplant within the rostral half-tectum showed later a field compression in accordance with the original topographic polarity of the 180 or 90 degrees rotated tectal tissue. 7. These results provide direct evidence for the compatibility between the retention of original topographic polarity by a reimplanted tectal tissue and the capability of the same tectal tissue to readjust to a disparity in size. 8. Histological examination of the operated half-tectum with a reimplant, stained by a modified rapid Golai method, revealed that the reimplanted tectal tissues retained highly organized cytoarchitectonic structures...

Animals↗

The evolution of Titan's mid-latitude clouds.

Spectra from Cassini's Visual and Infrared Mapping Spectrometer reveal that the horizontal structure, height, and optical depth of Titan's clouds are highly dynamic. Vigorous cloud centers are seen to rise from the middle to the upper troposphere within 30 minutes and dissipate within the next hour. Their development indicates that Titan's clouds evolve convectively; dissipate through rain; and, over the next several hours, waft downwind to achieve their great longitude extents. These and other characteristics suggest that temperate clouds originate from circulation-induced convergence, in addition to a forcing at the surface associated with Saturn's tides, geology, and/or surface composition.

Atmosphere↗

Capacity for plasticity in the adult owl auditory system expanded by juvenile experience.

In the process of creating a multimodal map of space, auditory-visual neurons in the optic tectum establish associations between particular values of auditory spatial cues and locations in the visual field. In the barn owl, tectal neurons reveal these associations in the match between their tuning for interaural time differences (ITDs) and the locations of their visual receptive fields (VRFs). In young owls ITD-VRF associations can be adjusted by experience over a wide range, but the range of adjustment normally becomes quite restricted in adults. This normal range of adjustment in adults was greatly expanded in owls that had previously learned abnormal ITD-VRF associations as juveniles. Thus, the act of learning abnormal associations early in life leaves an enduring trace in this pathway that enables unusual functional connections to be reestablished, as needed, in adulthood, even when the associations represented by these connections have not been used for an extended period of time.

Adaptation, Physiological↗

New insights into genetic comorbidity mechanisms: type 2 diabetes and primary open-angle glaucoma.

AIMS: To investigate the shared genetic mechanisms between type 2 diabetes (T2D) and primary open-angle glaucoma (POAG). Using large-scale genome-wide association study (GWAS) data, we performed single nucleotide polymorphism (SNP) level analysis to detect pleiotropic variants and loci, paired eQTL mapping analysis and gene-level analysis to identify candidate pleiotropic genes. In addition, Mendelian randomisation (MR) analysis was performed to assess causal associations. MATERIALS AND METHODS: We used POAG GWAS data from Finngen (9565 cases and 430 250 controls) and T2D GWAS data from 55 555 European ancestry samples. We used Linkage Disequilibrium SCore (LDSC) regression to assess the genetic association between T2D and POAG and further used PLeiotropic Analysis under the COmposite null hypothesis (PLACO) to identify shared genetic variants between paired traits. Finally, we further used MR analysis to explore the causal association between T2D and POAG at the genetic level. RESULTS: The LDSC results and MR analysis revealed that the T2D effect was significantly higher than that of the POAG (OR=1.09, 95% CI 1.03 to 1.14, p=1.50×10-3). The PLACO property analysis determined that the T2D sum POAG shared 178 individual SNPs, separate localisation of 79 individual causes. The five most popular choices are based on the effectiveness of CCND2, SVEP1, ST6GAL1, TCF7L2 and HMGA2. expression quantitative trait loci mapping further revealed 36 genes with regulatory roles in optic nerve-related brain tissues. Functional enrichment analyses indicated that these pleiotropic genes are involved in neurodevelopmental, neuroprotective and metabolic pathways, with tissue-specific enrichment observed in neural, pancreatic, adipose and retinal tissues. It is possible to present the main comorbid mechanisms of T2D and POAG. CONCLUSIONS: Our study provides new insights into the aetiology and pathogenesis of T2D and POAG at the genetic level.

Humans↗

Collins diffraction formula studied in quantum optics.

We find that the Collins diffraction formula in cylindrical coordinates is just the transformation matrix element of a three-parameter two-mode squeezing operator in the deduced entangled state representation. This is a new tie connecting the unitary transform in quantum optics to the generalized Hankel transform in Fourier optics. The group multiplication rule of the squeezing operators maps to the Collins formula related to two successive Hankel transforms.

Journal Article↗

Non-contact strain measurement of biological tissue.

Strain measurement in biological material is frequently problematic due to material in-homogeneity, high strain to failure, and the relatively low stiffness of most biological tissue. As an alternative to conventional strain measurement techniques, this study investigates the potential of a non-contact optical system capable of measuring three dimensional surface strain maps. The technique makes use of two CCD cameras and pattern recognition algorithms to track the motion of a random speckle pattern on the specimen and compute the displacement and strain fields. The application of this system on biological material is demonstrated on two tissue types that differ widely in material and surface characteristics (cortical bone and ligamentous tissue). A human tibia was loaded in quasi-static three-point bending and the medial collateral ligament from a human knee joint was loaded in tension. The strain field was computed and analyzed in each case. On the relatively stiff cortical bone, accurate results were obtained wherever high resolution imaging of the speckle pattern was possible. Since wicking and seepage from blood vessels during the test affect the speckle pattern, countermeasures are proposed. On the other hand, stretching of ligaments produced large surface strain discontinuities from tissue unfolding, which caused automated pattern recognition algorithms to fail.

Algorithms↗

Spatial relationships among three columnar systems in cat area 17.

In the primary visual cortex, neurons with similar response properties are arranged in columns. As more and more columnar systems are discovered it becomes increasingly important to establish the rules that govern the geometric relationships between different columns. As a first step to examine this issue we investigated the spatial relationships between the orientation, ocular dominance, and spatial frequency domains in cat area 17. Using optical imaging of intrinsic signals we obtained high resolution maps for each of these stimulus features from the same cortical regions. We found clear relationships between orientation and ocular dominance columns: many iso-orientation lines intersected the borders between ocular dominance borders at right angles, and orientation singularities were concentrated in the center regions of the ocular dominance columns. Similar, albeit weaker geometric relationships were observed between the orientation and spatial frequency domains. The ocular dominance and spatial frequency maps were also found to be spatially related: there was a tendency for the low spatial frequency domains to avoid the border regions of the ocular dominance columns. This specific arrangement of the different columnar systems might ensure that all possible combinations of stimulus features are represented at least once in any given region of the visual cortex, thus avoiding the occurrence of functional blind spots for a particular stimulus attribute in the visual field.

Animals↗

Retinal projections in the goldfish: a study using cobaltous-lysine.

Cobaltous lysine applied to the distal stump of a severed optic nerve was used to study the retinal projections of normal adult goldfish. Both the termination areas of optic axons and the pathways they traveled were established. Contrary to previous descriptions of the goldfish visual system, the optic nerves do not decussate completely at the optic chiasm. Fascicles that entered the ipsilateral optic tract innervated targets in the ipsilateral thalamus and optic tectum. Other optic fibers crossed the posterior commissure from the contralateral side of the brain and also innervated the ipsilateral tectum and thalamus. In addition, optic fibers bilaterally innervated a hypothalamic target in close proximity to the infundibulum that may correspond to the nucleus tuberis lateralis. The contralateral preoptic region contained two discrete areas of innervation, each served by separate fascicles. The ipsilateral preoptic region was similarly innervated, but more sparsely. Fibers that entered the controlateral ventral thalamus originated from three fascicles and terminated in three distinct targets. In contrast, three targets in the contralateral dorsal thalamus were served by one fascicle, and fibers passed from one nucleus to the other two. Innervation of the ipsilateral thalamus was similar to that seen contralaterally. Each main optic tract divided into three tracts, two of which entered the optic tectum, while the other innervated several pretectal areas. Other fibers innervated an accessory optic nucleus located near nucleus glomerulosus. The contralateral tectum contained numerous radially oriented optic fascicles. These fascicles represented optic fibers that left thalamic and pretectal targets to enter the optic tectum from beneath the stratum periventriculare. Optic fibers were also observed in the transverse commissure, tractus rotundus, horizontal commissure, tectobulbar tract, and fasciculus retroflexus. Therefore, it appears that many of the anomalous projections seen after tectal ablation or after optic nerve crush are not in fact aberrant. Such projections probably reflect the presence of unusually large numbers of optic fibers in tracts that normally contain optic axons, as well as increased innervation of areas that normally receive sparse retinal projections. Filled tectal cells that could represent cells projecting to the retina were not observed in either tectal lobe. The ipsilateral retinal projections could not be attributed to cobaltous-lysine being transneuronally transported in readily detectable amounts.

Animals↗

A quantitative three-dimensional model of the Drosophila optic lobes.

A big step in the neurobiology of Drosophila would be to establish a standard for brain anatomy to which to relate morphological, developmental and genetic data. We propose that only an average brain and its variance would be a biologically meaningful reference and have developed an averaging procedure. Here, we present a brief outline of this method and apply it to the optic lobes of Drosophila melanogaster wild-type Canton S. Whole adult brains are stained with a fluorescent neuropil marker and scanned with the confocal microscope. The resulting three-dimensional data sets are automatically aligned into a common coordinate system and intensity averages calculated. We use effect-size maps for the fast detection of differences between averages. For morphometric analysis, neuropil structures are labelled and superimposed to give a three-dimensional probabilistic map. In the present study, the method was applied to 66 optic lobes. We found their size, shape and position to be highly conserved between animals. Similarity was even higher between left and right optic lobes of the same animal. Sex differences were more pronounced. Female optic lobes were 6% larger than those of males. This value corresponds well with the higher number of ommatidia in females. As females have their additional ommatidia dorsally and ventrally, the additional neuropil in the medulla, lobula and lobula plate, accordingly, was found preferentially at these locations. For males, additional neuropil was found only at the posterior margin of the lobula. This finding supports the notion of male-specific neural processing in the lobula as described for muscid and calliphorid flies.

Animals↗

The organization of nerve fiber bundles in the primate optic nerve head.

Horseradish peroxidase was injected into various areas of the optic disc of monkeys to label retrograde axoplasmic transport and permit identification and mapping of ganglion cells projecting through the areas of injection. Peripheral ganglion cell axons project through the deeper layers of the peripapillary nerve fiber layer (NFL) and enter the peripheral optic nerve. Peripapillary ganglion cell axons project through those coming from peripheral locations to superficial positions in the NFL, then to the central optic nerve. The Bjerrum portion of the optic nerve head includes approximately the central 30 degrees of the superior and inferior temporal quadrants of the disc. The course of nerve fiber bundles corresponding to those most susceptible to glaucoma (Bjerrum area) is regularly and predictably organized horizontally and vertically in the nerve head.

Animals↗

Retinotopic organization of central optic projections in Rana pipiens.

The retinotopic organization of the anuran visual system has been investigated with the method of selective anterograde transport of horseradish peroxidase (HRP) following retinal lesions. The course of optic axons to specific structures was also confirmed by retrograde transport in the optic tract following HRP injections in the tectum and pretectum. As the optic nerve reaches the optic chiasm, the fibers from each of the four retinal quadrants appear as bands with the nasal (n) quadrant entering the chiasmal anterior pole, followed by ventral (v), temporal (t), and dorsal (d) quadrants. The preoptic nucleus is the first structure to be innervated, followed by the suprachiasmatic nucleus; both are innervated directly from fibers in the dorsal part of the optic nerve, which contains fibers from all the retinal quadrants. Each quadrant expands across the dorsoventral extent of the chiasm at the point where it enters. At this level the quadrants are arrayed along the rostrocaudal axis (as they are later in the marginal optic tract) in the sequence n-v-t-d. Optic fibers then spread across the chiasm, the nasal quadrant splits, taking up positions in the rostral and caudal margins of the optic radiation. Following the split in the nasal representation, the optic tract is transformed into topographically arranged sheets in the marginal optic tract. In the other retinorecipient nuclei, the sheet of optic axons is transformed back into the shape of the retinal hemisphere. Topographic maps of this kind display one of two possible orientations: (1) in the tectum and the nucleus lentiformis mesencephali (nLM), the temporal retina is represented in the anterior portion of the nucleus, whereas the nasal quadrant is found in the posterior portion; (2) in the thalamus, the retinotopic map is organized as a mirror-image reversal of that seen in the tectum and nLM (i.e., the nasal pole is anterior, whereas the temporal pole is in the posterior portion of the nucleus). Structures with this type of retinal map include the rostral visual nucleus, the corpus geniculatum, the nucleus of Bellonci, and the posterior thalamic nucleus. A third type of innervation occurs in the nucleus of the basal optic root (nBOR), which is the only mesencephalic visual nucleus not innervated by the marginal optic tract. The basal optic root is formed by the fibers exiting most caudally from the optic chiasm. All the retinal quadrants contribute to the basal optic root, but no evidence of retinotopy was found in nBOR.4+ target nuclei.

Animals↗

Regeneration in the mammalian optic nerve.

Since the first studies on axonal regeneration, the optic nerve (ON) of higher vertebrates has been considered a good experimental system to investigate the failure of mature CNS neurons to re-grow after axotomy. The optic nerve is composed of a single population of fibers the RGC axons and, being separated from the rest of the brain, it is easily accessible to surgical manipulations. All the fibers can be transected without massive damage to the surrounding tissue, so their reaction to axotomy is not perturbed by extended inflammation processes. Another advantage of the system is the accessibility of RGCs. Being in the more internal retinal layer, RGCs are directly exposed to the humor vitreus, the liquid filling the posterior chamber of the eye. Pharmaceutical treatments are easily injected into the eye and, diffusing in the vitreus, can reach all the RGCs. Last but not least, functional recovery can be easily monitored in the optic nerve; measurement of electrical activity in response to visual stimuli in CNS regions that receive inputs from the retina such as superior colliculus or visual cortex allows evaluation of the re-growth of ON fibers and the restoration of connections. All the experiments carried out so far indicate that the failure of regeneration in the ON, as in the majority of the CNS districts, is a multi-factorial phenomenon, involving three classes of negative events. 1) RGCs die after axotomy: in the adult rat, their number is reduced to a very small percentage in a few weeks after the lesion. 2) The majority of mature axotomised RGCs are not programmed to re-start the process of axonal elongation that they displayed in immature stages. 3) The optic nerve environment contains molecules many of them upregulated after the lesion that are inhibitory for axonal growth. This review, focused on experiments performed in the mammalian optic nerve, traces attempts made to overcome each of these three obstacles, and maps progress towards a combined therapeutic strategy.

Animals↗

Correlation among retinal thickness, optic disc, and visual field in glaucoma patients and suspects: a pilot study.

OBJECTIVE: To correlate losses of retinal thickness in the perifoveal area in glaucoma as measured by the Retinal Thickness Analyzer (Talia Technology Ltd, Israel) with optic nerve and visual field changes in glaucoma patients and suspects. METHODS: Observational case series of 55 consecutive patients from the Glaucoma Service who either presented with a diagnosis of glaucoma or were referred for evaluation of suspected glaucoma. The Retinal Thickness Analyzer (Talia Technology, Ltd.) was used to obtain retinal thickness maps. Retinal thickness analysis, visual field testing, and stereophotography of the optic nerve head were performed, and a glaucoma specialist who was masked to patient status and identity data randomly graded the level of severity of each parameter. Spearman rank correlations were used to assess the relationships among the three numerical measures. RESULTS: Retinal thickness losses correlated more strongly with severity of optic nerve head cupping (r = 0.75), whereas both of these measures correlated less strongly with the severity of visual field loss (r = 0.54). CONCLUSIONS: Retinal thickness measurements at the posterior pole provide another measure of neural loss in glaucoma, and may help in the clinical assessment of optic nerve cupping. However, there are limitations of the technology that must be considered.

Adult↗