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At least 55 records · Page 3Linked to original sources
PubMedDate not supplied

A new class of Gd-based DO3A-ethylamine-derived targeted contrast agents for MR and optical imaging.

Synthetic bifunctional probes based on [4,7-bis-carboxymethyl-10-(2-aminoethyl)-1,4,7,10-tetraaza-cyclododec-1-yl]-acetic acid (DO3A-ethylamine) preloaded with gadolinium were prepared for applications in targeted magnetic resonance imaging (MRI) and optical imaging. A convenient route of synthesis is reported, which allowed conjugation of this probe with biomolecules for the preparation of model MR contrast agents for targeted imaging. The conjugated probes have the following interesting properties: GdDO3A-ethylamido-biotin (Gd-9) can be used for targeted imaging using an avidin-biotin system. The fluorescent probe GdDO3A-ethylthiourea-fluorescein (Gd-12) is a bimodal compound, which can be used for both MR and optical imaging. The precursors, DO3A-ethylamidopropyl-maleimide and DO3A-ethyl-isothiocyanate contain a highly reactive moiety, which can interact with free SH-terminals and N-terminals of biological molecules, respectively. In vitro MR relaxivity studies were performed at 300 MHz using different concentrations and chemical environments. MR relaxivity for ligand Gd-9 at pH 7.4, r1 was (3.32 +/- 0.03) s(-1) mM(-1) and r2 was (5.02 +/- 0.14) s(-1) mM(-1). For the mixture of Gd-9 with avidin, at pH 7.4, relaxivity increased linearly with the avidin concentration. A relaxivity enhancement of 45% for r1 and more than 400% for r2 with respect to the unbound biotinylated Gd3+ complex was found at a ratio of 4:1. MR relaxivity for ligand Gd-12, r1 was (5.36 +/- 0.05) s(-1) mM(-1) at pH 7.4. Fluorescence microscopy and spectroscopy of Gd-12-labeled 3T3 mouse fibroblasts showed a concentration-dependent intracellular uptake, accompanied by a slight dose-dependent increase in toxicity up to 150 microM. MR studies on labeled cells indicated a contrast enhancement in both T1- and T2-weighted images by the internalized compound, with the effect being more pronounced in T2-weighted images. Our results indicate that DO3A-ethylamine is a multipurpose precursor, from which various targeted contrast agents can be synthesized after a single-step conjugation with organic/bioorganic molecules.

Animals↗
PubMed2004

Optical imaging of mice in oncologic research.

Optical imaging is a highly sensitive technique for detecting a variety of cellular, molecular and tissue processes in vivo and in vitro. Optical imaging systems are well suited to in vivo imaging in the laboratory setting for a variety of reasons, including low cost, ease of use and efficiency of imaging. Commercial availability of optical imaging detector systems has allowed more investigators to explore their use for a variety of applications. The ever-increasing number of naturally occurring and modified near-infrared probes, photoproteins, and fluorescent probes provide opportunities to improve detection and labeling. Technical advances in detector systems and imaging software have allowed the refinement of established techniques. Furthermore, the availability of mice genetically altered to express photo and fluorescent proteins have spurred tremendous growth in this area of research.

Animals↗
PubMed1999

Simulation of scanning laser techniques for optical imaging of blood-related intrinsic signals.

Optical imaging of intrinsic signals detects neural activation patterns by taking video images of the local activity-related changes in the light intensity reflected from neural tissue (intrinsic signals). At red light (605 nm), these signals are caused mainly by local variations of the tissue absorption following deoxygenation of blood. We characterize the image generation process during optical imaging by Monte Carlo simulations of light propagation through a homogeneous model tissue equipped with a local absorber. Conventional video imaging and scanning laser imaging are compared. We find that, compared with video imaging, scanning laser techniques drastically increase both the contrast and the lateral resolution of optical recordings. Also, the maximum depth up to which the signals can be detected is increased by roughly a factor of 2 when scanning laser optical imaging is used. Further, the radial profile of the diffuse-reflectance pattern for each pixel is subject to changes that correlate with the depth of the absorber within the tissue. We suggest a detection geometry for the online measurement of these radial profiles that can be realized by modifying a standard scanning laser ophthalmoscope.

Computer Simulation↗
PubMed2003

Spatiotemporal analysis of optical imaging data.

Previous methods for analyzing optical imaging data have relied heavily on temporal averaging. However, response dynamics are rich sources of information. Here, we develop and present a method that combines principal component analysis and multitaper harmonic analysis to extract the statistically significant spatial and temporal response from optical imaging data. We apply the method to both simulated data and experimental optical imaging data from the cat primary visual cortex.

Animals↗
PubMed2005

Optical imaging in drug discovery and diagnostic applications.

Optical imaging combines a variety of different diagnostic modalities which have shown great promise for biomedical imaging and as a tool in drug discovery. Several different principles to identify and characterize fundamental processes at the organ, tissue, cellular and molecular level have been exploited, supported by the design of novel imaging agents and biomolecular reporter systems. New optical imaging procedures will contribute considerably to the improvement of the knowledge of disease processes and the more efficient evaluation of drug effects in living laboratory animals. They may also find new diagnostic and therapeutic applications in human clinical practices. These techniques can be used in the field of molecular imaging to allow both visualization and quantification of molecular events associated with disease in a non-invasive and radiation-free manner using relatively simple equipment. The different aspects of imaging instrumentation and methods; the achievements in synthesis and evaluation of novel imaging agents and biochemical reporters; as well as the opportunities of optical imaging in drug delivery, drug discovery and imaging diagnostics will be discussed in this review article.

Animals↗
PubMed2001

The cortical representation of the hand in macaque and human area S-I: high resolution optical imaging.

High-resolution images of the somatotopic hand representation in macaque monkey primary somatosensory cortex (area S-I) were obtained by optical imaging based on intrinsic signals. To visualize somatotopic maps, we imaged optical responses to mild tactile stimulation of each individual fingertip. The activation evoked by stimulation of a single finger was strongest in a narrow transverse band ( approximately 1 x 4 mm) across the postcentral gyrus. As expected, a sequential organization of these bands was found. However, a significant overlap, especially for the activated areas of fingers 3-5, was found. Surprisingly, in addition to the finger-specific domains, we found that for each of the fingers, weak stimulation activated also a second "common patch" of cortex, located just medially to the representation of the finger. These results were confirmed by targeted multiunit and single-unit recordings guided by the optical maps. The maps remained very stable over many hours of recording. By optimizing the imaging procedures, we were able to obtain the functional maps extremely rapidly (e.g., the map of five fingers in the macaque monkey could be obtained in as little as 5 min). Furthermore, we describe the intraoperative optical imaging of the hand representation in the human brain during neurosurgery and then discuss the implications of the present results for the spatial resolution accomplishable by other neuroimaging techniques, relying on responses of the microcirculation to sensory-evoked electrical activity. This study demonstrates the feasibility of using high-resolution optical imaging to explore reliably short- and long-term plasticity of cortical representations, as well as for applications in the clinical setting.

Action Potentials↗
PubMed2005

Functional representation of the finger and face in the human somatosensory cortex: intraoperative intrinsic optical imaging.

We applied the intrinsic optical imaging technique to the human primary somatosensory cortex during brain tumor/epilepsy surgery for nine patients. The cortical surface was illuminated with a Xenon light through an operating microscope, and the reflected light, which passed through a 605 nm bandpass filter, was detected by a CCD camera-based optical imaging system. Individual electrical stimulation of five digits induced changes in the reflected light intensities. Visualizing the intrinsic optical responses, we constructed maps of finger representation in Brodmann's area 1. In the maps, response areas of Digits I to V were sequentially aligned along the central sulcus in the crown of the postcentral gyrus from the latero-inferior region (Digit I) to the medio-superior region (Digit V). The neighboring response areas partially overlapped each other, as previously described in the monkey somatosensory cortex. Similar results were obtained in the face region with stimulation of the three branches of the trigeminal nerve. These results suggest that the overlap of the response areas is a common feature in the somatosensory cortex not only in monkeys, but also in humans.

Adult↗
PubMed2005

Neurovascular coupling investigated with two-dimensional optical imaging spectroscopy in rat whisker barrel cortex.

Optical imaging slit spectroscopy is a powerful method for estimating quantitative changes in cerebral haemodynamics, such as deoxyhaemoglobin, oxyhaemoglobin and blood volume (Hbr, HbO2 and Hbt, respectively). Its disadvantage is that there is a large loss of spatial data as one image dimension is used to encode spectral wavelength information. Single wavelength optical imaging, on the other hand, produces high-resolution spatiotemporal maps of brain activity, but yields only indirect measures of Hbr, HbO2 and Hbt. In this study we perform two-dimensional optical imaging spectroscopy (2D-OIS) in rat barrel cortex during contralateral whisker stimulation to obtain two-dimensional maps over time of Hbr, HbO2 and Hbt. The 2D-OIS was performed by illuminating the cortex with four wavelengths of light (575, 559, 495 and 587 nm), which were presented sequentially at a high frame rate (32 Hz). The contralateral whisker pad was stimulated using two different durations: 1 and 16 s (5 Hz, 1.2 mA). Control experiments used a hypercapnic (5% CO2) challenge to manipulate baseline blood flow and volume in the absence of corresponding neural activation. The 2D-OIS method allowed separation of artery, vein and parenchyma regions. The magnitude of the haemodynamic response elicited varied considerably between different vascular compartments; the largest responses in Hbt were in the arteries and the smallest in the veins. Phase lags in the HbO2 response between arteries and veins suggest that a process of upstream signalling maybe responsible for dilating the arteries. There was also a consistent increase in Hbr from arterial regions after whisker stimulation.

Algorithms↗
PubMed1993

Optical imaging of bipolar cortical stimulation.

In order to better understand the degree of cortical activation that occurs during bipolar surface stimulation, the authors stimulated monkey visual cortex while monitoring the degree of activation with optical imaging. Optical imaging of intrinsic signals in monkey visual cortex during visual stimulation resulted in functional maps of ocular dominance and orientation selectivity. After functional maps of ocular dominance and orientation preference were obtained, bipolar surface stimulation was applied to activate just the cortical areas around the bipolar electrodes. Graded responses to changes in the stimulation intensity and duration were found. These findings demonstrate the reliability of bipolar cortical surface stimulation in localizing functional regions of cortex. The area of activation, at least in the region around the bipolar stimulating electrodes, did not appear to activate nearby ocular dominance columns or orientation patches. Intraoperative bipolar surface stimulation continues to be a consistently reliable technique for localizing rolandic cortex and essential language sites.

Animals↗
PubMed2003

Multimodal optical imaging.

The recent resurgence of interest in the use of intravital microscopy in lung research is a manifestation of extraordinary progress in visual imaging and optical microscopy. This review evaluates the tools and instrumentation available for a number of imaging modalities, with particular attention to recent technological advances, and addresses recent progress in use of optical imaging techniques in basic pulmonary research.1 Limitations of existing methods and anticipated future developments are also identified. Although there have also been major advances made in the use of magnetic resonance imaging, positron emission tomography, and X-ray and computed tomography to image intact lungs and while these technologies have been instrumental in advancing the diagnosis and treatment of patients, the purpose of this review is to outline developing optical methods that can be evaluated for use in basic research in pulmonary biology.

Animals↗
PubMed2002

What can we learn about cell signalling by combining optical imaging and patch clamp techniques?

Optical imaging is a powerful technique with which to investigate the activity, distribution and movement of biomolecules. The increased resolution of images obtained with confocal microscopy now allows us to visualize the signalling events in individual intracellular organelles. Local photobleaching and uncaging of caged compounds enable investigators to control the activity of many biologically important molecules in small localized regions of both cytosol and internal spaces of cellular organelles. Uncaging and photobleaching conveniently complement laser scanning confocal microscopy. The whole-cell recording configuration of the patch-clamp technique has been widely used not only to measure ionic currents, but also to control the concentration of important molecules in the cytosol. The cell-attached configuration of patch clamp was utilized for local stimulation of the cell and local delivery of the second messengers. This paper describes the advantages of combining patch-clamp and optical imaging methods as well as some of the recent achievements using this approach.

Calcium Signaling↗
PubMed1993

Characterization of functional organization within rat barrel cortex using intrinsic signal optical imaging through a thinned skull.

We used optical imaging of intrinsic signals to characterize the functional representations of mystacial vibrissae (whiskers) in rat somatosensory cortex. Stimulation of individual whiskers for 2 s at 5 Hz resulted in a discrete area of functional activity in the cortex. Images of whisker representations were collected both through the dura and through a thinned skull. We characterized the functional representation of a whisker both spatially and temporally with two-dimensional images and three-dimensional surface plots of intrinsic signal development in the cortex in response to whisker stimulation. Single unit recordings verified that the representation of the whisker obtained with optical imaging corresponded with the electrophysiological response area of that whisker in the cortex. Lesions in the center of the functional activity were found to be in the center of the dense cytochrome oxidase patch for the corresponding whisker. In addition, a 3 x 3 matrix of whiskers was stimulated and the distances between the centers of the imaged representations and the distances between the centers of the layer IV cytochrome oxidase staining of the nine whiskers were found to be highly correlated (r = 0.98). This study shows a striking correspondence among imaging, physiology, and anatomy in the rat somatosensory cortex. Furthermore, the ability to use optical imaging through a thinned skull should allow investigations into the long-term changes in a sensory representation within a single animal.

Animals↗
PubMed1995

BOLD based functional MRI at 4 Tesla includes a capillary bed contribution: echo-planar imaging correlates with previous optical imaging using intrinsic signals.

We show that the EPI time course in functional MR imaging at 4 Tesla displays a multiphasic response in response to photic stimulation. Focal areas of gray matter display an initial negative change in signal intensity that reaches a maximum of 1% about 2 s after the onset of photic stimulation. This component then changes sign, reaching a positive maximum about 5 s after the onset of the stimulus. Other areas, including those where draining veins are visible, show only a positive signal change, reaching a maximum of about 6% after the onset of the visual stimulus. These time constants are in very good agreement with published data obtained with intrinsic optical mapping techniques, where a deoxygenation phase has been shown to occur in functionally specific cortical columns, followed by an increase in blood volume which is more distributed in nature. Thus, we believe there is strong evidence that a sensitivity to capillary oxygenation state is present in high S/N functional MR images obtained with EPI at 4 T.

Artifacts↗
PubMed2006

[Progress in tissue optical imaging].

In this review, we introduce the basic principle and technology progress of tissue optical imaging from both diffuse optical imaging and coherence domain imaging, which include the continuous-wave imaging, time-resolved optical tomography, diffuse photon density waves tomography, ultrasound-modulated optical tomography, optical coherence tomography and laser speckle imaging. Applications of optical imaging in brain activity and tissue function are also discussed.

Brain↗
PubMed1994

Non-recursive linear algorithms for optical imaging in diffusive media.

Optical imaging has been used to image phantoms, animals, and humans. It offers the potential for the production of functional images of tissues, such as oxygenation of brain during stroke. Fast algorithms are needed to allow diagnostically useful images to be generated under realistic conditions, including the likelihood that transmission geometries will not be possible. We proposed a linear algorithm, while less than ideal, may allow rapid reconstruction of images and avoid the pitfalls of recursive, nonlinear solutions. Such techniques may also facilitate the use of varied but physiologic imaging geometries. We found that linear backprojection tomography is feasible for clinical use. Conversion of the present mechanically scanning device to a clinical scanner should be possible with retention of the current processing algorithms. Such a clinical scanner should ultimately be able to generate images in less than one minute with centimeter resolution at the center of living human brain.

Algorithms↗
PubMedDate not supplied

Functional architecture of cortex revealed by optical imaging of intrinsic signals.

Optical imaging of cortical activity offers several advantages over conventional electrophysiological and anatomical techniques. One can map a relatively large region, obtain successive maps to different stimuli in the same cortical area and follow variations in response over time. In the intact mammalian brain this imaging has been accomplished with the aid of voltage sensitive dyes. However, it has been known for many years that some intrinsic changes in the optical properties of the tissue are dependent on electrical or metabolic activity. Here we show that these changes can be used to study the functional architecture of cortex. Optical maps of whisker barrels in the rat and the orientation columns in the cat visual cortex, obtained by reflection measurements of the intrinsic signal, were confirmed with voltage sensitive dyes or by electrophysiological recordings. In addition, we describe an intrinsic signal originating from small arteries which can be used to investigate the communication between local neuronal activity and the microvasculature. One advantage of the method is that it is non-invasive and does not require dyes, a clear benefit for clinical applications.

Animals↗
PubMed2004

Bhattacharyya distance as a contrast parameter for statistical processing of noisy optical images.

In many imaging applications, the measured optical images are perturbed by strong fluctuations or boise. This can be the case, for example, for coherent-active or low-flux imagery. In such cases, the noise is not Gaussian additive and the definition of a contrast parameter between two regions in the image is not always a straightforward task. We show that for noncorrelated noise, the Bhattacharyya distance can be an efficient candidate for contrast definition when one uses statistical algorithms for detection, location, or segmentation. We demonstrate with numerical simulations that different images with the same Bhattacharyya distance lead to equivalent values of the performance criterion for a large number of probability laws. The Bhattacharyya distance can thus be used to compare different noisy situations and to simplify the analysis and the specification of optical imaging systems.

Journal Article↗
PubMed1997

Optical imaging of anatomical maps derived from magnetic resonance images using time-independent optical sources.

We present a model suitable for computing images of absorption cross sections of thick tissue structures illuminated at near infrared (NIR) wavelengths from tomographic projection data. Image reconstruction is accomplished by solving a system of linear equations derived from transport theory. Reconstruction results using different algebraic solvers are shown for anatomical maps of the breast, derived from magnetic resonance imaging data, containing two simulated pathologies, in which case qualitatively good reconstructions were obtained. Evaluation of magnetic resonance (MR) data to optimize NIR optical tomographic imaging methods and to assess the feasibility of a combined MR-optical measurement scheme is discussed.

Adipose Tissue↗