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Biomedical subjects

Rebekah A Drezek

Publications and source records attributed to Rebekah A Drezek.

7 recordsLinked to original sources

Metal nanoshells.

Metal nanoshells are a new class of nanoparticles with highly tunable optical properties. Metal nanoshells consist of a dielectric core nanoparticle such as silica surrounded by an ultrathin metal shell, often composed of gold for biomedical applications. Depending on the size and composition of each layer of the nanoshell, particles can be designed to either absorb or scatter light over much of the visible and infrared regions of the electromagnetic spectrum, including the near infrared region where penetration of light through tissue is maximal. These particles are also effective substrates for surface-enhanced Raman scattering (SERS) and are easily conjugated to antibodies and other biomolecules. One can envision a myriad of potential applications of such tunable particles. Several potential biomedical applications are under development, including immunoassays, modulated drug delivery, photothermal cancer therapy, and imaging contrast agents.

Animals↗

Near infrared laser-tissue welding using nanoshells as an exogenous absorber.

BACKGROUND AND OBJECTIVE: Gold nanoshells are a new class of nanoparticles that can be designed to strongly absorb light in the near infrared (NIR). These particles provide much larger absorption cross-sections and efficiency than can be achieved with currently used chemical chromophores without photobleaching. In these studies, we have investigated the use of gold nanoshells as exogenous NIR absorbers to facilitate NIR laser-tissue welding. STUDY DESIGN/MATERIALS AND METHODS: Gold nanoshells with peak extinction matching the NIR wavelength of the laser being used were manufactured and suspended in an albumin solder. Optimization work was performed on ex vivo muscle samples and then translated into testing in an in vivo rat skin wound-healing model. Mechanical testing of the muscle samples was immediately performed and compared to intact tissue mechanical properties. In the in vivo study, full thickness incisions in the dorsal skin of rats were welded, and samples of skin were excised at 0, 5, 10, 21, and 32 days for analysis of strength and wound healing response. RESULTS: Mechanical testing of nanoshell-solder welds in muscle revealed successful fusion of tissues with tensile strengths of the weld site equal to the uncut tissue. No welding was accomplished with this light source when using solder formulations without nanoshells. Mechanical testing of the skin wounds showed sufficient strength for closure and strength increased over time. Histological examination showed good wound-healing response in the soldered skin. CONCLUSIONS: The use of nanoshells as an exogenous absorber allows the usage of light sources that are minimally absorbed by tissue components, thereby, minimizing damage to surrounding tissue and allowing welding of thicker tissues.

Animals↗

Optical imaging of the cervix.

Recent advances in fiber optics, sources and detectors, imaging, and computer-controlled instrumentation have stimulated a period of unprecedented growth in the development of photonics technologies for a wide variety of diagnostic and therapeutic clinical applications. These include the application of quantitative optical spectroscopy and imaging for the detection of precancerous lesions in the uterine cervix, a topic of interest at the Second International Conference on Cervical Cancer, which was held April 11-14, 2002. Investigators have applied the Littenberg method of emerging technology assessment to new optical methods used to detect cervical neoplasia. Currently, such technologies as fluorescence spectroscopy (the combination of fluorescence and diffuse reflectance spectroscopy), tri-modal spectroscopy, and light-scattering spectroscopy that probe the spectral characteristics of tissue are being investigated. Optical technologies that create images of subcellular structure without biopsy subsequent to pathology that currently are under investigation include in vivo confocal imaging and optical coherence tomography. Numerous small studies have demonstrated the potential of these optical technologies. What remains to be elucidated are the fundamental biophysical origins of variations in remitted optical signals between normal and dysplastic tissue. Large multicenter randomized controlled trials are needed to confirm the detection and imaging capabilities of optical technology. Furthermore, the development of contrast agents that could boost detection with these technologies is needed, and basic biologic characterization of signals should be pursued. Applying the Littenberg assessment will help ensure that superior, not simply alternative, technologies are implemented.

Cervix Uteri↗

Oblique-incidence illumination and collection for depth-selective fluorescence spectroscopy.

Optimization of device-tissue interface parameters may lead to an improvement in the efficacy of fluorescence spectroscopy for minimally invasive disease detection. Although illumination-collection geometry has been shown to have a strong influence on the spatial origin of detected fluorescence, devices that deliver and/or collect light at oblique incidence are not well understood. Simulations are performed using a Monte Carlo model of light propagation in homogeneous tissue to characterize general trends in the intensity and spatial origin of fluorescence detected by angled geometries. Specifically, the influence of illumination angle, collection angle, and illumination-collection spot separation distance are investigated for low and high attenuation tissue cases. Results indicate that oblique-incidence geometries have the potential to enhance the selective interrogation of superficial or subsurface fluorophores at user-selectable depths up to about 0.5 mm. Detected fluorescence intensity is shown to increase significantly with illumination and collection angle. Improved selectivity and signal intensity over normal-incidence geometries result from the overlap of illumination and collection cones within the tissue. Cases involving highly attenuating tissue produce a moderate reduction in the depth of signal origin. While Monte Carlo modeling indicates that oblique-incidence designs can facilitate depth-selective fluorescence spectroscopy, optimization of device performance will require application-specific consideration of optical and biological parameters.

Algorithms↗

Optically tunable nanoparticle contrast agents for early cancer detection: model-based analysis of gold nanoshells.

Many optical diagnostic approaches rely on changes in scattering and absorption properties to generate optical contrast between normal and diseased tissue. Recently, there has been increasing interest in using exogenous agents to enhance this intrinsic contrast with particular emphasis on the development for targeting specific molecular features of disease. Gold nanoshells are a class of core-shell nanoparticles with an extremely tunable peak optical resonance ranging from the near-UV to the mid-IR wavelengths. Using current chemistries, nanoshells of a wide variety of core and shell sizes can easily be fabricated to scatter and/or absorb light with optical cross sections often several times larger than the geometric cross section. Using gold nanoshells of different size and optical parameters, we employ Monte Carlo models to predict the effect of varying concentrations of nanoshells on tissue reflectance. The models demonstrate the importance of absorption from the nanoshells on remitted signals even when the optical extinction is dominated by scattering. Furthermore, because of the strong optical response of nanoshells, a considerable change in reflectance is observed with only a very small concentration of nanoshells. Characterizing the optical behavior of gold nanoshells in tissue will aid in developing nanoshells as contrast agents for optical diagnostics.

Animals↗

Quantitative evaluation of optical coherence tomography signal enhancement with gold nanoshells.

Nanoshell-enhanced optical coherence tomography (OCT) is a novel technique with the potential for molecular imaging and improved disease detection. However, optimization of this approach will require a quantitative understanding of the influence of nanoshell parameters on detected OCT signals. In this study, OCT was performed at 1310 nm in water and turbid tissue-simulating phantoms to which nanoshells were added. The effect of nanoshell concentration, core diameter, and shell thickness on signal enhancement was characterized. Experimental results indicated trends that were consistent with predicted optical properties-a monotonic increase in signal intensity and attenuation with increasing shell and core size. Threshold concentrations for a 2-dB OCT signal intensity gain were determined for several nanoshell geometries. For the most highly backscattering nanoshells tested-291-nm core diameter, 25-nm shell thickness-a concentration of 10(9) nanoshells/mL was needed to produce this signal increase. Based on these results, we discuss various practical considerations for optimizing nanoshell-enhanced OCT. Quantitative experimental data presented here will facilitate optimization of OCT-based diagnostics and may also be relevant to other reflectance-based approaches as well.

Contrast Media↗

Endogenous fluorescence spectroscopy of cell suspensions for chemopreventive drug monitoring.

Cancer chemopreventive agents such as N-4-(hydroxyphenyl)retinamide (4HPR) are thought to prevent cancers by suppressing growth or inducing apoptosis in precancerous cells. Mechanisms by which these drugs affect cells are often not known, and the means to monitor their effects is not available. In this study endogenous fluorescence spectroscopy was used to measure metabolic changes in response to treatment with 4HPR in ovarian and bladder cancer cell lines. Fluorescence signals consistent with nicotinamide adenine dinucleotide (NADH), flavin adenine dinucleotide (FAD) and tryptophan were measured to monitor cellular activity through redox status and protein content. Cells were treated with varying concentrations of 4HPR and measured in a stable environment with a sensitive fluorescence spectrometer. Results suggest that redox signal of all cells changed in a similar dose-dependant manner but started at different baseline levels. Redox signal changes depended primarily on changes consistent with NADH fluorescence, whereas the FAD fluorescence remained relatively constant. Similarly, tryptophan fluorescence decreased with increased drug treatment, suggesting a decrease in protein production. Given that each cell line has been shown to have a different apoptotic response to 4HPR, fluorescence redox values along with changes in tryptophan fluorescence may be a response as well as an endpoint marker for chemopreventive drugs.

Anticarcinogenic Agents↗