Lattice layout and optimizer effect analysis for generating optimal transcranial electrical stimulation (tES) montages through the metaheuristic L1L1 method.

Introduction: This study focuses on broadening the applicability of the metaheuristic L1-norm fitted and penalized (L1L1) optimization method in finding a current pattern for multichannel transcranial electrical stimulation (tES). The metaheuristic L1L1 optimization framework defines the tES montage via linear programming by maximizing or minimizing an objective function with respect to a pair of hyperparameters. Methods: In this study, we explore the computational performance and reliability of different optimization packages, algorithms, and search methods in combination with the L1L1 method. The solvers from Matlab R2020b, MOSEK 9.0, Gurobi Optimizer, CVX's SeDuMi 1.3.5, and SDPT3 4.0 were employed to produce feasible results through different linear programming techniques, including Interior-Point (IP), Primal-Simplex (PS), and Dual-Simplex (DS) methods. To solve the metaheuristic optimization task of L1L1, we implement an exhaustive and recursive search along with a well-known heuristic direct search as a reference algorithm. Results: Based on our results, and the given optimization task, Gurobi's IP was, overall, the preferable choice among Interior-Point while MOSEK's PS and DS packages were in the case of Simplex methods. These methods provided substantial computational time efficiency for solving the L1L1 method regardless of the applied search method. Discussion: While the best-performing solvers show that the L1L1 method is suitable for maximizing either focality and intensity, a few of these solvers could not find a bipolar configuration. Part of the discrepancies between these methods can be explained by a different sensitivity with respect to parameter variation or the resolution of the lattice provided.

Standardized hierarchical adaptive Lp regression for noise robust focal epilepsy source reconstructions.

OBJECTIVE: To investigate the ability of standardization to reduce source localization errors and measurement noise uncertainties for hierarchical Bayesian algorithms with L1- and L2-norms as priors in electroencephalography and magnetoencephalography of focal epilepsy. METHODS: Description of the standardization methodology relying on the Hierarchical Bayesian framework, referred to as the Standardized Hierarchical Adaptive Lp-norm Regularization (SHALpR). The performance was tested using real data from two focal epilepsy patients. Simulated data that resembled the available real data was constructed for further localization and noise robustness investigation. RESULTS: The proposed algorithms were compared to their non-standardized counterparts, Standardized low-resolution brain electromagnetic tomography, Standardized Shrinking LORETA-FOCUSS, and Dynamic statistical parametric maps. Based on the simulations, the standardized Hierarchical adaptive algorithm using L2-norm was noise robust for 10 dB signal-to-noise ratio (SNR), whereas the L1-norm prior worked robustly also with 5 dB SNR. The accuracy of the standardized L1-normed methodology to localize focal activity was under 1 cm for both patients. CONCLUSIONS: Numerical results of the proposed methodology display improved localization and noise robustness. The proposed methodology also outperformed the compared methods when dealing with real data. SIGNIFICANCE: The proposed standardized methodology, especially when employing the L1-norm, could serve as a valuable assessment tool in surgical decision-making.

Modeling of blood flow in cerebral arterial circulation and its dynamic impact on electrical conductivity in a realistic multi-compartment head model.

BACKGROUND AND OBJECTIVE: This study aims to assess the dynamic impact of non-Newtonian cerebral arterial circulation on electrical conductivity within a realistic multi-compartment head model. Evaluating this research question is crucial and challenging due to its relevance to electrophysiological modalities like transcranial electrical stimulation (tES), electro-/magnetoencephalography (EEG/MEG), and electrical impedance tomography (EIT). In these modalities, accurate forward modeling depends on the electrical conductivity, which is affected by complex tortuous vessel networks, limited data acquisition in Magnetic Resonance Imaging (MRI), and non-linear blood flow phenomena, including shear rate and viscosity in non-Newtonian fluid. METHODS: To obtain an approximation for the blood concentration, we first use Navier-Stokes equations (NSEs) to solve for the pressure and velocity of the blood in the major vessels. Then Fick's law is used to solve for the blood concentration in the tissues. Finally, Archie's law is used to estimate the electrical conductivity distribution based on the blood concentration. RESULTS: The results, obtained with an open 7 Tesla MRI dataset, suggest that a dynamic model of cerebral blood flow (CBF) for both arterial and microcirculation can be established; we find blood pressure and electrical conductivity distributions given a numerically simulated pulse sequence and approximate the blood concentration and electrical conductivity inside the brain based on those. CONCLUSIONS: Our model provides an approximation of the dynamical blood flow and the corresponding electrical conductivity distribution in the different parts of the brain. The advantage of our approach is that it is applicable with limited a priori information about the blood flow and with an arbitrary head model distinguishing the arteries.

Pressure-Poisson equation in numerical simulation of cerebral arterial circulation and its effect on the electrical conductivity of the brain.

BACKGROUND AND OBJECTIVE: This study considers dynamic modeling of the cerebral arterial circulation and reconstructing an atlas for the electrical conductivity of the brain. Electrical conductivity is a governing parameter in several electrophysiological modalities applied in neuroscience, such as electroencephalography (EEG), transcranial electrical stimulation (tES), and electrical impedance tomography (EIT). While high-resolution 7-Tesla (T) Magnetic Resonance Imaging (MRI) data allow for reconstructing the cerebral arteries with a cross-sectional diameter larger than the voxel size, electrical conductivity cannot be directly inferred from MRI data. Brain models of electrophysiology typically associate each brain tissue compartment with a constant electrical conductivity, omitting any dynamic effects of cerebral blood circulation. Incorporating those effects poses the challenge of solving a system of incompressible Navier-Stokes equations (NSEs) in a realistic multi-compartment head model. However, using a simplified circulation model is well-motivated since, on the one hand, the complete system does not always have a numerically stable solution and, on the other hand, the full set of arteries cannot be perfectly reconstructed from the MRI data, meaning that any solution will be approximative. METHODS: We postulate that circulation in the distinguishable arteries can be estimated via the pressure-Poisson equation (PPE), which is coupled with Fick's law of diffusion for microcirculation. To establish a fluid exchange model between arteries and microarteries, a boundary condition derived from the Hagen-Poisseuille model is applied. The relationship between the estimated volumetric blood concentration and the electrical conductivity of the brain tissue is approximated through Archie's law for fluid flow in porous media. RESULTS: Through the formulation of the PPE and a set of boundary conditions (BCs) based on the Hagen-Poisseuille model, we obtained an equivalent formulation of the incompressible Stokes equation (SE). Thus, allowing effective blood pressure estimation in cerebral arteries segmented from open 7T MRI data. CONCLUSIONS: As a result of this research, we developed and built a useful modeling framework that accounts for the effects of dynamic blood flow on a novel MRI-based electrical conductivity atlas. The electrical conductivity perturbation obtained in numerical experiments has an appropriate overall match with previous studies on this subject. Further research to validate these results will be necessary.

Multi-compartment head modeling in EEG: Unstructured boundary-fitted tetra meshing with subcortical structures.

This paper introduces an automated approach for generating a finite element (FE) discretization of a multi-compartment human head model for electroencephalographic (EEG) source localization. We aim to provide an adaptable FE mesh generation tool for EEG studies. Our technique relies on recursive solid angle labeling of a surface segmentation coupled with smoothing, refinement, inflation, and optimization procedures to enhance the mesh quality. In this study, we performed numerical meshing experiments with the three-layer Ary sphere and a magnetic resonance imaging (MRI)-based multi-compartment head segmentation which incorporates a comprehensive set of subcortical brain structures. These experiments are motivated, on one hand, by the sensitivity of non-invasive subcortical source localization to modeling errors and, on the other hand, by the present lack of open EEG software pipelines to discretize all these structures. Our approach was found to successfully produce an unstructured and boundary-fitted tetrahedral mesh with a sub-one-millimeter fitting error, providing the desired accuracy for the three-dimensional anatomical details, EEG lead field matrix, and source localization. The mesh generator applied in this study has been implemented in the open MATLAB-based Zeffiro Interface toolbox for forward and inverse processing in EEG and it allows for graphics processing unit acceleration.

CutFEM forward modeling for EEG source analysis.

Introduction: Source analysis of Electroencephalography (EEG) data requires the computation of the scalp potential induced by current sources in the brain. This so-called EEG forward problem is based on an accurate estimation of the volume conduction effects in the human head, represented by a partial differential equation which can be solved using the finite element method (FEM). FEM offers flexibility when modeling anisotropic tissue conductivities but requires a volumetric discretization, a mesh, of the head domain. Structured hexahedral meshes are easy to create in an automatic fashion, while tetrahedral meshes are better suited to model curved geometries. Tetrahedral meshes, thus, offer better accuracy but are more difficult to create. Methods: We introduce CutFEM for EEG forward simulations to integrate the strengths of hexahedra and tetrahedra. It belongs to the family of unfitted finite element methods, decoupling mesh and geometry representation. Following a description of the method, we will employ CutFEM in both controlled spherical scenarios and the reconstruction of somatosensory-evoked potentials. Results: CutFEM outperforms competing FEM approaches with regard to numerical accuracy, memory consumption, and computational speed while being able to mesh arbitrarily touching compartments. Discussion: CutFEM balances numerical accuracy, computational efficiency, and a smooth approximation of complex geometries that has previously not been available in FEM-based EEG forward modeling.

In silicostudy of the effects of cerebral circulation on source localization using a dynamical anatomical atlas of the human head.

Objective.This study focuses on the effects of dynamical vascular modeling on source localization errors in electroencephalography (EEG). Our aim of thisin silicostudy is to (a) find out the effects of cerebral circulation on the accuracy of EEG source localization estimates, and (b) evaluate its relevance with respect to measurement noise and interpatient variation.Approach.We employ a four-dimensional (3D + T) statistical atlas of the electrical properties of the human head with a cerebral circulation model to generate virtual patients with different cerebral circulatory conditions for EEG source localization analysis. As source reconstruction techniques, we use the linearly constraint minimum variance (LCMV) beamformer, standardized low-resolution brain electromagnetic tomography (sLORETA), and the dipole scan (DS).Main results.Results indicate that arterial blood flow affects source localization at different depths and with varying significance. The average flow rate plays an important role in source localization performance, while the pulsatility effects are very small. In cases where a personalized model of the head is available, blood circulation mismodeling causes localization errors, especially in the deep structures of the brain where the main cerebral arteries are located. When interpatient variations are considered, the results show differences up to 15 mm for sLORETA and LCMV beamformer and 10 mm for DS in the brainstem and entorhinal cortices regions. In regions far from the main arteries vessels, the discrepancies are smaller than 3 mm. When measurement noise is added and interpatient differences are considered in a deep dipolar source, the results indicate that the effects of conductivity mismatch are detectable even for moderate measurement noise. The signal-to-noise ratio limit for sLORETA and LCMV beamformer is 15 dB, while the limit is under 30 dB for DS.Significance.Localization of the brain activity via EEG constitutes an ill-posed inverse problem, where any modeling uncertainty, e.g. a slight amount of noise in the data or material parameter discrepancies, can lead to a significant deviation of the estimated activity, especially in the deep structures of the brain. Proper modeling of the conductivity distribution is necessary in order to obtain an appropriate source localization. In this study, we show that the conductivity of the deep brain structures is particularly impacted by blood flow-induced changes in conductivity because large arteries and veins access the brain through that region.

L1-norm vs. L2-norm fitting in optimizing focal multi-channel tES stimulation: linear and semidefinite programming vs. weighted least squares.

BACKGROUND AND OBJECTIVE: This study focuses on Multi-Channel Transcranial Electrical Stimulation, a non-invasive brain method for stimulating neuronal activity under the influence of low-intensity currents. We introduce a mathematical formulation for finding a current pattern that optimizes an L1-norm fit between a given focal target distribution and volumetric current density inside the brain. L1-norm is well-known to favor well-localized or sparse distributions compared to L2-norm (least-squares) fitted estimates. METHODS: We present a linear programming approach that performs L1-norm fitting and penalization of the current pattern (L1L1) to control the number of non-zero currents. The optimizer filters a large set of candidate solutions using a two-stage metaheuristic search from a pre-filtered set of candidates. RESULTS: The numerical simulation results obtained with both 8- and 20-channel electrode montages suggest that our hypothesis on the benefits of L1-norm data fitting is valid. Compared to an L1-norm regularized L2-norm fitting (L1L2) via semidefinite programming and weighted Tikhonov least-squares method (TLS), the L1L1 results were overall preferable for maximizing the focused current density at the target position, and the ratio between focused and nuisance current magnitudes. CONCLUSIONS: We propose the metaheuristic L1L1 optimization approach as a potential technique to obtain a well-localized stimulus with a controllable magnitude at a given target position. L1L1 finds a current pattern with a steep contrast between the anodal and cathodal electrodes while suppressing the nuisance currents in the brain, hence, providing a potential alternative to modulate the effects of the stimulation, e.g., the sensation experienced by the subject.

Reconstructing subcortical and cortical somatosensory activity via the RAMUS inverse source analysis technique using median nerve SEP data.

This study concerns reconstructing brain activity at various depths based on non-invasive EEG (electroencephalography) scalp measurements. We aimed at demonstrating the potential of the RAMUS (randomized multiresolution scanning) technique in localizing weakly distinguishable far-field sources in combination with coinciding cortical activity. As we have shown earlier theoretically and through simulations, RAMUS is a novel mathematical method that by employing the multigrid concept, allows marginalizing noise and depth bias effects and thus enables the recovery of both cortical and subcortical brain activity. To show this capability with experimental data, we examined the 14-30 ms post-stimulus somatosensory evoked potential (SEP) responses of human median nerve stimulation in three healthy adult subjects. We aim at reconstructing the different response components by evaluating a RAMUS-based estimate for the primary current density in the nervous tissue. We present source reconstructions obtained with RAMUS and compare them with the literature knowledge of the SEP components and the outcome of the unit-noise gain beamformer (UGNB) and standardized low-resolution brain electromagnetic tomography (sLORETA). We also analyzed the effect of the iterative alternating sequential technique, the optimization technique of RAMUS, compared to the classical minimum norm estimation (MNE) technique. Matching with our previous numerical studies, the current results suggest that RAMUS could have the potential to enhance the detection of simultaneous deep and cortical components and the distinction between the evoked sulcal and gyral activity.

DUNEuro-A software toolbox for forward modeling in bioelectromagnetism.

Accurate and efficient source analysis in electro- and magnetoencephalography using sophisticated realistic head geometries requires advanced numerical approaches. This paper presents DUNEuro, a free and open-source C++ software toolbox for the numerical computation of forward solutions in bioelectromagnetism. Building upon the DUNE framework, it provides implementations of modern fitted and unfitted finite element methods to efficiently solve the forward problems of electro- and magnetoencephalography. The user can choose between a variety of different source models that are implemented. The software's aim is to provide interfaces that are extendable and easy-to-use. In order to enable a closer integration into existing analysis pipelines, interfaces to Python and MATLAB are provided. The practical use is demonstrated by a source analysis example of somatosensory evoked potentials using a realistic six-compartment head model. Detailed installation instructions and example scripts using spherical and realistic head models are appended.

Parametrizing the Conditionally Gaussian Prior Model for Source Localization with Reference to the P20/N20 Component of Median Nerve SEP/SEF.

In this article, we focused on developing the conditionally Gaussian hierarchical Bayesian model (CG-HBM), which forms a superclass of several inversion methods for source localization of brain activity using somatosensory evoked potential (SEP) and field (SEF) measurements. The goal of this proof-of-concept study was to improve the applicability of the CG-HBM as a superclass by proposing a robust approach for the parametrization of focal source scenarios. We aimed at a parametrization that is invariant with respect to altering the noise level and the source space size. The posterior difference between the gamma and inverse gamma hyperprior was minimized by optimizing the shape parameter, while a suitable range for the scale parameter can be obtained via the prior-over-measurement signal-to-noise ratio, which we introduce as a new concept in this study. In the source localization experiments, the primary generator of the P20/N20 component was detected in the Brodmann area 3b using the CG-HBM approach and a parameter range derived from the existing knowledge of the Tikhonov-regularized minimum norm estimate, i.e., the classical Gaussian prior model. Moreover, it seems that the detection of deep thalamic activity simultaneously with the P20/N20 component with the gamma hyperprior can be enhanced while using a close-to-optimal shape parameter value.

Combining dual-tree complex wavelets and multiresolution in iterative CT reconstruction with application to metal artifact reduction.

BACKGROUND: This paper investigates the benefits of data filtering via complex dual wavelet transform for metal artifact reduction (MAR). The advantage of using complex dual wavelet basis for MAR was studied on simulated dental computed tomography (CT) data for its efficiency in terms of noise suppression and removal of secondary artifacts. Dual-tree complex wavelet transform (DT-CWT) was selected due to its enhanced directional analysis of image details compared to the ordinary wavelet transform. DT-CWT was used for multiresolution decomposition within a modified total variation (TV) regularized inversion algorithm. METHODS: In this study, we have tested the multiresolution TV (MRTV) approach with DT-CWT on a 2D polychromatic jaw phantom model with Gaussian and Poisson noise. High noise and sparse measurement settings were used to assess the performance of DT-CWT. The results were compared to the outcome of the single-resolution reconstruction and filtered back-projection (FBP) techniques as well as reconstructions with Haar wavelet basis. RESULTS: The results indicate that filtering of wavelet coefficients with DT-CWT effectively removes the noise without introducing new artifacts after inpainting. Furthermore, adoption of multiple resolution levels yield to a more robust algorithm compared to varying the regularization strength. CONCLUSIONS: The multiresolution reconstruction with DT-CWT is also more robust when reconstructing the data with sparse projections compared to the single-resolution approach and Haar wavelets.

Gaussian Light Model in Brightfield Optical Projection Tomography.

This study focuses on improving the reconstruction process of the brightfield optical projection tomography (OPT). OPT is often described as the optical equivalent of X-ray computed tomography, but based on visible light. The detection optics used to collect light in OPT focus on a certain distance and induce blurring in those features out of focus. However, the conventionally used inverse Radon transform assumes an absolute focus throughout the propagation axis. In this study, we model the focusing properties of the detection by coupling Gaussian beam model (GBM) with the Radon transform. The GBM enables the construction of a projection operator that includes modeling of the blurring caused by the light beam. We also introduce the concept of a stretched GBM (SGBM) in which the Gaussian beam is scaled in order to avoid the modeling errors related to the determination of the focal plane. Furthermore, a thresholding approach is used to compress memory usage. We tested the GBM and SGBM approaches using simulated and experimental data in mono- and multifocal modes. When compared with the traditionally used filtered backprojection algorithm, the iteratively computed reconstructions, including the Gaussian models GBM and SGBM, provided smoother images with higher contrast.

A mathematical model and iterative inversion for fluorescent optical projection tomography.

Solving the fluorophore distribution in a tomographic setting has been difficult because of the lack of physically meaningful and computationally applicable propagation models. This study concentrates on the direct modelling of fluorescence signals in optical projection tomography (OPT), and on the corresponding inverse problem. The reconstruction problem is solved using emission projections corresponding to a series of rotational imaging positions of the sample. Similarly to the bright field OPT bearing resemblance with the transmission x-ray computed tomography, the fluorescent mode OPT is analogous to x-ray fluorescence tomography (XFCT). As an improved direct model for the fluorescent OPT, we derive a weighted Radon transform based on the XFCT literature. Moreover, we propose a simple and fast iteration scheme for the slice-wise reconstruction of the sample. The developed methods are applied in both numerical experiments and inversion of fluorescent OPT data from a zebrafish embryo. The results demonstrate the importance of propagation modelling and our analysis provides a flexible modelling framework for fluorescent OPT that can easily be modified to adapt to different imaging setups.

A realistic, accurate and fast source modeling approach for the EEG forward problem.

The aim of this paper is to advance electroencephalography (EEG) source analysis using finite element method (FEM) head volume conductor models that go beyond the standard three compartment (skin, skull, brain) approach and take brain tissue inhomogeneity (gray and white matter and cerebrospinal fluid) into account. The new approach should enable accurate EEG forward modeling in the thin human cortical structures and, more specifically, in the especially thin cortices in children brain research or in pathological applications. The source model should thus be focal enough to be usable in the thin cortices, but should on the other side be more realistic than the current standard mathematical point dipole. Furthermore, it should be numerically accurate and computationally fast. We propose to achieve the best balance between these demands with a current preserving (divergence conforming) dipolar source model. We develop and investigate a varying number of current preserving source basis elements n (n=1,…,n=5). For validation, we conducted numerical experiments within a multi-layered spherical domain, where an analytical solution exists. We show that the accuracy increases along with the number of basis elements, while focality decreases. The results suggest that the best balance between accuracy and focality in thin cortices is achieved with n=4 (or in extreme cases even n=3) basis functions, while in thicker cortices n=5 is recommended to obtain the highest accuracy. We also compare the current preserving approach to two further FEM source modeling techniques, namely partial integration and St. Venant, and show that the best current preserving source model outperforms the competing methods with regard to overall balance. For all tested approaches, FEM transfer matrices enable high computational speed. We implemented the new EEG forward modeling approaches into the open source duneuro library for forward modeling in bioelectromagnetism to enable its broader use by the brain research community. This library is build upon the DUNE framework for parallel finite elements simulations and integrates with high-level toolboxes like FieldTrip. Additionally, an inversion test has been implemented using the realistic head model to demonstrate and compare the differences between the aforementioned source models.

Advanced Boundary Electrode Modeling for tES and Parallel tES/EEG.

This paper explores advanced electrode modeling in the context of separate and parallel transcranial electrical stimulation (tES) and electroencephalography (EEG) measurements. We focus on boundary condition-based approaches that do not necessitate adding auxiliary elements, e.g., sponges, to the computational domain. In particular, we investigate the complete electrode model (CEM) which incorporates a detailed description of the skin-electrode interface including its contact surface, impedance, and normal current distribution. The CEM can be applied for both tES and EEG electrodes which are advantageous when a parallel system is used. In comparison to the CEM, we test two important reduced approaches: the gap model (GAP) and the point electrode model (PEM). We aim to find out the differences of these approaches for a realistic numerical setting based on the stimulation of the auditory cortex. The results obtained suggest, among other things, that GAP and GAP/PEM are sufficiently accurate for the practical application of tES and parallel tES/EEG, respectively. Differences between CEM and GAP were observed mainly in the skin compartment, where only CEM explains the heating effects characteristic to tES.

Comparison Study for Whitney (Raviart-Thomas)-Type Source Models in Finite-Element-Method-Based EEG Forward Modeling.

This study concentrates on finite-element-method (FEM)-based electroencephalography (EEG) forward simulation in which the electric potential evoked by neural activity in the brain is to be calculated at the surface of the head. The main advantage of the FEM is that it allows realistic modeling of tissue conductivity inhomogeneity. However, it is not straightforward to apply the classical model of a dipolar source with the FEM, due to its strong singularity and the resulting irregularity. The focus of this study is on comparing different methods to cope with this problem. In particular, we evaluate the accuracy of Whitney (Raviart-Thomas)-type dipole-like source currents compared to two reference dipole modeling methods: the St. Venant and partial integration approach. Common to all these methods is that they enable direct approximation of the potential field utilizing linear basis functions. In the present context, Whitney elements are particularly interesting, as they provide a simple means to model a divergence-conforming primary current vector field satisfying the square integrability condition. Our results show that a Whitney-type source model can provide simulation accuracy comparable to the present reference methods. It can lead to superior accuracy under optimized conditions with respect to both source location and orientation in a tetrahedral mesh. For random source orientations, the St. Venant approach turns out to be the method of choice over the interpolated version of the Whitney model. The overall moderate differences obtained suggest that practical aspects, such as the focality, should be prioritized when choosing a source model.

Hierarchical Bayesian inference for the EEG inverse problem using realistic FE head models: depth localization and source separation for focal primary currents.

The estimation of the activity-related ion currents by measuring the induced electromagnetic fields at the head surface is a challenging and severely ill-posed inverse problem. This is especially true in the recovery of brain networks involving deep-lying sources by means of EEG/MEG recordings which is still a challenging task for any inverse method. Recently, hierarchical Bayesian modeling (HBM) emerged as a unifying framework for current density reconstruction (CDR) approaches comprising most established methods as well as offering promising new methods. Our work examines the performance of fully-Bayesian inference methods for HBM for source configurations consisting of few, focal sources when used with realistic, high-resolution finite element (FE) head models. The main foci of interest are the correct depth localization, a well-known source of systematic error of many CDR methods, and the separation of single sources in multiple-source scenarios. Both aspects are very important in the analysis of neurophysiological data and in clinical applications. For these tasks, HBM provides a promising framework and is able to improve upon established CDR methods such as minimum norm estimation (MNE) or sLORETA in many aspects. For challenging multiple-source scenarios where the established methods show crucial errors, promising results are attained. Additionally, we introduce Wasserstein distances as performance measures for the validation of inverse methods in complex source scenarios.