Benchmark problems for transcranial ultrasound simulation: Intercomparison of compressional wave models.

Computational models of acoustic wave propagation are frequently used in transcranial ultrasound therapy, for example, to calculate the intracranial pressure field or to calculate phase delays to correct for skull distortions. To allow intercomparison between the different modeling tools and techniques used by the community, an international working group was convened to formulate a set of numerical benchmarks. Here, these benchmarks are presented, along with intercomparison results. Nine different benchmarks of increasing geometric complexity are defined. These include a single-layer planar bone immersed in water, a multi-layer bone, and a whole skull. Two transducer configurations are considered (a focused bowl and a plane piston operating at 500 kHz), giving a total of 18 permutations of the benchmarks. Eleven different modeling tools are used to compute the benchmark results. The models span a wide range of numerical techniques, including the finite-difference time-domain method, angular spectrum method, pseudospectral method, boundary-element method, and spectral-element method. Good agreement is found between the models, particularly for the position, size, and magnitude of the acoustic focus within the skull. When comparing results for each model with every other model in a cross-comparison, the median values for each benchmark for the difference in focal pressure and position are less than 10% and 1 mm, respectively. The benchmark definitions, model results, and intercomparison codes are freely available to facilitate further comparisons.

ESHO benchmarks for computational modeling and optimization in hyperthermia therapy.

BACKGROUND: The success of cancer hyperthermia (HT) treatments is strongly dependent on the temperatures achieved in the tumor and healthy tissues as it correlates with treatment efficacy and safety, respectively. Hyperthermia treatment planning (HTP) simulations have become pivotal for treatment optimization due to the possibility for pretreatment planning, optimization and decision making, as well as real-time treatment guidance. MATERIALS AND METHODS: The same computational methods deployed in HTP are also used for in silico studies. These are of great relevance for the development of new HT devices and treatment approaches. To aid this work, 3 D patient models have been recently developed and made available for the HT community. Unfortunately, there is no consensus regarding tissue properties, simulation settings, and benchmark applicators, which significantly influence the clinical relevance of computational outcomes. RESULTS AND DISCUSSION: Herein, we propose a comprehensive set of applicator benchmarks, efficacy and safety optimization algorithms, simulation settings and clinical parameters, to establish benchmarks for method comparison and code verification, to provide guidance, and in view of the 2021 ESHO Grand Challenge (Details on the ESHO grand challenge on HTP will be provided at https://www.esho.info/). CONCLUSION: We aim to establish guidelines to promote standardization within the hyperthermia community such that novel approaches can quickly prove their benefit as quickly as possible in clinically relevant simulation scenarios. This paper is primarily focused on radiofrequency and microwave hyperthermia but, since 3 D simulation studies on heating with ultrasound are now a reality, guidance as well as a benchmark for ultrasound-based hyperthermia are also included.

Tailored cancer therapy by magnetic nanoparticle hyperthermia: A virtual scenario simulation method.

BACKGROUND AND OBJECTIVE: Hyperthermia is a cancer treatment aiming to induce cell death by directly warming cancerous tissues above 40 °C. This technique can be applied both individually and together with other cancer therapies. The main challenge for researchers and medics is to heat only tumoral cells avoiding global or localized heating of sane tissues. The objective in this study is to provide a realistic virtual scenario to develop an optimized multi-site injection plan for tailored magnetic nanoparticle-mediated hyperthermia applications. METHODS: A three-dimensional model of a cat's back was tested in three different simulation scenarios, showing the impact of magnetic nanoparticles in each specific environment configuration. RESULTS: As a result of this study. This simulation method can, minimising the affection to healthy tissue. CONCLUSIONS: This virtual method will help real and personalized therapy planning and tailor the dose and distribution of magnetic nanoparticles for an enhanced hyperthermia cancer treatment.

Activity-dependent spinal cord neuromodulation rapidly restores trunk and leg motor functions after complete paralysis.

Epidural electrical stimulation (EES) targeting the dorsal roots of lumbosacral segments restores walking in people with spinal cord injury (SCI). However, EES is delivered with multielectrode paddle leads that were originally designed to target the dorsal column of the spinal cord. Here, we hypothesized that an arrangement of electrodes targeting the ensemble of dorsal roots involved in leg and trunk movements would result in superior efficacy, restoring more diverse motor activities after the most severe SCI. To test this hypothesis, we established a computational framework that informed the optimal arrangement of electrodes on a new paddle lead and guided its neurosurgical positioning. We also developed software supporting the rapid configuration of activity-specific stimulation programs that reproduced the natural activation of motor neurons underlying each activity. We tested these neurotechnologies in three individuals with complete sensorimotor paralysis as part of an ongoing clinical trial ( www.clinicaltrials.gov identifier NCT02936453). Within a single day, activity-specific stimulation programs enabled these three individuals to stand, walk, cycle, swim and control trunk movements. Neurorehabilitation mediated sufficient improvement to restore these activities in community settings, opening a realistic path to support everyday mobility with EES in people with SCI.

The impact of CT image parameters and skull heterogeneity modeling on the accuracy of transcranial focused ultrasound simulations.

Objective. Low-intensity transcranial ultrasound stimulation (TUS) is a promising non-invasive brain stimulation (NIBS) technique. TUS can reach deeper areas and target smaller regions in the brain than other NIBS techniques, but its application in humans is hampered by the lack of a straightforward and reliable procedure to predict the induced ultrasound exposure. Here, we examined how skull modeling affects computer simulations of TUS.Approach. We characterized the ultrasonic beam after transmission through a sheep skull with a hydrophone and performed computed tomography (CT) image-based simulations of the experimental setup. To study the skull model's impact, we varied: CT acquisition parameters (tube voltage, dose, filter sharpness), image interpolation, segmentation parameters, acoustic property maps (speed-of-sound, density, attenuation), and transducer-position mismatches. We compared the impact of modeling parameter changes on model predictions and on measurement agreement. Spatial-peak intensity and location, total power, and the Gamma metric (a measure for distribution differences) were used as quantitative criteria. Modeling-based sensitivity analysis was also performed for two human head models.Main results. Sheep skull attenuation assignment and transducer positioning had the most important impact on spatial peak intensity (overestimation up to 300%, respectively 30%), followed by filter sharpness and tube voltage (up to 20%), requiring calibration of the mapping functions. Positioning and skull-heterogeneity-structure strongly affected the intensity distribution (gamma tolerances exceeded in>80%, respectively>150%, of the focus-volume in water), necessitating image-based personalized modeling. Simulation results in human models consistently demonstrate a high sensitivity to the skull-heterogeneity model, attenuation tuning, and transducer shifts, the magnitude of which depends on the underlying skull structure complexity.Significance. Our study reveals the importance of properly modeling the skull-heterogeneity and its structure and of accurately reproducing the transducer position. The results raise red flags when translating modeling approaches among clinical sites without proper standardization and/or recalibration of the imaging and modeling parameters.

Transducer modeling for accurate acoustic simulations of transcranial focused ultrasound stimulation.

OBJECTIVE: Low-intensity transcranial ultrasound stimulation (TUS) is emerging as a non-invasive brain stimulation technique with superior spatial resolution and the ability to reach deep brain areas. Medical image-based computational modeling could be an important tool for individualized TUS dose control and targeting optimization, but requires further validation. This study aims to assess the impact of the transducer model on the accuracy of the simulations. APPROACH: Using hydrophone measurements, the acoustic beam of a single-element focused transducer (SEFT) with a flat piezoelectric disc and an acoustic lens was characterized. The acoustic beam was assessed in a homogeneous water bath and after transmission through obstacles (3D-printed shapes and skull samples). The acoustic simulations employed the finite-difference time-domain method and were informed by computed tomography (CT) images of the obstacles. Transducer models of varying complexity were tested representing the SEFT either as a surface boundary condition with variable curvature or also accounting for its internal geometry. In addition, a back-propagated pressure distribution from the first measurement plane was used as source model. The simulations and measurements were quantitatively compared using key metrics for peak location, focus size, intensity and spatial distribution. MAIN RESULTS: While a surface boundary with an adapted, 'effective' curvature radius based on the specifications given by the manufacturer could reproduce the measured focus location and size in a homogeneous water bath, it regularly failed to accurately predict the beam after obstacle transmission. In contrast, models that were based on a one-time calibration to the homogeneous water bath measurements performed substantially better in all cases with obstacles. For one of the 3D-printed obstacles, the simulated intensities deviated substantially from the measured ones, irrespective of the transducer model. We attribute this finding to a standing wave effect, and further studies should clarify its relevance for accurate simulations of skull transmission. SIGNIFICANCE: Validated transducer models are important to ensure accurate simulations of the acoustic beam of SEFTs, in particular in the presence of obstacles such as the skull.

Accurate anatomical head segmentations: a data set for biomedical simulations.

Detailed computational anatomical models of the entire head are needed for accurate in silico modeling in a variety of transcranial stimulation applications. Models from different subjects help to understand and account for population variability. To this end, we have developed a new library of head models of 20 individuals, segmented from co-aligned multi-modal medical image data. The acquired image modalities allow to accurately model tissues with different material properties, such as electrical conductivity or spatially varying acoustic properties. The usefulness of the models is illustrated for two example applications.

Functionalized anatomical models for EM-neuron Interaction modeling.

The understanding of interactions between electromagnetic (EM) fields and nerves are crucial in contexts ranging from therapeutic neurostimulation to low frequency EM exposure safety. To properly consider the impact of in vivo induced field inhomogeneity on non-linear neuronal dynamics, coupled EM-neuronal dynamics modeling is required. For that purpose, novel functionalized computable human phantoms have been developed. Their implementation and the systematic verification of the integrated anisotropic quasi-static EM solver and neuronal dynamics modeling functionality, based on the method of manufactured solutions and numerical reference data, is described. Electric and magnetic stimulation of the ulnar and sciatic nerve were modeled to help understanding a range of controversial issues related to the magnitude and optimal determination of strength-duration (SD) time constants. The results indicate the importance of considering the stimulation-specific inhomogeneous field distributions (especially at tissue interfaces), realistic models of non-linear neuronal dynamics, very short pulses, and suitable SD extrapolation models. These results and the functionalized computable phantom will influence and support the development of safe and effective neuroprosthetic devices and novel electroceuticals. Furthermore they will assist the evaluation of existing low frequency exposure standards for the entire population under all exposure conditions.