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Biomedical subjects

Israel Gannot

Publications and source records attributed to Israel Gannot.

6 recordsLinked to original sources

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↗

Theoretical and experimental investigation of the thermal effects within body cavities during transendoscopical CO2 laser-based surgery.

BACKGROUND AND OBJECTIVES: The recent development of flexible hollow waveguides for MID-IR lasers may be utilized transendoscopically to ablate selectively neoplastic, superficial tissues within body cavities. Study goals are to investigate theoretically and experimentally heat distribution and thermal response of cavity lining, during CO2 laser minimally invasive surgery (MIS), and to thermally optimize the procedure under practical conditions. STUDY DESIGN/MATERIALS AND METHODS: Mathematical model was developed to predict temperature distribution along cavity lining. Experimental setup was built, including all the necessary components for a fully feedback-controlled MIS, i.e., laser generator, gas insufflating system, surgical suction, and infrared imaging feedback mechanism, all controlled by central PC-based program. Thermal images of cavity lining were recorded and analyzed throughout varying conditions. RESULTS: Thermal gradients along the cavity lining, during and after the laser irradiation, were obtained mathematically and experimentally. Diverse modes of heat dispersions were observed, as well as the relative contributions of user-controlled parameters to the maximal heat of cavity lining. The software-controlled setup has demonstrated the capacity to instantly manage varying conditions, by which it automatically protects cavity lining from getting overheated. CONCLUSIONS: Analytical predictions and experimental measurements were highly correlated. The software-controlled system may serve a powerful tool to control thermal side effects during MIS within body cavities.

Carbon Dioxide↗

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↗

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↗

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↗

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↗