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At least 1,423 records · Page 79Linked to original sources

X-ray imaging of shock waves generated by high-pressure fuel sprays.

Synchrotron x-radiography and a fast x-ray detector were used to record the time evolution of the transient fuel sprays from a high-pressure injector. A succession of 5.1-microsecond radiographs captured the propagation of the spray-induced shock waves in a gaseous medium and revealed the complex nature of the spray hydrodynamics. The monochromatic x-radiographs also allow quantitative analysis of the shock waves that has been difficult if not impossible with optical imaging. Under injection conditions similar to those found in operating engines, the fuel jets can exceed supersonic speeds and result in gaseous shock waves.

Cerium↗

Anti-angiogenic cancer therapy based on integrin alphavbeta3 antagonism.

Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is a fundamental process during cancer progression. Anti-angiogenic strategies have been pursued for cancer treatment and prevention of cancer recurrence and metastasis. Integrins are a family of cell adhesion molecules consisting of two non-covalently bound transmembrane subunits (alpha and beta). Much research has demonstrated that integrin signaling plays a key role in tumor angiogenesis and metastasis. Integrin alphavbeta3 is highly expressed on activated endothelial cells and tumor cells but is not present in resting endothelial cells and most normal organ systems, which makes it a suitable target for anti-angiogenic cancer therapy. In this review we will focus on cancer therapy targeting integrin alphavbeta3 while other integrins (such as alpha5beta1, alphaIIbbeta3, alphavbeta5, alpha6beta4) will only be briefly mentioned when relevant. MEDI-522 (a humanized anti-human integrin alphavbeta3 monoclonal antibody) and Cilengitide (cyclic peptidic integrin alphavbeta3/alphavbeta5 antagonist) are currently in clinical trials for anti-angiogenic cancer therapy. Small interfering RNA (siRNA) that specifically silences integrin alphav and/or beta3 was reported to cause tumor shrinkage in preclinical xenograft models. Combination of anti-integrin alphavbeta3 therapy and other therapeutic approaches (such as chemotherapy, radiotherapy and gene therapy) has also been applied for cancer treatment. Mounting evidence suggests that there is potentially synergistic effect of combined therapeutic approaches over single modality alone. Lastly, integrin targeted delivery (drugs, genes, and radioisotopes) and imaging (optical, MRI, ultrasound, SPECT, and PET) is discussed in detail.

Angiogenesis Inhibitors↗

Application of the photon average trajectories method to real-time reconstruction of tissue inhomogeneities in diffuse optical tomography of strongly scattering media.

The possibility of application of the photon average trajectories (PAT) method to real-time reconstruction of tissue inhomogeneities in diffuse optical tomography of strongly scattering media has been substantiated. By this method, the inverse problem is reduced to solution of the integral equation with integration along a conditional PAT. Such an approach allows the standard fast algebraic algorithms commonly used in projection computed tomography to be applied to diffuse optical image reconstruction. To demonstrate the capabilities of the PAT method, a numerical experiment on cross-sectional reconstruction of cylindrical strongly scattering objects with absorbing inhomogeneities has been done. Relative shadows caused by inhomogeneities are simulated via numerical solution of the non-stationary diffusion equation. To solve the inverse problem, the QR-factorization least-squares algorithm and the multiplicative algebraic reconstruction technique are used. The results are compared with those obtained by a well-known software package for temporal optical absorption and scattering tomography based on multiple solution of the diffusion equation. It is shown that the PAT method allows reconstruction of the optical structure of objects with comparable accuracy while saving reconstruction time considerably.

Algorithms↗

Imaging of the optic disc and retinal nerve fiber layer in acute optic neuritis.

PURPOSE: To demonstrate whether optical coherence tomography (OCT-3) and scanning laser ophthalmoscopy (HRT-2) can be used to measure changes of the optic disc and peripapillary retinal nerve fiber layer (RNFL) in eyes with acute retrobulbar optic neuritis that have no clinically apparent optic disc swelling. To correlate these findings with presentation magnetic resonance imaging (MRI) of the affected optic nerve. METHODS: Eight consecutive patients with acute retrobulbar optic neuritis, who had no prior optic neuritis in either eye, were prospectively investigated at presentation and at between 1 and 3 months with clinical examination, OCT-3, HRT-2. At presentation, MRI of the optic nerves were performed in 7/8 patients. RESULTS: Compared to unaffected eyes, affected eyes without clinically seen optic disc swelling at baseline, there was a non-significant trend to increased thickness in the total RNFL, superior and nasal measurements. Baseline HRT in affected eyes showed smaller mean cup to disc ratio (p=0.003) and a smaller cup area (p=0.002) compared with the unaffected eye. The MRI-demonstrated optic nerve lesion did not correlate with OCT RNFL thickening or HRT decrease of the physiological cup. Follow-up imaging of the affected eyes showed normalization of HRT cup size parameters and OCT RNFL thickness (p<0.04). At follow-up, the temporal RNFL had thinning in 7/8 affected eyes (46.8 mum, p=0.021) compared with fellow unaffected eyes (57.8 mum), which did not change. CONCLUSION: OCT-3 and HRT demonstrate mild RNFL thickening or optic disc swelling in acute optic neuritis, even when swelling is not seen clinically. OCT-3 appears to reveal measurable RNFL thinning in the temporal quadrant after retrobulbar optic neuritis, even though vision improves. RNFL imaging may be useful in future studies of residual injury after optic neuritis.

Acute Disease↗

In vivo bioluminescence imaging.

In vivo bioluminescent imaging (BLI) is a versatile and sensitive tool that is based on detection of light emission from cells or tissues. Bioluminescence, the biochemical generation of light by a living organism, is a naturally occurring phenomenon. Luciferase enzymes, such as that from the North American firefly (Photinus pyralis), catalyze the oxidation of a substrate (luciferin), and photons of light are a product of the reaction. Optical imaging by bioluminescence allows a low-cost, noninvasive, and real-time analysis of disease processes at the molecular level in living organisms. Bioluminescence has been used to track tumor cells, bacterial and viral infections, gene expression, and treatment response. Bioluminescence in vivo imaging allows longitudinal monitoring of a disease course in the same animal, a desirable alternative to analyzing a number of animals at many time points during the course of the disease. We provide a brief introduction to BLI technology, specific examples of in vivo BLI studies investigating bacterial/viral pathogenesis and tumor growth in animal models, and highlight some future perspectives of BLI as a molecular imaging tool.

Animals↗

Magnetic resonance microscopy in cardiac development.

Magnetic resonance microscopy (MRM) is a fast and non-destructive imaging technique that can analyze the three-dimensional structure of the embryonic heart both qualitatively and quantitatively. Intravascular contrast agents have been developed to accentuate the anatomy of cardiac chambers, the cardiac outflow tract, and major arteries and veins throughout the embryonic body. MRM generates non-distorted three-dimensional data of vascular anatomy in a fraction of the time required by conventional optical image reconstruction techniques. The three-dimensional nature of these data allows the creation of visual models that can be manipulated for fast and easy interpretation of the complex relationships between heart chambers and aortic arches. This is particularly helpful because these relationships change in complex ways during development. The non-destructive nature of MRM makes it well suited for investigating rare or valuable specimens and live subjects. MRM techniques have been developed for imaging the embryo in utero and in vitro, although MRM studies of fixed embryo specimens are easier to perform and produce data with better contrast and higher resolution.

Animals↗

Electrophysiological imaging of functional architecture in the cortical middle temporal visual area of Cebus apella monkey.

We studied the spatial organization of directionally selective neurons in the cortical middle temporal visual area (area MT) of the Cebus monkey. We recorded neuronal activity from multielectrode arrays as they were stepped through area MT. The set of recording sites in each array penetration described a plane parallel to the cortical layers. At each recording site, we determined the preferred direction of motion. Responses recorded at successive locations from the same electrode in the array revealed gradual changes in preferred direction, along with occasional directional reversals. Comparisons of responses from adjacent electrodes at successive locations enabled electrophysiological imaging of the two-dimensional pattern of preferred directions across the cortex. Our results demonstrate a systematic organization for directionality in area MT of the New World Cebus monkey, which is similar to that known to exist in the Old World macaque. In addition, our results provide electrophysiological confirmation of map features that have been documented in other cortical areas and primate species by optical imaging. Specifically, the tangential organization of directional selectivity is characterized by slow continuous changes in directional preference, as well as lines (fractures) and points (singularities) that fragment continuous regions into patches. These electrophysiological methods also allowed a direct investigation of neuronal selectivities that give rise to map features. In particular, our results suggest that inhibitory mechanisms may be involved in the generation of fractures and singularities.

Animals↗

Targeting of MPEG-protected polyamino acid carrier to human E-selectin in vitro.

Targeted diagnostic agents are expected to have a significant impact in molecular imaging of cell-surface associated markers of proliferation, inflammation and angiogenesis. In this communication, we describe a new class of targeted polyamino acid-based protected graft copolymers (PGC) of poly-(L-lysine) and methyl poly-(ethylene glycol) (PGC) covalently conjugated with a monoclonal antibody fragment, F(ab')(2). We utilized targeted PGC conjugates as carriers of near-infrared indocyanine fluorophores (Cy5.5) for optical imaging of endothelial cell populations expressing IL-1 beta inducible proinflammatory marker E-selectin. We compared two conjugation chemistries, involving either introduction of sulfhydryl group to F(ab')(2), or via direct attachment of the antibody fragment directly to the chemically activated PGC. Both PGC-based targeted agents demonstrated high binding specificity (20-30 fold over non-specific uptake) and were utilized for imaging E-selectin expression on human endothelial cells activated with IL-1 beta.

Amino Acids↗

An aufwuchs chamber slide for high-resolution confocal laser scanning microscopy and stereo imaging of microbial communities in natural biofilms.

Aufwuchs chamber slides were constructed by attaching a silicone rubber gasket to a glass slide with epoxy cement. For biofilm growth, the slides were suspended in Cayuga Lake near Ithaca, NY, for 27 days. Biofilms in the chamber were stained with 0.05% acridine orange. After rinsing, the chamber was filled with molten 1% agarose to stabilize filaments and delicate polymer structures at the biofilm surface. Areas of biofilm approximately 0.5 mm thick on the inner face of the wall of the chamber were selected for side-on optical sectioning in a confocal laser scanning microscope (CLSM). Stacks of high-resolution optical images captured by the CLSM z-sectioning software, were used to create left-right stereo image pairs. At low magnification the stereo pairs showed 3-D details of the microbial landscape in the mature biofilms. Channels, pores, and other structural features of the biofilm matrix were observed in peripheral regions. Higher magnification images revealed the 3-D distribution of specific biofilm components such as filaments of sheathed bacteria projecting outward into the liquid milieu, and organic coatings, including bacterial cells on the surfaces of mineral particles.

Acridine Orange↗

Automatic decoding of sensor types within randomly ordered, high-density optical sensor arrays.

In this paper automatic sensor identification of sensor classes within a high-density randomized array, without a priori knowledge of sensor locations, is demonstrated. Two different fluorescence-based sensor types, with hundreds of replicates each, were randomly distributed into an optical imaging fiber array platform. The sensor element types were vapor-sensitive microspheres with the environmentally-sensitive fluorescent dye Nile Red adsorbed on their surface. Nile Red undergoes spectral changes when exposed to different microenvironmental polarity conditions, e.g. microsphere surface polarity or odor exposure. These reproducible sensor spectral changes, or sensor-response profiles, enable sensors within a randomized array to be grouped into categories by optical decoding methods. Two computational decoding methods (supervised and unsupervised) are introduced; equal classification rates were achieved for both. By comparing sensor responses from a randomized array with those obtained from known (control) arrays, 587 sensors were correctly classified with 99.32% accuracy. Although both methods were equally effective, the unsupervised method, which uses sensor response changes to odor exposure, is a better decoding model for the vapor-sensitive arrays studied, because it relies only on the odor-response profiles. Another decoding technique employed the emission spectra of the sensors and is more applicable to other types of multiplexed fluorescence-based arrays and assays. The sensor-decoding techniques are compared to demonstrate that sensors within high-density optical chemosensor arrays can be positionally-registered, or decoded, with no additional overhead in time or expense other than collecting the sensor-response profiles.

Journal Article↗

Characterization of cortical spreading depression by imaging of intrinsic optical signals.

The spatiotemporal progression of cortical spreading depression was investigated by imaging of activity-dependent intrinsic optical signals in rat sensorimotor cortex. In contrast to the traditional conception of a uniformly propagating event, the evolution of the spreading depression was characterized by an asymmetrical propagating wavefront and a non-uniform dispersion of optical signals behind the wavefront. As these optical signals are a reflection of underlying molecular and metabolic processes, the imaging approach to spreading depression might constitute a useful technique for investigating the functional organization as well the pathophysiology of the cerebral cortex.

Animals↗

Optical intrinsic signal imaging in a rodent seizure model.

The authors studied seizure activity with optical intrinsic signal (OIS) imaging in a rat seizure model. OIS, which measures vascular and metabolic effects associated with neuronal activity, showed significant cortical reflectance changes from penicillin-induced seizures, and correlated well with EEG epileptiform discharges. Furthermore, OIS changes often preceded initial EEG spikes. These observations suggest that OIS is well coupled with seizure activity, and may provide sensitive cues for seizure detection.

Animals↗

Rigorous analysis of shadowing effects in blazed transmission gratings.

Blazed transmission gratings have become crucial components in many hybrid optical systems. Shadowing effects are known to occur at their passive blaze facets, which may impair the system's efficiency performance. For optical designs, it is desirable to have a simple but accurate description of this phenomenon. We show that the efficiency reduction in low diffraction orders is dominated by a linear dependence on the ratio of wavelength to grating period rather than a quadratic dependence as proposed in extended scalar theory. The strength of the electromagnetic shadowing will be determined using rigorous diffraction methods and discussed with respect to imaging optical components. Results are compared to existing ray-optical models.

Journal Article↗

Aberrations of spherocylindrical spectacle lenses.

A procedure has been developed for tracing a bundle of rays through and ophthalmic lens and a schematic eye with its primary line of sight pointed through various parts of the lens. A bundle of eight rays can provide data for assessing the quality of the image formed by such a system. To test the procedure and to generate data which can help in selecting a method for evaluating image quality, we selected a single lens as an example. The lens selected has a spherical back surface (-5.00 diopters) and a toric front surface (+15.00 diopters in the vertical and /10.00 diopters in the horizontal). It has a center thickness of 5 mm and glass of index 1.523. Spot diagrams were generated with the eye pointed in various directions through the ophthalmic lens. The data generated showed that peripheral bundles which fall between the principal meridians emerge as astigmatic bundles. This leads to the proposal that blur circle theory can be used for evaluating the quality of the optical image and that it suffices in the case of a spherocylindrical ophthalmic lens to base the tolerances for refractive power on measurements made in the principal meridians.

Astigmatism↗

Automatic fluorescent tag detection in 3D with super-resolution: application to the analysis of chromosome movement.

In this paper, we describe an algorithmic framework for the automatic detection of diffraction-limited fluorescent spots in 3D optical images at a separation below the Rayleigh limit, i.e. with super-resolution. We demonstrate the potential of super-resolution detection by tracking fluorescently tagged chromosomes during mitosis in budding yeast. Our biological objective is to identify and analyse the proteins responsible for the generation of tensile force during chromosome segregation. Dynamic measurements in living cells are made possible by green fluorescent protein (GFP)-tagging chromosomes and spindle pole bodies to generate cells carrying four fluorescent spots, and observe the motion of the spots over time using 3D-fluorescence microscopy. The central problem in spot detection arises with the partial or complete overlap of spots when tagged objects are separated by distances below the resolution of the optics. To detect multiple spots under these conditions, a set of candidate mixture models is built, and the best candidate is selected from the set based on chi2-statistics of the residuals in least-square fits of the models to the image data. Even with images having a signal-to-noise ratio (SNR) as low as 5-10, we are able to increase the resolution two-fold below the Rayleigh limit. In images with a SNR of 5-10, the accuracy with which isolated tags can be localized is less than 5 nm. For two tags separated by less than the Rayleigh limit, the localization accuracy is found to be between 10 and 20 nm, depending on the effective point-to-point distance. This indicates the intimate relationship between resolution and localization accuracy.

Algorithms↗

Extraction of the average and differential dynamical response in stimulus-locked experimental data.

In optical imaging experiments of primary visual cortex, visual stimuli evoke a complicated dynamics. Typically, any stimulus with sufficient contrast evokes a response. Much of the response is the same regardless of which stimulus is presented. For instance, when oriented drifting gratings are presented to the visual system, over 90% of the response is the same from orientation to orientation. Small differences may be seen, however, between the responses to different orientations. A problem in the analysis of optical measurements of the response to stimulus in cortical tissue is the distinction of the 'global' or 'non-specific' response from the 'differential' or 'stimulus-specific' response. This problem arises whenever the signal of interest is the difference in response to various stimuli and is evident in many kinds of uni- and multivariate data. To this end, we present enhancements to a frequency-based method that we previously introduced called the periodic stacking method. These enhancements allow us to separately estimate the dynamics of both the average signal across all stimuli (the 'global' response) and deviations from the average amongst the various stimuli (the 'stimulus-specific' response) evoked in response to a set of stimuli. We also discuss improvements in the signal-to-noise ratio, relative to standard trial averaging methods, that result from the data-adaptive smoothing in our method.

Animals↗

Light microscopy of living tissue: the state and future of the art.

Since its introduction over a decade ago, confocal microscopy has found wide applicability in the microscopy of thick specimens and living tissue because of its ability to obtain images from deep inside the sample without interference from scattered or out-of-focus light. Three new instruments that are capable of imaging optically dense specimens such as the skin are considered here: a modified tandem-scanning confocal, the video-rate laser-scanning confocal microscope (both of which were developed specifically to examine skin in vivo), and the two-photon laser-scanning microscope, a design which is "inherently confocal." The tandem-scanning and video-rate confocals use visible and infra-red light, respectively, to acquire reflection images, whereas the two-photon scanner is a fluorescence microscope. The advantages and drawbacks of each of these instruments is considered.

Dermatology↗

Automated detection of diabetic retinopathy on digital fundus images.

AIMS: The aim was to develop an automated screening system to analyse digital colour retinal images for important features of non-proliferative diabetic retinopathy (NPDR). METHODS: High performance pre-processing of the colour images was performed. Previously described automated image analysis systems were used to detect major landmarks of the retinal image (optic disc, blood vessels and fovea). Recursive region growing segmentation algorithms combined with the use of a new technique, termed a 'Moat Operator', were used to automatically detect features of NPDR. These features included haemorrhages and microaneurysms (HMA), which were treated as one group, and hard exudates as another group. Sensitivity and specificity data were calculated by comparison with an experienced fundoscopist. RESULTS: The algorithm for exudate recognition was applied to 30 retinal images of which 21 contained exudates and nine were without pathology. The sensitivity and specificity for exudate detection were 88.5% and 99.7%, respectively, when compared with the ophthalmologist. HMA were present in 14 retinal images. The algorithm achieved a sensitivity of 77.5% and specificity of 88.7% for detection of HMA. CONCLUSIONS: Fully automated computer algorithms were able to detect hard exudates and HMA. This paper presents encouraging results in automatic identification of important features of NPDR.

Algorithms↗