Volumetric measurements of weak current-induced magnetic fields in the human brain at high resolution.

PURPOSE: Clinical use of transcranial electrical stimulation (TES) requires accurate knowledge of the injected current distribution in the brain. MR current density imaging (MRCDI) uses measurements of the TES-induced magnetic fields to provide this information. However, sufficient sensitivity and image quality in humans in vivo has only been documented for single-slice imaging. METHODS: A recently developed, optimally spoiled, acquisition-weighted, gradient echo-based 2D-MRCDI method has now been advanced for volume coverage with densely or sparsely distributed slices: The 3D rectilinear sampling (3D-DENSE) and simultaneous multislice acquisition (SMS-SPARSE) were optimized and verified by cable-loop experiments and tested with 1-mA TES experiments for two common electrode montages. RESULTS: Comparisons between the volumetric methods against the 2D-MRCDI showed that relatively long acquisition times of 3D-DENSE using a single slab with six slices hindered the expected sensitivity improvement in the current-induced field measurements but improved sensitivity by 61% in the Laplacian of the field, on which some MRCDI reconstruction methods rely. Also, SMS-SPARSE acquisition of three slices, with a factor 2 CAIPIRINHA (controlled aliasing in parallel imaging results in higher acceleration) acceleration, performed best against the 2D-MRCDI with sensitivity improvements for the ∆ B z , c $$ \Delta {B}_{z,c} $$ and Laplacian noise floors of 56% and 78% (baseline without current flow) as well as 43% and 55% (current injection into head). SMS-SPARSE reached a sensitivity of 67 pT for three distant slices at 2 × 2 × 3 mm3 resolution in 10 min of total scan time, and consistently improved image quality. CONCLUSION: Volumetric MRCDI measurements with high sensitivity and image quality are well suited to characterize the TES field distribution in the human brain.

On the reconstruction of magnetic resonance current density images of the human brain: Pitfalls and perspectives.

Magnetic resonance current density imaging (MRCDI) of the human brain aims to reconstruct the current density distribution caused by transcranial electric stimulation from MR-based measurements of the current-induced magnetic fields. So far, the MRCDI data acquisition achieves only a low signal-to-noise ratio, does not provide a full volume coverage and lacks data from the scalp and skull regions. In addition, it is only sensitive to the component of the current-induced magnetic field parallel to the scanner field. The reconstruction problem thus involves coping with noisy and incomplete data, which makes it mathematically challenging. Most existing reconstruction methods have been validated using simulation studies and measurements in phantoms with simplified geometries. Only one reconstruction method, the projected current density algorithm, has been applied to human in-vivo data so far, however resulting in blurred current density estimates even when applied to noise-free simulated data. We analyze the underlying causes for the limited performance of the projected current density algorithm when applied to human brain data. In addition, we compare it with an approach that relies on the optimization of the conductivities of a small number of tissue compartments of anatomically detailed head models reconstructed from structural MR data. Both for simulated ground truth data and human in-vivo MRCDI data, our results indicate that the estimation of current densities benefits more from using a personalized volume conductor model than from applying the projected current density algorithm. In particular, we introduce a hierarchical statistical testing approach as a principled way to test and compare the quality of reconstructed current density images that accounts for the limited signal-to-noise ratio of the human in-vivo MRCDI data and the fact that the ground truth of the current density is unknown for measured data. Our results indicate that the statistical testing approach constitutes a valuable framework for the further development of accurate volume conductor models of the head. Our findings also highlight the importance of tailoring the reconstruction approaches to the quality and specific properties of the available data.

Sensitivity and resolution improvement for in vivo magnetic resonance current-density imaging of the human brain.

PURPOSE: Magnetic resonance current-density imaging (MRCDI) combines MRI with low-intensity transcranial electrical stimulation (TES; 1-2 mA) to map current flow in the brain. However, usage of MRCDI is still hampered by low measurement sensitivity and image quality. METHODS: Recently, a multigradient-echo-based MRCDI approach has been introduced that presently has the best-documented efficiency. This MRCDI approach has now been advanced in three directions and has been validated by phantom and in vivo experiments. First, the importance of optimum spoiling for brain imaging was verified. Second, the sensitivity and spatial resolution were improved by using acquisition weighting. Third, navigators were added as a quality control measure for tracking physiological noise. Combining these advancements, the optimized MRCDI method was tested by using 1 mA TES for two different injection profiles. RESULTS: For a session duration of 4:20 min, the new MRCDI method was able to detect TES-induced magnetic fields at a sensitivity level of 84 picotesla, representing a twofold efficiency increase against our original method. A comparison between measurements and simulations based on personalized head models showed a consistent increase in the coefficient of determination of ΔR2 = 0.12 for the current-induced magnetic fields and ΔR2 = 0.22 for the current flow reconstructions. Interestingly, some of the simulations still clearly deviated from the measurements despite the strongly improved measurement quality. This highlights the utility of MRCDI to improve head models for TES simulations. CONCLUSION: The achieved sensitivity improvement is an important step from proof-of-concept studies toward a broader application of MRCDI in clinical and basic neuroscience research.

Human in-vivo brain magnetic resonance current density imaging (MRCDI).

Magnetic resonance current density imaging (MRCDI) and MR electrical impedance tomography (MREIT) are two emerging modalities, which combine weak time-varying currents injected via surface electrodes with magnetic resonance imaging (MRI) to acquire information about the current flow and ohmic conductivity distribution at high spatial resolution. The injected current flow creates a magnetic field in the head, and the component of the induced magnetic field ΔBz,c parallel to the main scanner field causes small shifts in the precession frequency of the magnetization. The measured MRI signal is modulated by these shifts, allowing to determine ΔBz,c for the reconstruction of the current flow and ohmic conductivity. Here, we demonstrate reliable ΔBz,c measurements in-vivo in the human brain based on multi-echo spin echo (MESE) and steady-state free precession free induction decay (SSFP-FID) sequences. In a series of experiments, we optimize their robustness for in-vivo measurements while maintaining a good sensitivity to the current-induced fields. We validate both methods by assessing the linearity of the measured ΔBz,c with respect to the current strength. For the more efficient SSFP-FID measurements, we demonstrate a strong influence of magnetic stray fields on the ΔBz,c images, caused by non-ideal paths of the electrode cables, and validate a correction method. Finally, we perform measurements with two different current injection profiles in five subjects. We demonstrate reliable recordings of ΔBz,c fields as weak as 1 nT, caused by currents of 1 mA strength. Comparison of the ΔBz,c measurements with simulated ΔBz,c images based on FEM calculations and individualized head models reveals significant linear correlations in all subjects, but only for the stray field-corrected data. As final step, we reconstruct current density distributions from the measured and simulated ΔBz,c data. Reconstructions from non-corrected ΔBz,c measurements systematically overestimate the current densities. Comparing the current densities reconstructed from corrected ΔBz,c measurements and from simulated ΔBz,c images reveals an average coefficient of determination R2 of 71%. In addition, it shows that the simulations underestimated the current strength on average by 24%. Our results open up the possibility of using MRI to systematically validate and optimize numerical field simulations that play an important role in several neuroscience applications, such as transcranial brain stimulation, and electro- and magnetoencephalography.

Sensitivity analysis of magnetic field measurements for magnetic resonance electrical impedance tomography (MREIT).

PURPOSE: Clinical use of magnetic resonance electrical impedance tomography (MREIT) still requires significant sensitivity improvements. Here, the measurement of the current-induced magnetic field (ΔBz,c ) is improved using systematic efficiency analyses and optimization of multi-echo spin echo (MESE) and steady-state free precession free induction decay (SSFP-FID) sequences. THEORY AND METHODS: Considering T1 , T2 , and T2* relaxation in the signal-to-noise ratios (SNRs) of the MR magnitude images, the efficiency of MESE and SSFP-FID MREIT experiments, and its dependence on the sequence parameters, are analytically analyzed and simulated. The theoretical results are experimentally validated in a saline-filled homogenous spherical phantom with relaxation parameters similar to brain tissue. Measurement of ΔBz,c is also performed in a cylindrical phantom with saline and chicken meat. RESULTS: The efficiency simulations and experimental results are in good agreement. When using optimal parameters, ΔBz,c can be reliably measured in the phantom even at injected current strengths of 1 mA or lower for both sequence types. The importance of using proper crusher gradient selection on the phase evolution in a MESE experiment is also demonstrated. CONCLUSION: The efficiencies observed with the optimized sequence parameters will likely render in-vivo human brain MREIT feasible. Magn Reson Med 79:748-760, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Safety evaluation of a new setup for transcranial electric stimulation during magnetic resonance imaging.

BACKGROUND: Transcranial electric stimulation during MR imaging can introduce safety issues due to coupling of the RF field with the stimulation electrodes and leads. OBJECTIVE: To optimize the stimulation setup for MR current density imaging (MRCDI) and increase maximum stimulation current, a new low-conductivity (σ = 29.4 S/m) lead wire is designed and tested. METHOD: The antenna effect was simulated to investigate the effect of lead conductivity. Subsequently, specific absorption rate (SAR) simulations for realistic lead configurations with low-conductivity leads and two electrode types were performed at 128 MHz and 298 MHz being the Larmor frequencies of protons at 3T and 7T. Temperature measurements were performed during MRI using high power deposition sequences to ensure that the electrodes comply with MRI temperature regulations. RESULTS: The antenna effect was found for copper leads at » RF wavelength and could be reliably eliminated using low-conductivity leads. Realistic lead configurations increased the head SAR and the local head SAR at the electrodes only minimally. The highest temperatures were measured on the rings of center-surround electrodes, while circular electrodes showed little heating. No temperature increase above the safety limit of 39 °C was observed. CONCLUSION: Coupling to the RF field can be reliably prevented by low-conductivity leads, enabling cable paths optimal for MRCDI. Compared to commercial copper leads with safety resistors, the low-conductivity leads had lower total impedance, enabling the application of higher currents without changing stimulator design. Attention must be paid to electrode pads.

Probing EEG activity in the targeted cortex after focal transcranial electrical stimulation.

BACKGROUND: Recording electroencephalography (EEG) from the targeted cortex immediately before and after focal transcranial electrical stimulation (TES) remains a challenge. METHODS: We introduce a hybrid stimulation-recording approach where a single EEG electrode is inserted into the inner electrode of a double-ring montage for focal TES. The new combined electrode was placed at the C3 position of the EEG 10-20 system. Neuronal activity was recorded in two volunteers before and after 20 Hz alternating-current TES at peak-to-peak intensities of 1 and 2 mA. TES-induced electric field distributions were simulated with SIMNIBS software. RESULTS: Using the hybrid stimulation-recording set-up, EEG activity was successfully recorded directly before and after TES. Simulations revealed comparable electrical fields in the stimulated cortex for the pseudomonopolar montage with and without embedded EEG electrode. CONCLUSION: The hybrid TES-EEG approach can be used to probe after-effects of focal TES on neuronal activity in the targeted cortex.

The stray magnetic fields in Magnetic Resonance Current Density Imaging (MRCDI).

PURPOSE: MR Current Density Imaging (MRCDI) involves weak current-injection into the head. The resulting magnetic field changes are measured by MRI. Stray fields pose major challenges since these can dominate the fields caused by tissue currents. We analyze the sources and influences of stray fields. METHODS: First, we supply validation data for a recently introduced MRCDI method with an unprecedented noise floor of ∼0.1 nT in vivo. Second, we assess the accuracy limit of the method and our corresponding cable current correction in phantoms ensuring high signal-to-noise ratio (SNR). Third, we simulate the influence of stray fields on current flow reconstructions for various realistic experimental set-ups. Fourth, we experimentally determine the physiological field variations. Finally, we explore the consequences of head positioning in an exemplary head coil, since off-center positioning provides space for limiting cable-induced fields. RESULTS: The cable correction method performs well except near the cables. Unless correcting for cable currents, the reconstructed current flow is easily misestimated by up to 45% for a realistic experimental set-up. Stray fields dominating the fields caused by tissue currents can occur, e.g. due to a wire segment 20 cm away from the imaged region, or due to a slight cable misalignment of 3°. The noise is increased by 40% due to physiological factors. Minor patient movements can cause field changes of ∼40 nT. Off-centered head positioning can locally reduce SNR by e.g. 30%. CONCLUSIONS: Quantification of stray fields showed that MRCDI requires careful field correction. After cable correction, physiological noise is a limiting factor.