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Microscale concert hall acoustics to produce uniform ultrasound stimulation for targeted sonogenetics in hsTRPA1-transfected cells

View ORCID ProfileAditya Vasan, Florian Allein, Marc Duque, Uri Magaram, View ORCID ProfileNicholas Boechler, View ORCID ProfileSreekanth H. Chalasani, View ORCID ProfileJames Friend
doi: https://doi.org/10.1101/2021.08.21.457135
Aditya Vasan
1Medically Advanced Devices Laboratory, Department of Mechanical and Aerospace Engineering, Jacobs School of Engineering and Department of Surgery, School of Medicine, University of California San Diego, La Jolla CA 92093 USA
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  • ORCID record for Aditya Vasan
Florian Allein
3Department of Mechanical and Aerospace Engineering, University of California San Diego, La Jolla CA 92093 USA
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Marc Duque
2Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037
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Uri Magaram
2Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037
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Nicholas Boechler
3Department of Mechanical and Aerospace Engineering, University of California San Diego, La Jolla CA 92093 USA
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Sreekanth H. Chalasani
2Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037
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James Friend
1Medically Advanced Devices Laboratory, Department of Mechanical and Aerospace Engineering, Jacobs School of Engineering and Department of Surgery, School of Medicine, University of California San Diego, La Jolla CA 92093 USA
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  • For correspondence: jfriend@ucsd.edu
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Abstract

The field of ultrasound neuromodulation has rapidly developed over the past decade, a consequence of the discovery of strain-sensitive structures in the membrane and organelles of cells extending into the brain, heart, and other organs. Notably, clinical trials are underway for treating epilepsy using focused ultrasound to elicit an organized local electrical response. A key limitation to this approach is the formation of standing waves within the skull. In standing acoustic waves, the maximum ultrasound intensity spatially varies from near zero to double the mean in one half a wavelength, and can lead to localized tissue damage and disruption of normal brain function while attempting to evoke a broader response. This phenomenon also produces a large spatial variation in the actual ultrasound exposure in tissue, leading to heterogeneous results and challenges with interpreting these effects. One approach to overcome this limitation is presented herein: transducer-mounted diffusers that result in spatiotemporally incoherent ultrasound. The signal is numerically and experimentally quantified in an enclosed domain with and without the diffuser. Specifically, we show that adding the diffuser leads to a two-fold increase in ultrasound responsiveness of hsTRPA1 transfected HEK cells. Furthermore, we demonstrate the diffuser allow us to produce an uniform spatial distribution of pressure in the rodent skull. Collectively, we propose that our approach leads to a means to deliver uniform ultrasound into irregular cavities for sonogenetics.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted August 22, 2021.
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Microscale concert hall acoustics to produce uniform ultrasound stimulation for targeted sonogenetics in hsTRPA1-transfected cells
Aditya Vasan, Florian Allein, Marc Duque, Uri Magaram, Nicholas Boechler, Sreekanth H. Chalasani, James Friend
bioRxiv 2021.08.21.457135; doi: https://doi.org/10.1101/2021.08.21.457135
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Microscale concert hall acoustics to produce uniform ultrasound stimulation for targeted sonogenetics in hsTRPA1-transfected cells
Aditya Vasan, Florian Allein, Marc Duque, Uri Magaram, Nicholas Boechler, Sreekanth H. Chalasani, James Friend
bioRxiv 2021.08.21.457135; doi: https://doi.org/10.1101/2021.08.21.457135

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