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Modelling the elastic properties of the anterior eye and their contribution to maintenance of image quality: the role of the limbus.

PURPOSE: The elastic moduli of the cornea, sclera, and limbus for different corneal eccentricities (e) and varying levels of intraocular pressure (IOP) were modelled in order to determine how the rheological properties, especially those of the limbus, need to alter to maintain optical image quality when the eye is subjected to small variations in IOP. METHODS: Finite element analysis (FEA) was used to construct eyeball models with four different corneal eccentricities (e=0, 0.33, 0.5, 0.65). Three values for Young's modulus of the cornea were tested in all models (0.2 megapascal (MPa), 1.2 and 10 MPa). For each corneal modulus, scleral moduli of 3, 4, 5, 7, and 10 times that of the corneal modulus were selected. The limbal modulus was varied to optimise image quality of the eye model subjected to IOP variations of +/-0.8 mmHg for three different levels of IOP (8, 16, and 32 mmHg). RESULTS: The elastic modulus of the limbal ring increases with an increase in corneal modulus and rises to a peak when the ratio of scleral to corneal moduli is between 5 and 7 depending on corneal eccentricity. Different levels of IOP produce only slight differences in the relative moduli required to maintain optical image quality. CONCLUSIONS: The significance of a peak in the value of Young's modulus of the limbus is not clear but suggests that there may be an optimal limbal modulus that must be balanced with the moduli of cornea and sclera for preservation of image quality.

Biomechanical Phenomena↗

[Image of optic nerve disc with laser scanning tomography and results of static perimetry in children with juvenile glaucoma].

UNLABELLED: The aim of our research was to estimate the correlation between optic nerve head parameters examined with laser scanning ophthalmoscope and results of central, visual field (MD and PSD) in the youth and the evaluation the role of this correlation in juvenile glaucoma early diagnosis. MATERIAL: Three groups of patients. Group I consisted of 32 eyes (16 children) with juvenile glaucoma in which trabeculectomy was performed. There were 72 eyes of 32 children with glaucoma juvenile suspect in the group II. Control group (III) contained 20 eyes of 10 children without glaucoma. The age of patients ranged from 9 to 18 years. The mean intraocular pressure was 16 mmHg in the I group, 18 mmHg in the II group and 15.6 mmHg in the III group. Simple Regression Analysis of mean values of biomorphometric parameters of optic nerve head for Mean Defect of central visual field was used in all three groups. RESULTS: The statistically significant correlation between Vol. B and MD was observed in the I group. There was no such correlation in the II group, but correlation between Av. Sl. and MD was presented. In the III group mean value of MD was the smallest one and correlated with Vol. B. Statistically significant correlation between mean values of PSD and Vol. B was observed in the I and II group, between PSD and Vol. A in group III. CONCLUSION: There was the correlation between optic nerve head parameters and mean deviation of retinal sensitivity of central visual field in the youth. This examination can be helpful in early diagnosis of primary juvenile glaucoma.

Adolescent↗

Slab-like functional architecture of higher order cortical area 21a showing oblique effect of orientation preference in the cat.

Optical imaging based on intrinsic signals is a powerful tool for in vivo studying functional organization of various cortices. Here, the functional architecture of orientation-sensitive neurons in higher order extrastriate cortical area 21a was investigated in cats using optical imaging combined with electrophysiological methods. It is found that neurons in area 21 with similar preferred orientations were functionally organized into a slab-like columnar structure orthogonal to the cortical surface, and the orientation columns were distributed more densely than those in area 17. The responsiveness and activated areas of optical maps visually elicited by the horizontal and vertical gratings were always larger than those by oblique gratings in areas 21a and 17. This neural oblique effect shown in orientation maps was more significant in area 21a than that in area 17. The findings suggest a neuronal mechanism in the higher order extrastriate cortex involving the visual perceptive process of the superiority of cardinal contours.

Animals↗

Challenges and opportunities for in vivo imaging in oncology.

Advances in genomics, proteomics and technology are changing medicine in fundamental ways. There are increasing clinical and laboratory requirements to obtain cellular and molecular information in vivo. This is particularly true in oncology, where the behavior of tumor cells is inextricably linked to their milieu. If cancer cells are removed from their microenvironment, their pattern of gene expression changes. Therefore, non-invasive, quantitative means of detecting gene and protein activity are essential. In vivo imaging is one methodology for achieving this. Marked advances in tracer methods for PET scanning or single-photon nuclear medicine techniques have occurred in the past few years. MRI contrast agents that reflect physiologic information are also being developed, although larger mass quantities of injectable material are required. The useful concept of "activatable agents" was pioneered in MRI. Similarly, ultrasound and computed tomography are being re-engineered to reflect information at the cellular level. In vivo optical imaging technologies have matured to the point where they are indispensable laboratory tools for small animal imaging. Human applications are in the feasibility testing stage, and the future for clinical optical imaging techniques looks bright. Merging these molecular imaging techniques with minimally or non-invasive image-guided therapeutic delivery techniques is a subsequent goal in the fight against cancer.

Humans↗

Nerve injury affects the capillary supply in rat slow and fast muscles differently.

The goal of this study was to determine the acute effects of permanent denervation on the length density of the capillary network in rat slow soleus (SOL) and fast extensor digitorum longus (EDL) muscles and the effect of short-lasting reinnervation in slow muscle only. Denervation was performed by cutting the sciatic nerve. Both muscles were excised 2 weeks later. Reinnervation was studied 4 weeks after nerve crush in SOL muscle only. Capillaries and muscle fibres were visualised by triple immunofluorescent staining with antibodies against CD31 and laminin and with fluorescein-labelled Griffonia (Bandeira) simplicifolia lectin. A recently developed stereological approach allowing the estimation of the length of capillaries adjacent to each individual fibre (Lcap/Lfib) was employed. Three-dimensional virtual test grids were applied to stacks of optical images captured with a confocal microscope and their intersections with capillaries and muscle fibres were counted. Interrelationships among capillaries and muscle fibres were demonstrated with maximum intensity projection of the acquired stacks of optical images. The course of capillaries in EDL seemed to be parallel to the fibre axes, whereas in SOL, their preferential direction deviated from the fibre axes and formed more cross-connections among neighbouring capillaries. Lcap/Lfib was clearly reduced in denervated SOL but remained unchanged in EDL, although the muscle fibres significantly atrophied in both muscle types. When soleus muscle was reinnervated, capillary length per unit fibre length was completely restored. The physiological background for the different responses of the capillary network in slow and fast muscle is discussed.

Animals↗

[Predicting visual acuity in media opacities and uncorrectable refractive errors. Assessing so-called "retinal visual acuity"].

Three different components contribute to the modulation transfer function of the visual system: (1) formation of the optical image (refractive media, pupil); (2) scattering of light in the prereceptoral layers of the retina; (3) neuronal processing in the retina und superior visual centers. In the presence of media opacities or non-correctable refractive errors, the clinical question often arises as to which macular function can be expected under the assumption of normal optical image formation (e.g. prior to cataract extraction, corneal transplantation, or vitrectomy). Simple tests such as light projection, color discrimination, and two-point discrimination cannot provide adequate information about macular function. The same holds true for the global luminance ERG. The X-ray phosphene is obsolete. The Maddox rod (with limitations), transilluminated Amsler grid, and various entoptic phenomena (Purkinje vascular phenomenon, foveal chagrin, Haidinger's brushes, blue field phenomenon) are available as qualitative subjective tests. Maxwellian view systems with pinhole aperture (potential acuity meter PAM) and the interferometers (retinometer, visometer, SITE-IRAS interferometer) provide quantitative subjective methods. The flash VECP is primarily a qualitative objective test that allows semiquantitative acuity prediction under special conditions (unilateral opacities). Psychophysical criteria that are less affected by the quality of the retinal image show promising developments in future subjective tests, e.g. optotypes in positive contrast, optotypes or targets superimposed on a background of optical noise, or hyperacuity. Future objective test developments are pattern VECP or even pattern ERG elicited by interferometric stimulation, speckle VECP and focal ERG.

Cataract↗

Simultaneous atomic-force and two-photon fluorescence imaging of biological specimens in vivo.

We describe in this paper a home-built scanning-probe setup that combines the high spatial resolution of a commercial atomic-force microscope (AFM) with the high sensitivity and the discriminative power of a confocal two-photon fluorescence microscope. This scheme offers the ability of acquiring simultaneous, directly correlated topography and optical images with high sensitivity and resolution, and was successfully tested using model systems, such as dye-loaded latex beads. As a first biological application, we studied the (un)stacking of grana membranes in the envelope-free plant chloroplasts. The topographs showed two grana layers attached together in a "native unit" 15-16 nm thick and 4 nm protrusions on their surface, which we assign to Photosystem II reaction center. The optical imaging did not resolve single photosynthetic proteins, but helped in identifying the grana and indicated that the protein conformation and the chromophore binding are intact. Furthermore, our instrument allowed a direct comparison between the cell morphology and the distribution of the signaling protein H-Ras in living cells, i.e. mouse fibroblasts. With our approach the nanometer-scale resolving power of AFM is improved with the chemical identification capabilities of optical techniques, thus opening up interesting possibilities in various areas of research, including material and life sciences.

Animals↗

Detection of dysplastic intestinal adenomas using enzyme-sensing molecular beacons in mice.

BACKGROUND & AIMS: Proteases play key roles in the pathogenesis of tumor growth and invasion. This study assesses the expression of cathepsin B in dysplastic adenomatous polyps. METHODS: Aged Apc(Min/+) mice served as an experimental model for familial adenomatous polyposis. The 4 experimental groups consisted of (a) animals injected with a novel activatable, cathepsin B sensing near infrared fluorescence (NIRF) imaging probe; (b) animals injected with a nonspecific NIRF; (c) uninjected control animals; and (d) non-APC(Min/+) mice injected with the cathepsin B probe. Lesions were analyzed by immunohistochemistry, Western blotting, reverse transcription-polymerase chain reaction, and optical imaging. RESULTS: Cathepsin B was consistently overexpressed in adenomatous polyps. When mice were injected intravenously with the cathepsin reporter probe, intestinal adenomas became highly fluorescent indicative of high cathepsin B enzyme activity. Even microscopic adenomas were readily detectable by fluorescence, but not light, imaging. The smallest lesion detectable measured 50 microm in diameter. Adenomas in the indocyanine green and/or noninjected group were only barely detectable above the background. CONCLUSIONS: The current experimental study shows that cathepsin B is up-regulated in a mouse model of adenomatous polyposis. Cathepsin B activity can be used as a biomarker to readily identify such lesions, particularly when contrasted against normal adjacent mucosa. This detection technology can be adapted to endoscopy or tomographic optical imaging methods for screening of suspicious lesions and potentially for molecular profiling in vivo.

Adenomatous Polyps↗

Optical spectroscopic imaging for non-invasive evaluation of tissue oxygenation.

Altered rates of oxygen delivery and uptake between and possibly within different organs occur during critical illness. The mechanisms governing this heterogeneity are as yet not fully understood and techniques directed at being able to map the course of oxygen to the mitochondria to produce ATP, the main molecule needed to drive energy requiring processes in the cell, would give valuable information about the mechanisms underlying organ dysfunction during disease. Oxidative phosphorylation occurring in the mitochondria is the main site for the production of ATP in mammalian cells. Metabolic substrates, ADP and Pi, and O2 are the ingredients needed to produce ATP. Due to the central role of oxidative phosphorylation in the metabolism of the cell, much attention has been directed at developing non-invasive techniques to measure intermediates of the oxidative phosphorylation in tissue as an indication of the metabolic state of tissue. One such method enables mapping the distribution of tissue hypoxia by use of a fluorescence technique based on the measurements reduced nicotine amide dinucleotide (NADH). NADH is situated at the high-energy side of the respiratory chain and during tissue hypoxia accumulates in concentration because less NADH is oxidized to NAD+. Excitation of NADH by 366 nm light produces, unlike NAD+, fluorescence at 460 nm light. Previously, however, producing images of NADH fluorescence distribution in tissue has been limited to saline perfused in vitro models. We recently undertook to develop an NADH videoflurometer sensitive enough to NADH fluorescence in vivo (Ince C, Bruining HA (1991) Optical Spectroscopy for the measurement of tissue hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Fluorometry↗

Non-PET functional imaging techniques: optical.

The strong and steady development of diffuse optical spectroscopy and tomography as new biomedical optics technologies promises to bring these optical techniques into clinical practice. This article provides a brief review of the light-tissue interaction, the instrumentation, and the theory relevant to this field. This is followed by a survey of the three main applications: brain imaging, muscle imaging, and breast imaging. Lastly, the future outlook of the technology is presented, highlighting the new promises based on recent breakthroughs.

Brain↗

Vascular imprints of neuronal activity: relationships between the dynamics of cortical blood flow, oxygenation, and volume changes following sensory stimulation.

Modern functional neuroimaging methods, such as positron-emission tomography (PET), optical imaging of intrinsic signals, and functional MRI (fMRI) utilize activity-dependent hemodynamic changes to obtain indirect maps of the evoked electrical activity in the brain. Whereas PET and flow-sensitive MRI map cerebral blood flow (CBF) changes, optical imaging and blood oxygenation level-dependent MRI map areas with changes in the concentration of deoxygenated hemoglobin (HbR). However, the relationship between CBF and HbR during functional activation has never been tested experimentally. Therefore, we investigated this relationship by using imaging spectroscopy and laser-Doppler flowmetry techniques, simultaneously, in the visual cortex of anesthetized cats during sensory stimulation. We found that the earliest microcirculatory change was indeed an increase in HbR, whereas the CBF increase lagged by more than a second after the increase in HbR. The increased HbR was accompanied by a simultaneous increase in total hemoglobin concentration (Hbt), presumably reflecting an early blood volume increase. We found that the CBF changes lagged after Hbt changes by 1 to 2 sec throughout the response. These results support the notion of active neurovascular regulation of blood volume in the capillary bed and the existence of a delayed, passive process of capillary filling.

Animals↗

Cortical activation via an implanted wireless retinal prosthesis.

PURPOSE: To demonstrate local cortical activations in the primary visual cortex of the cat as a result of retinal electrical stimulation by means of a completely wireless-controlled, implantable retinal prosthesis in a series of acute experiments. METHODS: The transfer of energy to drive the device and signals to activate any combination of 25 retinal electrodes was achieved completely wirelessly by an external transmitter positioned in front of the eye. Individually configured electrical stimuli were applied via any combination of 25 electrodes, on sending the necessary pulse parameters to the implant. Placement of the implant onto the retinal surface was achieved after lensectomy and vitrectomy in the cat. Fixation was performed with a retinal tack. Cortical activation patterns were recorded by means of optical imaging of intrinsic signals. RESULTS: Implantation and fixation were successfully performed in three cats. Wireless activation of the implant by radiofrequency was demonstrated by recording of stimulus artifacts from the sclera. Local activation of the visual cortex measured by optical imaging of intrinsic signals revealed a shift of cortical response that was well correlated with a change in the position of the activated retinal electrodes. CONCLUSIONS: The results demonstrate the retinotopic activation of the visual cortex using a completely wireless, remote-controlled retinal implant.

Animals↗

Clinical and magnetic resonance imaging in optic neuritis.

We found 23 of 48 patients (48%) with isolated monosymptomatic optic neuritis (ON) to have 1 to several brain lesions by MRI. All the brain lesions were clinically silent and had characteristics consistent with multiple sclerosis (MS). During 4 years of follow-up, 9 patients (19%) developed definite MS on clinical grounds. Six of the converting patients had abnormal MRIs; the other 3 had MRIs that were normal both initially (when they had ON only) and when repeated after they had developed MS. The other 17 patients with abnormal MRIs have not developed symptoms or signs of MS during follow-up. Thus, an abnormal MRI does not auger development of clinical MS within a mean of 4 years, nor does a normal MRI protect against development of disseminated disease. It is not prudent to give a patient with isolated monosymptomatic ON the diagnosis of MS (probable or definite) because of an abnormal MRI (with or without other laboratory abnormalities).

Adolescent↗

Liquid crystal polarization-converting devices for edge and corner extractions of images using optical wavelet transforms.

Optical properties of radially polarized light generated by liquid crystal (LC) polarization-converting devices with two LC molecular orientations (+/-180 degrees and +/-90 degrees twist modes) are measured and the applicability to optical wavelet transforms (WTs) are discussed. It is found that the radially polarized lights in both the +/-180 degrees and +/-90 degrees twist modes can be regarded as wavelets. Based on the principle of WT, feature extractions of a simple binary image are carried out by applying the LC polarization-converting device to a shadow-casting system. Unique feature extraction properties of the shadow-casting system using the LC polarization-converting device and a LC microlens array are discussed. It is experimentally confirmed that edge and corner features are successfully extracted using the LC polarization-converting device with +/-180 degrees and +/-90 degrees twist modes, respectively.

Journal Article↗

Direct evidence for surface plasmon-mediated enhanced light transmission through metallic nanohole arrays.

This paper provides direct evidence for the role of surface plasmons in the enhanced optical transmission of light through metallic nanoscale hole arrays. Near-field optical images directly confirmed the presence of surface plasmons on gold nanohole arrays with interhole spacings larger than the surface plasmon wavelength. A simple interference model provides an intuitive explanation of the two types of fringe wavelengths observed in the near-field optical images. Far-field spectroscopy revealed a surface plasmon band that contributed a factor > 8 to the transmission enhancement. Furthermore, silicon nanohole arrays did not exhibit any features in the near-field, which demonstrates that metallic materials are necessary for enhanced light transmission through nanohole arrays.

Computer Simulation↗

New methods and uses for fast optical scanning.

Advanced optical imaging techniques used in neurobiology commonly employ fluorescent molecules for studying the structure and function of neural tissue. To obtain adequate spatio-temporal resolution, sophisticated scanning schemes are used to manage the excitation light going to and emission light coming from objects under observation. Although the fundamental principles of these techniques remain the same, such as scanning point illumination and point detection for confocal imaging, their physical implementation is the subject of technological advance, for example, the advent of inertia-free discontinuous scanning schemes. In general, the aims of these technological advances are to improve the spatio-temporal resolution of and/or reduce potential photodamage caused by optical imaging in live neural tissue. The number of recent advances in scanning methods indicates their increasing importance in imaging techniques.

Animals↗

The diagnostic value of optic nerve imaging in early glaucoma.

In the last decade, new imaging techniques have been added to conventional fundus photography and have been evaluated for use in early glaucoma. They all measure the loss of neuroretinal rim or retinal nerve fiber layer as a correlate to glaucomatous ganglion cell and axon loss. The value of optic disc photography, planimetry, laser scanning tomography, laser scanning polarimetry, and optical coherence tomography for the diagnosis of glaucomatous eyes in a preperimetric or early perimetric stage is analyzed on the basis of sensitivity, specificity, and receiver operating characteristics (ROC) curves. It becomes clear that all these techniques allow a more or less semi-automated evaluation of the optic disc and retinal nerve fiber layer but still have their limitations in the diagnosis of a very early, preperimetric stage of the glaucoma disease.

Glaucoma↗

Automated three-dimensional analysis of particle measurements using an optical profilometer and image analysis software.

The automated collection of topographic images from an optical profilometer coupled with existing image analysis software offers the unique ability to quantify three-dimensional particle morphology. Optional software available with most optical profilers permits automated collection of adjacent topographic images of particles dispersed onto a suitable substrate. Particles are recognized in the image as a set of continuous pixels with grey-level values above the grey level assigned to the substrate, whereas particle height or thickness is represented in the numerical differences between these grey levels. These images are loaded into remote image analysis software where macros automate image processing, and then distinguish particles for feature analysis, including standard two-dimensional measurements (e.g. projected area, length, width, aspect ratios) and third-dimensional measurements (e.g. maximum height, mean height). Feature measurements from each calibrated image are automatically added to cumulative databases and exported to a commercial spreadsheet or statistical program for further data processing and presentation. An example is given that demonstrates the superiority of quantitative three-dimensional measurements by optical profilometry and image analysis in comparison with conventional two-dimensional measurements for the characterization of pharmaceutical powders with plate-like particles.

Glass↗