Computational modeling of microwave ablation with thermal accelerants.

PURPOSE: To develop a computational model of microwave ablation (MWA) with a thermal accelerant gel and apply the model toward interpreting experimental observations in ex vivo bovine and in vivo porcine liver. METHODS: A 3D coupled electromagnetic-heat transfer model was implemented to characterize thermal profiles within ex vivo bovine and in vivo porcine liver tissue during MWA with the HeatSYNC thermal accelerant. Measured temperature dependent dielectric and thermal properties of the HeatSYNC gel were applied within the model. Simulated extents of MWA zones and transient temperature profiles were compared against experimental measurements in ex vivo bovine liver. Model predictions of thermal profiles under in vivo conditions in porcine liver were used to analyze thermal ablations observed in prior experiments in porcine liver in vivo. RESULTS: Measured electrical conductivity of the HeatSYNC gel was ∼83% higher compared to liver at room temperature, with positive linear temperature dependency, indicating increased microwave absorption within HeatSYNC gel compared to tissue. In ex vivo bovine liver, model predicted ablation zone extents of (31.5 × 36) mm with the HeatSYNC, compared to (32.9 ± 2.6 × 40.2 ± 2.3) mm in experiments (volume differences 4 ± 4.1 cm3). Computational models under in vivo conditions in porcine liver suggest approximating the HeatSYNC gel spreading within liver tissue during ablations as a plausible explanation for larger ablation zones observed in prior in vivo studies. CONCLUSION: Computational models of MWA with thermal accelerants provide insight into the impact of accelerant on MWA, and with further development, could predict ablations with a variety of gel injection sites.

Transmission-Based Vertebrae Strength Probe Development: Far Field Probe Property Extraction and Integrated Machine Vision Distance Validation Experiments.

We are developing a transmission-based probe for point-of-care assessment of vertebrae strength needed for fabricating the instrumentation used in supporting the spinal column during spinal fusion surgery. The device is based on a transmission probe whereby thin coaxial probes are inserted into the small canals through the pedicles and into the vertebrae, and a broad band signal is transmitted from one probe to the other across the bone tissue. Simultaneously, a machine vision scheme has been developed to measure the separation distance between the probe tips while they are inserted into the vertebrae. The latter technique includes a small camera mounted to the handle of one probe and associated fiducials printed on the other. Machine vision techniques make it possible to track the location of the fiducial-based probe tip and compare it to the fixed coordinate location of the camera-based probe tip. The combination of the two methods allows for straightforward calculation of tissue characteristics by exploiting the antenna far field approximation. Validation tests of the two concepts are presented as a precursor to clinical prototype development.

Impact of Skin on Microwave Tomography in the Lossy Coupling Medium.

In microwave imaging, the effects of skin on recovering property distributions of tissue underneath the surface may be significant because it has high dielectric contrast with subcutaneous fat, which inevitably causes significant signal reflections. While the thickness of skin, especially relative to the wavelengths in use, would presumably have minor effects, it can introduce practical difficulties, for instance, in reflection-based imaging techniques, where the impact of the skin is large-often as high as two orders of magnitude greater than that of signals from underlying tumors in the breast imaging setting. However, in tomography cases utilizing transmission-based measurement data and lossy coupling materials, the situation is considerably different. Accurately implementing a skin layer for numerical modeling purposes is challenging because of the need to discretize the size and shape of the skin without increasing computational overhead substantially. In this paper, we assess the effects of the skin on field solutions in a realistic 3D model of a human breast. We demonstrate that the small changes in transmission field values introduced by including the skin cause minor differences in reconstructed images.

Open-Ended Transmission Coaxial Probes for Sarcopenia Assessment.

We developed a handheld, side-by-side transmission-based probe for interrogating tissue to diagnose sarcopenia-a condition largely characterized by muscle loss and replacement by fat. While commercial microwave reflection-based probes exist, they can only be used in a lab for a variety of applications. The penetration depth of these probes is only in the order of 0.3 mm, which does not even traverse the skin layer, and minor motion of the coaxial feedlines can completely dismantle the calibration. Our device builds primarily on the transmission-based concept that allows for substantially greater signal penetration depth operating over a very broad bandwidth. Additional features were integrated to further improve the penetration, optimize the geometry for a more focused planar excitation, and juxtapose the coaxial apertures for more controlled interrogation. The larger coaxial apertures further increased the penetration depth while retaining the broadband performance. Three-dimensional printing technology made it possible for the apertures to be compressed into ellipses for interrogation in a near-planar geometry. Finally, fixed side-by-side positioning provided repeatable and reliable performance. The probes were also not susceptible to multipath signal corruption due to the close proximity of the transmitting and receiving apertures. The new concept worked from 100 MHz to over 8 GHz and could sense property changes as deep as 2-3 cm. While the signal changes due to deeper feature aberrations were more subtle than for signals emanating from the skin and subcutaneous fat layers, the large property contrast between muscle and fat is a sarcopenic indication that helps to distinguish even the deepest objects. This device has the potential to provide needed specificity information about the relevant underlying tissue.

Discrete Dipole Approximation-Based Microwave Tomography for Fast Breast Cancer Imaging.

This paper describes a fast microwave tomography reconstruction algorithm based on the two-dimensional discrete dipole approximation. Synthetic data from a finite-element based solver and experimental data from a microwave imaging system are used to reconstruct images and to validate the algorithm. The microwave measurement system consists of 16 monopole antennas immersed in a tank filled with lossy coupling liquid and a vector network analyzer. The low-profile antennas and lossy nature of system make the discrete dipole approximation an ideal forward solver in the image reconstructions. The results show that the algorithm can readily reconstruct a 2D plane of a cylindrical phantom. The proposed forward solver combined with the nodal adjoint method for computing the Jacobian matrix enables the algorithm to reconstruct an image within 6 seconds. This implementation provides a significant time savings and reduced memory requirements and is a dramatic improvement over previous implementations.

Expansion of the Nodal-Adjoint Method for Simple and Efficient Computation of the 2D Tomographic Imaging Jacobian Matrix.

This paper focuses on the construction of the Jacobian matrix required in tomographic reconstruction algorithms. In microwave tomography, computing the forward solutions during the iterative reconstruction process impacts the accuracy and computational efficiency. Towards this end, we have applied the discrete dipole approximation for the forward solutions with significant time savings. However, while we have discovered that the imaging problem configuration can dramatically impact the computation time required for the forward solver, it can be equally beneficial in constructing the Jacobian matrix calculated in iterative image reconstruction algorithms. Key to this implementation, we propose to use the same simulation grid for both the forward and imaging domain discretizations for the discrete dipole approximation solutions and report in detail the theoretical aspects for this localization. In this way, the computational cost of the nodal adjoint method decreases by several orders of magnitude. Our investigations show that this expansion is a significant enhancement compared to previous implementations and results in a rapid calculation of the Jacobian matrix with a high level of accuracy. The discrete dipole approximation and the newly efficient Jacobian matrices are effectively implemented to produce quantitative images of the simplified breast phantom from the microwave imaging system.

MAS: Standalone Microwave Resonator to Assess Muscle Quality.

Microwave-based sensing for tissue analysis is recently gaining interest due to advantages such as non-ionizing radiation and non-invasiveness. We have developed a set of transmission sensors for microwave-based real-time sensing to quantify muscle mass and quality. In connection, we verified the sensors by 3D simulations, tested them in a laboratory on a homogeneous three-layer tissue model, and collected pilot clinical data in 20 patients and 25 healthy volunteers. This report focuses on initial sensor designs for the Muscle Analyzer System (MAS), their simulation, laboratory trials and clinical trials followed by developing three new sensors and their performance comparison. In the clinical studies, correlation studies were done to compare MAS performance with other clinical standards, specifically the skeletal muscle index, for muscle mass quantification. The results showed limited signal penetration depth for the Split Ring Resonator (SRR) sensor. New sensors were designed incorporating Substrate Integrated Waveguides (SIW) and a bandstop filter to overcome this problem. The sensors were validated through 3D simulations in which they showed increased penetration depth through tissue when compared to the SRR. The second-generation sensors offer higher penetration depth which will improve clinical data collection and validation. The bandstop filter is fabricated and studied in a group of volunteers, showing more reliable data that warrants further continuation of this development.

Comments on "Investigation of Histology Region Dielectric Measurements of Heterogeneous Tissues".

In the paper, "Investigation of histology region in dielectric measurements of heterogeneous tissues," by Porter and O'Halloran, the authors utilize a flexible phantom in a layered material dielectric property analysis to quantify the effective sensing volume of a coaxial dielectric probe. Ostensibly, this test has been used by others to characterize the region for which percent variation in the material composition in front of the probe corresponds to percent variation in the computed effective dielectric properties. By employing a compressible material, the authors fail to isolate features that are attributable solely to the probe, itself, and inadvertently incorporate confounding characteristics associated with the compressible nature of the material. The net effect is to exaggerate the probe's sensing volume which undermines conclusions drawn from the subsequent tissue dielectric property studies.

Low Cost, High Performance, 16-Channel Microwave Measurement System for Tomographic Applications.

We have developed a multichannel software defined radio-based transceiver measurement system for use in general microwave tomographic applications. The unit is compact enough to fit conveniently underneath the current illumination tank of the Dartmouth microwave breast imaging system. The system includes 16 channels that can both transmit and receive and it operates from 500 MHz to 2.5 GHz while measuring signals down to -140 dBm. As is the case with multichannel systems, cross-channel leakage is an important specification and must be lower than the noise floors for each receiver. This design exploits the isolation inherent when the individual receivers for each channel are physically separate; however, these challenging specifications require more involved signal isolation techniques at both the system design level and the individual, shielded component level. We describe the isolation design techniques for the critical system elements and demonstrate specification compliance at both the component and system level.

A Transmission-Based Dielectric Property Probe for Clinical Applications.

We have developed a transmission-based, open-ended coaxial dielectric probe that can be used in clinical situations and overcomes many of the limitations related to the typical reflection-based dielectric probes. The approach utilizes the low profile, open-ended coaxial cables enabling clinicians to still probe relatively compact spaces. The sensing depth can be extended to as large as 1.5 to 2 cm compared with the more typical range of 0.3 mm for conventional probes and is dramatically less affected by measurement technique variability including poor sample contact and cable bending. As a precursor to an actual clinical implementation, we study the technique in a range of homogeneous liquids with substantially varying dielectric properties. The initial results demonstrate good agreement between the transmission-based probe and commercial, reflection-based probes and pave the way for more substantial clinical implementation.

Electrical Characterization of Glycerin: Water Mixtures: Implications for Use as a Coupling Medium in Microwave Tomography.

We examine the broadband behavior of complex electrical properties of glycerin and water mixtures over the frequency range of 0.1 - 25.0 GHz, especially as they relate to using these liquids as coupling media for microwave tomographic imaging. Their combination is unique in that they are mutually miscible over the full range of concentrations which allows them to be tailored to dielectric property matching for biological tissues. While the resultant mixture properties are partially driven by differences in the inherent low frequency permittivity of each constituent, relaxation frequency shifts play a disproportionately larger role in increasing the permittivity dispersion while also dramatically increasing the effective conductivity over the frequency range of 1 to 3 GHz. For the full range of mixture ratios, the relaxation frequency shifts from 17.5 GHz for 0% glycerin to less than 0.1 GHz for 100% glycerin. Of particular interest is the fact that the conductivity stays above 1.0 S/m over the 1-3 GHz range for glycerin mixture ratios (70-90% glycerin) we use for microwave breast tomography. The high level of attenuation is critical for suppressing unwanted multipath signals. This paper presents a full characterization of these liquids along with a discussion of their benefits and limitations in the context of microwave tomography.

Open-Ended Coaxial Dielectric Probe Effective Penetration Depth Determination.

We have performed a series of experiments which demonstrate the effect of open-ended coaxial diameter on the depth of penetration. We used a two layer configuration of a liquid and movable cylindrical piece of either Teflon or acrylic. The technique accurately demonstrates the depth in a sample for which a given probe diameter provides a reasonable measure of the bulk dielectric properties for a heterogeneous volume. In addition we have developed a technique for determining the effective depth for a given probe diameter size. Using a set of simulations mimicking four 50 Ω coaxial cable diameters, we demonstrate that the penetration depth in both water and saline has a clear dependence on probe diameter but is remarkably uniform over frequency and with respect to the intervening liquid permittivity. Two different 50 Ω commercial probes were similarly tested and confirm these observations. This result has significant implications to a range of dielectric measurements, most notably in the area of tissue property studies.

Microwave Vertebrae Strength Probe Development: Robust and Fast Phase Unwrapping Technique.

We have developed a new transmission-based, open-ended coaxial probe for assessing vertebrae strength during spinal fusion surgery. The approach exploits the fact that the probes are within the far field of each other implying that the phase varies linearly with respect to propagation distance. Determining the absolute phase is critical for recovering the associated tissue dielectric properties from which bone strength will be determined. Unfortunately, unwanted multi-path signals corrupt the signals at the lower end of the operating frequency range from which our conventional unwrapping strategy depends. Our new approach requires only three measurements within the prime frequency range and can be determined robustly with a minimum of computations. This will be vital to developing a commercial device since the signal levels will be extremely low power requiring longer than usual data acquisition times, which will be mitigated by measuring the data at only a few frequencies. Fast and efficient operation will be critical for clinical success.

Microwave imaging for neoadjuvant chemotherapy monitoring: initial clinical experience.

INTRODUCTION: Microwave tomography recovers images of tissue dielectric properties, which appear to be specific for breast cancer, with low-cost technology that does not present an exposure risk, suggesting the modality may be a good candidate for monitoring neoadjuvant chemotherapy. METHODS: Eight patients undergoing neoadjuvant chemotherapy for locally advanced breast cancer were imaged longitudinally five to eight times during the course of treatment. At the start of therapy, regions of interest (ROIs) were identified from contrast-enhanced magnetic resonance imaging studies. During subsequent microwave examinations, subjects were positioned with their breasts pendant in a coupling fluid and surrounded by an immersed antenna array. Microwave property values were extracted from the ROIs through an automated procedure and statistical analyses were performed to assess short term (30 days) and longer term (four to six months) dielectric property changes. RESULTS: Two patient cases (one complete and one partial response) are presented in detail and demonstrate changes in microwave properties commensurate with the degree of treatment response observed pathologically. Normalized mean conductivity in ROIs from patients with complete pathological responses was significantly different from that of partial responders (P value = 0.004). In addition, the normalized conductivity measure also correlated well with complete pathological response at 30 days (P value = 0.002). CONCLUSIONS: These preliminary findings suggest that both early and late conductivity property changes correlate well with overall treatment response to neoadjuvant therapy in locally advanced breast cancer. This result is consistent with earlier clinical outcomes that lesion conductivity is specific to differentiating breast cancer from benign lesions and normal tissue.

Surface scanning through a cylindrical tank of coupling fluid for clinical microwave breast imaging exams.

PURPOSE: Microwave tomographic image quality can be improved significantly with prior knowledge of the breast surface geometry. The authors have developed a novel laser scanning system capable of accurately recovering surface renderings of breast-shaped phantoms immersed within a cylindrical tank of coupling fluid which resides completely external to the tank (and the aqueous environment) and overcomes the challenges associated with the optical distortions caused by refraction from the air, tank wall, and liquid bath interfaces. METHODS: The scanner utilizes two laser line generators and a small CCD camera mounted concentrically on a rotating gantry about the microwave imaging tank. Various calibration methods were considered for optimizing the accuracy of the scanner in the presence of the optical distortions including traditional ray tracing and image registration approaches. In this paper, the authors describe the construction and operation of the laser scanner, compare the efficacy of several calibration methods-including analytical ray tracing and piecewise linear, polynomial, locally weighted mean, and thin-plate-spline (TPS) image registrations-and report outcomes from preliminary phantom experiments. RESULTS: The results show that errors in calibrating camera angles and position prevented analytical ray tracing from achieving submillimeter accuracy in the surface renderings obtained from our scanner configuration. Conversely, calibration by image registration reliably attained mean surface errors of less than 0.5 mm depending on the geometric complexity of the object scanned. While each of the image registration approaches outperformed the ray tracing strategy, the authors found global polynomial methods produced the best compromise between average surface error and scanner robustness. CONCLUSIONS: The laser scanning system provides a fast and accurate method of three dimensional surface capture in the aqueous environment commonly found in microwave breast imaging. Optical distortions imposed by the imaging tank and coupling bath diminished the effectiveness of the ray tracing approach; however, calibration through image registration techniques reliably produced scans of submillimeter accuracy. Tests of the system with breast-shaped phantoms demonstrated the successful implementation of the scanner for the intended application.

3D-printed gear system for antenna motion in an MR environment: initial phantom imaging experiments.

We have developed a microwave imaging device for breast cancer imaging that can be used concurrently inside an MR imaging system. The microwave measurement system is comprised of a horizontal array of 16 monopole antennas that can be moved vertically for full 3D coverage of the breast. All compatibility issues have been addressed. The motion is achieved using a novel 3D printed gearing device. Initial results demonstrate that the system is capable of accurately recovering the size, shape, location and properties of a 3D shape varying object. This is a critical step towards clinical microwave breast imaging in the MR.

Motion-based microwave tomographic measurement device for three-dimensional coverage in a magnetic resonance system.

PURPOSE: We have developed a fully 3D data acquisition system for microwave breast imaging which can operate simultaneously inside a magnetic resonance imaging (MRI). MRI is used regularly for breast imaging to distinguish tumors from normal tissue. It generally has poor specificity unless used with a gadolinium contrast agent. Microwave imaging could fill this need because of the good endogenous tumor:normal tissue property contrast, especially in light of safety concerns for gadolinium. The antenna array consists of 16 monopole antennas positioned in a horizontal circle surrounding the breast which can then be moved vertically for 3D coverage of the breast. The tank system materials were chosen to minimize artifacts in the MR image within the specific shared imaging zone. The support rods are stainless steel, albeit positioned sufficiently far from the imaging target to have little effect. The mechanical motion parts are all 3D printed plastic. Unlike many conventional antennas, the monopoles consist of just the center conductor and insulator of the coaxial cable, making it one of the least possible metallic structures. METHODS: Data were acquired both inside and outside of the MR bore to confirm that the MR bore did not have adverse effects on the microwave imaging process. The imaging tank was filled with a mixture of glycerin and water to both provide a reasonable property match to the phantom and to highly attenuate the fields which also acted to suppress multi-path signals. Microwave images were reconstructed using our Gauss-Newton scheme combined with a log transformation for a more linear convergence. MR images were also acquired to assess the effects of the microwave tank structures on the imaging. RESULTS: The microwave measurement data were acquired in log magnitude and phase format at 200 MHz increments from 700-1900 MHz. Each antenna acted sequentially as a transmitter while the complement of 15 acted as a receiver. The single frequency images were reconstructed using a Gauss-Newton iterative technique with a standard log transformation to linearize the process. The data showed that the signal strengths were between 7-10 dB lower for the case when the array was inside the MRI versus when not. Notwithstanding, the image quality was still high because of the significant signal to noise ratio. The reconstructed images in both situations demonstrated good 3D object recovery of the vertically size and shaped varying object. The MR images were not adversely affected by the presence of antennas or feed structures. CONCLUSIONS: We have demonstrated that our technique can recover high-quality images of a 3D varying object within an MRI system. Compatibility issues have been addressed for both the microwave and MRI systems. The reduced SNR for the case operating in the MRI did not adversely affect the images. To the best of our knowledge, this is the first example of a microwave imaging system operating in an MRI with full 3D volumetric capability.

Viable Three-Dimensional Medical Microwave Tomography: Theory and Numerical Experiments.

Three-dimensional microwave tomography represents a potentially very important advance over 2D techniques because it eliminates associated approximations which may lead to more accurate images. However, with the significant increase in problem size, computational efficiency is critical to making 3D microwave imaging viable in practice. In this paper, we present two 3D image reconstruction methods utilizing 3D scalar and vector field modeling strategies, respectively. Finite element (FE) and finite-difference time-domain (FDTD) algorithms are used to model the electromagnetic field interactions in human tissue in 3D. Image reconstruction techniques previously developed for the 2D problem, such as the dual-mesh scheme, iterative block solver, and adjoint Jacobian method are extended directly to 3D reconstructions. Speed improvements achieved by setting an initial field distribution and utilizing an alternating-direction implicit (ADI) FDTD are explored for 3D vector field modeling. The proposed algorithms are tested with simulated data and correctly recovered the position, size and electrical properties of the target. The adjoint formulation and the FDTD method utilizing initial field estimates are found to be significantly more effective in reducing the computation time. Finally, these results also demonstrate that cross-plane measurements are critical for reconstructing 3D profiles of the target.

Magnetic resonance microwave absorption imaging: feasibility of signal detection.

PURPOSE: Magnetic resonance (MR) technique was used to detect small displacements induced by localized absorption of pulsed 434 MHz microwave power as a potential method for tumor detection. METHODS: Phase contrast subtraction was used to separate the phase change due to motion from thermoelastic expansion from other contributions to phase variation such as the bulk temperature rise of the medium and phase offsets from the MR scanner itself. A simple set of experiments was performed where the motion was constrained to be one dimensional which provided controls on the data acquisition and motion extraction procedures. Specifically, the MR-detected motion signal was isolated by altering the direction of the microwave-induced motion and sampling the response with motion encoding gradients in all three directions when the microwave power was turned on and turned off. RESULTS: Successful signal detection, as evidenced by the recording of a systematic alternating (zigzag) phase pattern, occurred only when the motion encoding was in parallel with either the vertical or horizontal direction of the microwave-induced motion on both 10 and 4 mm spatial scales. CONCLUSIONS: These results demonstrate, for the first time, that motion associated with thermoelastic expansion from the absorption of pulsed microwave power can be detected with MR.

The correlation of in vivo and ex vivo tissue dielectric properties to validate electromagnetic breast imaging: initial clinical experience.

Electromagnetic (EM) breast imaging provides low-cost, safe and potentially a more specific modality for cancer detection than conventional imaging systems. A primary difficulty in validating these EM imaging modalities is that the true dielectric property values of the particular breast being imaged are not readily available on an individual subject basis. Here, we describe our initial experience in seeking to correlate tomographic EM imaging studies with discrete point spectroscopy measurements of the dielectric properties of breast tissue. The protocol we have developed involves measurement of in vivo tissue properties during partial and full mastectomy procedures in the operating room (OR) followed by ex vivo tissue property recordings in the same locations in the excised tissue specimens in the pathology laboratory immediately after resection. We have successfully applied all of the elements of this validation protocol in a series of six women with cancer diagnoses. Conductivity and permittivity gauged from ex vivo samples over the frequency range 100 Hz-8.5 GHz are found to be similar to those reported in the literature. A decrease in both conductivity and permittivity is observed when these properties are gauged from ex vivo samples instead of in vivo. We present these results in addition to a case study demonstrating how discrete point spectroscopy measurements of the tissue can be correlated and used to validate EM imaging studies.