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Biomedical subjects

Ruikang K Wang

Publications and source records attributed to Ruikang K Wang.

At least 19 recordsLinked to original sources

Real-time flow imaging by removing texture pattern artifacts in spectral-domain optical Doppler tomography.

We present a new, simple method to suppress texture pattern artifacts induced by the optical heterogeneity of tissues to improve the performance of flow imaging for real-time phase-resolved optical Doppler tomography. The method performs transverse scanning of the probe beam in the forward and then reverse directions, and it takes average of the spatial phase changes between them to obtain the final velocity image. It relies on the fact that the phase changes between successive axial scans due to the optical heterogeneity of the sample are time independent, while those due to the moving particles are time dependent. We experimentally demonstrate this method by real-time imaging of a flow phantom.

Artifacts↗

A practical approach to eliminate autocorrelation artefacts for volume-rate spectral domain optical coherence tomography.

A simple method is introduced to eliminate the autocorrelation artefacts in ultrafast spectral domain optical coherence tomography (SOCT) by use of the ensemble average of spectra within an individual B scan as the background signal, and then subtracting this from all the A scans within that B scan before performing the FFTs. This is updated continuously frame by frame. The method is tested on a volume-rate (C-mode) SOCT system to image the human fingertip in vivo with a volume rate at 8 s.

Algorithms↗

Investigation of optical coherence tomography as an imaging modality in tissue engineering.

Monitoring cell profiles in 3D porous scaffolds presents a major challenge in tissue engineering. In this study, we investigate optical coherence tomography (OCT) as an imaging modality to monitor non-invasively both structures and cells in engineered tissue constructs. We employ time-domain OCT to visualize macro-structural morphology, and whole-field optical coherence microscopy to delineate the morphology of cells and constructs in a developing in vitro engineered bone tissue. The results show great potential for the use of OCT in non-invasive monitoring of cellular activities in 3D developing engineered tissues.

Adolescent↗

Matrix approach to quantitative refractive index analysis by Fourier domain optical coherence tomography.

The rapid development in the field of optical coherence tomography has demanded increasingly sophisticated numerical models to enable the interpretation of image data and extract quantitative results. We use a matrix formulation of Fresnel's equations for multilayered media to extract layer-dependent thickness and refractive index directly from Fourier domain optical coherence tomography spectrograms. An eigenanalysis spectral decomposition approach is used to constrain the least squares fitting algorithm, avoiding the need for initial estimates of the parameter values. We demonstrate this novel quantitative analysis approach by using a multilayered phantom and show good agreement with the known layer parameter values. This approach introduces a powerful tool for the analysis of layer-dependent optical properties that could have an important role in the differentiation of healthy and diseased tissue.

Algorithms↗

Comparing the synergistic effects of oleic acid and dimethyl sulfoxide as vehicles for optical clearing of skin tissue in vitro.

Recently, the tissue optical clearing technique has shown great potential in enhancing the capabilities of non-invasive light-based diagnostic and imaging techniques due to increased light penetration into tissue. In order to facilitate the clinical availability of the tissue optical clearing technique by the use of hyperosmotic agents, this study introduces oleic acid, a mono-unsaturated fatty acid which is generally recognised as safe, as an enhancer, and investigates the synergistic effect of oleic acid and propylene glycol on the optical clearing of skin tissue in vitro. Experimental results from near infrared spectroscopy, mass loss measurement and skin permeability assessment show that, when compared with dimethyl sulfoxide (DMSO) as an enhancer, oleic acid has a similar clearing effect. Due to its potential toxicity and the possible side effects, DMSO has been controversial in clinical applications. Therefore, in terms of optical application and clinic safety, the results presented reveal that oleic acid could be an optimal choice as an enhancer for optical clearing of skin tissue.

Animals↗

Improvement of low-level light imaging performance using optical clearing method.

Low-level light-emitting imaging technique often detects the light emerged at the tissue surface that is generated internally from a specific target. However, in most cases, the high scattering nature of biological tissue limits the sensitivity and spatial resolution of this imaging modality. In this paper, we report that a significant improvement of chemiluminescence (CL) imaging performance in terms of both sensitivity and spatial resolution can be achieved by use of the topical application of glycerol solution onto tissue sample, i.e. optical clearing approach. Monte Carlo (MC) simulation of internally-launched point source shows that the decrease of scattering coefficient of turbid medium, which can be achieved by optical tissue clearing approach, causes stronger peak intensity with a narrower full-width at half-maximum (FWHM). The improvement becomes more significant with the source depth increasing from 1 to 5 mm. The experimental results shows that tissue clearing with 50% glycerol solution could largely improve the brightness and the spatial resolution of CL imaging when the target is covered by biological tissue with a thickness of either 1 or 3mm. This method could have potential applications for the in vivo low-level light imaging techniques.

Algorithms↗

Use of optical coherence tomography in delineating airways microstructure: comparison of OCT images to histopathological sections.

An ideal diagnostic system for the human airways should be able to detect and define early development of premalignant pathological lesions, to facilitate optimal curative treatment and prevent irreversible and/or invasive lung disease. There is great need for exploration of safe, repeatable imaging techniques which can run at real-time and with high spatial resolution. In this study, optical coherence tomography (OCT) was utilized to acquire cross-sectional images of upper and lower airways using fresh pig lung resections as a model system. Obtained OCT images were compared with parallel tissue characterization by conventional histological analysis. Our objective was to determine whether OCT differentiates the composite structural layers and inherent anatomical variations along different airway locations. The data show that OCT can clearly display the multilayered structure of the airways. The subtle architectural differences in three separate anatomical locations including trachea, main bronchus and tertiary bronchus were clearly delineated. Images of the appropriate anatomical profiles, with depth of up to 2 mm and 10 microm spatial resolution were obtained by our current OCT system, which was sufficient for recognition of the epithelium, subepithelial tissues and cartilage. In addition, the relative thickness of individual structural components was accurately reflected and comparable to histological sections. These data support OCT as a highly feasible, optical biopsy tool, which merits further exploration for early diagnosis of human airway epithelial pathology.

Animals↗

Doppler optical coherence imaging of converging flow.

The experimental methods of Doppler optical coherence tomography are applied for two-dimensional flow mapping of highly scattering fluid in flow with complex geometry. Converging flow (die entry) is used to demonstrate non-invasive methods to map varying velocity profiles before and after the entry. Complex geometry flow is scanned with approximately 10 x 10 x 10 microm3 spatial resolution. Structural images of the phantom and specific velocity images are demonstrated. A variety of velocity profiles have been obtained before and after the entry. Concave, blunted, parabolic and triangular profiles are obtained at different distances after the entry. Application of the technique to the study of blood circulation is discussed.

Blood Flow Velocity↗

Synergistic effect of hyperosmotic agents of dimethyl sulfoxide and glycerol on optical clearing of gastric tissue studied with near infrared spectroscopy.

In an effort to find an effective concentration that could minimize the side effect for clinical applications, and to understand the potential synergistic effect of hyperosmotic agents on optical clearing of gastric tissues, porcine stomach tissues (pyloric mucosa) applied with a mixed solution of glycerol and dimethyl sulfoxide (DMSO) are investigated with near infrared reflectance spectroscopy. Five chemical solutions, containing 80% glycerol, 50% DMSO, 50% glycerol with 10% DMSO, 20% DMSO and 30% DMSO, respectively, are prepared and studied; all of which show significant improvement in light transmittance, and thus reduction of the light scattering of tissue. It is found that, among the solutions investigated, 50% glycerol with 30% DMSO achieves the best clearing effect on the improvement of light penetration. Light transmittance is increased approximately 29% and diffuse reflectance decreased approximately 31% at 30 min after the topical application of 50% glycerol with 30% DMSO. This solution shows significantly stronger effect than 80% glycerol on optical clearing even though they have the same osmolarity. 80% glycerol leads to 23% increase of light transmittance and 24% decrease of diffuse reflectance. The mixed solution of 50% glycerol and 20% DMSO has less osmolarity than the solution of 80% glycerol, but they achieve a similar degree of optical clearing. In other words, the clearing effect of glycerol is enhanced by adding DMSO into it. It is suggested that membrane penetration and carrier effect of DMSO probably accounts for this synergistic effect.

Animals↗

Enhanced sensitivity and spatial resolution for in vivo imaging with low-level light-emitting probes by use of biocompatible chemical agents.

We describe a technique that uses biocompatible chemical agents to enhance both the sensitivity and the resolution of in vivo imaging with low-level light-emitting probes. We demonstrate experimentally, with chemiluminescence (CL) imaging in vitro as an example, that the detected intensity of CL from treated 3-mm-thick skin tissue is approximately fivefold stronger than that from untreated skin. The spatial resolution correspondingly increases approximately threefold.

Animals↗

Imaging of non-parabolic velocity profiles in converging flow with optical coherence tomography.

The optical coherence tomography method was explored for two-dimensional flow mapping of a highly scattering fluid in flow with complex geometry. Converging flow (capillary entry) with 4:1 constriction was used for demonstration of non-invasive and remote methods of mapping varying velocity profiles. Downstream of the geometry was scanned with approximately 10 x 10 x 10 microm3 spatial resolution and structural imaging of the lumen and images of one particular velocity were acquired. Stable concave, blunted and parabolic profiles are obtained at different distances of the inlet length. Application of the technique for the blood circulation is also discussed.

Algorithms↗

Determination of flow velocity vector based on Doppler shift and spectrum broadening with optical coherence tomography.

We describe a technique that uses Doppler optical coherence tomography to estimate accurately the scattering fluid-flow velocity without a priori knowledge of the Doppler angle. Our technique is based on the combined use of the Doppler shift on the interference signal and the Doppler spectrum broadening caused by the particles moving across the probe beam. It is shown that the estimated values of the Doppler angle and average fluid velocity from the experiments agree well with the preset values.

Models, Theoretical↗

Effect of dextran-induced changes in refractive index and aggregation on optical properties of whole blood.

The purpose of the present study is to investigate systematically the mechanisms of alterations in the optical properties of whole blood immersed in the biocompatible agent dextran, and to define the optimal concentration of dextrans required for blood optical clearing in order to enhance the capability of light penetration depth for optical imaging applications. In the experiments, dextrans with different molecular weights and various concentrations were employed and investigated by the use of the optical coherence tomography technique. Changes in light attenuation, refractive index and aggregation properties of blood immersed in dextrans were studied. It was concluded from the results that the mechanisms for blood optical clearing are characteristic of the types of dextrans employed, their concentrations and the application stages. Among the substances applied, Dx500 at a concentration at 0.5 g dl(-1) gives the best result in improving light penetration depth through the blood. The increase of light transmission at the beginning of the addition of dextrans is mainly attributed to refractive index matching between the scattering centres and the ground matter. Thereafter, the transmission change is probably due to a dextran-induced aggregation-disaggregation effect. Overall, light scattering in the blood could be effectively reduced by the application of dextrans. It represents a promising approach to increasing the imaging depth for in vivo optical imaging of biological tissue, for example optical coherence tomography.

Adult↗

Investigation of changes in optical attenuation of bone and neuronal cells in organ culture or three-dimensional constructs in vitro with optical coherence tomography: relevance to cytochrome oxidase monitoring.

Changes in optical attenuation, relevant to cytochrome oxidase, of the rat bone periosteal tissue in explanted culture and human neuronal cells in three-dimensional agarose constructs have been monitored by the use of optical coherence tomography (OCT), with potential applications in tissue engineering and diagnosis. A superluminescent diode (SLD) with a peak emission wavelength (lambda = 820 nm) that is the near-infrared absorption band of the oxidized form of CytOx was employed. The attenuation coefficient was obtained from the depth-resolved reflectance profiles of liquid phantoms (naphthol green B with intralipid), explant culture (periosteum of calvaria from rats) and cells in 3D agarose constructs. The absorption coefficient of naphthol green B can be accurately quantified by the linear relationship between attenuation coefficients and the concentration. The difference in the attenuation coefficient of astrocytoma cells in agarose before and after reduction of CytOx is 0.26 +/- 0.10 mm(-1) ( n = 9), whereas no attenuation is observed with the agarose control. Reduction of the enzyme in periosteal tissue leads to a change in attenuation coefficient of 0.43 +/- 0.24 mm(-1) ( n = 7). For comparison, using a biochemical assay, the absorption coefficient of the oxidized-reduced form of CytOx is measured at approximately 8.3 +/- 1.5x10(-3) mm-1 ( n = 4) and 8.7 +/-2.5x10(-3) mm-1 ( n = 4) at 820 nm for astrocytoma cells and rat periosteum, respectively. The lower value of CytOx concentration using biochemical versus OCT measurements may result from shifts in the scattering profile and the amplifying influences of multiple heme-based oxidases, indicating that conventional OCT is not specific enough to monitor redox changes in cytochrome oxidase. However, qualitative shifts in oxidation state are apparent using the technique. Our results suggest the potential application of OCT in providing high-resolution tomographic imaging of tissues in organ culture and cells grown in three-dimensional constructs in vitro.

Animals↗

The role of water desorption on optical clearing of biotissue: studied with near infrared reflectance spectroscopy.

In order to understand the role of water desorption, i.e., the opposite of water adsorption, in optical clearing of biological tissue created by the application of hyperosmotic agents, dynamics of water loss in fresh porcine muscle tissue administrated with glycerol or ethylene glycol was investigated with the near-infrared reflectance spectroscopy. It is found that there exist three stages of water desorption with the elapse of time within the tissue after the application of agents: i.e., the rapid stage during the first minute; at the second stage (1-10 min) water loss increases linearly at the rate slower than at the first stage; at the third stage (10-30 min) water content decreases exponentially at the slowest rate and tends to equilibrate. The progress of optical clearing measured by the optical coherence tomography system and spectrophotometer, respectively, corresponds very well with the three stages of water desorption. It indicates that optical clearing induced by hyperosmotic agents is strongly correlated with dehydration. The overall water loss in fresh porcine muscle tissue at 30 min after the application of 80% glycerol and ethylene glycol are approximately 39% and 23% respectively. The second derivative spectra show that glycerol is able to make bulk and bound water desorb. As a consequence, due to its high refractive index and high dehydration capability, glycerol is a more effective agent in optical clearing than ethylene glycol.

Adsorption↗

Theoretical model of optical coherence tomography for system optimization and characterization.

We present a detailed analytical model to describe optical coherence tomography (OCT) systems, which considers the propagation of the optical field within a scattering medium in the framework of the extended Huygens-Fresnel principle. The model includes use of the discrete-particle model and the fractal approach in treating biological tissue as being packed with scattering particles with a power-law distribution. In contrast to previous models, an imaginary lens proximal to the tissue surface is introduced that approximates the real focusing lens in the sample arm of the OCT system. This treatment avoids the consideration of backscattering light as traveling in the free space between the focusing lens and the tissue surface before mixing with the reference beam. Experiments on tissue phantoms were carried out to verify the validity of this model.

Computer Simulation↗

Signal degradation by multiple scattering in optical coherence tomography of dense tissue: a Monte Carlo study towards optical clearing of biotissues.

Multiple scattering is a major source that limits light penetration into biotissues, thereby preventing visualization of the deep microstructures for high-resolution optical imaging techniques. The optical clearing approach is a new adventure in biomedical optics for manipulating the optical properties of tissue; for example, the scattering coefficient and the degree of forward scattering of photons, by the use of the chemical administration method in order to improve the optical imaging depth, particularly for the recently developed optical coherence tomography (OCT). This paper investigates systematically how the multiple scattering affects signal attenuation and localization in general, and how the alterations of optical properties of tissue enhance the optical imaging depth and signal localization in particular, by the use of Monte Carlo simulations through the separate considerations of the least scattered photons (LSP) and multiple scattered photons (MSP). The LSP are those photons that contribute to the precise OCT signal, i.e. localization, and the MSP are those that degrade the OCT signal. It is shown that with either the reduction of the scattering coefficient or the increase of the degree of forward scattering, signal localization and imaging depth for OCT is enhanced. Whilst the increase of the anisotropic factor of the medium is more efficient in improving signal localization, it introduces more scattering events for the photons travelling within the tissue for both the LSP and MSP. It is also found that the OCT imaging resolution is almost reduced exponentially with the increase of the probing depth as opposed to the claimed system resolution. We demonstrate that optical clearing could be a useful tool to improve the imaging resolution when the light progressively penetrates the high scattering medium. Experimental results are also presented to show intuitively how multiple scattering affects OCT signal profiles by the use of intralipid solution and healthy human whole blood, representing moderately and highly scattering media respectively.

Anisotropy↗

Dynamic optical coherence tomography in studies of optical clearing, sedimentation, and aggregation of immersed blood.

The concept of refractive-index matching to enhance the optical penetration depth of whole blood is discussed on the basis of in vitro studies that used the technique of near-infrared optical coherence tomography. It was found that optical clearing of blood is defined not only by refractive-index matching but also by changes in the size of red blood cells and in their aggregation ability when chemicals are added. For example, in whole blood diluted to twice its volume by saline with the addition of 6.5% glycerol, the total attenuation coefficient was reduced from 4.2 to 2.0 mm(-1), and the optical penetration at 820 nm was correspondingly increased to 117%. For the other agents tested (glucose, dextrans, propylene glycol, and trazograph) the enhancement of penetration was 20-150.5%. In the blood sedimentation study, regular or irregular oscillations or jumps of the red-blood cell-plasma boundary were observed. The 1-min time period of regular oscillations correlated well with the kinetics of the aggregation process as described by the two subsequent stages of formation of linear and three-dimensional aggregates. The results also showed that optical clearing of blood by osmotic agents is potentially useful not only in blood sedimentation and aggregation studies but also in intravascular optical coherence tomography imaging techniques.

Adult↗