Transcranial focused ultrasound

Transcranial focused ultrasound
Other namestFUS; Transcranial focused ultrasound stimulation
SpecialtyPsychiatry, neurology
UsesPsychiatric disorders; Neurological disorders

Transcranial focused ultrasound (tFUS) is a form of focused ultrasound (FUS) which is being investigated for the potential non-invasive treatment of psychiatric and neurological disorders.[1][2][3] It differs from other non-invasive brain stimulation methods such as magnetic (transcranial magnetic stimulation or TMS) and electrical (transcranial direct-current stimulation or tDCS) in that it has higher spatial resolution and precision (millimetric) and is able to reach deep brain structures.[1][3] Depending on the parameters, tFUS can inhibit, stimulate, and even ablate brain tissue.[1] Only a handful of clinical studies of tFUS for psychiatric conditions have been conducted as of 2024.[3]

As a Neuromodulation Tool

At lower acoustic intensities, generally below the FDA's 510(k) limit for diagnostic ultrasound of a Mechanical Index (MI) less than 1.9,[4] tFUS can provide a neuromodulatory effect without causing permanent tissue damage. While the exact nature of tFUS neuromodulation is not completely understood, at least three mechanisms probably act in consort to produce the effects, all of which implicate the neuronal membrane.[5]

  1. Acoustic cavitation, the formation and subsequent implosion of bubbles in the membrane, may transiently disrupt its insulation or capacitance.[6] However, since ultrasound neuromodulation has been described at intensities below those thought to cause cavitation, it is also possible that simple mechanical deformation of the membrane, mediated by the acoustic radiation force, causes the same effects.[7]
  2. Fluctuations in neural activity have been correlated to local temperature differences of less than 0.1C in the brain,[8] providing a plausible mechanism in heating induced by the absorption of ultrasound energy interacting with tissue. Temperature increases may also increase mobility of lipid rafts and enzymes in the neuronal membrane.
  3. Mechanosensitive ion channels in the neuronal membrane may react to the ordered mechanical deformation of ultrasound waves. Piezo1 has been shown to react to ultrasound stimulation in vitro.[9]

Applications of tFUS neuromodulation in clinical practice may include treatment of essential tremor,[10] treatment-resistant major depressive disorder (MDD),[11] post-stroke chronic pain,[12] epilepsy,[13] obsessive-compulsive disorder (OCD),[14] and anxiety.[15]

References

  1. ^ a b c di Biase L, Falato E, Di Lazzaro V (2019). "Transcranial Focused Ultrasound (tFUS) and Transcranial Unfocused Ultrasound (tUS) Neuromodulation: From Theoretical Principles to Stimulation Practices". Front Neurol. 10 549. doi:10.3389/fneur.2019.00549. PMC 6579808. PMID 31244747.
  2. ^ Baek H, Lockwood D, Mason EJ, Obusez E, Poturalski M, Rammo R, Nagel SJ, Jones SE (2022). "Clinical Intervention Using Focused Ultrasound (FUS) Stimulation of the Brain in Diverse Neurological Disorders". Front Neurol. 13 880814. doi:10.3389/fneur.2022.880814. PMC 9124976. PMID 35614924.
  3. ^ a b c Keihani A, Sanguineti C, Chaichian O, Huston CA, Moore C, Cheng C, Janssen SA, Donati FL, Mayeli A, Moussawi K, Phillips ML, Ferrarelli F (October 2024). "Transcranial Focused Ultrasound Neuromodulation in Psychiatry: Main Characteristics, Current Evidence, and Future Directions". Brain Sci. 14 (11): 1095. doi:10.3390/brainsci14111095. PMC 11592166. PMID 39595858.
  4. ^ "Marketing Clearance of Diagnostic Ultrasound Systems and Transducers Guidance for Industry and Food and Drug Administration Staff". Food and Drug Administration.
  5. ^ Darmani, G.; Bergmann, T. O.; Butts Pauly, K.; Caskey, C. F.; de Lecea, L.; Fomenko, A.; Fouragnan, E.; Legon, W.; Murphy, K. R.; Nandi, T.; Phipps, M. A.; Pinton, G.; Ramezanpour, H.; Sallet, J.; Yaakub, S. N. (2022-03-01). "Non-invasive transcranial ultrasound stimulation for neuromodulation". Clinical Neurophysiology. 135: 51–73. doi:10.1016/j.clinph.2021.12.010. hdl:1807/110342. ISSN 1388-2457. PMID 35033772.
  6. ^ Plaksin, Michael; Kimmel, Eitan; Shoham, Shy (May 2016). "Cell-Type-Selective Effects of Intramembrane Cavitation as a Unifying Theoretical Framework for Ultrasonic Neuromodulation". eNeuro. 3 (3): ENEURO.0136–15.2016. doi:10.1523/ENEURO.0136-15.2016. ISSN 2373-2822. PMC 4917736. PMID 27390775.
  7. ^ Menz, Mike D.; Ye, Patrick; Firouzi, Kamyar; Nikoozadeh, Amin; Pauly, Kim Butts; Khuri-Yakub, Pierre; Baccus, Stephen A. (2019-08-07). "Radiation Force as a Physical Mechanism for Ultrasonic Neurostimulation of the Ex Vivo Retina". Journal of Neuroscience. 39 (32): 6251–6264. doi:10.1523/JNEUROSCI.2394-18.2019. ISSN 0270-6474. PMC 6687898. PMID 31196935.
  8. ^ Owen, Scott F.; Liu, Max H.; Kreitzer, Anatol C. (July 2019). "Thermal constraints on in vivo optogenetic manipulations". Nature Neuroscience. 22 (7): 1061–1065. doi:10.1038/s41593-019-0422-3. ISSN 1546-1726. PMC 6592769. PMID 31209378.
  9. ^ Prieto, Martin Loynaz; Firouzi, Kamyar; Khuri-Yakub, Butrus T.; Maduke, Merritt (June 2018). "Activation of Piezo1 but Not NaV1.2 Channels by Ultrasound at 43 MHz". Ultrasound in Medicine & Biology. 44 (6): 1217–1232. doi:10.1016/j.ultrasmedbio.2017.12.020. PMC 5914535. PMID 29525457.
  10. ^ Deveney, Chloe; Surya, Jean-Rama; Haroon, Jonathan M.; Mahdavi, Kennedy D.; Hoffman, Katelyn R.; Enemuo, Kevin C.; Jordan, Kaya G.; Becerra, Sergio A.; Kuhn, Taylor; Bystritsky, Alexander; Spivak, Norman M.; Jordan, Sheldon E. (2025-01-01). "Update on Ongoing Open Label Trial of Focused Ultrasound for Essential Tremor". Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation. 18 (1): 446–447. doi:10.1016/j.brs.2024.12.683. ISSN 1935-861X.
  11. ^ Oh, Jooyoung; Ryu, Jin Sun; Kim, Junhyung; Kim, Soojeong; Jeong, Hyu Seok; Kim, Kyung Ran; Kim, Hyun-Chul; Yoo, Seung-Schik; Seok, Jeong-Ho (August 2024). "Effect of Low-Intensity Transcranial Focused Ultrasound Stimulation in Patients With Major Depressive Disorder: A Randomized, Double-Blind, Sham-Controlled Clinical Trial". Psychiatry Investigation. 21 (8): 885–896. doi:10.30773/pi.2024.0016. ISSN 1738-3684. PMC 11321877. PMID 39111747.
  12. ^ He, Sijin; Luo, Kaixuan; Li, Xiang; Duan, Jiajia; Ding, Lei; Chen, Moxian; Xu, Xuan; Sun, Xianghua; Ao, Lijuan; Feng, Xiangjun (2025). "A clinical case report on transcranial low-intensity focused ultrasound neuromodulation for central post-stroke pain". Frontiers in Neuroscience. 19 1686623. doi:10.3389/fnins.2025.1686623. ISSN 1662-4548. PMC 12630116. PMID 41278189.
  13. ^ Bubrick, Ellen J.; McDannold, Nathan J.; Orozco, Janet; Mariano, Timothy Y.; Rigolo, Laura; Golby, Alexandra J.; Tie, Yanmei; White, P. Jason (2024-01-01). "Transcranial ultrasound neuromodulation for epilepsy: A pilot safety trial". Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation. 17 (1): 7–9. doi:10.1016/j.brs.2023.11.013. ISSN 1935-861X. PMID 38070706.
  14. ^ Germann, Jürgen; Elias, Gavin J B; Neudorfer, Clemens; Boutet, Alexandre; Chow, Clement T; Wong, Emily H Y; Parmar, Roohie; Gouveia, Flavia Venetucci; Loh, Aaron; Giacobbe, Peter; Kim, Se Joo; Jung, Hyun Ho; Bhat, Venkat; Kucharczyk, Walter; Chang, Jin Woo (2021-12-16). "Potential optimization of focused ultrasound capsulotomy for obsessive compulsive disorder". Brain. 144 (11): 3529–3540. doi:10.1093/brain/awab232. ISSN 0006-8950. PMID 34145884.
  15. ^ Chou, Tina; Deckersbach, Thilo; Guerin, Bastien; Wong, Karianne Sretavan; Borron, Benjamin M.; Kanabar, Anish; Hayden, Ashley N.; Long, Marina P.; Daneshzand, Mohammad; Pace-Schott, Edward F.; Dougherty, Darin D. (2024-03-01). "Transcranial focused ultrasound of the amygdala modulates fear network activation and connectivity". Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation. 17 (2): 312–320. doi:10.1016/j.brs.2024.03.004. ISSN 1935-861X. PMID 38447773.
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