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.

Context-specific differences in fronto-parieto-occipital effective connectivity during short-term memory maintenance.

Although visual short-term memory (VSTM) performance has been hypothesized to rely on two distinct mechanisms, capacity and filtering, the two have not been dissociated using network-level causality measures. Here, we hypothesized that behavioral tasks challenging capacity or distraction filtering would both engage a common network of areas, namely dorsolateral prefrontal cortex (dlPFC), superior parietal lobule (SPL), and occipital cortex, but would do so according to dissociable patterns of effective connectivity. We tested this by estimating directed connectivity between areas using conditional Granger causality (cGC). Consistent with our prediction, the results indicated that increasing mnemonic load (capacity) increased the top-down drive from dlPFC to SPL, and cGC in the alpha (8-14Hz) frequency range was a predominant component of this effect. The presence of distraction during encoding (filtering), in contrast, was associated with increased top-down drive from dlPFC to occipital cortices directly and from SPL to occipital cortices directly, in both cases in the beta (15-25Hz) range. Thus, although a common anatomical network may serve VSTM in different contexts, it does so via specific functions that are carried out within distinct, dynamically configured frequency channels.

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.

Disrupted directed connectivity along the cingulate cortex determines vigilance after sleep deprivation.

The cingulate cortex is regarded as the backbone of structural and functional connectivity of the brain. While its functional connectivity has been intensively studied, little is known about its effective connectivity, its modulation by behavioral states, and its involvement in cognitive performance. Given the previously reported effects on cingulate functional connectivity, we investigated how eye-closure and sleep deprivation changed cingulate effective connectivity, estimated from resting-state high-density electroencephalography (EEG) using a novel method to calculate Granger Causality directly in source space. Effective connectivity along the cingulate cortex was dominant in the forward direction. Eyes-open connectivity in the forward direction was greater compared to eyes-closed, in well-rested participants. The difference between eyes-open and eyes-closed connectivity was attenuated and no longer significant after sleep deprivation. Individual variability in the forward connectivity after sleep deprivation predicted subsequent task performance, such that those subjects who showed a greater increase in forward connectivity between the eyes-open and the eyes-closed periods also performed better on a sustained attention task. Effective connectivity in the opposite, backward, direction was not affected by whether the eyes were open or closed or by sleep deprivation. These findings indicate that the effective connectivity from posterior to anterior cingulate regions is enhanced when a well-rested subject has his eyes open compared to when they are closed. Sleep deprivation impairs this directed information flow, proportional to its deleterious effect on vigilance. Therefore, sleep may play a role in the maintenance of waking effective connectivity.

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.

Causal Network Inference Via Group Sparse Regularization.

This paper addresses the problem of inferring sparse causal networks modeled by multivariate autoregressive (MAR) processes. Conditions are derived under which the Group Lasso (gLasso) procedure consistently estimates sparse network structure. The key condition involves a "false connection score" ψ. In particular, we show that consistent recovery is possible even when the number of observations of the network is far less than the number of parameters describing the network, provided that ψ < 1. The false connection score is also demonstrated to be a useful metric of recovery in nonasymptotic regimes. The conditions suggest a modified gLasso procedure which tends to improve the false connection score and reduce the chances of reversing the direction of causal influence. Computational experiments and a real network based electrocorticogram (ECoG) simulation study demonstrate the effectiveness of the approach.

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.

Assessing recurrent interactions in cortical networks: Modeling EEG response to transcranial magnetic stimulation.

BACKGROUND: The basic mechanisms underlying the electroencephalograpy (EEG) response to transcranial magnetic stimulation (TMS) of the human cortex are not well understood. NEW METHOD: A state-space modeling methodology is developed to gain insight into the network nature of the TMS/EEG response. Cortical activity is modeled using a multivariariate autoregressive model with exogenous stimulation parameters representing the effect of TMS. An observation equation models EEG measurement of cortical activity. An expectation-maximization algorithm is developed to estimate the model parameters. RESULTS: The methodology is used to assess two different hypotheses for the mechanisms underlying TMS/EEG in wakefulness and sleep. The integrated model hypothesizes that recurrent interactions between cortical regions are the source of TMS/EEG, while the segregated model hypothesizes that the TMS/EEG results from excitation of independent cortical oscillators. The results show that the relatively simple EEG response to TMS recorded during non-rapid-eye-movement sleep is described equally well by either the integrated or segregated model. However, the integrated model fits the more complex TMS/EEG of wakefulness much better than the segregated model. COMPARISON WITH EXISTING METHOD(S): Existing methods are limited to small numbers of cortical regions of interest or do not represent the effect of TMS. Our results are consistent with previous studies contrasting the complexity of TMS/EEG in wakefulness and sleep. CONCLUSION: The new method strongly suggests that effective feedback connections between cortical regions are required to produce the TMS/EEG in wakefulness.

Breast tumor characterization based on ultrawideband microwave backscatter.

Characterization of architectural tissue features such as the shape, margin, and size of a suspicious lesion is commonly performed in conjunction with medical imaging to provide clues about the nature of an abnormality. In this paper, we numerically investigate the feasibility of using multichannel microwave backscatter in the 1-11 GHz band to classify the salient features of a dielectric target. We consider targets with three shape characteristics: smooth, microlobulated, and spiculated; and four size categories ranging from 0.5 to 2 cm in diameter. The numerical target constructs are based on Gaussian random spheres allowing for moderate shape irregularities. We perform shape and size classification for a range of signal-to-noise ratios (SNRs) to demonstrate the potential for tumor characterization based on ultrawideband (UWB) microwave backscatter. We approach classification with two basis selection methods from the literature: local discriminant bases and principal component analysis. Using these methods, we construct linear classifiers where a subset of the bases expansion vectors are the input features and we evaluate the average rate of correct classification as a performance measure. We demonstrate that for 10 dB SNR, the target size is very reliably classified with over 97% accuracy averaged over 360 targets; target shape is classified with over 70% accuracy. The relationship between the SNR of the test data and classifier performance is also explored. The results of this study are very encouraging and suggest that both shape and size characteristics of a dielectric target can be classified directly from its UWB backscatter. Hence, characterization can easily be performed in conjunction with UWB radar-based breast cancer detection without requiring any special hardware or additional data collection.

Estimating the breast surface using UWB microwave monostatic backscatter measurements.

This paper presents an algorithm for estimating the location of the breast surface from scattered ultrawideband (UWB) microwave signals recorded across an antenna array. Knowing the location of the breast surface can improve imaging performance if incorporated as a priori information into recently proposed microwave imaging algorithms. These techniques transmit low-power microwaves into the breast using an antenna array, which in turn measures the scattered microwave signals for the purpose of detecting anomalies or changes in the dielectric properties of breast tissue. Our proposed surface identification algorithm consists of three procedures, the first of which estimates M points on the breast surface given M channels of measured microwave backscatter data. The second procedure applies interpolation and extrapolation to these M points to generate N > M points that are approximately uniformly distributed over the breast surface, while the third procedure uses these N points to generate a 3-D estimated breast surface. Numerical as well as experimental tests indicate that the maximum absolute error in the estimated surface generated by the algorithm is on the order of several millimeters. An error analysis conducted for a basic microwave radar imaging algorithm (least-squares narrowband beamforming) indicates that this level of error is acceptable. A key advantage of the algorithm is that it uses the same measured signals that are used for UWB microwave imaging, thereby minimizing patient scan time and avoiding the need for additional hardware.

Modeling Touch and Palpation Using Autoregressive Models.

OBJECTIVE: The human haptic system uses a set of reproducible and subconscious hand maneuvers to identify objects. Similar subconscious maneuvers are used during medical palpation for screening and diagnosis. The goal of this work was to develop a mathematical model that can be used to describe medical palpation techniques. METHODS: Palpation data were measured using a two-dimensional array of force sensors. A novel algorithm for estimating the hand position from force data was developed. The hand position data were then modeled using multivariate autoregressive models. Analysis of these models provided palpation direction and frequency as well as palpation type. The models were tested and validated using three different data sets: simulated data, a simplified experiment in which participant followed a known pattern, and breast simulator palpation data. RESULTS: Simulated data showed that the minimal error in estimating palpation direction and frequency is achieved when the sampling frequency is five to ten times the palpation frequency. The classification accuracy was for the simplified experiment and for the breast simulator data. CONCLUSION: Proper palpation is one of the vital components of many hands-on clinical examinations. In this study, an algorithm for characterizing medical palpation was developed. The algorithm measured palpation frequency and direction for the first time and provided classification of palpation type. SIGNIFICANCE: These newly developed models can be used for quantifying and assessing clinical technique, and consequently, lead to improved performance in palpation-based exams. Furthermore, they provide a general tool for the study of human haptics.

Simultaneous fetal magnetocardiography and ultrasound/Doppler imaging.

The difficulty of utilizing multimodality diagnostic imaging techniques for fetal surveillance remains one of the greatest challenges in providing enhanced prenatal care. In this Letter we demonstrate the feasibility of performing fetal magnetocardiography (fMCG) and ultrasound/Doppler imaging simultaneously, using a multichannel SQUID magnetometer and a portable ultrasound scanner. Despite large magnetic interference from the scanner, the implementation of simple noise reduction procedures and appropriate signal processing techniques yielded fMCG recordings of sufficient quality for assessment of fetal heart rate and rhythm. A variation of reference channel filtering, referred to here as synthetic reference channel filtering, was used to reduce nonstationary low-frequency interference. The combination of fMCG and/or fMEG with ultrasound/Doppler offers new possibilities for assessment of fetal well-being and fetal cardiac function.

Fetal QT Interval Estimation Using Sequential Hypothesis Testing.

Objective: Recent studies utilizing fetal magnetocardiography have demonstrated the efficacy of corrected QT interval (QTc) measurement for in utero diagnosis and prognosis of long QT syndrome, a leading cause of sudden death in early life. The objective of the study was to formulate and test a novel statistical estimation method to detect the end of the fetal T-wave and thereby improve the accuracy of fetal QT interval measurement. Methods: To detect the end of the T-wave, we apply a sequential composite hypothesis test to decide when the T-wave has returned to baseline. The method uses the generalized likelihood ratio test in conjunction with a low-rank spatiotemporal model that exploits the repetitive nature of cardiac signals. The unknown model parameters are determined using maximum likelihood estimation. Results: In realistic simulations, the detector was shown to be accurate to within 10 ms (95% prediction interval), even at noise-to-signal ratios as high as 6. When applied to real data from normal fetuses, the detector agreed well with measurements made by cardiologists ( 1.4 6.9 ms). Conclusions: The method was effective and practical. Detector performance was excellent despite the continual presence of strong maternal interference. Significance: This detector serves as a valuable adjunct to traditional measurement based on subjective assessment.Objective: Recent studies utilizing fetal magnetocardiography have demonstrated the efficacy of corrected QT interval (QTc) measurement for in utero diagnosis and prognosis of long QT syndrome, a leading cause of sudden death in early life. The objective of the study was to formulate and test a novel statistical estimation method to detect the end of the fetal T-wave and thereby improve the accuracy of fetal QT interval measurement. Methods: To detect the end of the T-wave, we apply a sequential composite hypothesis test to decide when the T-wave has returned to baseline. The method uses the generalized likelihood ratio test in conjunction with a low-rank spatiotemporal model that exploits the repetitive nature of cardiac signals. The unknown model parameters are determined using maximum likelihood estimation. Results: In realistic simulations, the detector was shown to be accurate to within 10 ms (95% prediction interval), even at noise-to-signal ratios as high as 6. When applied to real data from normal fetuses, the detector agreed well with measurements made by cardiologists ( 1.4 6.9 ms). Conclusions: The method was effective and practical. Detector performance was excellent despite the continual presence of strong maternal interference. Significance: This detector serves as a valuable adjunct to traditional measurement based on subjective assessment.

Cortical patch basis model for spatially extended neural activity.

A new source model for representing spatially distributed neural activity is presented. The signal of interest is modeled as originating from a patch of cortex and is represented using a set of basis functions. Each cortical patch has its own set of bases, which allows representation of arbitrary source activity within the patch. This is in contrast to previously proposed cortical patch models which assume a specific distribution of activity within the patch. We present a procedure for designing bases that minimize the normalized mean squared representation error, averaged over different activity distributions within the patch. Extension of existing algorithms to the basis function framework is straightforward and is illustrated using linearly constrained minimum variance (LCMV) spatial filtering and maximum-likelihood signal estimation/generalized likelihood ratio test (ML/GLRT). The number of bases chosen for each patch determines a tradeoff between representation accuracy and the ability to differentiate between distinct patches. We propose choosing the minimum number of bases that satisfy a constraint on the normalized mean squared representation accuracy. A mismatch analysis for LCMV and ML/GLRT is presented to show that this is an appropriate strategy for choosing the number of bases. The effectiveness of the patch basis model is demonstrated using real and simulated evoked response data. We show that significant changes in performance occur as the number of basis functions varies, and that very good results are obtained by allowing modest representation error.

Linear minimum mean-square error filtering for evoked responses: application to fetal MEG.

This paper describes a linear minimum mean-squared error (LMMSE) approach for designing spatial filters that improve the signal-to-noise ratio (SNR) of multiepoch evoked response data. This approach does not rely on availability of a forward solution and thus is applicable to problems in which a forward solution is not readily available, such as fetal magnetoencephalography (fMEG). The LMMSE criterion leads to a spatial filter that is a function of the autocorrelation matrix of the data and the autocorrelation matrix of the signal. The signal statistics are unknown, so we approximate the signal autocorrelation matrix using the average of the data across epochs. This approximation is reasonable provided the mean of the noise is zero across epochs and the signal mean is significant. An analysis of the error incurred using this approximation is presented. Calculations of SNR for the exact and approximate LMMSE filters and simple averaging for the rank-1 signal case are shown. The effectiveness of the method is demonstrated with simulated evoked response data and fetal MEG data.

MEG and EEG source localization in beamspace.

Beamspace methods are applied to EEG/MEG source localization problems in this paper. Beamspace processing involves passing the data through a linear transformation that reduces the data dimension prior to applying a desired statistical signal processing algorithm. This process generally reduces the data requirements of the subsequent algorithm. We present one approach for designing beamspace transformations that are optimized to preserve source activity located within a given region of interest and show that substantial reductions in dimension are obtained with negligible signal loss. Beamspace versions of maximum likelihood dipole fitting, MUSIC, and minimum variance beamforming source localization algorithms are presented. The performance improvement offered by the beamspace approach with limited data is demonstrated by bootstrapping somatosensory data to evaluate the variability of the source location estimates obtained with each algorithm. The quantitative benefits of beamspace processing depend on the algorithm, signal to noise ratio, and amount of data. Dramatic performance improvements are obtained in scenarios with low signal to noise ratio and a small number of independent data samples.

Ultrawideband microwave breast cancer detection: a detection-theoretic approach using the generalized likelihood ratio test.

Microwave imaging has been suggested as a promising modality for early-stage breast cancer detection. In this paper, we propose a statistical microwave imaging technique wherein a set of generalized likelihood ratio tests (GLRT) is applied to microwave backscatter data to determine the presence and location of strong scatterers such as malignant tumors in the breast. The GLRT is formulated assuming that the backscatter data is Gaussian distributed with known covariance matrix. We describe the method for estimating this covariance matrix offline and formulating a GLRT for several heterogeneous two-dimensional (2-D) numerical breast phantoms, several three-dimensional (3-D) experimental breast phantoms, and a 3-D numerical breast phantom with a realistic half-ellipsoid shape. Using the GLRT with the estimated covariance matrix and a threshold chosen to constrain the false discovery rate (FDR) of the image, we show the capability to detect and localize small (<0.6 cm) tumors in our numerical and experimental breast phantoms even when the dielectric contrast of the malignant-to-normal tissue is below 2:1.

A 3-D Level Set Method for Microwave Breast Imaging.

OBJECTIVE: Conventional inverse-scattering algorithms for microwave breast imaging result in moderate resolution images with blurred boundaries between tissues. Recent 2-D numerical microwave imaging studies demonstrate that the use of a level set method preserves dielectric boundaries, resulting in a more accurate, higher resolution reconstruction of the dielectric properties distribution. Previously proposed level set algorithms are computationally expensive, and thus, impractical in 3-D. In this paper, we present a computationally tractable 3-D microwave imaging algorithm based on level sets. METHODS: We reduce the computational cost of the level set method using a Jacobian matrix, rather than an adjoint method, to calculate Frechet derivatives. We demonstrate the feasibility of 3-D imaging using simulated array measurements from 3-D numerical breast phantoms. We evaluate performance by comparing full 3-D reconstructions to those from a conventional microwave imaging technique. We also quantitatively assess the efficacy of our algorithm in evaluating breast density. RESULTS: Our reconstructions of 3-D numerical breast phantoms improve upon those of a conventional microwave imaging technique. The density estimates from our level set algorithm are more accurate than those of the conventional microwave imaging, and the accuracy is greater than that reported for mammographic density estimation. CONCLUSION: Our level set method leads to a feasible level of computational complexity for full 3-D imaging, and reconstructs the heterogeneous dielectric properties distribution of the breast more accurately than conventional microwave imaging methods. SIGNIFICANCE: 3-D microwave breast imaging using a level set method is a promising low-cost, nonionizing alternative to current breast imaging techniques.