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At least 235 records · Page 13Linked to original sources

Quantitative optical imaging of the pharmacokinetics of fluorescent-specific antibodies to tumor markers through tissuelike turbid media.

Fluorescent optical imaging of tumors deep within tissue depends on specific binding of antibodies to the tumors' surface markers. These fluorescent antibodies propagating in the vicinity of the tumor can be attached to and (or) diffused away from it. We illustrate application of a new tool, based on the random-walk theory in turbid media, for extracting the pharmacokinetics of these fluorescent antibodies by data deconvolution, excluding the effect of upper turbid tissue layers.

Animals↗

Role of climbing fibers in determining the spatial patterns of activation in the cerebellar cortex to peripheral stimulation: an optical imaging study.

The spatial patterns of activation in the rat cerebellar cortex evoked by ipsilateral face stimulation were mapped using optical imaging based on the pH sensitive dye, Neutral Red. The aims of the study were to characterize the optical responses evoked by peripheral stimulation and test the hypothesis that the resultant parasagittal banding is due to climbing fiber activation. In the anesthetized rat Crus I and II of the cerebellar cortex were stained with Neutral Red. Epi-fluorescent changes produced by a train of stimuli (5-10s and 4-20 Hz) to the ipsilateral face were monitored in time using a fast, high resolution charge-coupled device camera. The patterns of activation were quantified using a two-dimensional fast Fourier transform analysis that removed signals with high spatial frequencies and minimized the contribution of horizontal structural elements (i.e. blood vessels). The dominant spatial pattern of activation evoked by face stimulation was that of parasagittal bands. The bands were highly frequency-dependent and were elicited most strongly by stimulus frequencies in the range of 6-8 Hz. There was a large fall-off in the response for frequencies above and below. The optical signal evoked by face stimulation built up over a period of 10s and then gradually decayed. Within a folium the individual parasagittal bands exhibited some frequency and temporal specificity. Stimulation of the contralateral inferior olive also resulted in the activation of parasagittal bands with characteristics similar to the bands evoked by face stimulation, including a preferred stimulus frequency which peaked at 10 Hz. Injection of lidocaine into the contralateral inferior olive blocked the parasagittal bands evoked by ipsilateral face stimulation, while control injections of saline had no effect. The results confirm that a parasagittal banding pattern is a dominant feature of the functional architecture of the cerebellar cortex. The parasagittal banding pattern observed with Neutral Red is due primarily to the activation of climbing fiber afferents. The frequency tuning of the responses, with the preference for peripheral stimuli of 6-8 Hz, is in agreement with previous findings that the inferior olive is inherently rhythmic. These observations support the hypothesis that inferior olivary neurons are dynamically coupled into groups that activate parasagittal bands of Purkinje cells in the cerebellar cortex. The frequency tuning also supports the hypothesis that the climbing fiber system is involved with timing. Activation of this afferent system may require stimuli with appropriate frequency content and stimuli synchronized to the rhythmicity of the inferior olive.

Action Potentials↗

Three distinct auditory areas of cortex (AI, AII, and AAF) defined by optical imaging of intrinsic signals.

Using pure-tone sound stimulation, three separate auditory areas are revealed by optical imaging of intrinsic signals in the temporal cortex of the chinchilla (Chinchilla laniger). These areas correlate with primary auditory cortex (AI) and two secondary areas, AII and the anterior auditory field (AAF). We have distinguished AI on the basis of concurrent single-unit electrophysiological recording; neurons within the AI intrinsic signal region have short (<15 ms) onset-response latencies compared with neurons recorded in AII and the AAF. Within AI, AII, and AAF we have been able to define cochleotopic or tonotopic organization from the differences in intrinsic signal areas evoked by pure tones at octave-spaced frequencies from 500 Hz to 16 kHz. The maps in AI and AII are arranged orthogonal to each other.

Animals↗

Optical imaging reveals characteristic seizure onsets, spread patterns, and propagation velocities in hippocampal-entorhinal cortex slices of juvenile rats.

We have combined recordings with extracellular microelectrodes or ion-sensitive electrodes and imaging of intrinsic optical signal changes to study the spatiotemporal pattern of seizure onset and spread during development. We have employed the entorhinal cortex-hippocampus brain slice preparation of juvenile rats at different stages of postnatal maturation. Three age groups were analyzed: 4-6 days (age group I), 10-14 days (age group II), and 20-23 days (age group III). Seizure-like events were induced by perfusion of slices with Mg(2+)-free artificial cerebrospinal fluid thereby removing the Mg(2+) block of the N-methyl-d-aspartate receptor. Seizure susceptibility was highest in age groups II and III. In age group I seizure-like events originated mainly in the hippocampus proper. Seizure-like events in age group II originated mainly in the entorhinal cortex and this tendency was even more pronounced in age group III. Invasion of the hippocampal formation via the perforant path-dentate gyrus and via the subiculum was seen in age groups I and II. In contrast, in age group III the hippocampus was invaded exclusively via the subiculum pathway. The velocity of spread at which seizure-like events propagated within different regions of the slice increased with postnatal age. The characteristics of onset, spread patterns, and propagation velocities as revealed by this study allow insight into the evolving properties of the developing brain.

Action Potentials↗

Seizure spread through the life cycle: optical imaging in combined brain slices from immature, adult, and senile rats in vitro.

The semiology of epileptic seizures changes during the lifetime. Hence, it can be assumed that age-related changes in brain plasticity influence the patterns of seizure onset, spread and propagation velocity. We employed the 4-aminopyridine model of epilepsy to study seizure-like events in vitro. Combined entorhinal cortex-hippocampus brain slices from juvenile (10-13 days), adult (2-3 months), and senile (24-27 months) rats were examined using electrophysiological recordings and imaging of intrinsic optical signals. In the juvenile group, seizure onset was multifocal in all slice regions including the hippocampus. Onset in adult animals was confined to the entorhinal cortex and to neocortical regions. In slices from senile animals, there was a preponderance of seizure onsets in the neocortex. Spread patterns were highly variable in the juvenile group and became gradually more monomorph with increasing age. Propagation velocities were highest in the adult group, with maximum values of 1.51 +/- 0.68 mm/s. In the juvenile group, they amounted to 0.97 +/- 0.39 mm/s, and to 1.18 +/- 0.42 mm/s in senile slices. The results of this study indicate that age-related changes in brain plasticity profoundly affect spread patterns, which may contribute to the clinically observed changes in seizure semiology during early childhood, adulthood and senescence.

Aging↗

Optical imaging reveals reduced seizure spread and propagation velocities in aged rat brain in vitro.

Old age is the most common time for patients to develop epileptic seizures, and due to their frequent unusual clinical presentation the diagnosis of epilepsy is often delayed in the elderly. It is as yet unknown if pronounced alterations in the plastic properties of aging nervous tissue contribute to these phenomena. We employed a non-lesional in vitro epilepsy model to study seizure susceptibility, spread pattern, and propagation velocities in combined hippocampal-entorhinal cortex slices of aged rats and controls using electrophysiological methods and imaging of intrinsic optical signals. In aged animals we saw a less extensive spread of seizure-like events into areas adjacent to the region of onset of activity and a decreased spread velocity in various anatomical regions. In addition, both the activity-dependent shrinkage of the extracellular space (ECS)-volume and the extracellular K(+) concentration were significantly reduced compared to controls. The results of this study are consistent with the clinical observation that epileptic seizures in the elderly have a reduced tendency to spread. In addition, our data suggest that in the absence of structural lesions seizure susceptibility in the aging brain is not increased.

Aging↗

Optical imaging of excitation propagation evoked by stimulation to the trigeminal caudalis.

The present study reports on a characteristic spatio-temporal propagation of differential fluorescent images in the rat brain stem slice by a high-speed optical imaging technique. Coronal or sagittal slices were stained with a voltage-sensitive dye RH-414, and the superficial layer of the trigeminal caudalis (Vc) was then electrically stimulated. The marginal layer and substantia gelatinosa showed larger rostrocaudal excitation than coronal, despite a lack of tract stimulation expansion in either direction. A perfusion of 0.5 micromol/l TTX, not 10 micromol/l CNQX suppressed these propagations. These findings suggest that the superficial layer of Vc has spatial differences in neuronal excitation propagation, as evidenced by morphological observations that dendrites in the superficial layers extend in the rostrocaudal direction.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Orientation mosaic in barn owl's visual Wulst revealed by optical imaging: comparison with cat and monkey striate and extra-striate areas.

Using the technique of intrinsic signal optical imaging, orientation preference maps were obtained from the Wulst of the barn owl in the area that represents central vision, and from the visual cortices (V1 and V2) of cat and marmoset monkey. Iso-orientation domains in barn owl's visual Wulst were patch-like structures with an inter-patch distance of approximately 0.9 mm, arranged in a pinwheel-like manner around singularity points. The size of the iso-orientation domains in barn owl was larger than those found in area V1, but comparable to those found in area V2, of cat and monkey. Superficial layers of the owl visual Wulst may be equivalent to extra-striate visual areas of primates and carnivores, as already suggested by electrophysiologists discussing the much increased radial dimensions of the Wulst compared with neocortex in mammals.

Animals↗

New paradigm for optical imaging: temporally encoded maps of intrinsic signal.

We present a new technique for acquiring and analyzing intrinsic signal optical images of brain activity, using continuous stimulus presentation and data acquisition. The main idea is to present a temporally periodic stimulus and to analyze the component of the response at the stimulus frequency. Advantages of the new technique include the removal of heart, respiration, and vasomotor artifacts, a dramatic increase in spatial resolution, and a 30-fold or greater reduction in acquisition time. We also present a novel approach to localizing instantaneous neuronal responses using time-reversed stimuli that is widely applicable to brain imaging. To demonstrate the power of the technique, we present high-resolution retinotopic maps of five visual areas in mouse cortex and orientation maps in cat visual cortex.

Animals↗

Polarization filter for biomedical tissue optical imaging.

A technique based on the degree that light is depolarized when propagating inside tissues is demonstrated for optical imaging in biomedical systems. The difference in the degree of polarization of the emerging light allows for the discrimination of different types of tissues. The technique was investigated in the transillumination and back-scattering geometry and in both cases the potential of this method to image and separate out different types of tissues is demonstrated.

Animals↗

Convolution picture of the boundary conditions in photon migration and its implications in time-resolved optical imaging of biological tissues.

To model the effect of a tissue-air boundary on time-resolved optical measurements, a convolution picture is presented based on the photon migration picture. It is demonstrated that the boundary conditions (either index matched or index mismatched) can be formulated as a spatiotemporal convolution of two terms, with the first being identical to the solution in the infinite medium and the second being independent of the original light source. The conditions under which the spatial convolution part in the second term becomes negligible are also determined thus permitting the complete separation of the two terms by use of a temporal Laplace or Fourier transformation. This result is promising, since it, suggests a method of removing the effect of the boundary conditions in the applications of time-resolved optical imaging (in both the time domain and the frequency domain) in biological tissues.

Diagnostic Imaging↗

Seeing right through you: applications of optical imaging to the study of the human brain.

A new set of techniques allows for the study of brain function by near-infrared light, exploiting two optical phenomena: Changes in light absorption are determined by changes in the concentration of substances like oxy- and deoxyhemoglobin, and changes in light scattering occur as a consequence of variations of properties of membranes and corpuscles in the neural tissue. Methods based on light absorption can be used to study hemodynamic changes in the brain, whereas those based on light scattering can be used to study neuronal activity and to provide anatomical information at a cellular and subcellular level. Three optical imaging approaches can be used to study living tissue: reflection, optical coherence tomography (OCT), and photon migration. These three approaches vary in their penetration (from less than a millimeter for reflection to up to 3-5 cm for photon migration) and spatial resolution (from a micron level for reflection and OCT to a millimeter and centimeter level for photon migration). This issue includes a collection of articles reviewing applications of these technologies to the study of brain and other bodily functions in humans.

Brain↗

A novel optical imaging method for the early detection, quantitative grading, and mapping of cancerous and precancerous lesions of cervix.

This paper describes a novel optical imaging method for the in vivo early detection, quantitative staging, and mapping of cervical cancer and precancer. A multispectral imaging system was developed, which is capable of performing time-resolved imaging spectroscopy. The system was used in order to assess quantitatively the alterations in the light scattering properties of the cervix, induced selectively and reversibly in cervical neoplasias, after the application of acetic acid solution. Spectral imaging and analysis of cervix show that the maximum contrast between acetic acid responsive and nonresponsive areas is obtained at 525 +/- 15 nm, which is further enhanced by cutting off the regular component of tissue reflection, with the aid of two linear cross polarizers. Successive snapshot imaging at this spectral band enables the quantitative assessment of the temporal alterations in the intensity of the backscattered light, in any spatial location of the examined area. Initial clinical trials show that optical contrast enhancement results in a notable improvement of the sensitivity in detecting incipient lesions. It was also shown that the measured temporal characteristics of the phenomenon contain specific information, which enables the differentiation between neoplastic and nonneoplastic lesions, as well as between neoplasias of different grade. The demonstrated improved sensitivity and specificity highlight the potential of the method in both clinical research and noninvasive diagnosis.

Acetic Acid↗

Adaptive Optics Imaging of the CLASS Gravitational Lens System B1359+154 with the Canada-France-Hawaii Telescope.

We present adaptive optics imaging of the CLASS gravitational lens system B1359+154 obtained with the Canada-France-Hawaii Telescope (CFHT) in the infrared K band. The observations show at least three brightness peaks within the ring of lensed images, which we identify as emission from multiple lensing galaxies. The results confirm the suspected compound nature of the lens, as deduced from preliminary mass modeling. The detection of several additional nearby galaxies suggests that B1359+154 is lensed by the compact core of a small galaxy group. We attempted to produce an updated lens model based on the CFHT observations and new 5 GHz radio data obtained with the MERLIN array, but there are too few constraints to construct a realistic model at this time. The uncertainties inherent with modeling compound lenses make B1359+154 a challenging target for Hubble constant determination through the measurement of differential time delays. However, time delays will offer additional constraints to help pin down the mass model. This lens system therefore presents a unique opportunity to directly measure the mass distribution of a galaxy group at intermediate redshift.

Journal Article↗

Optical imaging reveals the functional architecture of neurons processing shape and motion in owl monkey area MT.

We have used optical imaging based on intrinsic signals to explore the functional architecture of owl monkey area MT, a cortical region thought to be involved primarily in visual motion processing. As predicted by previous single-unit reports, we found cortical maps specific for the direction of moving visual stimuli. However, these direction maps were not distributed uniformly across all of area MT. Within the direction-specific regions, the activation produced by stimuli moving in opposite directions overlapped significantly. We also found that stimuli of differing shapes, moving in the same direction, activated different cortical regions within area MT, indicating that direction of motion is not the only parameter according to which area MT of owl monkey is organized. Indeed, we found clear evidence for a robust organization for orientation in area MT. Across all of MT, orientation preference changes smoothly, except at isolated line- or point-shaped discontinuities. Generally, paired regions of opposing direction preference were encompassed within a single orientation domain. The degree of segregation in the orientation maps was 3-5 times that found in direction maps. These results suggest that area MT, like V1 and V2, has a rich and multidimensional functional organization, and that orientation, a shape variable, is one of these dimensions.

Animals↗

Optical imaging of the layout of functional domains in area 17 and across the area 17/18 border in cat visual cortex.

Optical imaging based on intrinsic signals was used to investigate the functional architecture of cat area 17 and the border between areas 17 and 18. The visual stimuli were gratings of different spatial frequencies moving at different angles, in different directions and with different speeds. In area 17 the iso-orientation domains were usually organized in patches rather than as elongated bands. Patches with different orientation preferences were arranged radially forming 'pinwheels' around 'orientation centres'. The pinwheel density was approximately 1.7-fold higher than in area 18. To explore clustering according to direction of motion, stimuli having the same orientation but moving in opposite directions were used. These two stimuli yielded very similar activity maps giving no indication of robust directionality clustering. Using near infrared light we were able to simultaneously image ocular-dominance and iso-orientation domains. A quantitative assessment of the relative strengths of the two subsystems showed that in upper cortical layers clustering according to orientation preference was three-fold stronger than clustering according to ocular dominance. The functional organization of spatial frequency was also examined. When we compared the activated regions by stimuli having different spatial frequency and moving at different velocities we observed that neurons were clustered also in these respects. We also investigated the functional architecture at the area 17/18 border and found that orientation maps at both sides of the border were not independent of each other. The map of area 17 smoothly blended into that of area 18. Similarly, the preferred spatial frequency of the neurons changed gradually over a distance of approximately 0.8 mm at the region of the area 17/18 border.

Animals↗

Optical imaging of spontaneous breast tumors using protease sensing 'smart' optical probes.

OBJECTIVE: The objective of this study was to determine if spontaneous breast cancer lesions can be detected by fluorescence reflectance imaging (FRI) and fluorescence mediated tomography (FMT) using protease-sensing optical probes. MATERIALS AND METHODS: Transgenic (FVB/N-TgN (WapHRAS)69Lin Y)) mice, which spontaneously develop breast cancer, were injected intravenously with a cathepsin-sensing fluorescent imaging probe. FRI and FMT were performed 24 hours after probe injection and region of interest (ROI) analysis was performed. Magnetic resonance images were acquired for anatomic coregistration with the FMT data. Moreover, correlative immunohistochemistry and fluorescence microscopy were performed. RESULTS: All tumor nodules were clearly delineated by FRI showing an average signal intensity of 380 +/- 106 AU. Similarly, tumors were clearly detected by FMT imaging. Immunohistochemistry confirmed cathepsin-B expression of primary tumors and fluorescence microscopy revealed a strong Cy 5.5 deposition in the tissue. CONCLUSIONS: FRI and FMT using "smart" protease sensing probes permits detection of experimental spontaneous breast cancers. Because the expression levels of various proteases correlate with patient outcome, this technique may not only help to detect, but also to differentiate breast cancers noninvasively.

Animals↗

Improving performance of reflectance diffuse optical imaging using a multicentered mode.

We propose a novel multicentered mode for arrangement of optical fibers to improve the imaging performance of reflectance diffuse optical imaging (rDOI). Simulations performed using a semi-infinite model show that the proposed multicentered geometries can achieve a maximum of 42 overlapping measurements. The contrast-to-noise ratio (CNR) analysis indicates that the best spatial resolution is 1 mm in radius and the contrast resolution is less than 1.05 for the multicentered geometries. The results from simulations indicate significant improvement in image quality compared to the single-centered mode and previous geometries. Additional experimental results on a single human subject lead to the conclusion that the proposed multicentered geometries are appropriate for exploring activations in the human brain. From the results of this research, we conclude that the proposed multicentered mode could advance the performance of rDOI both in image quality and practical convenience.

Algorithms↗