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[Introduction to tissue optics and optical dosimetry].

The spatial distribution of radiation during medical laser application is determined by the characteristics of the beam (power, time, beam geometry) and the optical properties of the tissue. The irradiance E (in W/m2) describes the primary laser beam. Scattered radiation, in turn, is taken into account by the fluence rate phi (also in W/m2). The basic parameters of tissue optics are the absorption coefficient mu a, the scattering coefficient mu s and the anisotropy factor g. In addition, derived parameters are also used, i.e., total attenuation coefficient mu t, reduced scattering coefficient mu s', effective attenuation coefficient mu eff, mean free path of a photon d and penetration depth delta. Further tissue properties are the diffuse reflectance Rd and the back-scattering factor k. In an one-dimensional model the fluence rate phi in tissue is a nearly exponential function characterized by the penetration depth delta. At the tissue surface, the relationship exists phi = kE. This model is compared with the results of a computer program based on the finite element method.

Dose-Response Relationship, Radiation↗

Optical excitations in organic dendrimers investigated by time-resolved and nonlinear optical spectroscopy.

Our research is concerned with the optical properties of covalently bound branched multichromophore systems. The presence of strong intramolecular interactions in dendrimers and other branched macromolecules has stimulated new approaches toward improved energy transfer and light-emitting and enhanced nonlinear optical materials, as well as the possibility of delocalized (exciton) excitations in molecular aggregates. This Account summarizes some of our investigations, which combine the use of different time-resolved techniques to examine the dynamics in organic (conjugated) branched structures and provide important structure-function correlations necessary for applications.

Energy Transfer↗

Computer simulation of the linear and nonlinear optical susceptibilities of p-nitroaniline in cyclohexane, 1,4-dioxane, and tetrahydrofuran in quadrupolar approximation. II. Local field effects and optical susceptibilitities.

This is the second part of a study to elucidate the local field effects on the nonlinear optical properties of p-nitroaniline (pNA) in three solvents of different multipolar character, that is, cyclohexane (CH), 1,4-dioxane (DI), and tetrahydrofuran (THF), employing a discrete description of the solutions. By the use of liquid structure information from molecular dynamics simulations and molecular properties computed by high-level ab initio methods, the local field and local field gradients on p-nitroaniline and the solvent molecules are computed in quadrupolar approximation. To validate the simulations and the induction model, static and dynamic (non)linear properties of the pure solvents are also computed. With the exception of the static dielectric constant of pure THF, a good agreement between computed and experimental refractive indices, dielectric constants, and third harmonic generation signals is obtained for the solvents. For the solutions, it is found that multipole moments up to two orders higher than quadrupole have a negligible influence on the local fields on pNA, if a simple distribution model is employed for the electric properties of pNA. Quadrupole effects are found to be nonnegligible in all three solvents but are especially pronounced in the 1,4-dioxane solvent, in which the local fields are similar to those in THF, although the dielectric constant of DI is 2.2 and that of the simulated THF is 5.4. The electric-field-induced second harmonic generation (EFISH) signal and the hyper-Rayleigh scattering signal of pNA in the solutions computed with the local field are in good to fair agreement with available experimental results. This confirms the effect of the "dioxane anomaly" also on nonlinear optical properties. Predictions based on an ellipsoidal Onsager model as applied by experimentalists are in very good agreement with the discrete model predictions. This is in contrast to a recent discrete reaction field calculation of pNA in 1,4-dioxane, which found that the predicted first hyperpolarizability of pNA deviated strongly from the predictions obtained using Onsager-Lorentz local field factors.

Aniline Compounds↗

Optical biopsy and imaging using optical coherence tomography.

Optical coherence tomography is a new imaging technique that can perform high-resolution, micrometre-scale, cross-sectional imaging in biological systems. The technology has been developed, and reduced to, preliminary clinical practice in ophthalmology. The challenging problem that OCT may address is the development of 'optical biopsy' techniques. These techniques can provide diagnostic imaging of tissue morphology without the need for excision of specimens. Many investigations remain to identify optimal areas for clinical application, and additional engineering must be done to integrate vertically the technology and to reduce it to clinical practice. Nevertheless, preliminary studies indicate the feasibility of developing this technology for a wide range of clinical and research diagnostic imaging applications. The ability to non-excisionally evaluate tissue morphology using a catheter or an endoscope could have a significant impact on the diagnosis and management of a wide range of diseases.

Arteries↗

Visual function following neurosurgical optic nerve decompression for compressive optic neuropathy.

AIMS: To assess the course of visual function after neurosurgical decompression of the optic nerve during resection of intracranial tumours. To obtain information that may be used to counsel patients. METHODS: A retrospective review of the acuity and visual fields of 27 patients undergoing neurosurgical decompression of 36 optic nerves in a regional neurosurgical centre. Two groups were considered, those undergoing craniotomy for sphenoid wing meningioma en plaque, and those undergoing an extended transbasal approach to intracranial tumours. RESULTS: At the last follow-up (1-97 months), improvement in acuity was seen in 47% of eyes with decompressed nerves. One-third of these showed late improvement, and two-thirds showed immediate improvement. In total, 20% of eyes had worse acuity at the last follow-up compared with preoperative values, just under one-third of these showed late deterioration, and the remainder showed immediate deterioration. In total, 33% of eyes achieved acuities equal to those recorded preoperatively, 6% improving to this level postoperatively. CONCLUSIONS: The majority of eyes in this study maintained or improved acuity after decompression. A proportion of eyes continue to improve after surgery, and a proportion deteriorate. There is no relation between duration of preoperative symptoms or the level of preoperative acuity and the change in acuity achieved.

Adult↗

Optical coherence tomography: an emerging technology for biomedical imaging and optical biopsy.

Optical coherence tomography (OCT) is an emerging technology for performing high-resolution cross-sectional imaging. OCT is analogous to ultrasound imaging, except that it uses light instead of sound. OCT can provide cross-sectional images of tissue structure on the micron scale in situ and in real time. Using OCT in combination with catheters and endoscopes enables high-resolution intraluminal imaging of organ systems. OCT can function as a type of optical biopsy and is a powerful imaging technology for medical diagnostics because unlike conventional histopathology which requires removal of a tissue specimen and processing for microscopic examination, OCT can provide images of tissue in situ and in real time. OCT can be used where standard excisional biopsy is hazardous or impossible, to reduce sampling errors associated with excisional biopsy, and to guide interventional procedures. In this paper, we review OCT technology and describe its potential biomedical and clinical applications.

Animals↗

[Computer-controlled analysis of the optic papilla with the Optic Nerve Head Analyzer: normal values and various age dependent papilla parameters].

The Rodenstock Optic Nerve Head Analyzer was used to study the disk parameters of 194 eyes of 122 healthy subjects. No age-related changes in the neuroretinal rim area or in the cup/disk ratio could be detected. Furthermore, no significant differences in the mean values of disk parameters were found when right eyes were compared with left eyes or when eyes of male and female subjects were compared. It was thus possible to base calculations of normal values for disk parameters on the entire sample of 194 eyes, irrespective of age and sex. It was also possible to determine the range of variation of these parameters. Statistical analysis of the data produced the following results: the smallest mean neuroretinal rim area is in the temporal disk quadrant; the largest is in the nasal disk quadrant. The mean neuroretinal rim area of the upper quadrant is almost as large as that of the lower quadrant. Consequently, the temporal quadrant has the largest cup/disk ratio, while the nasal quadrant has the smallest. The cup/disk ratios of the upper and lower quadrants are almost identical. The range of variation of all disk parameters was found to be considerable, i.e., the neuroretinal rim area of the whole disk, as well as that of each disk quadrant may be very small, not only in glaucomatous but even in normal eyes. Accordingly, the cup/disk ratio may be large even in normal eyes. Due to the broad range of interindividual variation of disk parameters, a single examination with the Optic Nerve Head Analyzer is not sufficient to distinguish normal from glaucomatous disks. Follow-up examinations are therefore required for early diagnosis of glaucoma, because the finding of a reduction in neuroretinal rim area during follow-up must be interpreted as an important sign of early glaucoma damage.

Adolescent↗

[Measuring the optic papilla with planimetry and the optic nerve head analyzer in glaucoma and suspected glaucoma. I. Comparison of the 2 measuring methods].

Two-dimensional planimetric measurement of the neuroretinal rim using the method described by Betz has proved to be one of the most objective parameters in evaluating the optic nerve head. Using a three-dimensional stereoscopic measuring procedure (ONHA) described by Cornsweet, the volume of the papillary excavation can be quantified. The two methods were compared in a study involving 67 eyes with confirmed and suspected glaucoma. In agreement with published data, the correlation between the two measuring procedures was good as regards the disk surface (r2 = 0.73), the surface of the excavation (r2 = 0.90), and the cup/disk ratio (r2 = 0.63), although the last-mentioned parameter is calculated differently. While the disk surface as measured by planimetry was significantly greater than with ONHA, the cup surface measurements were almost exactly the same. In contrast to the results of other authors, the measurements of the neuroretinal rim surface correlated poorly (r2 = 0.09). The difference between the two methods in measuring the rim surfaces depends to a great extent on their absolute size and on the cup surface. The different procedures for defining the boundary of the excavation (in planimetry horizontal boundary definition, with the ONHA 150 micrometers below the retinal surface) are considered responsible for this. Advantages and drawbacks of these two clinical measuring methods are discussed. Once the currently excessive variability in the measurements has been reduced, measurement of the excavation volume could prove to be an important parameter for assessing the development of the optic nerve head in confirmed or suspected glaucoma cases.

Adolescent↗

'Generic-view principle' for three-dimensional-motion perception: optics and inverse optics of a moving straight bar.

The generic-view principle (GVP) states that given a 2-D image the visual system interprets it as a generic view of a 3-D scene when possible. The GVP was applied to 3-D-motion perception to show how the visual system decomposes retinal image motion into three components of 3-D motion: stretch/shrinkage, rotation, and translation. First, the optical process of retinal image motion was analyzed, and predictions were made based on the GVP in the inverse-optical process. Then experiments were conducted in which the subject judged perception of stretch/shrinkage, rotation in depth, and translation in depth for a moving bar stimulus. Retinal-image parameters-2-D stretch/shrinkage, 2-D rotation, and 2-D translation-were manipulated categorically and exhaustively. The results were highly consistent with the predictions. The GVP seems to offer a broad and general framework for understanding the ambiguity-solving process in motion perception. Its relationship to other constraints such as that of rigidity is discussed.

Bayes Theorem↗

Type III 3-methylglutaconic aciduria (optic atrophy plus syndrome, or Costeff optic atrophy syndrome): identification of the OPA3 gene and its founder mutation in Iraqi Jews.

Type III 3-methylglutaconic aciduria (MGA) (MIM 258501) is a neuro-ophthalmologic syndrome that consists of early-onset bilateral optic atrophy and later-onset spasticity, extrapyramidal dysfunction, and cognitive deficit. Urinary excretion of 3-methylglutaconic acid and of 3-methylglutaric acid is increased. The disorder has been reported in approximately 40 patients of Iraqi Jewish origin, allowing the mapping of the disease to chromosome 19q13.2-q13.3, by linkage analysis. To isolate the causative gene, OPA3, we sequenced four genes within the critical interval and identified, in the intronic sequence of a gene corresponding to cDNA clone FLJ22187, a point mutation that segregated with the type III MGA phenotype. The FLJ22187-cDNA clone, which we identified as the OPA3 gene, consists of two exons and encodes a peptide of 179 amino acid residues. Northern blot analysis revealed a primary transcript of approximately 5.0 kb that was ubiquitously expressed, most prominently in skeletal muscle and kidney. Within the brain, the cerebral cortex, the medulla, the cerebellum, and the frontal lobe, compared to other parts of the brain, had slightly increased expression. The intronic G-->C mutation abolished mRNA expression in fibroblasts from affected patients and was detected in 8 of 85 anonymous Israeli individuals of Iraqi Jewish origin. Milder mutations in OPA3 should be sought in patients with optic atrophy with later onset, even in the absence of additional neurological abnormalities.

Amino Acid Sequence↗

Feasibility of three-dimensional optical coherence tomography and optical Doppler tomography of malignancy in hamster cheek pouches.

OBJECTIVE: Hamster cheek pouches (HCP) with various degrees of 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced dysplasia and malignancies were imaged with OCT/ODT in vivo and in vitro to assess the potential for three-dimensional high-resolution optical localization of airway malignancy. BACKGROUND DATA: Optical coherence tomography (OCT)/optical doppler tomography (ODT) provide potential capability for real-time in vivo high-resolution (2-20 microm) cross-sectional imaging of tissues and spatially resolved blood flow in microvasculature for pathology diagnostics. METHODS: DMBA was applied to the right side of the cheek pouch (HCP), and mineral oil (control) to the left side three times weekly for 10-18 weeks in Syrian Golden Hamsters using a standard protocol for malignancy induction. HCP were imaged in vivo with OCT/ODT as well as in vitro post-excision, using a prototype 1310-nm broadband superluminescent diode-based OCT/ODT device constructed in our laboratory. Three-dimensional images were constructed, and compared to standard and three-dimensional histology hematoxylin and eosin staining. RESULTS AND CONCLUSION: OCT imaging offered exceptional resolution of the HCP to depths of 1-2 mm and confirmed ability to detect dysplasia and malignancy. Three-dimensional OCT images were readily constructed, allowing visualization of extent and localization of tumor margins. ODT demonstrated increased vascularity in the area of neoplasia. OCT/ODT is a promising new technology for oral airway diagnostics.

Animals↗

Fibre-optic assessment of tracheal tube position. A comparison of tracheal tube position as estimated by fibre-optic bronchoscopy and by chest X-ray.

The distance between the tip of a tracheal tube and the carina was measured in twenty five patients who required tracheal intubation and artificial ventilation of the lungs. Two methods of evaluation of this distance--limited-optic bronchoscopy and chest X-ray--were compared. There was no significant difference between the distance measured by either method. The advantages of checking tracheal tube placement by fibre-optic bronchoscopy are discussed.

Adult↗

Responses of neurons of the nucleus of the optic tract and the dorsal terminal nucleus of the accessory optic tract in the awake monkey.

The nucleus of the optic tract (NOT) and the dorsal terminal nucleus of the accessory optic tract (DTN) are essential nuclei for the generation of slow-phase eye movements during horizontal optokinetic nystagmus. We recorded from 101 neurons (all directionally selective) in four NOT/DTN of three trained and behaving rhesus monkeys. Neuronal activity increased when stimuli moved ipsiversively with respect to the recording site and decreased below spontaneous activity when stimuli moved contraversively. While the monkey fixated a small spot, some NOT/DTN neurons did not respond at all to the retinal image slip of a whole-field random dot pattern; others showed a monotonic increase of activity to increasing velocities of that stimulus. The velocity range tested was up to 100 degrees/s. During the execution of optokinetic nystagmus, 39 of 73 cells tested showed a velocity-tuned response with an average optimum at 21 degrees/s retinal image slip. Following saccades during optokinetic nystagmus (quick phases), the NOT/DTN neuronal activity briefly attained the level of spontaneous activity, as predicted from the velocity selectivity during optokinetic nystagmus. Immediately upon cessation of optokinetic stimulation in the preferred direction, NOT/DTN activity returned to the spontaneous level and did not reflect the ongoing optokinetic afternystagmus in darkness. Most NOT/DTN neurons displayed direction selectivity also during smooth pursuit. Twenty-one of 50 cells tested (42%) always responded to the retinal slip of the target (target velocity cells), 16 cells (32%) responded to the retinal slip of the background (background velocity cells), and 13 cells (26%) did not respond at all during smooth pursuit. We conclude from our results that the NOT/DTN is an essential structure for the processing of the direction and speed of retinal image slip. This information is then used for the generation and maintenance of slow eye movements, preferentially during horizontal optokinetic nystagmus but also during pursuit eye movements.

Animals↗

Dynamic optical clearing effect of tissue impregnated with hyperosmotic agents and studied with optical coherence tomography.

The depth of light penetration into highly scattering tissues can be improved by the application of biocompatible and osmotically active chemical agents. We compare the dynamics of optical clearing of tissue by the topical application of glycerol and dimethyl sulfoxide (DMSO) using optical coherence tomography (OCT). It is demonstrated experimentally that both agents can largely improve the OCT imaging depth for porcine stomach tissue. During a period of approximately 20 to 30 min after the application of glycerol image contrast is also enhanced. This enhancement disappears over time. Such enhancement of image contrast is not observed with DMSO. Glycerol causes a higher degree of dehydration of the tissue than DMSO does. We suggest that these phenomena are caused by a two-stage diffusion of the chemicals. The first stage of diffusion is from the top tissue to the intercellular space, and the second is into the cell matrix. During the first stage, the imaging contrast could be improved by dehydration.

Animals↗

Measuring red blood cell flow dynamics in a glass capillary using Doppler optical coherence tomography and Doppler amplitude optical coherence tomography.

Blood, being a suspension of deformable red cells suspended in plasma, displays flow dynamics considerably more complicated than those of an ideal Newtonian fluid. Flow dynamics in blood capillaries of a few hundred micrometers in diameter are investigated using Doppler optical coherence tomography (DOCT) and Doppler amplitude optical coherence tomography (DAOCT), a novel extension of DOCT. Velocity profiles and concentration distributions of normal and rigidified in vitro red blood cell suspensions are shown to vary as functions of mean flow velocity, cell concentration, and cell rigidity. Deviation from the parabolic velocity profile expected for Pouseille flow is observed for both rigid and normal cells at low flow rates. Axial red cell migration both toward and away from the tube axis is observed for both rigid and normal cells as a function of flow velocity. Good agreement is found between our measurements, and theoretical expectations.

Blood Flow Velocity↗

In vivo endoscopic optical biopsy with optical coherence tomography.

Current medical imaging technologies allow visualization of tissue anatomy in the human body at resolutions ranging from 100 micrometers to 1 millimeter. These technologies are generally not sensitive enough to detect early-stage tissue abnormalities associated with diseases such as cancer and atherosclerosis, which require micrometer-scale resolution. Here, optical coherence tomography was adapted to allow high-speed visualization of tissue in a living animal with a catheter-endoscope 1 millimeter in diameter. This method, referred to as "optical biopsy," was used to obtain cross-sectional images of the rabbit gastrointestinal and respiratory tracts at 10-micrometer resolution.

Anatomy, Cross-Sectional↗

Visual receptive field properties in kitten pretectal nucleus of the optic tract and dorsal terminal nucleus of the accessory optic tract.

1. Neurons in the pretectal nucleus of the optic tract (NOT) and dorsal terminal nucleus of the accessory optic tract (DTN) were recorded in anesthetized and paralyzed kittens on postnatal days 18 to 48 (P18-P48) as well as in adult cats. 2. Spontaneous as well as stimulus driven discharge rates of NOT-DTN neurons in the youngest kittens (P18-P23) are significantly lower than in older kittens (P27-P33) or adult cats. 3. Visual latencies of NOT-DTN neurons in P18-P23 kittens are significantly longer than in P27-P33 kittens. They further decrease as the animals reach adulthood. 4. Already in the youngest animals recorded in this experimental series (P18) NOT-DTN neurons were selective for ipsiversive horizontal stimulus movement. When expressed as the difference between response strength during stimulation in the preferred and the nonpreferred direction, P18-P23 NOT-DTN neurons are less direction selective than NOT-DTN cells in older animals. However, the normalized directional tuning expressed as percent change in discharge rate per degree change in stimulus direction away from the preferred direction (where discharge rate is set 100%) is about equal in all age groups. 5. NOT-DTN neurons in P18-P23 kittens respond to a rather limited range of stimulus speeds with an optimum at approximately 10 degrees/s. In P27-P33 kittens, NOT-DTN neurons increase their responsive range to higher stimulus speeds. As the animals approach adulthood, the range of effective stimulus speeds further broadens to include very low ones. 6. In P18-P23 kittens, the majority of NOT-DTN neurons is exclusively activated by the contralateral eye; only a few neurons receive an additional input from the ipsilateral eye. In P27-P48 kittens, the influence of the ipsilateral eye has significantly increased but with the majority of NOT-DTN cells still being dominated by the contralateral eye. Finally, in adults, a further strengthening of the ipsilateral input leads to a more binocularly balanced input to NOT-DTN cells. 7. Electrical stimulation in areas 17 and 18 did not elicit orthodromic action potentials in NOT-DTN neurons before P27. Thus the cortical input to the NOT-DTN in kittens becomes functional only at 4 wk of age. 8. In conclusion, the significant changes of visual response properties of NOT-DTN neurons coincide with the time when the cortical input to the NOT-DTN becomes functional.(ABSTRACT TRUNCATED AT 400 WORDS)

Accessory Nerve↗

Studies on the optic chiasm of the leopard frog. II. Organization of retinotectal fibers in the optic chiasm.

The organization of retinotectal fibers in the optic chiasm was investigated using horseradish peroxidase (HRP) histochemistry and electrophysiological recording. HRP injection into a small region of the tectum led to retrograde staining of labeled fibers in a circumscribed region of the chiasm and staining of labeled ganglion cells in the contralateral retina. In each instance labeled tissue was spread over a greater proportion of the area of a chiasm section than over the flattened retina. Fibers originating in central (older) retina are located in dorsal chiasm. Fibers originating in peripheral (younger) retina are located in ventral chiasm. Viewed with the electron microscope, labeled unmyelinated fibers are admixed with labeled myelinated fibers. Neuronal activity was monitored with an extracellular microelectrode from points in dorsoventral tracks in the chiasm. Multiple units were recorded at each chiasm location. Using visual stimuli, the receptive fields of the units were mapped. The fields were distributed along an arc across the visual field. At ventral chiasm recording sites the arc was in the peripheral part of the visual field. In succeeding dorsal sites the arcs were concentrically arranged so that the more dorsal the chiasm recording site, the more central was the arc in the visual field. Thus, in the optic chiasm, retinal fibers appear to be organized chronotopically but not retinotopically. Fibers of the same age but from different locations in the retina are mixed together.

Animals↗