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Retinal thickness at the posterior pole in glaucoma and ocular hypertension.

PURPOSE: Ganglion cells with nerve fibre layer contribute a substantial fraction to the retinal thickness (RT). In contrast to the analysis of papillary and peripapillary area, which have shown large variability in normal eyes, the variation of retinal cell density in the perifoveal region is reported to be less than 10%. By measuring RT at the posterior pole we wanted to detect retinal changes due to glaucoma and determine their correspondence with visual field (VF) changes. METHODS: The Retinal Thickness Analyzer (RTA) was used to obtain RT maps in 21 normal eyes, 20 eyes with ocular hypertension and 22 eyes with glaucoma. A green laser slit (540 nm) of the RTA was focused on the retina at an angle and its intersection with the retina was imaged. The distance between the reflections from the vitreo-retinal and retina-retinal pigment interface is directly proportional to the RT. Five locations covering the central 20 degrees were scanned, generating 10 optical cross sections that were transformed into colour-coded RTA maps. Numerical data were presented for the perifoveal and posterior pole region. RESULTS: In glaucomatous eyes significant localised thinning of the retina was present, identified as the increased number of clusters including at least four points that are 2 standard deviations below normal. The minimum retinal thickness was decreased in glaucoma eyes and the perifoveal temporal modulation and perifoveal temporal/nasal asymmetry--indicators of greater RT loss in the temporal and the nasal quadrant, respectively--were higher in eyes with glaucoma, but with overlapping global indices between the groups. In 16 of 22 eyes with glaucoma there was good agreement of RT changes with VF defects. In two eyes with typical glaucomatous damage at the optic disc but without VF defects localised changes of RT were detected. CONCLUSIONS: The RTA enables objective noninvasive evaluation of the posterior pole and could become helpful in diagnosis of glaucoma before the onset of functional damage. However, at present its clinical usefulness is limited by overlapping values of retinal thickness between normal and glaucomatous populations.

Adult↗

Development of the nucleus isthmi in Xenopus, II: Branching patterns of contralaterally projecting isthmotectal axons during maturation of binocular maps.

The tectum of Xenopus frogs receives input from both eyes. The contralateral eye's projection reaches the tectum directly, via the optic nerve, and the ipsilateral eye's projection reaches the tectum indirectly, via the nucleus isthmi. Under normal conditions, the topography of the ipsilateral map relayed from the nucleus isthmi is in register with the topography of the retinotectal map from the contralateral eye. During development, the process of aligning the two maps is complicated by the dramatic changes in binocular overlap of the two eyes' visual fields which take place during late tadpole and juvenile stages. The goal of this study is to determine the branching patterns of contralaterally projecting isthmotectal axons before, during, and after the period of rapid eye migration. Isthmotectal axons were filled by anterograde transport of horseradish peroxidase (HRP) from the nucleus isthmi. The results show that crossed isthmotectal axons enter the entire extent of the tectum before binocular overlap begins to increase. Therefore, binocular overlap is not necessary for the initial isthmotectal projection to span the tectum. The density of isthmotectal branches rises dramatically at the same time that the eyes begin to shift. During the period when eye migration is most rapid, many isthmotectal axons form arbors which resemble adult arbors but which extend over greater proportions of the tectal surface. The axons appear to be directed toward appropriate mediolateral positions as they enter the tectum. Their trajectories are roughly rostocaudal, with relatively little change along the mediolateral dimension. These data, when combined with available physiological data, suggest that mediolateral order is initially established by vision-independent mechanisms but can be altered by vision-dependent mechanisms. Rostrocaudal order becomes discernable only at the time when binocular visual cues become available and appears to be established primarily on the basis of the activity of the retinotectal and isthmotectal axons.

Animals↗

Effects of neonatal splitting of the optic chiasm on the development of feline visual callosal connections.

During normal postnatal development, there is an overproduction and subsequent partial elimination of the callosal projections of cortical areas 17 and 18 in the cat. In the present study, we investigated how neonatal splitting of the optic chiasm affects this process. Our results indicate that neonatal splitting of the optic chiasm exaggerates the normally occurring partial elimination of immature callosal projections: it causes a significant reduction in the total number of neurons in the supragranular layers that send an axon through the corpus callosum. It does not, however, cause a significant change in the number of callosally projecting neurons in the infragranular layers. These data suggest that in addition to other factors previously described, the level or spatial distribution of correlated binocular input to visual cortical neurons may influence the stabilization/elimination of immature callosal connections.

Animals↗

Isthmotectal connections in plethodontid salamanders.

In the plethodontid salamander species Plethodon jordani and Hydromantes italicus, the morphology and connectivity of isthmic cells were investigated by means of intracellular staining with biocytin. Dendritic arborization, axonal pathways, and size and morphology of telodendritic structures in the fiber layers of the optic tectum were determined. The latter were studied electron microscopically. The majority of isthmic neurons project to both tectal hemispheres, each cell forming telodendritic structures of different extent in the ipsilateral and contralateral hemisphere. These structures are column-like with diameters of about 60 microm. The ipsilateral terminals extend through layers 1-3 of the tectal white matter and intermingle with terminals of contralateral retinal afferents in layers 1-3, as well as with ipsilateral retinal afferents in layer 3. The corresponding contralateral telodendritic structures are confined to layer 1 and are not in direct contact with ipsilateral retinal afferents in layer 3. Both telodendritic structures are located in the rostral two-thirds of the optic tectum, which are binocularly innervated. The rostrocaudal and mediolateral sites of isthmic telodendra are in register with the direct retinal map in each tectal hemisphere. Few isthmic cells project to the caudal one-third of the optic tectum, which is monocularly driven. These cells form only one axonal terminal in the ipsilateral tectal hemisphere. Size and structure of these ipsilateral terminals are similar to the ipsilateral telodendra of bilaterally projecting isthmic neurons.

Animals↗

Suprachiasmatic nucleus and retinohypothalamic projections in moles.

The suprachiasmatic nucleus of the hypothalamus (SCN) and the retinohypothalamic projections were identified in one species of old-world moles, all of whom are blind as a result of natural loss of vision. A cyto-architectonic study revealed that the SCN is well developed, even though other visual nuclei in the dorsal thalamus and the midbrain are not. An immunohistochemical study showed that vasoactive intestinal polypeptide (VIP)-like immunoreactive cell bodies and fibers were distributed in the SCN, as has been reported in other mammals. Following intraocular injections of wheatgerm agglutinin conjugated to horseradish peroxidase (WGA-HRP), the central retinal projections were examined. The results indicated that the SCN receives a direct projection from the retina, as seen in many other mammals. In addition to the projection to the SCN, retinal fibers were seen to terminate in the anterior hypothalamic region and the retrochiasmatic area, as observed in some other mammals. In moles, retinohypothalamic projections are bilateral, with an ipsilateral predominance. Considering that the retinogeniculate and retinotectal projections are vestigial, it is highly probable that the optic pathway in moles primarily consists of retinohypothalamic projections, which are devoted to the entrainment of circadian and circannual rhythms.

Animals↗

Alpha-adrenergic receptor antagonism prevents intestinal vasoconstriction but not hypoperfusion following resuscitated hemorrhage.

Resuscitation (RES) after hemorrhage (HEM) results in persistent arteriolar constriction and hypoperfusion of the small intestine (SI) despite restoration of mean arterial pressure (MAP) and cardiac output (CO) to normal values. We postulated that increased adrenergic activity contributes to this vasoconstriction and impairment of flow. A loop of SI from decerebrate rats was exteriorized and suffused with Krebs' solution (37 degrees C, pH 7.4). In initial experiments, the effectiveness of alpha-adrenergic receptor antagonism by phentolamine (PHEN) was assessed. Subsequent groups received either topical PHEN (10(-6) M, n = 6) or saline (n = 6) in the suffusion and were then bled to 50% baseline (BL) MAP for 60 min and resuscitated to BL with shed blood/lactated Ringer's. Intravital microscopy and optical Doppler velocimetry were used to measure large (A1) and small, premucosal (A3) arteriolar diameters and RBC velocity; microvascular blood flow was calculated. MAP and transpulmonary CO were measured. During HEM, control animals developed A1 constriction and hypoperfusion with A3 arteriolar dilation. PHEN treatment prevented A1 constriction and enhanced A3 dilation but did not improve flow. Immediately after RES in controls, microvascular diameters and A1 flow returned to BL; however, over the 2-hr post-RES period there was progressive A1 and A3 vasoconstriction and hypoperfusion despite maintenance of BL MAP and CO. After RES in PHEN-treated animals, A1 flow returned to BL, but progressive hypoperfusion was only partially prevented. alpha-Adrenergic-mediated vasoconstriction contributes to intestinal hypoperfusion after HEM, but other mechanisms are also involved in microvascular responses during RES.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

Spatial distribution of phase singularities in ventricular fibrillation.

BACKGROUND: Multiple excitation wavelets are present during ventricular fibrillation (VF). The underlying wavelet organization of VF is unclear. Phase singularities (PSs)-locations of ambiguous activation state-underlie reentry and wavelet splitting and represent the sources of VF. Understanding the mechanisms of PS formation might be important in the development of effective therapies for sudden death. METHODS AND RESULTS: We performed voltage, phase, and PS mapping in fibrillating ventricles, applying an automated PS detection algorithm to optically recorded fibrillation signals. PS clustering was noted along epicardial vessels, ridges of endocardial trabeculae, and papillary muscle insertions. Microscopically, these locations correlated with areas of apposition of fibers with different angulations and intramural vessels. A total of 83.2% of PSs were formed at and meandered about these anatomic structures, which acted as stabilizers: PSs colocalizing at anatomic substrates had longer life spans than nonanatomic PS (82.46+/-60.8 versus 40.5+/-31.9 ms, P<0.01). The RV endocardium had a higher PS incidence than the epicardium (42.3+/-9.2 versus 23.5+/-11.6 PS/s, P<0.01). Autocorrelation showed that irregular behavior was spatially restricted to anatomic heterogeneities compared with other areas, which had nearly periodic behaviors. Simple spatial PS distributions underlay complex and variable activation patterns attributable to variable PS behaviors, life spans, and inter-PS interactions. CONCLUSIONS: PSs occur in a nonrandom spatial distribution and colocalize with normal anatomic heterogeneities. Varying PS behaviors and life spans but stable PS spatial distributions cause ever-changing activation patterns that characterize VF.

Animals↗

Regenerated optic fibers in goldfish reestablish a crude sectoral order in the visual pathway.

The goldfish optic pathway is regenerated after an optic nerve crush. We have examined the axonal topography of the regenerated pathway by labeling, with horseradish peroxidase (HRP), axons originating from retinal sectors or annuli. The positions of the labeled axons in the cross section of the pathway were compared to the normal and related to the factors that may influence axonal pathfinding. The positions of retinal axons in the cross section of the normal pathway are predictable from the retinal addresses of the ganglion cells described by the polar coordinates r (the distance from the optic disc) and theta (the sectoral or clockface position). The two coordinates map orthogonally onto the cross section of the pathway; r varies monotonically along one axis; theta varies along a perpendicular axis. The normal r-order, present in the nonregenerated stump of the experimental nerve, was severely degraded and perhaps lost entirely in the regenerated optic nerve, tract, and brachia. Sectoral order was also lost as the axons passed the crush site, but it was reestablished, albeit crudely, in the regenerated tract and brachia where axons tended to occupy positions appropriate to their dorsal, ventral, nasal, and temporal retinal origins. The exit sequence of the regenerated axons from the stratum opticum into the tectal neuropil was normal: temporal first, nasal last. These results suggest that the regenerating fibers followed some theta-specific cue located in the nonaxonal environment. It seems likely that the original axons probably followed the same cue. In contrast, the absence of r-order suggests that there is no r-specific cue for the regenerates to follow. It seems likely that the original r-order was a consequence of nonspecific influences--the orderly spatiotemporal growth of the retina and the existence of a permissive region for axonal growth.

Animals↗

Eigenvector-based spatial filtering for reduction of physiological interference in diffuse optical imaging.

Diffuse optical imaging is an effective technique for noninvasive functional brain imaging. However, the measurements respond to systemic hemodynamic fluctuations caused by the cardiac cycle, respiration, and blood pressure, which may obscure or overwhelm the desired stimulus-evoked response. Previous work on this problem employed temporal filtering, estimation of systemic effects from background pixels, or modeling of interference signals with predefined basis functions, with some success. However, weak signals are still lost in the interference, and other complementary methods are desirable. We use the spatial behavior of measured baseline signals to identify the interference subspaces. We then project signals components in this subspace out of the stimulation data. In doing so, we assume that systemic interference components will be more global spatially, with higher energy, than the stimulus-evoked signals of interest. Thus, the eigenvectors corresponding to the largest eigenvalues of an appropriate correlation matrix form the basis for an interference subspace. By projecting the data onto the orthogonal nullspace of these eigenvectors, we can obtain more localized response, as reflected in improved contrast-to-noise ratio and correlation coefficient maps.

Artifacts↗

New field with tonotopic organization in guinea pig auditory cortex.

In guinea pig auditory cortex, two core areas, a primary area (AI) and a dorsocaudal field (DC), and two belt regions ventral to AI and DC (VRB and VCB) with an intermediate zone (T) in between, together with a small field (S) rostral to AI, have been reported in single-electrode studies although field S and zone T have not been observed in imaging studies. Using a high-resolution in vivo optical-imaging system with the voltage-sensitive dye RH-795, we report here the successful imaging of a rostral small field and zone T and a ventral-to-dorsal frequency gradient in zone T. Further, we found that VRB can be subdivided into two areas, a ventrorostral field (VR) with properties similar to those reported for VRB, and a ventrocaudal field (VC) with novel properties. With increasing stimulus tone frequency, activation in VR shifted caudally while activation in VC shifted rostrally. Thus we have newly identified field VC that has mirror-symmetric tonotopy to that of VR.

Acoustic Stimulation↗

"Thermal stability" maps for several double-stranded DNA fragments of known sequence.

The origin of cooperatively melting regions in DNA, which appear as fine structures in the optical melting profile, has been examined for DNA fragments of known base sequences from bacteriophages phiX174 and fd. Thermal stability maps, which indicate the states of base pairs along these DNA strands, were constructed within the established theoretical framework using the parameters which best reproduce the melting profiles obtained by high temperature resolution experiments. By comparing these stability maps with genetic maps, it was found that several cooperatively melting regions which span several hundred bases have some correlation with the gene locations.

Base Sequence↗

[Early positive component of the evoked potential of the midbrain tectum of the dogfish shark during electric stimulation of the optic nerve].

Midbrain tectal evoked responses to electric stimulation of the optic nerve were investigated in shark (Squalus acanthias). An early positive component was found as a part of negative phase of "classic" negative-positive evoked potential. Similar component was recorded from the ipsilateral tectal hemisphere as well. An increase of the positive component along with penetration of the electrode, its resistance to functional blockade by KCl application to the tectum surface and recording of a similar potential from the ventricular floor surface after extirpation of the tectum suggested the localization of the source of this component outside the tectum. Existence of a focus of maximal activity located in the rostral part of undertectal brain structures and disappearance of early positive component after functional blockade and extirpation of this brain area indicate the leading role of thalamic nuclei in generation of this component.

Animals↗

Retinal pigment epithelium translocation after choroidal neovascular membrane removal in age-related macular degeneration.

PURPOSE: To test the feasibility of a new surgical technique and to assess visual function over the translocated retinal pigment epithelium (RPE) cells in patients operated on for subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (ARMD). DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Nine patients with previously untreated exudative ARMD underwent surgical excision of the subfoveal CNV with RPE translocation and were observed for 12 to 32 months. METHODS: The surgery consisted of a standard three-port pars plana vitrectomy, excision of the CNV, and RPE translocation. Pre- and postoperative ocular examination included best-corrected visual acuity measurement, fundus color stereo photography, and fundus fluorescein angiography. Optical coherence tomography and confocal laser scanning ophthalmoscopy (cLSO) were performed after surgery. A crossfixation target and a single-point flashing light were projected on different areas of the posterior pole using a cLSO. Photopic 10 to 2 perimetry, photopic fine matrix mapping, and cLSO microperimetry were also performed after surgery in six patients. MAIN OUTCOME MEASURES: Optical coherence tomography cross-sectional scans and cLSO RPE autofluorescence were recorded to detect the presence of viable translocated RPE. Visual acuity, fixation, photopic 10 to 2 perimetry, photopic fine matrix mapping, and cLSO microperimetry were used to test central visual function. RESULTS: Retinal pigment epithelium was translocated successfully at the time of CNV removal from the edge of the RPE defect to a subfoveal location in seven of nine patients. One patient experienced proliferative vitreoretinopathy, but significant hemorrhage was not a feature. Optical coherence tomography showed the translocated RPE as an area of increased optical reflectivity with optical shadowing external to it. Confocal laser scanning ophthalmoscopy showed autofluorescence of the translocated RPE. The crossfixation target was seen when projected on the translocated RPE. During eccentric fixation, the patients could see a flashing point-target projected on the translocated RPE. Photopic 10 to 2 perimetry, photopic fine-matrix mapping, and cLSO microperimetry showed the presence of central visual function. CONCLUSIONS: The authors propose that translocation of RPE at the time of CNV removal, from the edge of the RPE defect to a subfoveal location, may have a role in the surgical management of ARMD.

Aged↗

Remote biomedical spectroscopic imaging of human artery wall.

We discuss a general technique, laser spectroscopic imaging (LSI), remote acquisition of spectroscopic images of biological tissues and tissue conditions. The technique employs laser-induced spectroscopic signals, collected and transmitted via an array of optical fibers, to produce discrete pixels of information from which a map or image of a desired tissue characteristic is constructed. We describe a prototype LSI catheter that produces spectral images of the interior of human arteries for diagnosis of atherosclerosis. The diagnostic is based on the fact that normal artery wall and atherosclerotic plaque exhibit distinct fluorescence spectra in the 500-650 nm range when excited by 476-nm laser light; the fluorescence from blood is minimal. The catheter is composed of 19 optical fibers enclosed in a transparent, protective shield. Argon ion laser radiation is used for excitation, and an optical multichannel spectral analyzer is used for detection. Sequential sampling is used to minimize crosstalk among fibers and reduce blurring of the image. Computer-processed 19-pixel spectroscopic images are produced of fresh cadaver artery in vitro. Regions of normal tissue, plaque, and blood are identified, and the diagnoses are confirmed histologically and by direct spatial correlation. The results demonstrate the concept of using this laser catheter system for real-time imaging.

Arteriosclerosis↗

Three-dimensional Bayesian optical image reconstruction with domain decomposition.

Most current efforts in near-infrared optical tomography are effectively limited to two-dimensional reconstructions due to the computationally intensive nature of full three-dimensional (3-D) data inversion. Previously, we described a new computationally efficient and statistically powerful inversion method APPRIZE (automatic progressive parameter-reducing inverse zonation and estimation). The APPRIZE method computes minimum-variance estimates of parameter values (here, spatially variant absorption due to a fluorescent contrast agent) and covariance, while simultaneously estimating the number of parameters needed as well as the size, shape, and location of the spatial regions that correspond to those parameters. Estimates of measurement and model error are explicitly incorporated into the procedure and implicitly regularize the inversion in a physically based manner. The optimal estimation of parameters is bounds-constrained, precluding infeasible values. In this paper, the APPRIZE method for optical imaging is extended for application to arbitrarily large 3-D domains through the use of domain decomposition. The effect of subdomain size on the performance of the method is examined by assessing the sensitivity for identifying 112 randomly located single-voxel heterogeneities in 58 3-D domains. Also investigated are the effects of unmodeled heterogeneity in background optical properties. The method is tested on simulated frequency-domain photon migration measurements at 100 MHz in order to recover absorption maps owing to fluorescent contrast agent. This study provides a new approach for computationally tractable 3-D optical tomography.

Bayes Theorem↗