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Birefringence measurements in human skin using polarization-sensitive optical coherence tomography.

Optical coherence tomography enables cross-sectional imaging of tissue structure to depths of around 1.5 mm, at high-resolution and in real time. Incorporation of polarization sensitivity (PS) provides an additional contrast mechanism which is complementary to images mapping backscattered intensity only. We present here polarization-sensitive optical coherence tomography (OCT) images of human skin in vivo, demonstrating the ability of the technique to visualize and quantify the birefringent properties of skin. Variation in normal skin birefringence according to anatomical location is demonstrated, and discussed in relation to collagen distribution at each location. From measurements on a sample of five human volunteers, mean double-pass phase retardation rates of 0.340+/-0.143, 0.250+/-0.076, and 0.592+/-0.142 deg/microm were obtained for the dorsal hand, temple, and lower back regions, respectively. We demonstrate how averaging the Stokes parameters of backscattered light over a range of axial and lateral dimensions results in a reduction of speckle-induced noise. Examples of PS-OCT images from skin sites following wound healing and repair are also presented and discussed.

Adult↗

Endoscopic, rapid near-infrared optical tomography.

This is believed to be the first demonstration of near-infrared (NIR) optical tomography employed at the endoscope scale and at a rapid sampling speed that allows translation to in vivo use. A spread-spectral-encoding technique based on a broadband light source and linear-to-circular fiber bundling was used to provide endoscopic probing of many source-detector fibers for tomography as well as parallel sampling of all source-detector pairs for rapid imaging. Endoscopic NIR tomography at an 8 Hz frame rate was achieved in phantoms and tissue specimens with a 12 mm probe housing eight sources and eight detectors. This novel approach provides the key feasibility studies to allow this blood-based contrast imaging technology to be attempted in detection of cancer in internal organs via endoscopic interrogation.

Computer Systems↗

Methods for parallel-detection-based ultrasound-modulated optical tomography.

The research reported here focuses on ultrasound-modulated optical tomography based on parallel speckle detection. Four methods were investigated for signal acquisition and analysis, in which laser speckle statistics was applied. The methods were compared with the previously used four-phase method in the imaging of all-biological-tissue samples, in which the buried objects were also biological tissues. The image quality obtained with these methods was comparable with that obtained with the four-phase method; in addition, these methods have advantages in reducing acquisition time and improving the signal-to-noise ratio.

Animals↗

Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement.

We present quantitative optical images of human breast in vivo. The images were obtained by using near-infrared diffuse optical tomography (DOT) after the administration of indocyanine green (ICG) for contrast enhancement. The optical examination was performed concurrently with a magnetic resonance imaging (MRI) exam on patients scheduled for excisional biopsy or surgery so that accurate image coregistration and histopathological information of the suspicious lesions was available. The ICG-enhanced optical images coregistered accurately with Gadolinium-enhanced magnetic resonance images validating the ability of DOT to image breast tissue. In contrast to simple transillumination, we found that DOT provides for localization and quantification of exogenous tissue chromophore concentrations. Additionally our use of ICG, an albumin bound absorbing dye in plasma, demonstrates the potential to differentiate disease based on the quantified enhancement of suspicious lesions.

Aged↗

Optical coherence tomography in optic disk pit maculopathy treated by the macular buckling procedure.

PURPOSE: To report optical coherence tomography in optic disk pit maculopathy treated with macular scleral buckling procedure. METHODS: Twenty six eyes (26 patients) with optic disk pit maculopathy were treated with macular buckling procedure and evaluated with optical coherence tomography. In group 1, five eyes were evaluated with optical coherence tomography before and after macular buckling procedure. In group 2, 21 eyes were evaluated with optical coherence tomography after macular buckling procedure. With optical coherence tomography, cross-sectional, horizontal retinal images were obtained through the fovea and optic disk pit. RESULTS: In group 1, four of five eyes showed absorption of intraretinal fluid 7 to 9 months after macular buckling procedure. After absorption of fluid, retinal thickness in the foveal center ranged from 128 to 178 microm. In one eye the channel from optic disk to fovea reopened and fluid reappeared. In group 2, 20 of 21 eyes showed absorption of intraretinal schisis and subretinal fluid after macular buckling procedure. After absorption of fluid, retinal thickness in the foveal center ranged from 119 to 216 microm. CONCLUSIONS: In optic disk pit maculopathy, optical coherence tomography enabled morphologic assessment of the retina before and after macular buckling procedure. In the successfully treated cases the permanent closure of the connection between the optic disk pit and the intraretinal schisis was demonstrated. Eventual disappearance of schisis and subretinal fluid was depicted. It was also proved that the thickness of the macula returned to normal and visual acuity improved.

Adolescent↗

Visuospatial imagery is a fruitful strategy for the digit span backward task: a study with near-infrared optical tomography.

Our newly developed 64-channel time-resolved optical tomographic imaging system using near-infrared light enables us to obtain a quantitative image of hemoglobin concentration changes associated with neuronal activation in the human brain ¿H. Eda, I. Oda, Y. Ito, Y. Wada, Y. Oikawa, Y. Tsunazawa, M. Takada, Y. Tsuchiya, Y. Yamashita, M. Oda, A. Sassaroll, Y. Yamada, M. Tamura, Multi-channel time-resolved optical tomographic imaging system, Rev. Sci. Instrum., 70 (1999) 3595-3602. Here, we used this optical imaging system to demonstrate that the backward digit span (DB) task activated the dorsolateral prefrontal cortex (DLPFC) of each hemisphere more than the forward digit span (DF) task in healthy adult volunteers, and higher performance of the DB task was closely related to the activation of the right DLPFC. These results suggest that visuospatial imagery is a useful strategy for the DB task. Optical tomography described here is a new modality of neuropsychological studies.

Adult↗

Preparation of solid phantoms with defined scattering and absorption properties for optical tomography.

We have developed diffusely scattering solid phantoms with optical (scattering) properties amenable to theoretical calculations. Monodisperse quartz glass spheres were used as scatterers embedded in polyester resin. An infrared dye was added to simulate absorption by biological tissue. Solid phantoms were tested for their macroscopic homogeneity. Several phantoms were built with well-defined spatial variations in their transport scattering and absorption coefficients to be used for optical tomography. Scattering, transport scattering, and absorption coefficients of solid, homogeneous phantoms and of aqueous suspensions of monodisperse quartz glass spheres were derived from measurements of time-integrated collimated transmittance and time-resolved diffuse transmittance. For aqueous suspensions of monodisperse quartz glass spheres at known number density scattering and transport scattering coefficients calculated by Mie theory are in quantitative agreement with experimentally derived values. In addition, diffuse reflectance and diffuse transmittance of aqueous suspensions at various number densities were measured and found to be in excellent agreement with results of Monte Carlo calculations using theoretical values for the scattering coefficients and anisotropy parameters.

Humans↗

[Optical coherence tomography].

Optical coherence tomography is a novel, noninvasive, noncontact and repetitive imaging technique which produces high depth resolution cross-sectional tomographs of ocular tissue. It's value is given by the possibility of achieving pseudo-histological images of the target tissue. It is optically based, analogue to ultrasound B-scan examination and similar to laser reflectometry. Optical coherence tomography involves shining low-level infrared light on a tissue specimen, an interferometer and a computerized imaging system. The most attractive applications of optical coherence tomography are the diseases of the retina such as: central serous retinopathy, macular hole, chronic macular edema, age-related macular degenerescence.

Diagnostic Techniques, Ophthalmological↗

Multiplicative optical tomography of cardiac electrical activity.

Cardiac electrical activity can be mapped today through the response of voltage-sensitive dyes; but poor transparency of muscle tissue has enforced shallow-depth imaging. We present a three-dimensional (3D) reconstruction method for electrical activity deep inside the myocardial wall. Our approach is nonlinear and differs substantially from standard diffusive optical tomography. It does not require matrix inversion, data regularization or a priori information concerning the original object. Opposite sides of a slab-shaped preparation are scanned in parallel by detection and illumination points with a constant vector offset between illumination and detection axes (biaxial scanning). Scanning is performed in two perpendicular directions. In each direction, a pair of 2D images is obtained under offsets of opposite signs. These two pairs are the input for a multiplicative reconstruction algorithm, whose output is a 3D image. The overall procedure was successfully tested on computer-generated sources that include points, lines and hemispheres, patterned after actual electrophysiological excitations. The algorithm is computationally efficient and stable with respect to varying noise levels in the raw data.

Algorithms↗

Diagnostic imaging of breast cancer using fluorescence-enhanced optical tomography: phantom studies.

Molecular targeting with exogenous near-infrared excitable fluorescent agents using time-dependent imaging techniques may enable diagnostic imaging of breast cancer and prognostic imaging of sentinel lymph nodes within the breast. However, prior to the administration of unproven contrast agents, phantom studies on clinically relevant volumes are essential to assess the benefits of fluorescence-enhanced optical imaging in humans. Diagnostic 3-D fluorescence-enhanced optical tomography is demonstrated using 0.5 to 1 cm(3) single and multiple targets differentiated from their surroundings by indocyanine green (micromolar) in a breast-shaped phantom (10-cm diameter). Fluorescence measurements of referenced ac intensity and phase shift were acquired in response to point illumination measurement geometry using a homodyned intensified charge-coupled device system modulated at 100 MHz. Bayesian reconstructions show artifact-free 3-D images (3857 unknowns) from 3-D boundary surface measurements (126 to 439). In a reflectance geometry appropriate for prognostic imaging of lymph node involvement, fluorescence measurements were likewise acquired from the surface of a semi-infinite phantom (8x8x8 cm(3)) in response to area illumination (12 cm(2)) by excitation light. Tomographic 3-D reconstructions (24,123 unknowns) were recovered from 2-D boundary surface measurements (3194) using the modified truncated Newton's method. These studies represent the first 3-D tomographic images from physiologically relevant geometries for breast imaging.

Algorithms↗

Optical tomography of the breast using a multi-channel time-resolved imager.

A time-resolved optical tomography system has been used to generate cross-sectional images of the human breast. Images are reconstructed using an iterative, nonlinear algorithm and measurements of mean photon flight time relative to those acquired on a homogeneous reference phantom. Thirty-eight studies have been performed on three healthy volunteers and 21 patients with a variety of breast lesions including cancer. We have successfully detected 17 out of 19 lesions, and shown that optical images of the healthy breast of the same volunteer display a heterogeneity which is repeatable over a period of months. However, results also indicate that the lack of accurate quantitation of optical parameters and limited morphological information limits the ability to characterize different types of lesions and distinguish benign from malignant tissues. Drawbacks of our current methodology and plans for overcoming them are discussed.

Adult↗

Streak camera: a multidetector for diffuse optical tomography.

We describe an experimental setup for time-resolved diffuse optical tomography that uses a seven-channel light guide to transmit scattered light to a streak camera. This setup permits the simultaneous measurement of the time profiles of photons reemitted at different boundary sites of the objects studied. The instrument, its main specifications, and detector-specific data analysis before image reconstruction are described. The instrumentation was tested with phantoms simulating biological tissue, and the absorption and reduced scattering images that were obtained are discussed.

Optics and Photonics↗

Generalized diffusion model in optical tomography with clear layers.

We introduce a generalized diffusion equation that models the propagation of photons in highly scattering domains with thin nonscattering clear layers. Classical diffusion models break down in the presence of clear layers. The model that we propose accurately accounts for the clear-layer effects and has a computational cost comparable to that of classical diffusion. It is based on modeling the propagation in the clear layer as a local tangential diffusion process. It can be justified mathematically in the limit of small mean free paths and is shown numerically to be very accurate in two- and three-dimensional idealized cases. We believe that this model can be used as an accurate forward model in optical tomography.

Diffusion↗

Consideration of a spread-out source in problems of near-infrared optical tomography.

When the light propagates in media where absorption is not negligible and/or scattering is weak, a contribution to the energy density coming from ballistic photons cannot be neglected. A point source effectively spreads out over a scattering volume and its spatial distribution is described by the source function. We consider a boundary value problem of light propagation in half-space for such a source on the basis of the telegraph equation. A solution is found by convolution of Green's function with the source function. The final result shows a significant difference in the behavior of the radiant energy density between the solution obtained for a distributed source and the diffusion approximation. Our results agree well with the Monte Carlo simulations over a broad range of scattering and/or absorption conditions. The obtained results are of practical importance in luminescence optical tomography because an erroneous shape of the energy density function may lead to an incorrect estimate of the light source depth after image reconstruction. The range of applications of the diffusion approximation is also discussed.

Algorithms↗

Signal-to-noise-ratio expressions in optical diffusion tomography.

Optical diffusion tomography is a technology that is employed to obtain images of the heterogeneous nature of turbid media by using optical radiation. Noise ultimately limits the achievable spatial resolution in these reconstructed images; therefore it is of interest to develop signal-to-noise-ratio expressions that relate spatial resolution in the images to the underlying system and material properties. In this study, Fourier-domain signal-to-noise-ratio expressions are derived for two types of optical diffusion tomography systems: those that use amplitude-modulated illumination sources and those that use continuous-wave illumination sources. The signal-to-noise-ratio expressions are compared for these two types of systems and are validated by laboratory data.

Diffusion↗

Optical tomography of a realistic neonatal head phantom.

We have begun clinical trials of optical tomography of the neonatal brain. To validate this research, we have built and imaged an anatomically realistic, tissue-equivalent neonatal head phantom that is hollow, allowing contrasting objects to be placed inside it. Images were reconstructed by use of two finite-element meshes, one generated from a computed tomography image of the phantom and the other spherical. The phantom was filled with a liquid of the same optical properties as the outer region, and two perturbations were placed inside. These were successfully imaged with good separation between the absorption and scatter coefficients. The phantom was then refilled with a liquid of increased absorption compared with the background to simulate the brain, and the absolute properties of the two regions were found. These were used as a priori information for the complete reconstruction. Both perturbations were visible, superimposed on the increased absorption of the central region. The head-shaped mesh performed slightly better than the spherical mesh, particularly when the absorption of the central region of the phantom was increased.

Head↗

Application of the photon average trajectories method to real-time reconstruction of tissue inhomogeneities in diffuse optical tomography of strongly scattering media.

The possibility of application of the photon average trajectories (PAT) method to real-time reconstruction of tissue inhomogeneities in diffuse optical tomography of strongly scattering media has been substantiated. By this method, the inverse problem is reduced to solution of the integral equation with integration along a conditional PAT. Such an approach allows the standard fast algebraic algorithms commonly used in projection computed tomography to be applied to diffuse optical image reconstruction. To demonstrate the capabilities of the PAT method, a numerical experiment on cross-sectional reconstruction of cylindrical strongly scattering objects with absorbing inhomogeneities has been done. Relative shadows caused by inhomogeneities are simulated via numerical solution of the non-stationary diffusion equation. To solve the inverse problem, the QR-factorization least-squares algorithm and the multiplicative algebraic reconstruction technique are used. The results are compared with those obtained by a well-known software package for temporal optical absorption and scattering tomography based on multiple solution of the diffusion equation. It is shown that the PAT method allows reconstruction of the optical structure of objects with comparable accuracy while saving reconstruction time considerably.

Algorithms↗

Diffuse optical tomography of highly heterogeneous media.

We investigate the performance of diffuse optical tomography to image highly heterogeneous media, such as breast tissue, as a function of background heterogeneity. To model the background heterogeneity, we have employed the functional information derived from Gadolinium-enhanced magnetic resonance images of the breast. We demonstrate that overall image quality and quantification accuracy worsens as the background heterogeneity increases. Furthermore we confirm the appearance of characteristic artifacts at the boundaries that scale with background heterogeneity. These artifacts are very similar to the ones seen in clinical examinations and can be misinterpreted as actual objects if not accounted for. To eliminate the artifacts and improve the overall image reconstruction, we apply a data-correction algorithm that yields superior reconstruction results and is virtually independent of the degree of the background heterogeneity.

Algorithms↗