A Pilot Study of the Impact of Microwave Ablation on the Dielectric Properties of Breast Tissue.

Percutaneous microwave ablation (MWA) is a promising technology for patients with breast cancer, as it may help treat individuals who have less aggressive cancers or do not respond to targeted therapies in the neoadjuvant or pre-surgical setting. In this study, we investigate changes to the microwave dielectric properties of breast tissue that are induced by MWA. While similar changes have been characterized for relatively homogeneous tissues, such as liver, those prior results are not directly translatable to breast tissue because of the extreme tissue heterogeneity present in the breast. This study was motivated, in part by the expectation that the changes in the dielectric properties of the microwave antenna's operation environment will be impacted by tissue composition of the ablation target, which includes not only the tumor, but also its margins. Accordingly, this target comprises a heterogeneous mix of malignant, healthy glandular, and adipose tissue. Therefore, knowledge of MWA impact on breast dielectric properties is essential for the successful development of MWA systems for breast cancer. We performed ablations in 14 human ex-vivo prophylactic mastectomy specimens from surgeries that were conducted at the UW Hospital and monitored the temperature in the vicinity of the MWA antenna during ablation. After ablation we measured the dielectric properties of the tissue and analyzed the tissue samples to determine both the tissue composition and the extent of damage due to the ablation. We observed that MWA induced cell damage across all tissue compositions, and found that the microwave frequency-dependent relative permittivity and conductivity of damaged tissue are lower than those of healthy tissue, especially for tissue with high fibroglandular content. The results provide information for future developments on breast MWA systems.

Ionomycin-Induced Changes in Membrane Potential Alter Electroporation Outcomes in HL-60 Cells.

Previous studies have shown greater fluorophore uptake during electroporation on the anode-facing side of the cell than on the cathode-facing side. Based on these observations, we hypothesized that hyperpolarizing a cell before electroporation would decrease the requisite pulsed electric field intensity for electroporation outcomes, thereby yielding a higher probability of reversible electroporation at lower electric field strengths and a higher probability of irreversible electroporation (IRE) at higher electric field strengths. In this study, we tested this hypothesis by hyperpolarizing HL-60 cells using ionomycin before electroporation. These cells were then electroporated in a solution containing propidium iodide, a membrane integrity indicator. After 20 min, we added trypan blue to identify IRE cells. Our results showed that hyperpolarizing cells before electroporation alters the pulsed electric field intensity thresholds for reversible electroporation and IRE, allowing for greater control and selectivity of electroporation outcomes.

The impact of frequency on the performance of microwave ablation.

PURPOSE: The use of higher frequencies in percutaneous microwave ablation (MWA) may offer compelling interstitial antenna design advantages over the 915 MHz and 2.45 GHz frequencies typically employed in current systems. To evaluate the impact of higher frequencies on ablation performance, we conducted a comprehensive computational and experimental study of microwave absorption and tissue heating as a function of frequency. METHODS: We performed electromagnetic and thermal simulations of MWA in ex vivo and in vivo porcine muscle at discrete frequencies in the 1.9-26 GHz range. Ex vivo ablation experiments were performed in the 1.9-18 GHz range. We tracked the size of the ablation zone across frequency for constant input power and ablation duration. Further, we conducted simulations to investigate antenna feed line heating as a function of frequency, input power, and cable diameter. RESULTS: As the frequency was increased from 1.9 to 26 GHz the resulting ablation zone dimensions decreased in the longitudinal direction while remaining relatively constant in the radial direction; thus at higher frequencies the overall ablation zone was more spherical. However, cable heating at higher frequencies became more problematic for smaller diameter cables at constant input power. CONCLUSION: Comparably sized ablation zones are achievable well above 1.9 GHz, despite increasingly localised power absorption. Specific absorption rate alone does not accurately predict ablation performance, particularly at higher frequencies where thermal diffusion plays an important role. Cable heating due to ohmic losses at higher frequencies may be controlled through judicious choices of input power and cable diameter.

A TSVD Analysis of the Impact of Polarization on Microwave Breast Imaging using an Enclosed Array of Miniaturized Patch Antennas.

Microwave breast imaging performance is fundamentally dependent on the quality of information contained within the scattering data. We apply a truncated singular-value decomposition (TSVD) method to evaluate the information contained in a simulated scattering scenario wherein a compact, shielded array of miniaturized patch antennas surrounds an anatomically realistic numerical breast phantom. In particular, we investigate the impact of different antenna orientations (and thus polarizations), namely two array configurations with uniform antenna orientations and one mixed-orientation array configuration. The latter case is of interest because it may offer greater flexibility in antenna and array design. The results of this analysis indicate that mixed-polarization configurations do not degrade information quality compared to uniform-polarization configurations and in fact may enhance imaging performance, and thus represent viable design options for microwave breast imaging systems.

Beamforming-Enhanced Inverse Scattering for Microwave Breast Imaging.

We present a focal-beamforming-enhanced formulation of the distorted Born iterative method (DBIM) for microwave breast imaging. Incorporating beamforming into the imaging algorithm has the potential to mitigate the effect of noise on the image reconstruction. We apply the focal-beamforming-enhanced DBIM algorithm to simulated array measurements from two MRI-derived, anatomically realistic numerical breast phantoms and compare its performance to that of the DBIM formulated with two non-focal schemes. The first scheme simply averages scattered field data from reciprocal antenna pairs while the second scheme discards reciprocal pairs. Images of the dielectric properties are reconstructed for signal-to-noise ratios (SNR) ranging from 35 dB down to 0 dB. We show that, for low SNR, the focal beamforming algorithm creates reconstructions that are of higher fidelity with respect to the exact dielectric profiles of the phantoms as compared to reconstructions created using the non-focal schemes. At high SNR, the focal and non-focal reconstructions are of comparable quality.

Electric pulse exposure reduces AAV8 dosage required to transduce HepG2 cells.

We demonstrate that applying electric field pulses to hepatocytes, in vitro, in the presence of enhanced green fluorescent protein (EGFP)-expressing adeno-associated virus (AAV8) vectors reduces the viral dosage required for a given transduction level by more than 50-fold, compared to hepatocytes exposed to AAV8-EGFP vectors without electric field pulse exposure. We conducted 48 experimental observations across 8 exposure conditions in standard well plates. The electric pulse exposures involved single 80-ms pulses with 375 V/cm field intensity. Our study suggests that electric pulse exposure results in enhanced EGFP expression in cells, indicative of increased transduction efficiency. The enhanced transduction observed in our study, if translated successfully to an in vivo setting, would be a promising indication of potential reduction in the required dose of AAV vectors. Understanding the effects of electric field pulses on AAV transduction in vitro is an important preliminary step.

Microwave dielectric properties of normal, fibroelastotic, and malignant human lung tissue.

Technological development of microwave treatment and detection techniques for lung cancer requires accurate and comprehensive knowledge of the microwave dielectric properties of human lung tissue. We characterize the dielectric properties of room temperature human lung tissue from 0.5 to 10 GHz for three lung tissue groups: normal, fibroelastotic, and malignant. We fit a two-pole Debye model to the measured frequency-dependent complex permittivity and calculate the median Debye parameters for the three groups. We find that malignant lung tissue is approximately 10% higher in relative permittivity and conductivity compared to normal lung tissue; this trend matches previously reported normal versus malignant data for other biological tissues. There is little contrast between benign lung tissue with fibroelastosis and malignant lung tissue. We extrapolate our data from room temperature to 37 °C using a temperature-dependence model for animal lung tissue and use the Maxwell-Garnett dielectric mixing model to predict the dielectric properties of inflation-dynamic human lung tissue; both approximations correspond with previously reported dielectric data of bovine and porcine lung tissue.

Multi-Band Miniaturized Patch Antennas for a Compact, Shielded Microwave Breast Imaging Array.

We present a comprehensive study of a class of multi-band miniaturized patch antennas designed for use in a 3D enclosed sensor array for microwave breast imaging. Miniaturization and multi-band operation are achieved by loading the antenna with non-radiating slots at strategic locations along the patch. This results in symmetric radiation patterns and similar radiation characteristics at all frequencies of operation. Prototypes were fabricated and tested in a biocompatible immersion medium. Excellent agreement was obtained between simulations and measurements. The trade-off between miniaturization and radiation efficiency within this class of patch antennas is explored via a numerical analysis of the effects of the location and number of slots, as well as the thickness and permittivity of the dielectric substrate, on the resonant frequencies and gain. Additionally, we compare 3D quantitative microwave breast imaging performance achieved with two different enclosed arrays of slot-loaded miniaturized patch antennas. Simulated array measurements were obtained for a 3D anatomically realistic numerical breast phantom. The reconstructed breast images generated from miniaturized patch array data suggest that, for the realistic noise power levels assumed in this study, the variations in gain observed across this class of multi-band patch antennas do not significantly impact the overall image quality. We conclude that these miniaturized antennas are promising candidates as compact array elements for shielded, multi-frequency microwave breast imaging systems.

Cultivating well-being in engineering graduate students through mindfulness training.

The mental health crisis in graduate education combined with low treatment rates among engineering graduate students underscores the need for engineering graduate programs to provide effective methods to promote well-being. There is an extensive body of neuroscience research showing that contemplative practices, such as mindfulness, produce measurable effects on brain function and overall well-being. We hypothesized that a mindfulness-based training program designed for engineering graduate students would improve emotional well-being and, secondarily, enhance research capacity. An initial pilot study was conducted at a single institution (Phase 1), followed by a larger study conducted at both the original and a second institution (Phase 2) to gather additional data and show the program's transferability. The program comprised eight weekly mindfulness training sessions. Individuals in the study were randomly assigned to either an intervention group or wait-list control group. We administered pre- and post-test surveys with quantitative measures designed to assess emotional and physical well-being, as well as creativity, research satisfaction, and desire to contribute to the betterment of society. Participants also completed a summative survey to evaluate the impact of the program on their well-being and research. Analysis revealed statistically significant findings: improved emotional health, decreased neuroticism, increased positive affect, decreased negative affect, and increased mindfulness in the intervention groups compared to the control groups. Intervention groups in Phase 2 also reported statistically significant improvement in satisfaction with their research. Our findings suggest that mindfulness training has the potential to play a vital professional and personal development role in graduate engineering education.

Quantitative Microwave Imaging of Realistic Numerical Breast Phantoms Using an Enclosed Array of Multiband, Miniaturized Patch Antennas.

We present a 3-D microwave breast imaging study in which we reconstruct the dielectric profiles of MRI-derived numerical breast phantoms from simulated array measurements using an enclosed array of multiband, miniaturized patch antennas. The array is designed to overcome challenges relating to the ill-posed nature of the inverse scattering system. We use a multifrequency formulation of the distorted Born iterative method to image four normal-tissue breast phantoms, each corresponding to a different density class. The reconstructed fibroglandular distributions are very faithful to the true distributions in location and basic shape. These results establish the feasibility of using an enclosed array of miniaturized, multiband patch antennas for quantitative microwave breast imaging.

MRI-Derived 3-D-Printed Breast Phantom for Microwave Breast Imaging Validation.

We propose a 3-D-printed breast phantom for use in preclinical experimental microwave imaging studies. The phantom is derived from an MRI of a human subject; thus, it is anthropomorphic, and its interior is very similar to an actual distribution of fibroglandular tissues. Adipose tissue in the breast is represented by the solid plastic (printed) regions of the phantom, while fibroglandular tissue is represented by liquid-filled voids in the plastic. The liquid is chosen to provide a biologically relevant dielectric contrast with the printed plastic. Such a phantom enables validation of microwave imaging techniques. We describe the procedure for generating the 3-D-printed breast phantom and present the measured dielectric properties of the 3-D-printed plastic over the frequency range 0.5-3.5 GHz. We also provide an example of a suitable liquid for filling the fibroglandular voids in the plastic.

Microwave-induced thermoacoustic signal characteristics in a dynamic temperature environment.

We conduct a simulation-based study to investigate the impact of a dynamic temperature environment on the characteristics of microwave-induced thermoacoustic signals. We investigate thermoacoustic signals that are generated using an interstitial microwave ablation antenna powered by a microsecond pulsed microwave source. Two temperature regimes are examined: first, a spatially uniform temperature throughout the medium to experimentally validate the simulation model, and second, the realistic, spatially nonuniform temperature profiles that arise during microwave ablation. We employ a multi-physics model that considers electromagnetics, heat transfer, and acoustic physics to simulate the coupled processes of microwave absorption and heating of the medium and thermoacoustic signal generation and propagation. An interstitial coaxial antenna is used to generate microsecond microwave pulses that simultaneously induce microwave heating and excite thermoacoustic signals via microwave pulse absorption. We find that thermoacoustic signal characteristics are highly temperature-dependent and thus change significantly within an environment where temperature varies through space and time. Furthermore, the temperature-dependent properties within the active region of the antenna drive the evolution of thermoacoustic signal characteristics. Temperature-dependent thermoacoustic signal characteristics can be exploited to track the progress of microwave ablation. Consequently, microwave-induced thermoacoustic imaging is a promising method for monitoring microwave ablation in real-time.

Ex Vivo Performance of a Flexible Microwave Ablation Antenna.

OBJECTIVE: In this study, we investigate the performance of a flexible microwave ablation antenna for generating localized ablation zones. METHODS: We designed a helical dipole antenna to operate at 1.9 GHz in egg white and liver. Semi-rigid prototypes of the antenna were fabricated and used to perform ablation experiments in egg white and perfused liver. Pulsed and continuous-wave power deliveries at different power levels were used. Flexible prototypes of the antenna were fabricated and used to perform ex vivo ablation experiments in perfused liver. RESULTS: Pulsing was effective in reducing the shaft heating of semi-rigid cables. The antenna was capable of producing substantial ablation zones in perfused liver. Typical diameters (perpendicular to the antenna axis) of generated ablation zones with semi-rigid antennas in egg white and perfused liver were 30 mm and 20 mm, respectively. The flexible antenna had a good impedance match while bent. Average diameter of generated ablation zones by the flexible antenna with 10-W continuous-wave experiments in perfused liver was 26 mm. No significant difference was observed between the performances of semi-rigid and flexible prototypes. CONCLUSION: The flexible helical dipole antenna is capable of maintaining its good impedance match while bent and can generate substantial ablation zones in presence of perfusion. SIGNIFICANCE: The proposed flexible antenna is promising for minimally invasive treatment of tumors that are otherwise inaccessible by rigid antennas. One example is lung where a catheter-based deployment of the flexible antenna into the tumor via airways may substantially reduce risks associated with using rigid antennas.

Three-dimensional microwave imaging of realistic numerical breast phantoms via a multiple-frequency inverse scattering technique.

PURPOSE: Breast density measurement has the potential to play an important role in individualized breast cancer risk assessment and prevention decisions. Routine evaluation of breast density will require the availability of a low-cost, nonionizing, three-dimensional (3-D) tomographic imaging modality that exploits a strong properties contrast between dense fibroglandular tissue and less dense adipose tissue. The purpose of this computational study is to investigate the performance of 3-D tomography using low-power microwaves to reconstruct the spatial distribution of breast tissue dielectric properties and to evaluate the modality for application to breast density characterization. METHODS: State-of-the-art 3-D numerical breast phantoms that are realistic in both structural and dielectric properties are employed. The test phantoms include one sample from each of four classes of mammographic breast density. Since the properties of these phantoms are known exactly, these testbeds serve as a rigorous benchmark for the imaging results. The distorted Born iterative imaging method is applied to simulated array measurements of the numerical phantoms. The forward solver in the imaging algorithm employs the finite-difference time-domain method of solving the time-domain Maxwell's equations, and the dielectric profiles are estimated using an integral equation form of the Helmholtz wave equation. A multiple-frequency, bound-constrained, vector field inverse scattering solution is implemented that enables practical inversion of the large-scale 3-D problem. Knowledge of the frequency-dependent characteristic of breast tissues at microwave frequencies is exploited to obtain a parametric reconstruction of the dispersive dielectric profile of the interior of the breast. Imaging is performed on a high-resolution voxel basis and the solution is bounded by a known range of dielectric properties of the constituent breast tissues. The imaging method is validated using a breast phantom with a single, high-contrast interior scattering target in an otherwise homogeneous interior. The method is then used to image a set of realistic numerical breast phantoms of varied fibroglandular tissue density. RESULTS: Imaging results are presented for each numerical phantom and show robustness of the method relative to tissue density. In each case, the distribution of fibroglandular tissues is well represented in the resulting images. The resolution of the images at the frequencies employed is wider than the feature dimensions of the normal tissue structures, resulting in a smearing of their reconstruction. CONCLUSIONS: The results of this study support the utility of 3-D microwave tomography for imaging the distribution of normal tissues in the breast, specifically, dense fibroglandular tissue versus less dense adipose tissue, and suggest that further investigation of its use for volumetric evaluation of breast density is warranted.

A Sparsity Regularization Approach to the Electromagnetic Inverse Scattering Problem.

We investigate solving the electromagnetic inverse scattering problem using the distorted Born iterative method (DBIM) in conjunction with a variable-selection approach known as the elastic net. The elastic net applies both ℓ1 and ℓ2 penalties to regularize the system of linear equations that result at each iteration of the DBIM. The elastic net thus incorporates both the stabilizing effect of the ℓ2 penalty with the sparsity encouraging effect of the ℓ1 penalty. The DBIM with the elastic net outperforms the commonly used ℓ2 regularizer when the unknown distribution of dielectric properties is sparse in a known set of basis functions. We consider two very different 3-D examples to demonstrate the efficacy and applicability of our approach. For both examples, we use a scalar approximation in the inverse solution. In the first example the actual distribution of dielectric properties is exactly sparse in a set of 3-D wavelets. The performances of the elastic net and ℓ2 approaches are compared to the ideal case where it is known a priori which wavelets are involved in the true solution. The second example comes from the area of microwave imaging for breast cancer detection. For a given set of 3-D Gaussian basis functions, we show that the elastic net approach can produce a more accurate estimate of the distribution of dielectric properties (in particular, the effective conductivity) within an anatomically realistic 3-D numerical breast phantom. In contrast, the DBIM with an ℓ2 penalty produces an estimate which suffers from multiple artifacts.

Dual-Band Miniaturized Patch Antennas for Microwave Breast Imaging.

We present a miniaturized, dual-band patch antenna array element that is designed for use in a 3-D microwave tomography system for breast imaging. Dual-band operation is achieved by manipulating the fundamental resonant mode of the patch antenna and one of its higher-order modes. Miniaturization and tuning of the resonant frequencies are achieved by loading the antenna with non-radiating slots at strategic locations along the patch. This results in a compact, dual-band antenna with symmetric radiation patterns and similar radiation characteristics at both bands of operation. The performance of the antenna in a biocompatible immersion medium is verified experimentally.

Multi-physics modeling of thermoacoustic pulse generation and propagation during pulsed microwave ablation of tissue.

Microwave-induced thermoacoustic (TA) imaging is a potential alternative to conventional real-time imaging methods for monitoring microwave ablation (MWA). In this study, we develop a multi-physics model for the generation and propagation of microwave-induced TA signals during pulsed MWA. Our model couples electromagnetics, heat transfer, and acoustics physics. We compare simulation and experimental results for a pulsed MWA system wherein a coaxial MWA antenna is used to heat water. The simulated and experimentally measured TA signals for this configuration are in good qualitative agreement. This multi-physics modeling tool is valuable for understanding the fundamentals of TA signal generation and propagation from within an evolving ablation zone.

Toward contrast-enhanced microwave-induced thermoacoustic imaging of breast cancer: an experimental study of the effects of microbubbles on simple thermoacoustic targets.

Microwave-induced thermoacoustic tomography (MI-TAT) is an imaging technique that exploits dielectric contrast at microwave frequencies while creating images with ultrasound resolution. We propose the use of microbubbles as a dielectric contrast agent for enhancing the sensitivity of MI-TAT for breast cancer detection. As an initial investigation of this concept, we experimentally studied the extent to which the microwave-induced thermoacoustic response of a dielectric target is modified by the presence of air-filled glass microbubbles. We created mixtures of ethylene glycol with varying weight percentages of microbubbles and characterized both their microwave properties (0.5-6 GHz) and thermoacoustic response when irradiated with microwave energy at 3 GHz. Our data show that the microbubbles considerably lowered the relative permittivity, electrical conductivity and thermoacoustic response of the ethylene glycol mixtures. We hypothesize that the interstitial infusion of microbubbles to a tumor site will similarly create a smaller thermoacoustic response compared to the pre-contrast-agent response, thereby enhancing sensitivity through the use of differential imaging techniques.

The Performance of Higher Frequency Microwave Ablation in the Presence of Perfusion.

OBJECTIVE: In this paper, we investigate the impact of perfusion on the performance of microwave ablation across a large frequency range. METHODS: We designed multiple microwave ablation antennas to operate in liver tissue at discrete frequencies in the range 1.9-18 GHz. We performed electromagnetic simulations to calculate microwave power absorption patterns. Five-minute, 25 W ablation experiments were performed at each frequency in perfused and nonperfused ex vivo porcine livers, and thermal lesion dimensions were measured. RESULTS: The volume of greatest microwave power absorption shrinks by two orders of magnitude as the frequency is increased from 1.9 to 18 GHz. Mean thermal lesion volumes are consistent across the frequency range for a given perfusion state and are about three times smaller under active perfusion. Typical thermal lesion diameters (perpendicular to the antenna axis) were 24 mm and 16 mm for nonperfused and perfused ablations, respectively. No significant differences in axial ratio were observed among different frequency groups in active-perfusion experiments. CONCLUSION: Higher-frequency microwave ablation produces thermal lesions with volumes comparable to those achieved at lower frequencies, even in strongly perfused environments. SIGNIFICANCE: Higher-frequency microwave ablation is appealing because it allows for more flexibility in antenna design. A critical issue concerning the feasibility of higher frequency microwave ablation, considering its strong dependence on heat diffusion to grow thermal lesions, is its performance in strongly perfused environments. This paper shows that higher frequency microwave ablation achieves thermal lesions comparable to those from microwave ablation performed at conventional frequencies in both non- and strongly perfused environments.

Amplified total internal reflection: theory, analysis, and demonstration of existence via FDTD.

The explanation of wave behavior upon total internal reflection from a gainy medium has defied consensus for 40 years. We examine this question using both the finite-difference time-domain (FDTD) method and theoretical analyses. FDTD simulations of a localized wave impinging on a gainy half space are based directly on Maxwell's equations and make no underlying assumptions. They reveal that amplification occurs upon total internal reflection from a gainy medium; conversely, amplification does not occur for incidence below the critical angle. Excellent agreement is obtained between the FDTD results and an analytical formulation that employs a new branch cut in the complex "propagation-constant" plane.