Biomedical subjects

Victor Chernomordik

Publications and source records attributed to Victor Chernomordik.

12 recordsLinked to original sources

PubMed2005

Real time in vivo non-invasive optical imaging using near-infrared fluorescent quantum dots.

RATIONALE AND OBJECTIVE: Deep-tissue optical imaging is of particular interest, as the equipment costs are lower than for competing technologies such as MRI. For this purpose, the development of novel contrast agents with near-infrared (NIR) fluorescence is especially important. We report on the use of NIR semiconductor nanocrystals in deep-tissue in vivo optical imaging. MATERIALS AND METHODS: Semiconductor nanocrystals of CdMnTe/Hg were grown in aqueous solution and then coated with bovine serum albumin (BSA). The nanocrystals were approximately 5 nm in diameter and have a broad fluorescence peak in the NIR (770 nm). Nanocrystals were injected either subcutaneously or intravenously into athymic NCR NU/NU and C3H/HENCR MTV mice and then excited with a spatially broad 633 nm source; the resulting fluorescence was captured with a sensitive CCD camera. RESULTS: We have demonstrated that the nanocrystals are a useful angiographic contrast agent for vessels surrounding and penetrating a murine squamous cell carcinoma in a C3H mouse. Preliminary assessment of the depth of penetration for excitation and emission was done by imaging a beating mouse heart, both through an intact thorax and after a thoracotomy. The temporal resolution associated with imaging the nanocrystals in circulation has been addressed, and the blood clearance for this contrast agent has also been measured. CONCLUSIONS: There was no significant photobleaching or degradation of the nanocrystals after an hour of continuous excitation. The stability of the nanocrystals together with the time resolution of the optical detection makes them particularly attractive candidates for pharmacokinetic imaging studies.

Animals↗

PubMed2004

Experimental evaluation of an anisotropic scattering model of a slab geometry.

A model has been developed based on random walk theory that allows the diffusion of light along a principal axis to differ from that in orthogonal directions. We present expressions that describe the time-resolved intensity measured across a slab and on the surface of a semi-infinite medium for a principal axis oriented parallel or perpendicular to the surface. The model of time-resolved transmittance is compared with experimental data acquired by use of a phantom consisting of wax fibers arranged within a solid cube of resin. It is shown that a single set of optical parameters is sufficient to model the experimental measurements acquired across all three orientations of the cube.

Algorithms↗

PubMed2004

Photon migration in turbid media with anisotropic optical properties.

We analyse properties of photon migration in reflectance measurements made on a semi-infinite medium bounded by a plane, in which optical parameters may vary in directions neither parallel to, nor perpendicular to the bounding plane. Our aim in doing this is to develop the formulae necessary to deduce parameters of directionality from both time-gated and continuous wave measurements. The mathematical development is based on a diffusion picture, in which the bounding plane is regarded as being totally absorbing so that all photons reaching the surface contribute to the reflectance.

Algorithms↗

PubMed2004

Quantitative optical imaging of the pharmacokinetics of fluorescent-specific antibodies to tumor markers through tissuelike turbid media.

Fluorescent optical imaging of tumors deep within tissue depends on specific binding of antibodies to the tumors' surface markers. These fluorescent antibodies propagating in the vicinity of the tumor can be attached to and (or) diffused away from it. We illustrate application of a new tool, based on the random-walk theory in turbid media, for extracting the pharmacokinetics of these fluorescent antibodies by data deconvolution, excluding the effect of upper turbid tissue layers.

Animals↗

PubMed2004

Functional optical detection based on pH dependent fluorescence lifetime.

BACKGROUND AND OBJECTIVES: Detection of possible alterations of physiological parameters (e.g., pH and temperature), resulting from malignant transformation of initially healthy tissue, can be a powerful diagnostic tool for earlier cancer detection. Such variations can be observed by comparing these parameters with those of healthy tissue surrounding the abnormality. Time-resolved spectroscopy of specifically targeted fluorescent labeled antibodies can be sensitive to such variations and provide a high resolution functional image of the region of interest. The goal of this study was to establish a forward experimental setup for calibration of the lifetime dependencies of near-IR fluorescent dyes on physiological parameters, and to develop analytical solutions, taking into account the effects of light propagation in turbid media (e.g., tissue), that was able to extract an original lifetime fluorescence signal from time-of-flight intensity distributions, measured in vivo from a deeply embedded live organ for further analysis. STUDY DESIGN/MATERIALS AND METHODS: Tissue-like phantoms with embedded fluorescent dyes and background optical properties simulating those of live tissues were designed and created. Fluorescence decay curves were measured for different fluorophore positions, and pH values. Those measurements were made with a system based on a time-correlated single photon counting (TCSPC) instrument and a tunable femtosecond Ti-Sapphire system built by our group. RESULTS: Decay curves were recorded for fluorophore depths of up to 5 mm and source-detector separation of 7 mm. It was shown that a forward model, based on the random walk theory, adequately described the experimental data. Measured pH dependencies of the fluorescence lifetime were characterized for two different dyes. CONCLUSIONS: Good correlation between experimental data and predictions of the theoretical model allows the use of close-form analytical solutions to separate the effects of photon time delays due to multiple scattering in tissues from the original intensity fluorescence time decay curve, determined by the fluorophore itself and its immediate surroundings. It is the latter dependence that can be diagnostically important. Experimentally obtained scaling between lifetime and a parameter of interest can be used in vivo to obtain a map of physiological parameter changes which can serve as a base for an in vivo specific diagnostic system.

Animals↗

PubMed2003

In vivo quantitative three-dimensional localization of tumor labeled with exogenous specific fluorescence markers.

We introduce a diffused optical detection system based on the administration of a fluorophore-antibody conjugate to diseased tissue. The conjugate interacts with the antigens expressed by the diseased tissue, resulting in fluorescent labeling of the antigen. By combining an optical detection system with a reconstruction algorithm developed on the basis of the random-walk model, we were able to determine the position of the fluorophore (and, thus, of the diseased cells) in the tissue. We present three-dimensional reconstructions of the location of a fluorophore (FITC-fluorescein isothiocyanate) in the tongues of mice. Measurements were performed with the fluorophore embedded at various simulated depths. The simulations were performed with agarose-based gel slabs applied to the tongue as tissuelike phantoms. Reconstructed fluorophore locations agree well with the actual values.

Algorithms↗

PubMed2003

Tissue characterization by quantitative optical imaging methods.

Optical methods have a long history in the field of medical diagnosis. The biomolecular specificity possible with optical methods has been particularly valuable in microscopy and histopathology while in vivo imaging of deep structures has traditionally been the domain of X-ray and MRI. The use of optical methods in deep tissue has been limited by multiple-scattering which blurs or distorts the optical signal. New stochastic methods which account for multiple scattering have been developed that are extending the usefulness of optical methods deep into tissue. In optical mammography, photons may travel through 10 cm of tissue before arriving at the detector. We have developed a method for quantifying parameters of anomalous sites in breast tissue that may be used for functional characterization of tumors. In other work presented here, we are developing fluorescence based methods to detect and monitor tumor status. The immune response to a tumor is a target for fluorescently labeled specific antibodies. We have developed a method to localize the tumor site using CW fluorescence. Additionally, we have developed a method which uses time-resolved data and capitalizes on probe lifetime sensitivity to metabolic parameters such as pH and temperature to obtain functional information from the tumor site.

Algorithms↗

PubMed2002

Quantification of optical properties of a breast tumor using random walk theory.

For the first time we use a random walk methodology based on time-dependent contrast functions to quantify the optical properties of breast tumors (invasive ductal carcinoma) of two patients. Previously this theoretical approach was successfully applied for analysis of embedded objects in several phantoms. Data analysis was performed on distributions of times of flight for photons transmitted through the breast which were recorded in vivo using a time-domain scanning mammograph at 670 and 785 nm. The size of the tumors, their optical properties, and those of the surrounding tissue were reconstructed at both wavelengths. The tumors showed increased absorption and scattering. From the absorption coefficients at both wavelengths blood oxygen saturation was estimated for the tumors and the surrounding tissue.

Absorption↗

PubMed2002

Analytical calculation of the mean time spent by photons inside an absorptive inclusion embedded in a highly scattering medium.

The mean time spent by photons inside a nonlocalized optically abnormal embedded inclusion has been derived analytically. The accuracy of the results has been tested against Monte Carlo and experimental data. We show that for quantification of the absorption coefficient of absorptive inclusions, a corrective factor that takes into account the size of the inclusion is needed. This finding suggests that perturbation methods derived for very small inclusions which are used in inverse algorithms require a corrective factor to adequately quantify the differential absorption coefficient of nonlocalized targets embedded in optically turbid media.

Biophysical Phenomena↗

PubMedDate not supplied

Use of small-angle neutron scattering to study tubulin polymers.

Small-angle neutron scattering has been used to examine taxol-stabilized microtubules and other tubulin samples in both H(2)O and D(2)O buffers. Measurements were made at pH/pD values between 6.0 and 7.8, and observed scattered intensities, I(Q), have been interpreted in terms of multicomponent models of microtubules and related tubulin polymers. A semiquantitative curve fitting procedure has been used to estimate the relative amounts of the supramolecular components of the samples. At both pH and pD 7.0 and above, the tubulin polymers are seen to be predominantly microtubules. Although in H(2)O buffer the polymer distribution is little changed as the pH varies, when pD is lowered the samples appear to contain an appreciable amount of sheetlike structures and the average microtubule protofilament number increases from ca. 12.5 at pD > or = approximately 7.0 to ca. 14 at pD approximately 6.0. Such structural change indicates that analysis of microtubule solutions based on H(2)O/D(2)O contrast variation must be performed with caution, especially at lower pH/pD.

Biopolymers↗

PubMedDate not supplied

Differential oblique angle spectroscopy of the oral epithelium.

Increasing evidence suggests that inflammation may contribute to the process of carcinogenesis. This is the basis of several clinical trials evaluating potential chemopreventive drugs. These trials require quantitative assessments of inflammation, which, for the oral epithelium, are traditionally provided by histopathological evaluation. To reduce patient discomfort and morbidity of tissue biopsy procedures, we develop a noninvasive alternative using diffuse reflectance spectroscopy to measure epithelial thickness as an index of tissue inflammation. Although any optical system has the potential for probing near-surface structures, traditional methods of accounting for scattering of photons are generally invalid for typical epithelial thicknesses. We develop a single-scattering theory that is valid for typical epithelial thicknesses. The theory accurately predicts a distinctive feature that can be used to quantify epithelial thickness given intensity measurements with sources at two different angles relative to the tissue surface. This differential measure approach has acute sensitivity to small, layer-related changes in scattering coefficients. To assess the capability of our method to quantify epithelial thickness, detailed Monte Carlo simulations and measurements on phantom models of a two-layered structure are performed. The results show that the intensity ratio maximum feature can be used to quantify epithelial thickness with an error less than 30% despite fourfold changes in scattering coefficients and 10-fold changes in absorption coefficients. An initial study using a simple two-source, four-detector probe on patients shows that the technique has promise. We believe that this new method will perform well on patients with diverse tissue optical characteristics and therefore be of practical clinical value for quantifying epithelial thickness in vivo.

Algorithms↗

PubMedDate not supplied

Intensity profiles of linearly polarized light backscattered from skin and tissue-like phantoms.

Anisotropy of mouse and human skin is investigated in vivo using polarized videoreflectometry. An incident beam (linearly polarized, wavelength 650 nm) is focused at the sample surface. Two types of tissuelike media are used as controls to verify the technique: isotropic delrin and highly anisotropic demineralized bone with a priori knowledge of preferential orientation of collagen fibers. Equi-intensity profiles of light, backscattered from the sample, are fitted with ellipses that appear to follow the orientation of the collagen fibers. The ratio of the ellipse semiaxes is well correlated with the ratio of reduced scattering coefficients obtained from radial intensity distributions. Variation of equi-intensity profiles with distance from the incident beam is analyzed for different initial polarization states of the light and the relative orientation of polarization filters for incident and backscattered light. For the anisotropic media (demineralized bone and human and mouse skin), a qualitative difference between intensity distributions for cross- and co-polarized orientations of the polarization analyzer is observed up to a distance of 1.5 to 2.5 mm from the entry point. The polarized videoreflectometry of the skin may be a useful tool to assess skin fibrosis resulting from radiation treatment.

Animals↗