High-dimensional multivariate autoregressive model estimation of human electrophysiological data using fMRI priors.

Multivariate autoregressive (MVAR) model estimation enables assessment of causal interactions in brain networks. However, accurately estimating MVAR models for high-dimensional electrophysiological recordings is challenging due to the extensive data requirements. Hence, the applicability of MVAR models for study of brain behavior over hundreds of recording sites has been very limited. Prior work has focused on different strategies for selecting a subset of important MVAR coefficients in the model to reduce the data requirements of conventional least-squares estimation algorithms. Here we propose incorporating prior information, such as resting state functional connectivity derived from functional magnetic resonance imaging, into MVAR model estimation using a weighted group least absolute shrinkage and selection operator (LASSO) regularization strategy. The proposed approach is shown to reduce data requirements by a factor of two relative to the recently proposed group LASSO method of Endemann et al (Neuroimage 254:119057, 2022) while resulting in models that are both more parsimonious and more accurate. The effectiveness of the method is demonstrated using simulation studies of physiologically realistic MVAR models derived from intracranial electroencephalography (iEEG) data. The robustness of the approach to deviations between the conditions under which the prior information and iEEG data is obtained is illustrated using models from data collected in different sleep stages. This approach allows accurate effective connectivity analyses over short time scales, facilitating investigations of causal interactions in the brain underlying perception and cognition during rapid transitions in behavioral state.

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.

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.

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.

Estimating cortical column sensory networks in rodents from micro-electrocorticograph (µECoG) recordings.

Micro-electrocorticograph (µECoG) arrays offer the flexibility to record local field potentials (LFPs) from the surface of the cortex, using high density electrodes that are sub-mm in diameter. Research to date has not provided conclusive evidence for the underlying signal generation of µECoG recorded LFPs, or if µECoG arrays can capture network activity from the cortex. We studied the pervading view of the LFP signal by exploring the spatial scale at which the LFP can be considered elemental. We investigated the underlying signal generation and ability to capture functional networks by implanting, µECoG arrays to record sensory-evoked potentials in four rats. The organization of the sensory cortex was studied by analyzing the sensory-evoked potentials with two distinct modeling techniques: (1) The volume conduction model, that models the electrode LFPs with an electrostatic representation, generated by a single cortical generator, and (2) the dynamic causal model (DCM), that models the electrode LFPs with a network model, whose activity is generated by multiple interacting cortical sources. The volume conduction approach modeled activity from electrodes separated < 1000 µm, with reasonable accuracy but a network model like DCM was required to accurately capture activity > 1500 µm. The extrinsic network component in DCM was determined to be essential for accurate modeling of observed potentials. These results all point to the presence of a sensory network, and that µECoG arrays are able to capture network activity in the neocortex. The estimated DCM network models the functional organization of the cortex, as signal generators for the µECoG recorded LFPs, and provides hypothesis-testing tools to explore the brain.

Dynamic vehicle routing with time windows in theory and practice.

The vehicle routing problem is a classical combinatorial optimization problem. This work is about a variant of the vehicle routing problem with dynamically changing orders and time windows. In real-world applications often the demands change during operation time. New orders occur and others are canceled. In this case new schedules need to be generated on-the-fly. Online optimization algorithms for dynamical vehicle routing address this problem but so far they do not consider time windows. Moreover, to match the scenarios found in real-world problems adaptations of benchmarks are required. In this paper, a practical problem is modeled based on the procedure of daily routing of a delivery company. New orders by customers are introduced dynamically during the working day and need to be integrated into the schedule. A multiple ant colony algorithm combined with powerful local search procedures is proposed to solve the dynamic vehicle routing problem with time windows. The performance is tested on a new benchmark based on simulations of a working day. The problems are taken from Solomon's benchmarks but a certain percentage of the orders are only revealed to the algorithm during operation time. Different versions of the MACS algorithm are tested and a high performing variant is identified. Finally, the algorithm is tested in situ: In a field study, the algorithm schedules a fleet of cars for a surveillance company. We compare the performance of the algorithm to that of the procedure used by the company and we summarize insights gained from the implementation of the real-world study. The results show that the multiple ant colony algorithm can get a much better solution on the academic benchmark problem and also can be integrated in a real-world environment.

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.

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.

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.

Reversal of cortical information flow during visual imagery as compared to visual perception.

The role of bottom-up and top-down connections during visual perception and the formation of mental images was examined by analyzing high-density EEG recordings of brain activity using two state-of-the-art methods for assessing the directionality of cortical signal flow: state-space Granger causality and dynamic causal modeling. We quantified the directionality of signal flow in an occipito-parieto-frontal cortical network during perception of movie clips versus mental replay of the movies and free visual imagery. Both Granger causality and dynamic causal modeling analyses revealed an increased top-down signal flow in parieto-occipital cortices during mental imagery as compared to visual perception. These results are the first direct demonstration of a reversal of the predominant direction of cortical signal flow during mental imagery as compared to perception.

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.

Characterizing touch using pressure data and auto regressive models.

Palpation plays a critical role in medical physical exams. Despite the wide range of exams, there are several reproducible and subconscious sets of maneuvers that are common to examination by palpation. Previous studies by our group demonstrated the use of manikins and pressure sensors for measuring and quantifying how physicians palpate during different physical exams. In this study we develop mathematical models that describe some of these common maneuvers. Dynamic pressure data was measured using a simplified testbed and different autoregressive models were used to describe the motion of interest. The frequency, direction and type of motion used were identified from the models. We believe these models can a provide better understanding of how humans explore objects in general and more specifically give insights to understand medical physical exams.

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.

Detection of T-wave alternans in fetal magnetocardiography using the generalized likelihood ratio test.

T-wave alternans (TWA) is an indicator of cardiac instability and is associated with life-threatening ventricular arrhythmias. Detection of TWA in the adult has been widely investigated and is used routinely for cardiac risk assessment. Detection of TWA in the fetus, however, is much more difficult due to the low amplitude and variable configuration of the signal, the presence of strong interferences, and the brevity of fetal TWA episodes. In this paper, we present a statistical detector based on the generalized likelihood ratio test that is designed for detection of TWA in the fetus. The performance of the detector is evaluated by constructing receiver-operator characteristic curves, using simulated data and real data from subjects with macroscopic TWA. The detector is capable of detecting TWA episodes as brief as 20 beats. The detection performance is improved significantly by modeling the fetal T-wave as a low-rank, low bandwidth signal, and using maximum likelihood estimation to estimate the model parameters. This approach enables all of the data to be used to estimate the noise statistics, providing highly effective suppression of interference, including maternal interference. The method is suitable for routine use because it can be applied to raw, unprocessed recordings, allowing automated analysis of extended fetal magnetocardiography recordings.

Multivariate autoregressive models with exogenous inputs for intracerebral responses to direct electrical stimulation of the human brain.

A multivariate autoregressive (MVAR) model with exogenous inputs (MVARX) is developed for describing the cortical interactions excited by direct electrical current stimulation of the cortex. Current stimulation is challenging to model because it excites neurons in multiple locations both near and distant to the stimulation site. The approach presented here models these effects using an exogenous input that is passed through a bank of filters, one for each channel. The filtered input and a random input excite a MVAR system describing the interactions between cortical activity at the recording sites. The exogenous input filter coefficients, the autoregressive coefficients, and random input characteristics are estimated from the measured activity due to current stimulation. The effectiveness of the approach is demonstrated using intracranial recordings from three surgical epilepsy patients. We evaluate models for wakefulness and NREM sleep in these patients with two stimulation levels in one patient and two stimulation sites in another resulting in a total of 10 datasets. Excellent agreement between measured and model-predicted evoked responses is obtained across all datasets. Furthermore, one-step prediction is used to show that the model also describes dynamics in pre-stimulus and evoked recordings. We also compare integrated information-a measure of intracortical communication thought to reflect the capacity for consciousness-associated with the network model in wakefulness and sleep. As predicted, higher information integration is found in wakefulness than in sleep for all five cases.

Interhemispheric effective and functional cortical connectivity signatures of spina bifida are consistent with callosal anomaly.

The impact of the posterior callosal anomalies associated with spina bifida on interhemispheric cortical connectivity is studied using a method for estimating cortical multivariable autoregressive models from scalp magnetoencephalography data. Interhemispheric effective and functional connectivity, measured using conditional Granger causality and coherence, respectively, is determined for the anterior and posterior cortical regions in a population of five spina bifida and five control subjects during a resting eyes-closed state. The estimated connectivity is shown to be consistent over the randomly selected subsets of the data for each subject. The posterior interhemispheric effective and functional connectivity and cortical power are significantly lower in the spina bifida group, a result that is consistent with posterior callosal anomalies. The anterior interhemispheric effective and functional connectivity are elevated in the spina bifida group, a result that may reflect compensatory mechanisms. In contrast, the intrahemispheric effective connectivity is comparable in the two groups. The differences between the spina bifida and control groups are most significant in the θ and α bands.

Seizure detection using the phase-slope index and multichannel ECoG.

Detection and analysis of epileptic seizures is of clinical and research interest. We propose a novel seizure detection and analysis scheme based on the phase-slope index (PSI) of directed influence applied to multichannel electrocorticogram data. The PSI metric identifies increases in the spatio-temporal interactions between channels that clearly distinguish seizure from interictal activity. We form a global metric of interaction between channels and compare this metric to a threshold to detect the presence of seizures. The threshold is chosen based on a moving average of recent activity to accommodate differences between patients and slow changes within each patient over time. We evaluate detection performance over a challenging population of five patients with different types of epilepsy using a total of 47 seizures in nearly 258 h of recorded data. Using a common threshold procedure, we show that our approach detects all of the seizures in four of the five patients with a false detection rate less than two per hour. A variation on the global metric is proposed to identify which channels are strong drivers of activity in each patient. These metrics are computationally efficient and suitable for real-time application.

Dielectric characterization of PCL-based thermoplastic materials for microwave diagnostic and therapeutic applications.

We propose the use of a polycaprolactone (PCL)-based thermoplastic mesh as a tissue-immobilization interface for microwave imaging and microwave hyperthermia treatment. An investigation of the dielectric properties of two PCL-based thermoplastic materials in the frequency range of 0.5-3.5 GHz is presented. The frequency-dependent dielectric constant and effective conductivity of the PCL-based thermoplastics are characterized using measurements of microstrip transmission lines fabricated on substrates comprised of the thermoplastic meshes. We also examine the impact of the presence of a PCL-based thermoplastic mesh on microwave breast imaging. We use a numerical test bed comprised of a previously reported 3-D anatomically realistic breast phantom and a multi-frequency microwave inverse scattering algorithm. We demonstrate that the PCL-based thermoplastic material and the assumed biocompatible medium of vegetable oil are sufficiently well matched such that the PCL layer may be neglected by the imaging solution without sacrificing imaging quality. Our results suggest that PCL-based thermoplastics are promising materials as tissue immobilization structures for microwave diagnostic and therapeutic applications.

Cross validation for selection of cortical interaction models from scalp EEG or MEG.

A cross-validation (CV) method based on state-space framework is introduced for comparing the fidelity of different cortical interaction models to the measured scalp electroencephalogram (EEG) or magnetoencephalography (MEG) data being modeled. A state equation models the cortical interaction dynamics and an observation equation represents the scalp measurement of cortical activity and noise. The measured data are partitioned into training and test sets. The training set is used to estimate model parameters and the model quality is evaluated by computing test data innovations for the estimated model. Two CV metrics normalized mean square error and log-likelihood are estimated by averaging over different training/test partitions of the data. The effectiveness of this method of model selection is illustrated by comparing two linear modeling methods and two nonlinear modeling methods on simulated EEG data derived using both known dynamic systems and measured electrocorticography data from an epilepsy patient.

A TSVD analysis of microwave inverse scattering for breast imaging.

A variety of methods have been applied to the inverse scattering problem for breast imaging at microwave frequencies. While many techniques have been leveraged toward a microwave imaging solution, they are all fundamentally dependent on the quality of the scattering data. Evaluating and optimizing the information contained in the data are, therefore, instrumental in understanding and achieving optimal performance from any particular imaging method. In this paper, a method of analysis is employed for the evaluation of the information contained in simulated scattering data from a known dielectric profile. The method estimates optimal imaging performance by mapping the data through the inverse of the scattering system. The inverse is computed by truncated singular-value decomposition of a system of scattering equations. The equations are made linear by use of the exact total fields in the imaging volume, which are available in the computational domain. The analysis is applied to anatomically realistic numerical breast phantoms. The utility of the method is demonstrated for a given imaging system through the analysis of various considerations in system design and problem formulation. The method offers an avenue for decoupling the problem of data selection from the problem of image formation from that data.