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At least 1,405 records · Page 78Linked to original sources
PubMed2001

Brief visual stimulation allows mapping of ocular dominance in visual cortex using fMRI.

We have used high spatial resolution (0.55 mm x 0.55 mm) functional magnetic resonance imaging (fMRI) to show that when stimulus duration is brief (<6 sec), the hyperoxic hemodynamic response to neural activity can resolve the columnar architecture of ocular dominance within the primary visual cortex of humans. Our fMRI maps of ocular dominance columns are strikingly similar in appearance, size, and orientation to those reported in the literature using optical imaging of intrinsic signals (OIS) in animal cortex and histology of post-mortem human specimens. We also demonstrate that under brief visual stimulation conditions, our results are consistent over repeated experiments. This is not the case for long duration stimuli (> or = 10 sec). A simulated random data set exhibited the same response properties as maps obtained when using these prolonged visual stimuli. Our results suggest that brief visual stimulation is essential for fMRI to successfully resolve ocular dominance columns using the hyperoxic phase of the hemodynamic response to neural activity at our prescribed spatial resolution.

Brain Mapping↗
PubMed1999

Topography of contextual modulations mediated by short-range interactions in primary visual cortex.

Neurons in primary visual cortex (V1) respond differently to a simple visual element presented in isolation from when it is embedded within a complex image. This difference, a specific modulation by surrounding elements in the image, is mediated by short- and long-range connections within V1 and by feedback from other areas. Here we study the role of short-range connections in this process, and relate it to the layout of local inhomogeneities in the cortical maps of orientation and space. By measuring correlation between neuron pairs located in optically imaged maps of V1 orientation columns we show that the strength of local connections between cells is a graded function of lateral separation across cortex, largely radially symmetrical and relatively independent of orientation preferences. We then show the contextual influence of flanking visual elements on neuronal responses varies systematically with a neuron's position within the cortical orientation map. The strength of this contextual influence on a neuron can be predicted from a model of local connections based on simple overlap with particular features of the orientation map. This indicates that local intracortical circuitry could endow neurons with a graded specialization for processing angular visual features such as corners and T junctions, and this specialization could have its own functional cortical map, linked with the orientation map.

Animals↗
PubMed1996

A cell model for the detection of local image motion on the magnocellular pathway of the visual cortex.

We propose that five types of cell on the magnocellular pathway of the visual cortex constitute a function hierarchy for detecting local image motion. Lateral geniculate nucleus cells and two simple cell types analyse one-dimensional velocities perpendicular to oriented components within a moving stimulus. Combining these velocities, a group of complex cells along a sine wave fire over the cell array. The amplitude and phase of the wave correspond to the local motion's speed and direction. A motion-detection cell in the middle temporal area then extracts the wave of activated complex cells to detect the motion. Applying Hough and inverse Hough transforms and Reichardt's spatio-temporal correlation to the hierarchy, we modeled these cell types as a series of formulas that represent the synaptic functions of neurons. The modeled cells reflect the response to various stimuli in actual cells, and explain Adelson and Movshon's two-stage hypothesis neurophysiologically. The intersection-of-constraint-lines solution of the hypothesis is equivalent to the inverse Hough transform processed in motion-detection cells. We propose tests for validating this cell model using microelectrodes and optical imaging.

Geniculate Bodies↗
PubMed1991

A tandem-lens epifluorescence macroscope: hundred-fold brightness advantage for wide-field imaging.

The design of a macroscope constructed with photography lenses is described and several applications are demonstrated. The macroscope incorporates epi-illumination, a 0.4 numerical aperture, and a 40 mm working distance for imaging wide fields in the range of 1.5-20 mm in diameter. At magnifications of 1X to 2.5X, fluorescence images acquired with the macroscope were 100-700 times brighter than those obtained with commercial microscope objectives at similar magnifications. In several biological applications, the improved light collection efficiency (20-fold, typical) not only minimized bleaching effects, but, in concert with improved illumination throughput (15-fold, typical), significantly enhanced object visibility as well. Reduced phototoxicity and increased signal-to-noise ratios were observed in the in vivo real-time optical imaging of cortical activity using voltage-sensitive dyes. Furthermore, the macroscope has a depth of field which is 5-10 times thinner than that of a conventional low-power microscope. This shallow depth of field has facilitated the imaging of cortical architecture based on activity-dependent intrinsic cortical signals in the living primate brain. In these reflection measurements large artifacts from the surface blood vessels, which were observed with conventional lenses, were eliminated with the macroscope.

Animals↗
PubMed1998

Optical responses evoked by single-pulse stimulation to the dorsal root in the rat spinal dorsal horn in slice.

Neuronal excitation evoked after dorsal-root (DR) stimulation in the spinal dorsal horn (DH) of rats was visualized with a high-resolution optical-imaging method, and the propagation mechanism was studied. Transverse slices of the spinal cord were obtained from 2-4 week-old rats and stained with the voltage-sensitive dye RH-482. Single-pulse stimulation to the primary-afferent A fibers in the DR attached to the slice evoked a weak, brief (<10 ms) excitatory optical response in the laminae I and III-V. When the stimulus intensity and duration were increased to activate both A and C fibers, an additional, much greater, and longer-lasting (>100 ms) excitatory response was generated in the laminae I-III, most intensely in the lamina II. A treatment with excitatory amino acid (EAA) antagonists, dl-2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2, 3-dione, significantly reduced the amplitude and duration of the response in the lamina II. The optical response in the antagonists-containing solution was quite similar to that recorded in a Ca2+-free solution that blocked afferent synaptic transmission. The late component (>10 ms) was, however, slightly greater than that in the Ca2+-free solution. Treatment with the ATP-receptor antagonist, suramin, had a minimal effect on the response in the presence of EAA antagonists. These results suggested that the propagation of the DR-stimulus-elicited excitation was contributed largely by EAA receptors, but also by other receptors to a much lesser extent.

Animals↗
PubMed1989

Phase conjugation model for information transfer in the nervous system.

In the nervous system, dispersion in propagation time sometimes brings delay distortion or phase distortion on the information transmission. Also in the memory retrieval processes in the brain, some parts of images may be retrieved more slowly than others. For smooth control of fast movements as well as for keeping exact thinking, these distortions have to be taken out. To understand the distortion cancelling mechanism, new neural network models for compensating the phase distortion are proposed. The models stand on the concept of "phase conjugate mirror" which is used in optical image processing. Simulation studies based on the model resulted in successful cancellation of the delay dispersion involved in the information transmission in the nervous system.

Computer Simulation↗
PubMed2000

Model-based analysis of optically mapped epicardial activation patterns and conduction velocity.

A novel parametric model-based method was developed to quantify epicardial conduction patterns and velocity in an isolated Langendorff-perfused rabbit heart. The method incorporated geometric and anatomical features of the left and right ventricles into the analysis. Optical images of propagation were obtained using the voltage-sensitive dye DI-4-ANEPPS, and a high-speed digital camera. Activation maps were extracted from these images and interpolated onto a three-dimensional finite-element model of epicardial geometry and fiber structure. Activation time was expressed as a function of local parametric coordinates, and a conduction velocity vector field was computed from the gradient of the scalar field. Activation times measured using bipolar electrodes did not differ significantly from times measured using the optical mapping technique. The method was able to detect a 34% decrease in average fiber velocity and a 28% decrease in average cross-fiber velocity following the addition of 0.5 mM heptanol into the perfusate. The combination of optical mapping with a three-dimensional geometric model of the ventricles provides a new tool to quantify wave-front propagation relative to anatomy at a relatively high spatial resolution.

Animals↗
PubMed2006

Contrast-enhanced in vivo imaging of breast and prostate cancer cells by MRI.

The development of effective cancer therapies has been hampered, in part, by the inability to noninvasively follow tumor progression from the initial cancerous lesion through to metastasis. We have previously shown that superparamagnetic iron oxide particles can be used as magnetic resonance imaging contrast agents to label embryonic, mesenchymal and hematopoietic stem cells in vivo. Improving the capacity to non-invasively image cancer progression is an appealing method that could be useful for assessing the efficacy of anticancer therapies. We have established that human prostate (LNCaP, DU145, PC3), rodent prostate (TRAMPC1, YPEN-1), human breast (MDA-MB-231) and mouse mammary (Myc/VEGF) cancer cell lines were readily labeled by fluorescent superparamagnetic sub-micron particles of iron oxide (MPIOs). The MPIOs were essentially inert with respect to cell proliferation and tumor formation. Fluorescence stereomicroscopy and three dimensional magnetic resonance imaging (MRI) determined that subcutaneous, intramuscular or orthotopically implanted labeled cancer cells could be imaged, in vivo, despite in some cases being undetectable by manual palpation. The MPIO-labeled cancer cells could also be imaged, in vivo, at least 6 weeks after implantation. The fluorescent MPIOs further allowed for the ex vivo identification of tumors cells from histological sections. This study demonstrates the feasibility of using fluorescent MPIOs in prostate and breast cancer cell lines as both a negative contrast agent for in vivo MRI as well as a fluorescent tumor marker for optical imaging in vivo and ex vivo.

Animals↗
PubMed2005

Functionality of androgen receptor-based gene expression imaging in hormone refractory prostate cancer.

PURPOSE: A highly augmented, prostate-specific two-step transcriptional amplification (TSTA) method was developed with the ultimate goal of delivering an effective and safe gene-based treatment to prostate cancer patients. Because very limited treatment options are available for recurrent hormone refractory prostate cancer (HRPC), it is imperative to assess whether the prostate-specific antigen (PSA) promoter-based TSTA gene therapy will be functional in HRPC. EXPERIMENTAL DESIGN: We tested the TSTA-driven adenovirus vector on three androgen-dependent and six HRPC models. Real-time gene expression was monitored by both optical imaging and the combined modality of positron emission tomography (PET) and computed tomography. RESULTS: The TSTA-driven firefly luciferase expressing adenoviral vector was active in all androgen receptor (AR)-expressing HRPC models, but inactive in AR- and PSA-negative lines. Interestingly, the TSTA-mediated gene expression was induced by hydrocortisone in MDA PCa 2b, a cell line with mutated AR that possesses altered ligand specificity. In animal models, the TSTA-mediated optical signal was more robust in the HRPC than androgen-dependent tumors. In a parallel trend, a TSTA vector that expresses the herpes simplex virus thymidine kinase PET reporter gene also displayed more robust PET signal in the HRPC tumor. CONCLUSIONS: The activity of TSTA system is AR dependent and it recapitulates the functional status of endogenous AR. These data support the conclusion that AR function is activated in HRPC despite castrated levels of androgen. Together with the fact that majority of recurrent prostate cancers express AR and PSA, we foresee that the TSTA approach can be a promising gene therapy strategy for the advanced stages of prostate cancer.

Adenoviridae↗
PubMed2006

Peptide-labeled near-infrared quantum dots for imaging tumor vasculature in living subjects.

We report the in vivo targeting and imaging of tumor vasculature using arginine-glycine-aspartic acid (RGD) peptide-labeled quantum dots (QDs). Athymic nude mice bearing subcutaneous U87MG human glioblastoma tumors were administered QD705-RGD intravenously. The tumor fluorescence intensity reached maximum at 6 h postinjection with good contrast. The results reported here open up new perspectives for integrin-targeted near-infrared optical imaging and may aid in cancer detection and management including imaging-guided surgery.

Animals↗
PubMed2006

Non-display applications and the next generation of liquid crystal over silicon technology.

The next generation of applications for liquid crystal (LC) over silicon technology will be non-display oriented systems such as adaptive optical interconnects, optical switches and optical image processors. These new non-display applications have a different set of material parameters, which means that existing display-based materials are not entirely optimal. This is particularly the case when the application is driven by phase modulation at high frame rates (more than 1 kHz). An example of such a non-display application is in adaptive optical interconnects. Optical data transmission between printed circuit boards is becoming more and more important as the data rate in electronic systems increases into the gigahertz region. One way of avoiding the data bottlenecks in board to board interconnects is to use optical links to transmit the data. Recent research into free-space optical links has shown that a high level of manufacturing tolerance must be used to maintain the link. However, one way of avoiding these limitations is to use a reconfigurable LC phase hologram as a beam-steering element to compensate for movement between the boards and maintain the optical data path.

Journal Article↗
PubMed1998

Optical responses evoked by cerebellar surface stimulation in vivo using neutral red.

The pH sensitive dye, Neutral Red, was used with optical imaging techniques to map intracellular pH shifts elicited by cortical surface stimulation of the rat cerebellum. In the in vivo rat cerebellar cortex stained with Neutral Red, a brief stimulus train (three stimuli at 33 Hz) evoked a longitudinal beam of increased fluorescence (acidic shift) running parallel to the long axis of the folium within 100 ms of stimulation onset. A 5-10 s stimulus train (5-20 Hz) produced a biphasic optical response consisting of a beam of increased fluorescence (acidic shift) which returned to baseline in approximately 60 s, followed by a beam of decreased fluorescence (alkaline shift) for up to 120 s. A close spatial correspondence was observed between electrophysiological and optical maps of the response to surface stimulation. Application of acetazolamide enhanced the optical signals, acetabenzolamide-phenoxyethene had no effect, and the glutamate antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, decreased the optical signals. Increased fluorescence was produced by superfusion of the cerebellar cortex with acidic Ringer solutions and a decrease in fluorescence by basic solutions. These fluorescence changes also occurred in the presence of several ion channel/receptor blockers. Increased fluorescence resulted from superfusion with Ringer solution containing sodium propionate and decreased fluorescence with the transition from 5% carbon dioxide to nominally carbon dioxide-free Ringer solution. Recovery from acid loading with ammonium chloride was prevented by amiloride, an inhibitor of the Na+/H+ transporter. Application of Ringer solution with high potassium concentration produced an increase in fluorescence but only a decrease in fluorescence was detected when neuronal blockers were present, an effect consistent with a glial contribution. This decrease in fluorescence was blocked by adding barium. No epifluorescent optical signals were obtained from unstained preparations or preparations stained with cell-permeant fluorescence markers, suggesting little contribution from activity-dependent volume changes and other intrinsic signals. These results demonstrate that the Neutral Red optical signals evoked by cerebellar surface stimulation are primarily pH based and include a significant component related to intracellular pH shifts. The large amplitudes of these optical signals are particularly useful for mapping neuronal activity. Furthermore, this technique provides a novel tool for the study of pH changes in vivo at both high spatial and temporal resolution.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2001

Atomic force microscopy and its related techniques in biomedicine.

The atomic force microscope (AFM), invented in 1986, is a new instrument which provides three-dimensional surface images of samples by scanning a sharp probing tip over the sample surface. Unlike electron microscopes (EM), the AFM has the advantage to obtain high-resolution pictures not only in a vacuous but also in a non-vacuous (i.e., air or liquid) environment. This paper reviews our recent studies on the AFM application to the biomedical fields. AFM is useful for observing biological structures such as DNA, collagen molecules, collagen fibrils and chromosomes. AFM images of living cultured cells in liquid can be used for investigating the movement of cellular processes in relation to subcellular cytoskeletal elements. Recently, numerous AFM-related microscopes, or scanning probe microscopes (SPM), have been invented in parallel with the development of the AFM itself. These microscopes allow the simultaneous collection of topographical and other (e.g., viscoelastic, near-field optical) images of samples in the same portions. Thus, the combination of AFM and the other SPM has great potential for providing valuable new findings on structure and function of cells and tissues.

Animals↗
PubMedDate not supplied

Image subtraction approach to screening one-bead-one-compound combinatorial libraries with complex protein mixtures.

To screen one-bead-one-compound (OBOC) combinatorial bead libraries,(1) one generally uses tagged purified protein as the screening probe. Compound beads that interact with the purified protein are then identified, for example, via an enzyme-linked colorimetric assay, and isolated for structure determination. In this report, we demonstrate a rapid and efficient method to screen OBOC combinatorial libraries utilizing two protein mixtures as screening probes, and by comparing optical images of the beads stained by one protein mixture but not the other, ligand beads unique to one of the two protein mixtures can be identified. The significance of this method is that it allows for rapid selection of ligands directed against proteins unique to one mixture while screening out positive beads resulting from proteins common to both mixtures as well as beads that are positive as a result of interactions with chemical and protein components found in the assay itself. The method is fast, efficient, and uses off-the-shelf equipment.

Amino Acid Sequence↗
PubMed2003

Fluorescence imaging analysis of upstream regulators and downstream targets of STAT3 in melanoma precursor lesions obtained from patients before and after systemic low-dose interferon-alpha treatment.

Atypical nevi are the precursors and risk markers of melanoma. Apart from persistently monitoring these nevocytic lesions and resecting them at the earliest signs of clinical changes, there is as yet no systemic clinical treatment available to interfere with their progression to melanoma. To explore clinical treatments that might interfere with and possibly prevent atypical nevus progression, a previous study documented that 3 months systemic low-dose interferon-alpha (IFN-alpha) treatment of patients with a clinical history of melanoma and numerous atypical nevi, led to inactivation of the STAT1 and STAT3 transcription factors in atypical nevi. Based upon this finding, we initiated a second study to determine whether systemic low-dose IFN-alpha treatment also impairs the expression of upstream regulators and downstream targets of STAT1 and STAT3 in atypical nevi. Using cyanine dye-conjugated antibodies, fluorescence imaging analysis revealed expression of JAK2, JNK1, AKT1, NF-kappa B, and IFN-alpha/beta receptor in benign and atypical nevi, and early- and advanced-stage melanomas. To determine possible changes in the level of expression of these molecules in atypical nevi, excised before and after 3 months of systemic low-dose IFN-alpha treatment, newly designed optical imaging software was used to quantitate the captured fluorescent hybridization signals on a cell-by-cell basis and across an entire nevus section. The results of this analysis did not provide evidence that systemic low-dose IFN-alpha treatment alters the level of expression of upstream regulators or downstream targets of STAT1 and STAT3.

DNA-Binding Proteins↗
PubMed1994

Development of glomerular structure in rabbit olfactory bulb: three-dimensional reconstruction under the confocal laser scanning microscopy.

Confocal laser scanning imaging was used to reconstruct the three-dimensional distribution of the aggregates of olfactory receptor axons terminating within individual glomeruli in the rabbit main olfactory bulb. Two monoclonal antibodies, R2D5 and R4B12, were used to mark selectively the olfactory receptor axons. Thick coronal sections (100-200 microns in thickness) through the bulb were labeled with either of the antibodies, and then serial optical sectioning was performed to reconstruct three-dimensional optic images of the labeled axons in the glomeruli. The results revealed an intricate internal structure of the glomeruli with a mesh-like arrangement of bundles of terminal olfactory axons. Developmental study showed that primitive glomeruli lacking the internal structure of the adult form first appear in the 22-day embryo and that the characteristic internal structure of the glomeruli develops mainly during postnatal days. The confocal laser scanning image method together with specific molecular markers provides a simple tool for the three-dimensional analysis of the glomerular structure.

Age Factors↗
PubMed1977

Marginal aberrations of different bifocal-lens designs.

Marginal astigmatism and longitudinal chromatic aberration were measured (with a modified Vertometer) for +2-D bifocal lenses of different designs, base curves, and major-lens powers. At a reading level 20 deg below the pole of the major lens, deterioration of the optical image occurred and was created by the interaction of marginal astigmatism (tangential error) and lateral chromatic aberration (prismatic dispersion). Suggestions for selecting an optimal bifocal-lens design for different types of refractice error are presented.

Lenses↗
PubMed2003

Near-field microscopy: throwing light on the nanoworld.

Optical microscopy with nanoscale resolution, beyond that which is possible with conventional diffraction-limited microscopy, may be achieved by scanning a nanoantenna in close proximity to a sample surface. This review will first aim to provide an overview of the basic principles of this technique of scanning near-field optical microscopy (SNOM), before moving on to consider the most widely implemented form of this microscopy, in which the sample is illuminated through a small aperture held less than 10 nm from the sample surface for optical imaging with a resolution of ca. 50 nm. As an example of the application of this microscopy, the results of SNOM measurements of light-emitting polymer nanostructures are presented. In particular, SNOM enables the unambiguous identification of the different phases present in the nanostructures, through the local analysis of the fluorescence from the polymers. The exciting new possibilities for high-resolution optical microscopy and spectroscopy promised by apertureless SNOM techniques are also considered. Apertureless SNOM may involve local scattering of light from a sample surface by a tip, local enhancement of an optical signal by a metal tip, or the use of a fluorescent molecule or nanoparticle attached to a tip as a local optical probe of a surface. These new optical nanoprobes offer the promise of optical microscopy with true nanometre spatial resolution.

Fiber Optic Technology↗