Contrast-enhanced microwave imaging of breast tumors: a computational study using 3-D realistic numerical phantoms.

The detection of early-stage tumors in the breast by microwave imaging is challenged by both the moderate endogenous dielectric contrast between healthy and malignant glandular tissues and the spatial resolution available from illumination at microwave frequencies. The high endogenous dielectric contrast between adipose and fibroglandular tissue structures increases the difficulty of tumor detection due to the high dynamic range of the contrast function to be imaged and the low level of signal scattered from a tumor relative to the clutter scattered by normal tissue structures. Microwave inverse scattering techniques, used to estimate the complete spatial profile of the dielectric properties within the breast, have the potential to reconstruct both normal and cancerous tissue structures. However, the ill-posedness of the associated inverse problem often limits the frequency of microwave illumination to the UHF band within which early-stage cancers have sub-wavelength dimensions. In this computational study, we examine the reconstruction of small, compact tumors in three-dimensional numerical breast phantoms by a multiple-frequency inverse scattering solution. Computer models are also employed to investigate the use of exogenous contrast agents for enhancing tumor detection. Simulated array measurements are acquired before and after the introduction of the assumed contrast effects for two specific agents currently under consideration for breast imaging: microbubbles and carbon nanotubes. Differential images of the applied contrast demonstrate the potential of the approach for detecting the preferential uptake of contrast agents by malignant tissues.

The Role of Plasmalemmal-Cortical Anchoring on the Stability of Transmembrane Electropores.

The structure of eukaryotic cells is maintained by a network of filamentous actin anchored subjacently to the plasma membrane. This structure is referred to as the actin cortex. We present a locally constrained surface tension model for electroporation in order to address the influence of plasmalemmal-cortical anchoring on electropore dynamics. This model predicts that stable electropores are possible under certain conditions. The existence of stable electropores has been suggested in several experimental studies. The electropore radius at which stability is achieved is a function of the characteristic radii of locally constrained regions about the plasma membrane. This model opens the possibility of using actin-modifying compounds to physically manipulate cortical density, thereby manipulating electroporation dynamics. It also underscores the need to improve electroporation models further by incorporating the influence of trans-electropore ionic and aqueous flow, cortical flexibility, transmembrane protein mobility, and active cellular wound healing mechanisms.

Quantification of electroporative uptake kinetics and electric field heterogeneity effects in cells.

We have conducted experiments quantitatively investigating electroporative uptake kinetics of a fluorescent plasma membrane integrity indicator, propidium iodide (PI), in HL60 human leukemia cells resulting from exposure to 40 mus pulsed electric fields (PEFs). These experiments were possible through the use of calibrated, real-time fluorescence microscopy and the development of a microcuvette: a specialized device designed for exposing cell cultures to intense PEFs while carrying out real-time microscopy. A finite-element electrostatic simulation was carried out to assess the degree of electric field heterogeneity between the microcuvette's electrodes allowing us to correlate trends in electroporative response to electric field distribution. Analysis of experimental data identified two distinctive electroporative uptake signatures: one characterized by low-level, decelerating uptake beginning immediately after PEF exposure and the other by high-level, accelerating fluorescence that is manifested sometimes hundreds of seconds after PEF exposure. The qualitative nature of these fluorescence signatures was used to isolate the conditions required to induce exclusively transient electroporation and to discuss electropore stability and persistence. A range of electric field strengths resulting in transient electroporation was identified for HL60s under our experimental conditions existing between 1.6 and 2 kV/cm. Quantitative analysis was used to determine that HL60s experiencing transient electroporation internalized between 50 and 125 million nucleic acid-bound PI molecules per cell. Finally, we show that electric field heterogeneity may be used to elicit asymmetric electroporative PI uptake within cell cultures and within individual cells.

Simultaneous optical wavelength interchange with a two-dimensional second-order nonlinear photonic crystal.

We present a theoretical analysis for simultaneous optical wavelength interchange and isolation of a pair of collinear input optical signals by use of two concurrent difference-frequency-generation processes in a two-dimensional second-order nonlinear photonic crystal. We have derived a set of relations, including a general nonlinear Bragg condition, that we use to determine the parameters of the nonlinear lattice, given the input wavelengths and desired exit angles of the wavelength-interchanged outputs.

Two-dimensional FDTD analysis of a pulsed microwave confocal system for breast cancer detection: fixed-focus and antenna-array sensors.

A novel focused active microwave system is investigated for detecting tumors in the breast. In contrast to X-ray and ultrasound modalities, the method reviewed here exploits the breast-tissue physical properties unique to the microwave spectrum, namely, the translucent nature of normal breast tissues and the high dielectric contrast between malignant tumors and surrounding lesion-free normal breast tissues. The system uses a pulsed confocal technique and time-gating to enhance the detection of tumors while suppressing the effects of tissue heterogeneity and absorption. Using published data for the dielectric properties of normal breast tissues and malignant tumors, we have conducted a two-dimensional (2-D) finite-difference time-domain (FDTD) computational electromagnetics analysis of the system. The FDTD simulations showed that tumors as small as 2 mm in diameter could be robustly detected in the presence of the background clutter generated by the heterogeneity of the surrounding normal tissue. Lateral spatial resolution of the tumor location was found to be about 0.5 cm.

Finite-difference time-domain analysis of a complete transverse electromagnetic cell loaded with liquid biological media in culture dishes.

Transverse electromagnetic (TEM) cells can be used for exposing biological culture specimens to electromagnetic fields and observing possible anomalous effects. The uniformity of field exposure is critical to quantifying the biological response versus the electromagnetic dose. Standing waves and other electromagnetic field nonuniformities can cause nonuniform exposure. This paper reports the results of high-resolution three-dimensional finite-difference time-domain (FDTD) simulations of a complete TEM cell designed for operation at 837 MHz. Several different cases were studied in which the number of culture dishes, the depth of the culture liquid, and the orientation of the culture dishes were varied. Further, the effect of the culture-dish glass bottom thickness and the meniscus of the liquid medium were examined. The FDTD results show that there is a significant nonuniform field and specific absorption rate (SAR) distribution within the culture medium for each case examined. Hence, biological dose-response experiments using the TEM cells should account for the possibility of strong localized SAR peaking in the culture media to provide useful data in setting exposure standards for wireless communications.

Waveguide-coupled AlGaAs / GaAs microcavity ring and disk resonators with high f inesse and 21.6-nm f ree spectral range.

We report the realization and demonstration of novel semiconductor waveguide-coupled microcavity ring and disk resonators. For a 10.5-microm-diameter disk resonator, we measure a finesse of 120, a resonant linewidth of 0.18 nm, and a free-spectral range of 21.6 nm in the 1.55-mum-wavelength region. We present the nanofabrication methods and the experimental results for 10.5- and 20.5-mum-diameter ring and disk resonators to show the feasibility of such devices.