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PubMed2003

Processing deficits in primary visual cortex of amblyopic cats.

Early esotropic squint frequently results in permanent visual deficits in one eye, referred to as strabismic amblyopia. The neurophysiological substrate corresponding to these deficits is still a matter of investigation. Electrophysiological evidence is available for disturbed neuronal interactions in both V1 and higher cortical areas. In this study, we investigated the modulation of responses in cat V1 to gratings at different orientations and spatial frequencies (SFs; 0.1-2.0 cycles/degrees) with optical imaging of intrinsic signals. Maps evoked by both eyes were well modulated at most spatial frequencies. The layout of the maps resembled that of normal cats, and iso-orientation domains tended to cross adjacent ocular dominance borders preferentially at right angles. Visually evoked potentials (VEPs) were recorded at SFs ranging from 0.1 to 3.5 cycles/degrees and revealed a consistently weaker eye for the majority of squinting cats. At each SF, interocular differences in VEP amplitudes corresponded well with differences in orientation response and selectivity in the maps. At 0.7-1.3 cycles/ degrees, population orientation selectivity was significantly lower for the weaker eye in cats with VEP differences compared with those with no VEP amplitude differences. In addition, the cutoff SF, above which gratings no longer induced orientation maps, was lower for the weaker eye (> or =1.0 cycles/degrees). These data reveal a close correlation between the loss of visual acuity in amblyopia as assessed by VEPs and the modulation of neuronal activation as seen by optical imaging of intrinsic signals. Furthermore, the results indicate that amblyopia is associated with altered intracortical processing already in V1.

Amblyopia↗
PubMed1996

Functional organization for direction of motion and its relationship to orientation maps in cat area 18.

The goal of this study was to explore the functional organization of direction of motion in cat area 18. Optical imaging was used to record the activity of populations of neurons. We found a patchy distribution of cortical regions exhibiting preference for one direction over the opposite direction of motion. The degree of clustering according to preference of direction was two to four times smaller than that observed for orientation. In general, direction preference changed smoothly along the cortical surface; however, discontinuities in the direction maps were observed. These discontinuities formed lines that separated pairs of patches with preference for opposite directions. The functional maps for direction and for orientation preference were closely related; typically, an iso-orientation patch was divided into regions that exhibited preference for opposite directions, orthogonal to the orientation. In addition, the lines of discontinuity within the direction map often connected points of singularity in the orientation map. Although the organization of both domains was related, the direction and the orientation selective responses were separable; whereas the selective response according to direction of motion was nearly independent of the length of bars used for visual stimulation, the selective response to orientation decreased significantly with decreasing length of the bars. Extensive single and multiunit electrical recordings, targeted to selected domains of the functional maps, confirmed the features revealed by optical imaging. We conclude that significant processing of direction of motion is performed early in the cat visual pathway.

Age Factors↗
PubMed2001

Increased oxygen consumption following activation of brain: theoretical footnotes using spectroscopic data from barrel cortex.

Optical imaging spectroscopy (OIS) and laser Doppler flowmetry (LDF) data sequences from anesthetized rats were used to determine the relationship between changes in oxy-and deoxygenated hemoglobin concentration and changes in blood volume and flow in the presence and absence of stimulation. The data from Jones et al. (accompanying paper) were used to explore the differences between two theoretical models of flow activation coupling. The essential difference between the two models is the extension of the model of Buxton and Frank by Hyder et al. (1998, J. Appl. Physiol. 85: 554--564) to incorporate change in capillary diffusivity coupled to flow. In both models activation-increased flow changes increase oxygen transport from the capillary; however, in Hyder et al.'s model the diffusivity of the capillary itself is increased. Hyder et al. proposed a parameter (Omega), a scaling "constant" linking increased blood flow and oxygen "diffusivity" in the capillary bed. Thus, in Buxton and Frank's theory, Omega = 0; i.e., there are no changes in diffusivity. In Hyder et al.'s theory, 0 < Omega < 1, and changes in diffusivity are assumed to be linearly related to flow changes. We elaborate the theoretical position of both models to show that, in principle, the different predictions from the two theories can be evaluated using optical imaging spectroscopy data. We find that both theoretical positions have limitations when applied to data from brief stimulation and when applied to data from mild hypercapnia. In summary, the analysis showed that although Hyder et al.'s proposal that diffusivity increased during activation did occur; it was shown to arise from an implementation of Buxton and Frank's theory under episodes of brief stimulation. The results also showed that the scaling parameter Omega is not a constant as the Hyder et al. model entails but in fact varies over the time course of the flow changes. Data from experiments in which mild hypercapnia was administered also indicated changes in the diffusivity of the capillary bed, but in this case the changes were negative; i.e., oxygen transport from the capillary decreased relative to baseline under hypercapnia. Neither of the models could account for the differences between the hypercapnia and activation data when matched for equivalent flow changes. A modification to the models to allow non-null tissue oxygen concentrations that can be moderated by changes due to increased metabolic demand following increased neural activity is proposed. This modification would allow modulation of oxygen transport from the capillary bed (e.g., changes in diffusivity) by tissue oxygen tension and would allow a degree of decoupling of flow and oxygen delivery, which can encompass both the data from stimulation and from hypercapnia.

Animals↗
PubMed2002

Protection by rapid chemical preconditioning of stressed hippocampal slice: a study of cellular swelling using optical scatter imaging.

It has been demonstrated that anoxic preconditioning protects against a subsequent 'lethal' injury in the hippocampal slice. The goal of this paper was to test the hypothesis that chemical preconditioning could help reduce the cellular swelling observed in excitotoxically injured hippocampal slices. The control slice was given a 10-min insult of 100 microM N-methyl-D-aspartate (NMDA) to simulate ischemic injury, followed by 30-min perfusion of standard Ringers solution. Cellular swelling was observed with a microscope designed to image light scatter changes resulting from cellular swelling. After the control NMDA injury, the average peak scatter change for CA1, CA3 and DG regions was 31.0 +/- 3.4, 22.4 +/- 4.8 and 27.6 +/- 4.6%, respectively. The peak scatter change of the overall slice was 26.0 +/- 3.6%. The experimental slices were preconditioned by three short 100 microM NMDA insults of 15 s each separated by 10 min of standard Ringers solution perfusion. The slices then received 10 min of 'lethal' injury by 100 microM NMDA. It was observed that the overall scatter signal, as a measure of cellular swelling, was reduced by 8.0% (P<0.05, n=11) after preconditioning. A regional heterogeneity in the responses was also observed. Cellular swelling in CA1, CA3 and DG were reduced by 9.8% (P<0.001, n=11), 9.2% (P<0.005, n=11) and 7.7% (P<0.05, n=11), respectively, when compared to the control. This study presents experimental evidence that short episodes of preconditioning may protect against acute cellular swelling under ischemic conditions.

Animals↗
PubMed2006

An integrated instrumental setup for the combination of atomic force microscopy with optical spectroscopy.

In recent years, the study of single biomolecules using fluorescence microscopy and atomic force microscopy (AFM) techniques has resulted in a plethora of new information regarding the physics underlying these complex biological systems. It is especially advantageous to be able to measure the optical, topographical, and mechanical properties of single molecules simultaneously. Here an AFM is used that is especially designed for integration with an inverted optical microscope and that has a near-infrared light source (850 nm) to eliminate interference between the optical experiment and the AFM operation. The Tip Assisted Optics (TAO) system consists of an additional 100 x 100-microm(2) X-Y scanner for the sample, which can be independently and simultaneously used with the AFM scanner. This allows the offset to be removed between the confocal optical image obtained with the sample scanner and the simultaneously acquired AFM topography image. The tip can be positioned exactly into the optical focus while the user can still navigate within the AFM image for imaging or manipulation of the sample. Thus the tip-enhancement effect can be maximized and it becomes possible to perform single molecule manipulation experiments within the focus of a confocal optical image. Here this is applied to simultaneous measurement of single quantum dot fluorescence and topography with high spatial resolution.

Image Processing, Computer-Assisted↗
PubMed1996

Variability and interhemispheric asymmetry of single-whisker functional representations in rat barrel cortex.

1. The rat whisker-to-barrel system was used to investigate the variability and interhemispheric asymmetry in the functional organization of primary somatosensory cortex as assessed with intrinsic signal optical imaging. The areal extent of whisker D1 functional representation was determined for both the left and right barrel cortex of each of 10 adult male rats. The average size of whisker D1 functional representation and the amount of variability away from this average across animals were determined. In addition, interhemispheric asymmetry was addressed at both the population level and the individual level. The degree of side preference for thigmotactic scanning (typical whisker-related rodent behavior) was determined for each rat in an attempt to find a behavioral correlate for the degree of interhemispheric asymmetry in the size of whisker D1 functional representation. 2. The average areal extent of whisker D1 functional representation (defined as area at half-height) was large (1.95 +/- 0.14 mm2, mean +/- SE, N = 10 rats), suggesting that stimulation of a single whisker evokes activity over a large cortical area that includes other whisker representations. 3. The average size of whisker D1 functional representation was not significantly different between the left (1.86 +/- 0.21 mm2) and right (2.04 +/- 0.15 mm2) hemispheric side, suggesting that interhemispheric functional asymmetry of barrel cortex is not systematic toward a specific hemispheric side at the population level. 4. The degree of variability in the size of whisker D1 functional representation from the left hemisphere ranged between 54.6% smaller than to 50.6% larger than the left average areal extent. A large degree of variability was also observed for the right D1 representation, 37.6% smaller than to 34.9% larger than the right average areal extent. Thus it appears that a large variability in the size of unmanipulated single-whisker functional representations exists across animals from the same species and is not exclusive to a particular hemispheric side. 5. In 5 of 10 rats, the size of whisker D1 functional representation between the two hemispheres differed by > or = 25% within an individual animal. Of these five rats, four had a larger representation in their right hemisphere. The degree and direction of behavioral asymmetry was not linearly correlated with the interhemispheric asymmetry in the size of D1 functional representation (r = 0.494). 6. The large size of a single-whisker functional representation as defined with intrinsic signal optical imaging is discussed with respect to previous anatomic and 2-deoxyglucose autoradiography studies, whereas the large variability in this size across animals is discussed with respect to the individuality of each animal. In addition, the results of the present study have implications for projects that plan to investigate relative changes in the size of single-whisker functional representations.

Animals↗
PubMed2000

Effect of compensation for spherical aberration on the transverse displacement of laser speckle patterns

When a rough surface illuminated by coherent light is displaced perpendicularly to the optical axis of an imaging optical system the speckle pattern in the conjugate plane is transversally displaced too. This displacement has two components. The first one is proportional to the object displacement, and the second one depends on wave-front aberrations and, consequently, is strongly related to the optical system that is used. Usually, well-corrected photographic objectives are used for the measurement of transverse displacements by double-exposure laser speckle photography. Since in well-corrected objectives aberrations tend to compensate one another, it seems that the complementary displacement of the speckle pattern, caused by aberrations, is near zero and does not affect the accuracy of the measurement. Here it is analytically shown that the compensation of spherical aberrations does not guarantee a negligible complementary displacement. From the results obtained it follows that well-corrected objectives for laser speckle photography can be regarded as a particular class of photographic objectives, since they not only yield high-quality images but also minimize complementary displacement.

Journal Article↗
PubMedDate not supplied

Time-resolved measurements of brain activation after a short visual stimulus: new results on the physiological mechanisms of the cortical response.

This paper presents examinations of the time course of the signal from the visual cortex following a brief (2 s) light stimulus. Signal was generated from a 2 x 2 x 2 ml voxel using a modified point-resolved spectroscopy experiment. In accordance with previous studies a triphasic time course was observed. The results indicate that the observable signal contains contributions from non blood oxygen level dependent signal changes occurring immediately after the onset of stimulation. The response to multiple stimuli could be fitted with a response model which is linear with respect to the BOLD-phase of the response. This suggests that the experiments using a very weak stimulus were performed below the limit of the arterial reserve. This is in marked contrast to other studies performed by functional magnetic resonance imaging as well as optical imaging. First results using echo planar imaging confirm the common origin of the signals in the activated cortical areas.

Adult↗
PubMed1993

Optical CT imaging of hemoglobin oxygen-saturation using dual-wavelength time gate technique.

Our results may be summarized as follows: 1. In-vivo hemoglobin oxygen-saturation images of rat brain can be obtained using near-infrared light. 2. The transmitted light has multiple scattered components, which degrade spatial resolution, though most of the scattering can be excluded by a suitable time-gating technique. 3. The hemoglobin oxygen-saturation of the cerebellum is higher than that of the cerebrum in untreated anesthetized rats. Although further improvements in the technique should result in better resolution, we have demonstrated the feasibility of using near-infrared light to obtain in-vivo hemoglobin oxygen-saturation images.

Animals↗
PubMed1998

Semi-automatic tool for segmentation and volumetric analysis of medical images.

Segmentation software is described, developed for medical image processing and run on Windows. The software applies basic image processing techniques through a graphical user interface. For particular applications, such as brain lesion segmentation, the software enables the combination of different segmentation techniques to improve its efficiency. The program is applied for magnetic resonance imaging, computed tomography and optical images of cryosections. The software can be utilised in numerous applications, including pre-processing for three-dimensional presentations, volumetric analysis and construction of volume conductor models.

Brain Ischemia↗
PubMed1998

Early motor influences on visuomotor transformations for reaching: a positive image of optic ataxia.

Coding of reaching in the cerebral cortex is based on the operation of distributed populations of parietal and frontal neurons, whose main functional characteristics reside in their combinatorial power, i.e., in the capacity for combining different information related to the spatial aspects of reaching. The tangential distribution of reach-related neurons endowed with different functional properties changes gradually in the cortex and defines, in the parieto-frontal network, trends of functional properties. These visual-to-somatic gradients imply the existence of cortical regions of functional overlaps, i.e., of combinatorial domains, where the integration of different reach-related signals occurs. Studies of early coding of reaching in the mesial parietal areas show how somatomotor information, such as that related to arm posture and movement, influences neuronal activity in the very early stages of the visuomotor transformation underlying the composition of the motor command and is not added "downstream" in the frontal cortex. This influence is probably due to re-entrant signals traveling through fronto-parietal-association connections. Together with the gradient architecture of the network and the reciprocity of cortico-cortical connections, this implies that coding of reaching cannot be regarded as a top-down, serial sequence of coordinate transformation, each performed by a given cortical area, but as a recursive process, where different signals are progressively matched and further elaborated locally, due to intrinsic cortical connections. This model of reaching is also supported by psychophysical studies stressing the parallel processing of the different relevant parameters and the "hybrid" nature of the reference frame where they are combined. The theoretical frame presented here can also offer a background for a new interpretation of a well-known visuomotor disorder, due to superior parietal lesions, i.e., optic ataxia. More than a disconnection syndrome, this can now be interpreted as the consequence of the breakdown of the operations occurring in the combinatorial domains of the superior parietal segment of the parieto-frontal network.

Animals↗
PubMed2006

Neuroplasticity and brain imaging research: implications for rehabilitation.

Advanced brain imaging technologies have been used recently to investigate neuroplasticity in relation to recovery and treatment of neurologic injury and disease. The contributors to this supplement present data and synthesize the extant literature on the use of functional magnetic resonance imaging, magnetic resonance spectroscopy, optical imaging, transcranial magnetic stimulation, and transcranial direct current stimulation to study remodeling of cortical representation of motor and cognitive abilities after stroke and other etiologies of neurologic impairment. In general, the collective findings of these studies support use-dependent neuroplasticity as a mechanism of recovery and response to training. Brain imaging findings support the role of training effects on increased activation of brain regions ipsilateral to unilateral vascular lesions in facilitating recovery from stroke. The articles in this supplement also report the potential therapeutic application of stimulation techniques to enhance reorganization of function.

Brain Diseases↗
PubMed2006

Fluorophor-labeled spermidine derivatives as fluorescent markers in optical tumor imaging.

Up-regulation of polyamine transporters on the surface of tumor cells and the internalization of biogenic polyamines by active transport processes may be exploited for the accumulation of spermidine derivatives as reporter molecules. We have synthesized and tested fluorophor-labeled spermidine derivatives for the development of a new class of intraoperative tumor imaging agents. In vitro uptake experiments and initial in vivo imaging studies illustrated that fluorophor tagged spermidine derivatives show tumor accumulation.

Animals↗
PubMed2006

Anterior segment imaging using optical coherence tomography and ultrasound biomicroscopy in secondary pigmentary glaucoma associated with in-the-bag intraocular lens.

A 43-year-old man with high myopia developed unilateral pigmentary glaucoma with recurrent episodes of painless blurred vision in the left eye following uneventful phacoemulsification. Bilateral cataract surgery was performed with capsular bag implantation of a +4.00 diopter AcrySof MA60 intraocular lens (IOL) (Alcon Laboratories) followed by a neodymium:YAG laser capsulotomy. Secondary iatrogenic dispersion syndrome in the left eye with subsequent intraocular pressure elevation was suspected in the presence of anterior chamber pigmented cells, circular epithelial iris loss around the pupil, and trabecular hyperpigmentation. Close contact between the edge of the IOL and the posterior pigmented iris epithelium, which was clinically suggested by anterior biomicroscopy, was documented by ultrasound biomicroscopy and optical coherence tomography of the anterior segment.

Adult↗
PubMed2004

Time-lapse microscopy of brain development.

Zebrafish embryos represent an ideal vertebrate model organism for noninvasive intravital imaging because of their optical clarity, external embryogenesis, and fast development. Many different labeling techniques have been adopted from other model organisms or newly developed to address a wealth of different developmental questions directly inside the living organism. The parallel advancements in the field of optical imaging let us now observe dynamic processes at the cellular and subcellular resolution. Combined with the repertoire of available surgical and genetic manipulations, zebrafish embryos provide the powerful and almost unique possibility to observe the interplay of molecular signals with cellular, morphological, and behavioral changes directly within a living and developing vertebrate organism. A bright future for zebrafish is yet to come, let there be light.

Animals↗
PubMed2004

[Automated imaging of the optic nerve and optic nerve fibers is essential to daily clinical practice].

Chronic open-angle glaucoma is a progressive optical neuropathy. Automated imaging of the optic disc and optic nerve fibers provides reliable analysis of the optic nerve as well as long-term follow-up of neuropathy patients. HRT, GDX-VCC, and OCT, which analyze the optic disc and optical fibers, provide indisputable assistance in improving screening techniques and the follow-up of progressive glaucoma.

Chronic Disease↗
PubMed2003

Near-infrared fluorescence imaging of microcalcification in an animal model of breast cancer.

RATIONALE AND OBJECTIVES: At present, there is no animal model of breast cancer that forms reproducible microcalcification. The aim of this study was to develop a straightforward, reproducible model system that could be used to develop multimodality contrast agents for the identification of breast cancer microcalcification. METHODS: The R3230 mammary adenocarcinoma cell line was implanted in the mammary fat pad of female Fischer 344 rats (two rats with two implanted tumors and two rats with a single implanted tumor). After growth to 1-2 cm in diameter, tumors were implanted with 100 microm hydroxyapatite crystals (positive control) or calcium oxalate crystals (negative control). Twenty-four hours after crystal implantation, rats were injected intravenously with a previously described near-infrared fluorescent bisphosphonate derivative known as Pam78, and the tumors were imaged using a reflectance optical imaging system. RESULTS: Tumors implanted with hydroxyapatite displayed bright, focal, near-infrared fluorescence in the area of crystal implantation. Control tumors, grown in the same animal and implanted with calcium oxalate, did not display any near-infrared fluorescence, even along the needle track used for crystal implantation. CONCLUSIONS: A simple and rapid animal model of focal calcification in breast cancer tumors has been developed and validated. The model used Pam78, a near-infrared fluorescent contrast agent specific for hydroxyapatite. The potential usefulness of the model for developing similar contrast agents for magnetic resonance and other imaging modalities is discussed.

Animals↗