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At least 19 recordsLinked to original sources

Cell tracking with gadophrin-2: a bifunctional contrast agent for MR imaging, optical imaging, and fluorescence microscopy.

The purpose of this study was to assess the feasibility of use of gadophrin-2 to trace intravenously injected human hematopoietic cells in athymic mice, employing magnetic resonance (MR) imaging, optical imaging (OI), and fluorescence microscopy. Mononuclear peripheral blood cells from GCSF-primed patients were labeled with gadophrin-2 (Schering AG, Berlin, Germany), a paramagnetic and fluorescent metalloporphyrin, using established transfection techniques with cationic liposomes. The labeled cells were evaluated in vitro with electron microscopy and inductively coupled plasma atomic emission spectrometry. Then, 1x10(6)-3x10(8) labeled cells were injected into 14 nude Balb/c mice and the in vivo cell distribution was evaluated with MR imaging and OI before and 4, 24, and 48 h after intravenous injection (p.i.). Five additional mice served as controls: three mice were untreated controls and two mice were investigated after injection of unlabeled cells. The contrast agent effect was determined quantitatively for MR imaging by calculating signal-to-noise-ratio (SNR) data. After completion of in vivo imaging studies, fluorescence microscopy of excised organs was performed. Intracellular cytoplasmatic uptake of gadophrin-2 was confirmed by electron microscopy. Spectrometry determined an uptake of 31.56 nmol Gd per 10(6) cells. After intravenous injection, the distribution of gadophrin-2 labeled cells in nude mice could be visualized by MR, OI, and fluorescence microscopy. At 4 h p.i., the transplanted cells mainly distributed to lung, liver, and spleen, and 24 h p.i. they also distributed to the bone marrow. Fluorescence microscopy confirmed the distribution of gadophrin-2 labeled cells to these target organs. Gadophrin-2 is suited as a bifunctional contrast agent for MR imaging, OI, and fluorescence microscopy and may be used to combine the advantages of each individual imaging modality for in vivo tracking of intravenously injected hematopoietic cells.

Animals↗

Fine-scale organization of SI (area 3b) in the squirrel monkey revealed with intrinsic optical imaging.

Optical imaging of intrinsic cortical activity was used to study the somatotopic map and the representation of pressure, flutter, and vibration in area 3b of the squirrel monkey (Saimiri sciureus) cortex under pentothal or isoflurane anesthesia. The representation of the fingerpads in primary somatosensory cortex was investigated by stimulating the glabrous skin of distal fingerpads (D1-D5) with Teflon probes (3-mm diam) attached through an armature to force feedback-controlled torque motors. Under pentothal anesthesia, intrinsic signal maps in area 3b obtained in response to stimulation (trapezoidal indentation) of individual fingerpads showed focal activations. These activations (ranging from 0.5 to 1.0 mm) were discrete and exhibited minimal overlap between adjacent fingerpad representations. Consistent with previously published maps, a somatotopic representation of the fingerpads was observed with an orderly medial to lateral progression from the D5 to D1 fingerpads. Under isoflurane anesthesia, general topography was still maintained, but the representation of fingerpads on adjacent fingers had higher degrees of overlap than with pentothal anesthesia. Multi- and single-unit recordings in the activation zones confirmed the somatotopic maps. To examine preferential inputs from slowly adapting type I (SA) and rapidly adapting type I (RA) and type II (PC) mechanoreceptors, we applied stimuli consisting of sinusoidal indentations that produce sensations of pressure (1 Hz), flutter (30 Hz), and vibration (200 Hz). Under pentothal anesthesia, activation patterns to these different stimuli were focal and coincided on the cortex. Under isoflurane, activation zones from pressure, flutter, and vibratory stimuli differed in size and shape and often contained multiple foci, although overall topography was maintained. Subtraction and vector maps revealed cortical areas (approximate 250-microm diam) that were preferentially activated by the sensations of pressure, flutter, and vibration. Multi- and single-unit recordings aided in the interpretation of the imaging maps. In conclusion, the cortical signals observed with intrinsic signal optical imaging delineated a somatotopic organization of area 3b and revealed different topographical cortical activation patterns for pressure, flutter, and vibratory stimuli. These patterns were dependent on anesthesia type. Possible relationships of these anesthesia effects to somatosensory cortical plasticity are discussed.

Anesthesia↗

Brain mapping: new wave optical imaging.

Optical imaging of intrinsic signals is widely used for high-resolution brain mapping in various animal species. A new approach using continuous data acquisition and Fourier decomposition of the signal allows for much faster mapping, opening up the possibility of applying this method to new experimental questions.

Animals↗

[Applications of optical imaging].

Optical imaging in the form of near infrared fluorescence and bioluminescence has proven useful for a wide range of applications in the field of molecular imaging. Both techniques provide a high sensitivity (in the nanomolar range), which is of particular importance for molecular imaging. Imaging with near infrared fluorescence is especially cost-effective and can be performed, in contrast to radioactivity-based methods, with fluorescence dyes that remain stable for months. The most important advantage of bioluminescence, in turn, is the lack of background signal. Although molecular imaging with these techniques is still in the experimental phase, an application of near infrared fluorescence is already foreseeable for the imaging of superficial structures.

Animals↗

Horizontal propagation of excitation in rat visual cortical slices revealed by optical imaging.

Optical imaging with high spatial and temporal resolution of neural activity in rat cortical slices was used to investigate the dynamics of signal transmission through neural connections in the visual cortex. When inhibition due to gamma-aminobutyric acid was slightly suppressed, horizontal propagation of excitation in both the supra- and infragranular layers became prominent. This propagation was not affected by vertical cuts in either the supra- or infragranular layer, which suggests that excitation is at least partially conveyed horizontally by reciprocal vertical connections between neurons in these layers.

Animals↗

Comparison of noninvasive fluorescent and bioluminescent small animal optical imaging.

Optical imaging is a modality that is cost-effective, rapid, easy to use, and can be readily applied to studying disease processes and biology in vivo. For this study, we used a green fluorescent protein (GFP)- and luciferase-expressing mouse tumor model to compare and contrast the quantitative and qualitative capabilities of a fluorescent reporter gene (GFP) and a bioluminescent reporter gene (luciferase). We describe the relationship between tumor volume, tumor mass, and bioluminescent/fluorescent intensity for both GFP and luciferase. Bioluminescent luciferase imaging was shown to be more sensitive than fluorescent GFP imaging. Luciferase-expressing tumors were detected as early as 1 day after tumor cell inoculation, whereas GFP-expressing tumors were not detected until 7 days later. Both bioluminescent and fluorescent intensity correlated significantly and linearly with tumor volume and tumor weight, as measured by caliper. Compared to bioluminescent imaging, fluorescent imaging does not require the injection of a substrate and may be appropriate for applications where sensitivity is not as critical. Knowing the relative strengths of each imaging modality will be important in guiding the decision to use fluorescence or bioluminescence.

Animals↗

Functional magnetic resonance imaging and optical imaging for dominant-hemisphere perisylvian arteriovenous malformations.

OBJECTIVE: In this study, we developed an a priori system to stratify surgical intervention of perisylvian arteriovenous malformations (AVMs) in 20 patients. We stratified the patients into three categories based on preoperative functional magnetic resonance imaging (fMRI) language activation pattern and relative location of the AVM. METHODS: In Group I (minimal risk), the AVM was at least one gyrus removed from language activation, and patients subsequently underwent asleep resection. In Group II (high risk), the AVM and language activation were intimately associated. Because the risk of postoperative language deficit was high, these patients were then referred to radiosurgery. In Group III (indeterminate risk), the AVM and language were adjacent to each other. The risk of language deficit could not be predicted on the basis of the fMRI alone. These patients underwent awake craniotomy with electrocortical stimulation mapping and optical imaging of intrinsic signals for language mapping. RESULTS: All patients from Group I (minimal risk) underwent asleep resection without deficit. All Group II (high-risk) patients tolerated radiosurgery without complication. In Group III (indeterminate risk), three patients underwent successful resection, whereas two underwent aborted resection after intracranial mapping. CONCLUSION: We advocate the use of fMRI to assist in the preoperative determination of operability by asleep versus awake craniotomy versus radiosurgery referral. In addition, we advocate the use of all three functional mapping (fMRI, electrocortical stimulation mapping, and optical imaging of intrinsic signals) techniques to clarify the eloquence score of the Spetzler-Martin system before definitive treatment (anesthetized resection versus radiosurgery versus intraoperative resection versus intraoperative closure and radiosurgery referral).

Adult↗

PET imaging and optical imaging with D-luciferin [11C]methyl ester and D-luciferin [11C]methyl ether of luciferase gene expression in tumor xenografts of living mice.

New carbon-11 labeled D-luciferin analogs D-luciferin [(11)C]methyl ester ([(11)C]LMEster, [(11)C]1) and D-luciferin [(11)C]methyl ether ([(11)C]LMEther, [(11)C]2) were synthesized in 25-55% radiochemical yield. PET studies with [(11)C]LMEster and [(11)C]LMEther demonstrate a lower retention of the C-11 label at 45 min post-injection in luciferase expression tumor. Optical imaging with unlabeled substrate D-luciferin and radiotracers [(11)C]LMEster and [(11)C]LMEther gave tumor luciferase images within a few minutes of photon counting.

Animals↗

Comparison of two tricarbocyanine-based dyes for fluorescence optical imaging.

Optical technologies are evolving in many biomedical areas including the biomedical imaging disciplines. Regarding the absorption properties of physiological molecules in living tissue, the optical window ranging from 700 to 900 nm allows to use fluorescent dyes for novel diagnostic solutions. Here we investigate the potential of two different carbocyanine-based dyes fluorescent in the near infrared as contrast agents for in vivo imaging of subcutaneously grown tumours in laboratory animals. The primary aim was to modify the physicochemical properties of the previously synthesized dye SIDAG to investigate the effect on the in vivo imaging properties.

Animals↗

New Al2O3:C,Mg crystals for radiophotoluminescent dosimetry and optical imaging.

Optical and dosimetric properties of a new radiophotoluminescent material based on aluminum oxide doped with carbon and magnesium (Al2O3:C,Mg) and having aggregate oxygen vacancy defects are presented. The Al2O3:C,Mg crystals are characterized by several new optical absorption and emission bands. It is suggested that the main optical properties of this material are due to the formation of aggregate defects composed of two oxygen vacancies and two Mg-impurity atoms. Radiation-induced optical absorption bands are centered at 335 and 620 nm and produce fluorescent emission at 750 nm with a 75 +/- 5 ns lifetime. The dose measurements are performed by illumination of the Al2O3:C,Mg crystal with 335 nm or 650 nm light and by measuring the intensity of the 750 nm fluorescence. The detector material is insensitive to room light before and after the irradiation and the traps are stable up to 600 degrees C. A dose measurement range between 5 mGy and 200 Gy, suitable for therapeutic radiology applications, was demonstrated. The short luminescent lifetime and nondestructive readout is favorable for imaging applications.

Aluminum Oxide↗

Signal propagation from piriform cortex to the endopiriform nucleus in vitro revealed by optical imaging.

Optical signals were recorded from the posterior piriform cortex slices of guinea pigs stained with a voltage-sensitive dye to analyse spatio-temporal spread of neural activity evoked by electrical stimulation of afferent fibers. After propagation of activity along layers II and III, an isolated island of activity appeared deep to the layer III and moved caudally. Histological inspection revealed that the area where the island appeared corresponded well to the endopiriform nucleus. The present results provided an evidence for one of the main outflows of olfactory information from the posterior piriform cortex.

Animals↗

Development of biological tissue-equivalent phantoms for optical imaging.

Optical characteristics of freshly isolated tissues depend on their color and composition. The surface backscattered profile, which account for the tissue compositional variation in fresh excised sheep's heart, lungs, bone and muscle, were measured by multi-probe reflectometer. Optical phantoms were prepared from paraffin wax by mixing a specific combination of wax color materials till the surface backscattered profile of these matched with that of the biological tissues. The optical parameters absorption coefficient (micro(a)), reduced scattering coefficient (micro(s)) and anisotropy factor (g) of these phantoms, are the same as that of biological tissues and are obtained by matching their surface backscattered profiles with that as simulated by Monte Carlo procedure. The maximum and minimum values of absorption coefficient are for the phantoms of lungs (1.0 cm(-1)) and muscle (0.02 cm(-1)), whereas, for scattering coefficient these values are for muscle (21.2 cm(-1)) and bone (13.08 cm(-1)).

Animals↗

Special report: Noninvasive multi-parameter functional optical imaging of the eye.

Advancement in the treatment of blindness depends on the development of new technologies that enable early detection, follow-up, and treatment of disease. The authors describe direct, noninvasive imaging of four parameters: blood flow, blood oximetry, metabolic state, and hidden vasculature, particularly capillaries. These are functional parameters of the retina known to be degraded by retinal disease. The new Retinal Function Imager (Optical Imaging, Ltd., Rehovot, Israel) can image all four parameters as intrinsic reflectance intensity differences over the retina's surface. During the past 2 decades, imaging of small optical signals has been a powerful tool for high-resolution functional mapping in the neocortex. In this article, this technology is applied to the retina and demonstrates a general tool for noninvasively probing retinal function in many modalities. Imaging functional changes before anatomic consequences arise holds promise as a powerful tool for early diagnosis and treatment of retinal disease.

Adult↗

[Progress in optical imaging].

Different optical imaging technologies have significantly progressed over the last years. Besides advances in imaging techniques and image reconstruction, new "smart" optical contrast agents have been developed which can be used to detect molecular targets (such as endogenous enzymes) in vivo. The combination of novel imaging technologies coupled with smart agents bears great diagnostic potential both clinically and experimentally. This overview outlines the basic principles of optical imaging and summarizes the current state of the art.

Animals↗

Voltage-sensitive dye versus intrinsic signal optical imaging: comparison of optically determined functional maps from rat barrel cortex.

Using intrinsic and voltage-sensitive dye optical imaging methods, somatosensory-evoked neural activity and the consequent metabolic activity were visualized in the barrel cortex at high temporal and spatial resolution. We compared maps of neural and metabolic activity from the perspective of spatial distribution in the cortex. There was good agreement between the two functional maps, if the extent of metabolic activity before a prominent increase in cerebral blood volume (CBV) was assessed. This result indicates that oxygen consumption occurs before CBV changes, in approximately the same cortical area as that in which the preceding neural activity was evoked. This also suggests that the intrinsic signal reflects subthreshold synaptic activity, as well as spiking activity, which is similar to the dye-related signals.

Afferent Pathways↗

Calculating direction maps from intrinsic signals revealed by optical imaging.

Previous optical imaging studies used the vector-summation (VS) method for calculating direction and orientation preference maps. However, for direction maps it often resulted in direction vectors which showed a steep angle to that of orientation vectors violating the 'aperture rule'. The present report provides a simple procedure for calculating direction preference maps using the 'electro- physiologist's ear' approach. This approach takes into account the strongest directional response component (vector-maximum, VM) in each pixel of the optical image, reminiscent of how electro- physiologists determine direction preference by audio-monitoring of the firing rate of neurons. The major advantage of this method is that the orthogonal relationship between orientation and direction preference vectors is preserved and that for most image pixels direction preference can be faithfully described by a single vector parameter. Here we used the VM method for calculating direction and the VS method for calculating orientation preference maps and quantified their spatial relationship. The results showed that, typically, an iso-orientation domain contained a pair of patches that preferred opposite directions orthogonal to the orientation. Rate-of-change maps for direction revealed that virtually all direction discontinuity lines linked orientation centres. Close to orientation centres, direction discontinuity lines ran chiefly parallel with iso-orientation lines, whereas more remotely they had either parallel or perpendicular courses.

Animals↗

Applicability of deconvolution and nonlinear optimization for reconstructing optical images from near-field optical microscope images.

We have made a computer reconstruction of a nanometric optical image of a sample from an observed near-field optical image. The near-field microscope image used for investigation was obtained numerically in three dimensions with the finite-difference time-domain (FDTD) method. The sample is dielectric substrate containing nanometric two strips made of dielectric or metal. Deconvolution with non-negativity constraint is used to reconstruct the nanometric structure of dielectric strips, while nonlinear optimization is used to reconstruct the metallic strips. The difference in choice of reconstruction method between two samples comes from the difference in degree of interaction or multiple scattering of the sample structure and the probe. It is shown in the results, the resolution limit attainable in deconvolution is as fine as the size of aperture of probe.

Journal Article↗

Noninvasive measurement of neuronal activity with near-infrared optical imaging.

Diffuse optical imaging (DOI) alone offers the possibility of simultaneously and noninvasively measuring neuronal and vascular signals in the brain with temporal resolution of up to 1 ms. However, while optical measurement of hemodynamic signals is well established, optical measurement of neuronal activation (the so-called fast signal) is just emerging and requires further optimization and validation. In this work, we present preliminary studies in which we measured the fast signal in 10 healthy volunteers during finger-tapping, tactile stimulation, and electrical median nerve stimulation. We used an instrument (CW4) with 8 source (690 and 830 nm) and 16 detector positions-more optodes than the instruments in previously reported studies. This allowed us to record the ipsilateral and contralateral sensorimotor cortex simultaneously, while at the same time measuring the evoked hemodynamic response. We used an acquisition time of 25 ms per image; after averaging approximately 1000 events, the signal-to-noise ratio was approximately 10(4). Since the expected relative intensity changes due to the fast signal (approximately 10(-3)) are smaller than the relative intensity changes due to physiological effects (approximately 10(-1)), we enhanced the suppression of competing signals such as the heartbeat-associated intensity changes, and established five criteria with which to assess the robustness of the fast signal. We detected the fast signal in 43% of the measurements during finger-tapping, 60% of those during tactile stimulation, and 23% of those during electrical median nerve stimulation. The relative changes in intensity associated with the fast signal were approximately 0.07% and the latency of the signal was approximately 100 ms.

Adult↗