Ultrasound-transparent neural interfaces for multimodal interaction
Source abstract
Abstract
Abstract Neural interfaces that unify diagnostic and therapeutic functionalities hold particular promise for advancing both fundamental neuroscience and clinical neurotechnology. Functional ultrasound imaging (fUSI) has recently emerged as a powerful modality for high-resolution, non-invasive monitoring of brain function and structure. However, conventional metal-based microelectrodes typically impede ultrasound propagation, limiting compatibility with fUSI. Here, we present flexible, ultrasound-transparent neural interfaces that retain practical metal thicknesses while achieving high acoustic transparency. We introduce a theoretical and simulation-based framework to investigate the conditions under which commonly used polymers and metals in neural interfaces can become acoustically transparent. Based on these insights, we propose design guidelines that maximise ultrasound transmission through soft neural interfaces. We experimentally validate our approach through immersion experiments and by demonstrating the acoustic transparency of a suitably engineered interface using fUSI in phantom and in vivo experiments. Finally, we discuss the potential extension of this approach to therapeutic focused ultrasound (FUS). This work establishes a foundation for the development of multimodal neural interfaces with enhanced diagnostic and therapeutic capabilities, enabling both scientific discovery and translational impact.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Ultrasound and Hyperthermia Applications · Ultrasound Imaging and Elastography · Photoacoustic and Ultrasonic Imaging
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (100+)
Show source-provided references
1. Hong, G. & Lieber, C. M. Novel electrode technologies for neural recordings. Nat. Rev. Neurosci. 20, 330–345 (2019).10.1038/s41583-019-0140-6 ↗
2. Won, S. M. et al. Recent advances in materials, devices, and systems for neural interfaces. Adv. Mater. 30, 1800534 (2018).10.1002/adma.201800534 ↗
3. Chen, R., Canales, A. & Anikeeva, P. Neural recording and modulation technologies. Nat. Rev. Mater. 2, 1–16 (2017).10.1038/natrevmats.2016.93 ↗
4. Li, L. et al. Multimodal technologies for closed-loop neural modulation and sensing. Adv. Healthc. Mater. 13, 2303289 (2024).10.1002/adhm.202303289 ↗
5. Wang, L. et al. Recent advances in implantable neural interfaces for multimodal electrical neuromodulation. Adv. Healthc. Mater. 13, 2303316 (2024).10.1002/adhm.202303316 ↗
6. Won, S. M., Song, E., Reeder, J. T. & Rogers, J. A. Emerging modalities and implantable technologies for neuromodulation. Cell 181, 115–135 (2020).10.1016/j.cell.2020.02.054 ↗
7. Walton, F. et al. Magneto-optogenetic deep-brain multimodal neurostimulation. Adv. Intell. Syst. 4, 2100082 (2022).10.1002/aisy.202100082 ↗
8. Sung, C. et al. Multimaterial and multifunctional neuralinterfaces: from surface-type and implantableelectrodes to fiber-based devices. J. Mater. Chem. B 8, 6624 (2020).10.1039/D0TB00872A ↗
9. Yu, Y. et al. Sleep fmri with simultaneous electrophysiology at 9.4 t in male mice. Nat. Commun. 2023 14:1 14, 1–18 (2023).
10. Dijk, G., Kaszas, A., Pas, J. & O’Connor, R. P. Fabrication and in vivo 2-photon microscopy validation of transparent pedot:pss microelectrode arrays. Microsyst. Nanoeng. 8, 1–8 (2022).10.1038/s41378-022-00434-7 ↗
11. Cho, M. et al. Fully bioresorbable hybrid opto-electronic neural implant system for simultaneous electrophysiological recording and optogenetic stimulation. Nat. Commun. 15, 1–16 (2024).10.1038/s41467-024-45803-0 ↗
12. Fekete, Z., Zátonyi, A., Kaszás, A., Madarász, M. & Slézia, A. Transparent neural interfaces: challenges and solutions of microengineered multimodal implants designed to measure intact neuronal populations using high-resolution electrophysiology and microscopy simultaneously. Microsyst. Nanoeng. 9, 1–30 (2023).10.1038/s41378-023-00519-x ↗
13. Belloir, T. et al. Large-scale multimodal surface neural interfaces for primates. iScience 26, 105866 (2023).10.1016/j.isci.2022.105866 ↗
14. Koschinski, L. et al. Validation of transparent and flexible neural implants for simultaneous electrophysiology, functional imaging, and optogenetics. J. Mater. Chem. B 11, 9639–9657 (2023).10.1039/D3TB01191G ↗
15. Tian, H., Xu, K., Zou, L. & Fang, Y. Multimodal neural probes for combined optogenetics and electrophysiology. iScience 25, 103612 (2022).10.1016/j.isci.2021.103612 ↗
16. Yang, F. et al. Principles and applications of sono-optogenetics. Adv. Drug Deliv. Rev. 194, 114711 (2023).10.1016/j.addr.2023.114711 ↗
17. Norman, S. L. et al. Single-trial decoding of movement intentions using functional ultrasound neuroimaging. Neuron 109, 1554–1566 (2021).10.1016/j.neuron.2021.03.003 ↗
18. Rabut, C. et al. Ultrasound technologies for imaging and modulating neural activity. Neuron 108, 93–110 (2020).10.1016/j.neuron.2020.09.003 ↗
19. Deffieux, T., Demene, C., Pernot, M. & Tanter, M. Functional ultrasound neuroimaging: a review of the preclinical and clinical state of the art. Curr. Opin. Neurobiol. 50, 128–135 (2018).10.1016/j.conb.2018.02.001 ↗
20. Tyler, W. J., Lani, S. W. & Hwang, G. M. Ultrasonic modulation of neural circuit activity. Curr. Opin. Neurobiol. 50, 222–231 (2018).10.1016/j.conb.2018.04.011 ↗
21. Tanter, M. & Fink, M. Ultrafast imaging in biomedical ultrasound. IEEE Trans. Ultrason., Ferroelectr. Frequency Control 61, 102–119 (2014).10.1109/TUFFC.2014.2882 ↗
22. Maresca, D. et al. Biomolecular ultrasound and sonogenetics. Annu. Rev. Chem. Biomol. Eng. 9, 229–252 (2018).10.1146/annurev-chembioeng-060817-084034 ↗
23. Griggs, W. S. et al. Functional ultrasound neuroimaging reveals mesoscopic organization of saccades in the lateral intraparietal area. Nat. Commun. 16, 8752 (2025).10.1038/s41467-025-63826-z ↗
24. Soloukey, S. et al. Mobile human brain imaging using functional ultrasound. Sci. Adv. 11, 9133 (2025).10.1126/sciadv.adu9133 ↗
25. Bergel, A., Deffieux, T., Demené, C., Tanter, M. & Cohen, I. Local hippocampal fast gamma rhythms precede brain-wide hyperemic patterns during spontaneous rodent rem sleep. Nat. Commun. 9, 1–12 (2018).10.1038/s41467-018-07752-3 ↗
26. Bergel, A. & Pouget, P. Combined electrophysiology and functional ultrasound imaging: Opportunities, challenges and future directions. Preprints (2024).10.20944/preprints202412.1572.v1 ↗
27. Dell’Italia, J., Sanguinetti, J. L., Monti, M. M., Bystritsky, A. & Reggente, N. Current state of potential mechanisms supporting low intensity focused ultrasound for neuromodulation. Front. Hum. Neurosci. 16, 872639 (2022).10.3389/fnhum.2022.872639 ↗
28. Blackmore, J., Shrivastava, S., Sallet, J., Butler, C. R. & Cleveland, R. O. Ultrasound neuromodulation: a review of results, mechanisms and safety. Ultrasound Med. Biol. 45, 1509 (2019).10.1016/j.ultrasmedbio.2018.12.015 ↗
29. Matt, E., Radjenovic, S., Mitterwallner, M. & Beisteiner, R. Current state of clinical ultrasound neuromodulation. Front. Neurosci. 18, 1420255 (2024).10.3389/fnins.2024.1420255 ↗
30. Kamimura, H. A., Conti, A., Toschi, N. & Konofagou, E. E. Ultrasound neuromodulation: Mechanisms and the potential of multimodal stimulation for neuronal function assessment. Front. Phys. 8, 1–9 (2020).10.3389/fphy.2020.00150 ↗
31. Zhang, J. M. et al. Concurrent functional ultrasound imaging with graphene-based dc-coupled electrophysiology as a platform to study slow brain signals and cerebral blood flow under control and pathophysiological brain states. Nanoscale Horizons 9, 544--554 (2024).10.1039/D3NH00521F ↗
32. Rabut, C. et al. Functional ultrasound imaging of human brain activity through an acoustically transparent cranial window. Sci. Transl. Med. 16, 3143 (2024).10.1126/scitranslmed.adj3143 ↗
33. Hill, R. & El-Dardiry, S. M. A theory for optimization in the use of acoustic emission transducers. J. Acoust. Soc. Am. 67, 673–682 (1980).10.1121/1.383893 ↗
34. Jimenez, N., Groby, J. P. & Romero-García, V. The transfer matrix method in acoustics: modelling one-dimensional acoustic systems, phononic crystals and acoustic metamaterials. Top. Appl. Phys. 143, 103–164 (2021).10.1007/978-3-030-84300-7_4 ↗
35. Brekhovskikh, L.Waves in Layered Media (Academic Press, 1980), 2nd edn.
36. Nayfeh, A. H. & Taylor, T. W. Interaction of ultrasonic waves with layered media. Acousto-Ultrasonics 23–34 (Springer, 1988).10.1007/978-1-4757-1965-9_2 ↗
37. Lacour, S. P. et al. Flexible and stretchable micro-electrodes for in vitro and in vivo neural interfaces. Med. Biol. Eng. Comput. 48, 945–954 (2010).10.1007/s11517-010-0644-8 ↗
38. Lee, J. M. et al. The ultra-thin, minimally invasive surface electrode array neuroweb for probing neural activity. Nat. Commun. 14, 1–14 (2023).
39. Hong, W. et al. Ultrathin gold microelectrode array using polyelectrolyte multilayers for flexible and transparent electro-optical neural interfaces. Adv. Funct. Mater. 32, 2106493 (2022).10.1002/adfm.202106493 ↗
40. Chung, T. et al. Electrode modifications to lower electrode impedance and improve neural signal recording sensitivity. J. Neural Eng. 12, 056018 (2015).10.1088/1741-2560/12/5/056018 ↗
41. Harris, A. R. et al. Endovascular neural stimulation with platinum and platinum black modified electrodes. Sci. Rep. 15, 1–15 (2025).10.1038/s41598-025-93941-2 ↗
42. Damle, S. et al. Minimizing iridium oxide electrodes for high visual acuity subretinal stimulation. eNeuro 8, 506 (2021).10.1523/ENEURO.0506-20.2021 ↗
43. Maeng, J. et al. High-charge-capacity sputtered iridium oxide neural stimulation electrodes deposited using water vapor as a reactive plasma constituent. J. Biomed. Mater. Res. Part B Appl. Biomater. 108, 880–891 (2020).10.1002/jbm.b.34442 ↗
44. Ghazavi, A., Maeng, J., Black, M., Salvi, S. & Cogan, S. F. Electrochemical characteristics of ultramicro-dimensioned sirof electrodes for neural stimulation and recording. J. Neural Eng. 17, 016022 (2020).10.1088/1741-2552/ab52ab ↗
45. Vatsyayan, R. et al. Electrochemical and electrophysiological considerations for clinical high channel count neural interfaces. MRS Bull. 48, 531--545 (2023).10.1557/s43577-023-00537-0 ↗
46. Wang, Y., Yang, X., Zhang, X., Wang, Y. & Pei, W. Implantable intracortical microelectrodes: reviewing the present with a focus on the future. Microsyst. Nanoeng. 9, 1–17 (2023).10.1038/s41378-022-00451-6 ↗
47. Chiang, C. H. et al. Flexible, high-resolution thin-film electrodes for human and animal neural research. J. Neural Eng. 18, 045009 (2021).10.1088/1741-2552/ac02dc ↗
48. Oldroyd, P. & Malliaras, G. G. Achieving long-term stability of thin-film electrodes for neurostimulation. Acta Biomaterialia 139, 65–81 (2022).10.1016/j.actbio.2021.05.004 ↗
49. Liu, X., Gong, Y., Jiang, Z., Stevens, T. & Li, W. Flexible high-density microelectrode arrays for closed-loop brain-machine interfaces: a review. Front. Neurosci. 18, 1348434 (2024).10.3389/fnins.2024.1348434 ↗
50. Lv, S. et al. Long-term stability strategies of deep brain flexible neural interface. npj Flex. Electron. 9, 1–17 (2025).10.1038/s41528-025-00410-x ↗
51. Waasdorp, R. et al. Adaptive transcranial ultrasound doppler imaging of the brain. bioRxiv (2025).10.1101/2025.05.27.656275 ↗
52. Darrow, D. P. Focused ultrasound for neuromodulation. Neurotherapeutics 16, 88 (2018).10.1007/s13311-018-00691-3 ↗
53. Beisteiner, R., Lozano, A., Lazzaro, V. D., George, M. S. & Hallett, M. Clinical recommendations for non-invasive ultrasound neuromodulation. Brain Stimul. 17, 890–895 (2024).10.1016/j.brs.2024.07.013 ↗
54. Rintoul, J. L., Neufeld, E., Butler, C., Cleveland, R. O. & Grossman, N. Remote focused encoding and decoding of electric fields through acoustoelectric heterodyning. Communi. Phys. 6, 79 (2023).10.1038/s42005-023-01198-w ↗
55. Zhang, H. et al. Biological current source imaging method based on acoustoelectric effect: A systematic review. Front. Neurosci. 16, 807376 (2022).10.3389/fnins.2022.807376 ↗
56. Zhou, Y. et al. Acoustoelectric brain imaging with different conductivities and acoustic distributions. Front. Physiol. 14, 1241640 (2023).10.3389/fphys.2023.1241640 ↗
57. Song, X. et al. An adaptive acoustoelectric signal decoding algorithm based on fourier fitting for brain function imaging. Front. Physiol. 13, 1054103 (2022).10.3389/fphys.2022.1054103 ↗
58. Song, X., Xu, Y. & Dong, F. An image reconstruction framework based on boundary voltages for ultrasound modulated electrical impedance tomography. Meas. Sci. Technol. 27, 114003 (2016).10.1088/0957-0233/27/11/114003 ↗
59. Zhang, M., Tang, Z., Liu, X. & der Spiegel, J. V. Electronic neural interfaces. Nat. Electron. 3, 191–200 (2020).10.1038/s41928-020-0390-3 ↗
60. Collins, M. N. & Mesce, K. A. Focused ultrasound neuromodulation and the confounds of intracellular electrophysiological investigation. eNeuro 7, 213 (2020).10.1523/ENEURO.0213-20.2020 ↗
61. Kim, M. G., Yu, K., Niu, X. & He, B. Investigation of displacement of intracranial electrode induced by focused ultrasound stimulation. IEEE Trans. Instrum. Measure. 70, 9600509 (2021).10.1109/TIM.2021.3125978 ↗
62. Nguyen, D., Konofagou, E. & Dmochowski, J. P. Mechanical artifacts during transcranial focused ultrasound mimic biologically evoked responses. bioRxiv 2025.04.30.650712 (2025).10.1101/2025.04.30.650712 ↗
63. Wang, L. & Rokhlin, S. I. Stable reformulation of transfer matrix method for wave propagation in layered anisotropic media. Ultrasonics 39, 413–424 (2001).10.1016/S0041-624X(01)00082-8 ↗
64. Luque-Raigon, J. M., Halme, J., Miguez, H. & Lozano, G. Symmetry analysis of the numerical instabilities in the transfer matrix method. J. Opt. 15, 125719 (2013).10.1088/2040-8978/15/12/125719 ↗
65. Angla, C., Larrat, B., Gennisson, J. L. & Chatillon, S. Transcranial ultrasound simulations: a review. Med. Phys. 50, 1051–1072 (2023).10.1002/mp.15955 ↗
66. Chen, M. et al. Numerical and experimental evaluation of low-intensity transcranial focused ultrasound wave propagation using human skulls for brain neuromodulation. Med. Phys. 50, 38–49 (2023).10.1002/mp.16090 ↗
67. Haqshenas, S. R., Gélat, P., van ’t Wout, E., Betcke, T. & Saffari, N. A fast full-wave solver for calculating ultrasound propagation in the body. Ultrasonics 110, 106240 (2021).10.1016/j.ultras.2020.106240 ↗
68. Treeby, B. E. et al. Modeling nonlinear ultrasound propagation in heterogeneous media with power law absorption using a k-space pseudospectral method. J. Acoust. Soc. Am. 131, 4324–4336 (2012).10.1121/1.4712021 ↗
69. Donahue, M. J. et al. Wireless optoelectronic devices for vagus nerve stimulation in mice. J. Neural Eng. 19, 066031 (2022).10.1088/1741-2552/aca1e3 ↗
70. Maresca, D., Correia, M., Tanter, M., Ghaleh, B. & Pernot, M. Adaptive spatiotemporal filtering for coronary ultrafast doppler angiography. IEEE Trans. Ultrason. Ferroelectr. Frequency Control 65, 2201–2204 (2018).10.1109/TUFFC.2018.2870083 ↗
71. Panskus, R. et al. Ultrasound transparent neural interfaces for multimodal interaction (collection). 4TU.ResearchData, https://doi.org/10.4121/b398b7bc-7f88-4d54-93b0-1ef0b8372392.v2 (2025).10.4121/b398b7bc-7f88-4d54-93b0-1ef0b8372392.v2 ↗
72. Cho, Y. U., Lim, S. L., Hong, J. H. & Yu, K. J. Transparent neural implantable devices: a comprehensive review of challenges and progress. npj Flex. Electron. 6, 1–18 (2022).10.1038/s41528-022-00178-4 ↗
73. Panskus, R. Created in biorender. (2025) https://BioRender.com/r1wf2h2.
74. Lee, J. H., Lee, K. J., Park, H. G. & Kim, J. H. Possibility of air-filled rubber membrane for reducing hull exciting pressure induced by propeller cavitation. Ocean Eng. 103, 160–170 (2015).10.1016/j.oceaneng.2015.04.073 ↗
75. Miller, W.Properties and behavior of polymers (Wiley, 2012).
76. Manwar, R., Saint-Martin, L. & Avanaki, K. Couplants in acoustic biosensing systems. Chemosensors 10, 181 (2022).10.3390/chemosensors10050181 ↗
77. Feng, G. H. & Liu, W. F. A spherically-shaped pzt thin film ultrasonic transducer with an acoustic impedance gradient matching layer based on a micromachined periodically structured flexible substrate. Sensors 13, 13543–13559 (2013).10.3390/s131013543 ↗
78. Johnsen, C. A., Bagwell, T. L., Henderson, J. L. & Bray, R. C. Polyimide as an acoustic absorber for high frequency saw applications. Ultrason. Symp. Proc. 1, 279–284 (1988).
79. Fu, Y., Kabir, I. I., Yeoh, G. H. & Peng, Z. A review on polymer-based materials for underwater sound absorption. Polym. Test. 96, 107115 (2021).10.1016/j.polymertesting.2021.107115 ↗
80. Hadimioglu, B. & Khuri-Yakub, B. T. Polymer films as acoustic matching layers. Ultrason. Symp. Proc. 3, 1337–1340 (1990).10.1109/ULTSYM.1990.171581 ↗
81. Li, Z. et al. Pulse-echo acoustic properties evaluation method using high-frequency transducer. Meas. Sci. Technol. 31, 125011 (2020).10.1088/1361-6501/aba0d8 ↗
82. Liu, P., Yao, Z., Li, L. & Zhou, J. In situ synthesis and mechanical, thermal properties of polyimide nanocomposite film by addition of functionalized graphene oxide. Polym. Compos. 37, 907–914 (2016).10.1002/pc.23249 ↗
83. Chitrakar, C., Hedrick, E., Adegoke, L. & Ecker, M. Flexible and stretchable bioelectronics. Materials 15, 1664 (2022).10.3390/ma15051664 ↗
84. Kim, B. J. & Meng, E. Micromachining of parylene c for biomems. Polym. Adv. Technol. 27, 564–576 (2016).10.1002/pat.3729 ↗
85. Hassler, C., Boretius, T. & Stieglitz, T. Polymers for neural implants. J. Polym. Sci. Part B Polym. Phys. 49, 18–33 (2011).10.1002/polb.22169 ↗
86. Kanbur, Y. & Tayfun, U. Investigating mechanical, thermal, and flammability properties of thermoplastic polyurethane/carbon nanotube composites. J. Thermoplast. Composite Mater. 31, 1661–1675 (2018).10.1177/0892705717743292 ↗
87. Petersmann, S., Huemer, M., Hentschel, L. & Arbeiter, F. Effects of simulated body fluid on the mechanical properties of polycarbonate polyurethane produced via material jetting. Polym. Test. 120, 107977 (2023).10.1016/j.polymertesting.2023.107977 ↗
88. Ghaill, N. N. A. & Little, E. G. Determination of the mechanical properties of bionate 80a and bionate 75d for the stress analysis of cushion form bearings. Proc. Inst. Mech. Eng. Part H J. Eng. Med. 222, 683–694 (2008).10.1243/09544119JEIM372 ↗
89. Warnes, L. A. Some acoustical properties of certain polyurethane elastomers. Ultrasonics 27, 97–100 (1989).10.1016/0041-624X(89)90020-6 ↗
90. Genovés, V., Maini, L., Roman, C., Hierold, C. & Cesarovic, N. Variation in the viscoelastic properties of polydimethylsiloxane (pdms) with the temperature at ultrasonic frequencies. Polym. Test. 124, 108067 (2023).10.1016/j.polymertesting.2023.108067 ↗
91. Hosono, Y., Itsumi, K. & Yamashita, Y. Low sound speed and acoustic attenuation silicone rubber lens based on heavy density ceramic nanopowder composite for medical array probe. Proceedings - IEEE Ultrasonics Symposium 1913–1916 (IEEE, 2007).10.1109/ULTSYM.2007.481 ↗
92. Ba, A., Kovalenko, A., Aristégui, C., Mondain-Monval, O. & Brunet, T. Soft porous silicone rubbers with ultra-low sound speeds in acoustic metamaterials. Sci. Rep. 7, 1–6 (2017).10.1038/srep40106 ↗
93. Zhang, W., Luan, W., Dong, H., Wu, C. & Qu, Z. The density, viscosity, speed of sound, excess properties of binary mixtures of linear polydimethylsiloxane and various alkanes at temperatures in the range (288.15-328.15) k. J. Chem. Thermodyn. 161, 106537 (2021).10.1016/j.jct.2021.106537 ↗
94. Lötters, J. C., Olthuis, W., Veltink, P. H. & Bergveld, P. The mechanical properties of the rubber elastic polymer polydimethylsiloxane for sensor applications. J. Micromech. Microeng. 7, 145 (1997).10.1088/0960-1317/7/3/017 ↗
95. Delplanque, E. et al. Mechanical characterization of bulk sylgard 184 for microfluidics and microengineering. J. Micromech. Microeng. 24, 035017 (2014).10.1088/0960-1317/24/3/035017 ↗
96. Megone, W., Roohpour, N. & Gautrot, J. E. Impact of surface adhesion and sample heterogeneity on the multiscale mechanical characterisation of soft biomaterials. Sci. Rep. ∣ 8, 6780 (2018).10.1038/s41598-018-24671-x ↗
97. Dharmadasa, B. Y., McCallum, M. & Jiménez, F. L. Characterizing and modeling the viscoplastic behavior of creases in kapton polyimide films. AIAA Scitech 2020 Forum1 PartF 6, 2165 (2020).10.2514/6.2020-2165 ↗
98. Moučka, R., Sedlačík, M., Osička, J. & Pata, V. Mechanical properties of bulk sylgard 184 and its extension with silicone oil. Scientific Reports11 (2021).10.1038/s41598-021-98694-2 ↗
99. Velea, A. I. et al. Effects of soft encapsulation on the receive performance of pmuts for implantable devices. IEEE Trans. Ultrasonics Ferroelect. Frequency Control 72, 1282--1292 (2025).10.1109/TUFFC.2025.3592740 ↗
100. Levassort, F., Tran-Huu-Hue, L. P., Marechal, P., Ringgaard, E. & Lethiecq, M. Characterisation of thin layers of parylene at high frequency using pzt thick film resonators. J. Eur. Ceram. Soc. 25, 2985–2989 (2005).10.1016/j.jeurceramsoc.2005.03.208 ↗