Authors: Kasra Naftchi-Ardebili*, Karanpartap Singh*, Reza Pourabolghasem, Gerald R. Popelka, Kim Butts Pauly   (*equal contribution)

Manuscript in Preparation, ISTU 2023 Presentation (Best Talk Award Winner)

Abstract: Transcranial ultrasound stimulation (TUS) has emerged as a promising tool in both clinical and research settings due to its potential to modulate neuronal activity non-invasively. The method delivers focused ultrasound waves to precise regions in the brain, enabling targeted energy deposition. The medical importance of TUS is evidenced by the thirty three ongoing clinical trials, covering conditions such as opioid addiction, Alzheimer's disease, dementia, epilepsy, and glioblastoma. In addition to careful design of ultrasound parameters, treatments with TUS require precise computation of the location and pressure at the focal spot. Heterogeneity of the skull aberrates the incident ultrasound beams, and if uncorrected, poses the risk of off-target sonication or inadequate energy delivery to the neural tissue. For clinical settings, this phase aberration correction must be done within a few seconds. However, physics-informed simulation software suffer from an inherent trade-off between accuracy and efficiency. As such, commercial devices use fast but lower accuracy methods to meet the efficient run times suitable for clinical applications. We present TUSNet, a deep learning approach to address this inherent trade-off between accuracy and efficiency. TUSNet can compute the transcranial ultrasound pressure field within a fraction of a second (1000x faster than k-Wave, a MATLAB-based acoustic simulation package), while achieving over 99% accuracy of the peak pressure at the focal spot with a mean positioning error of 0.1 mm, when compared to a ground truth from k-Wave.


Visual comparison between the TUSNet outputs and the ground truth over two examples. Compared to the ground truth, TUSNet predicts ultrasound pressure fields with nearly identical peak focal pressure, focal spot shape, and reflections inside the skull. Input: Input consists of the transducer elements lined up above the skull, a waveguide, and the target. Background is removed. Ground Truth: k-wave is tasked with simulating the ground truth phase aberration-corrected pressure field using time reversal. TUSNet Output, Absolute Pressure Field: The TUSNet-generated pressure field in Pascals, rather than normalized to some arbitrary maximum value. TUSNet Output, Phase Vector: Phase aberration-corrected pressure field simulated by k-wave based on the TUSNet phase vector rather than time reversal.

Authors: Kasra Naftchi-Ardebili*, Karanpartap Singh*, Reza Pourabolghasem, Pejman Ghanouni, Gerald R. Popelka, Kim Butts Pauly    (*equal contribution)

Under Revision, arXiv Preprint

Abstract: Deep learning offers potential for various healthcare applications involving the human skull but requires extensive datasets of curated medical images. To overcome this challenge, we propose SkullGAN, a generative adversarial network (GAN), to create large datasets of synthetic skull CT slices, reducing reliance on real images and accelerating the integration of machine learning into healthcare. In our method, CT slices of 38 subjects were fed to SkullGAN, a neural network comprising over 200 million parameters. The synthetic skull images generated were evaluated based on three quantitative radiological features: skull density ratio (SDR), mean thickness, and mean intensity. They were further analyzed using t-distributed stochastic neighbor embedding (t-SNE) and by applying the SkullGAN discriminator as a classifier. The results showed that SkullGAN-generated images demonstrated similar key quantitative radiological features to real skulls. Further definitive analysis was undertaken by applying the discriminator of SkullGAN, where the SkullGAN discriminator classified 56.5% of a test set of real skull images and 55.9% of the SkullGAN-generated images as reals (the theoretical optimum being 50%), demonstrating that the SkullGAN-generated skull set is indistinguishable from the real skull set - within the limits of our nonlinear classifier. Therefore, SkullGAN makes it possible to generate large numbers of synthetic skull CT segments, necessary for training neural networks for medical applications involving the human skull. This mitigates challenges associated with preparing large, high-quality training datasets, such as access, capital, time, and the need for domain expertise.

1. A. Stanziola et al., Journal of Computational Physics, vol. 441, p. 110430, 2021. 


SkullGAN generator and training pipeline. SkullGAN was first pre-trained on the Celeb-A dataset, and then trained on human skull CTs. In contrast to random initialization of the weights for training on the human skull CTs, pre-training yielded layers with fine-tuned weights for detecting edges and resulted in better quality skull segment images, with finer definition both in contour and interior bone structure.

Authors: Karanpartap Singh, Benjamin G. Hawkins

bioRxiv Preprint

Abstract: Electrowetting is an electrokinetic effect whereby an applied electric field induces changes in the measured contact angle at a fluid-surface contact line. On hydrophobic, dielectric electrode surfaces, this effect generates droplet motion termed “electrowetting on dielectric” or EWOD. Applications of this phenomenon range from lab-on-a-chip to liquid lenses capable of altering their topology and focus within milliseconds. Electrowetting or EWOD theoretical models quantifying this effect fall into two paradigms: the Young-Lippman and the electromechanical theories. In this work, both paradigms were simulated to predict the velocity of a water droplet moving over an array of electrodes. Results were compared to experimental observations of measured velocities for two dielectric films: ETFE and household cling film. Theoretical model parameters, namely the length scale of the Maxwell force on the droplet, were also determined to align simulation and experiment. The results reveal the trend of droplet velocity in relation to applied voltage, and recapitulate the relationship between the two models.


A) Filmed droplet motion displaying the initial deformation and subsequent motion of the droplet in an open electrowetting configuration. B) Young-Lippman model simulation with only deformation and contact angle change modeled. Colors and color bars represent the velocity fields of the droplets. C) Electromechanical model simulation with only the electromechanical force on the droplet modeled.

Authors: Karanpartap Singh, Mi Hyun Choi, Gerald Popelka, Kim Butts Pauly

Tool Available Here

Abstract: Previous studies have demonstrated that transcranial ultrasound stimulation (TUS) leads to varying levels of suppression or excitation of neural activity at the targeted brain region depending on signal parameters – including signal intensity, signal duration, pulse repetition frequency, and pulse duration1-5. However, many studies underreport or inconsistently report these metrics6, preventing the field from converging on a clear relationship between sonication parameters and respective neural effects. To advance TUS as a neuromodulatory tool that can create predictable neural responses, there is a need for systematic testing and reporting of safe and confound-free parameters and brain regions. A safety metric based on FDA guidelines for mechanical and thermal indices7 and an audibility metric for assessing unintended auditory activation confounds in mice were incorporated into a web-based computational tool8, written in Python and hosted through the Flask library. When users either manually input experimental parameters (Figure 1A) or upload hydrophone measurements, the tool provides a standardized report on key TUS parameters (Figure 1B). The report also includes an ideal reconstruction of the inputted signal for confirmation as well as an assessment of the signal’s audibility in mice. This tool is easily accessible to aid in the selection of appropriate, safe, and inaudible signals for neuromodulation and can be used to guide standardized parameter reporting across studies, facilitating reproducibility and inter-study comparisons.

1. S.S. Yoo et al., Neuroimage, vol. 56, p. 1267-1275, 2021. 2. R.L. King et al., Biol., vol. 39, pp. 312-331, 2013. 3. H. Kim et al., Brain Stimul., vol. 7, pp. 748-756, 2014. 4. M. Plaksin et al., Eneuro, vol. 3, 2016. 5. K. Yu et al., IEEE Trans. Biomed., Eng. 63, p. 1787–1794, 2016. 6. C. Pasquinelli et al., Brain stimulation, vol. 12(6), p. 1367–1380, 2019. 7. T. R. Nelson et al., vol. 28(2), p. 139–150, 2009. 8. K. Singh,, 2021.


A) Ultrasound parameters inputted by the user. B) Returned safety and wave metrics to be reported by the user in the relevant literature.