Focused Ultrasound Therapy
Focused ultrasound is a noninvasive, therapeutic technology with the potential to improve the quality of life and decrease the cost of care for patients with Alzheimer’s disease. This novel technology focuses beams of ultrasonic energy precisely and accurately on targets deep in the brain without damaging the surrounding normal tissue.
How it Works
Where the beams converge, focused ultrasound produces several therapeutic effects without incisions or radiation. One mechanism is the temporary opening of the blood-brain barrier (BBB), which may aid in the removal of beta amyloid or tao from the brain. In addition, potentially promising drug and antibody therapies are often limited by their inability to cross the BBB in high enough concentrations to have an impact in the brain, and opening the BBB may enable these therapeutic agents (such as intravenous immunoglobulin [IVIG]or tropomyosin receptor kinase A [TrkA])to gain access the brain. An additional mechanism is the ability to use neuromodulation to increase the activity of selected targets in patients with Alzheimer’s disease.
Promising preclinical studies continue to demonstrate the potential of focused ultrasound to enhance the delivery of therapeutic drugs or antibodies to the brain. Focused ultrasound in combination with microbubbles can safely open the BBB and enable enhanced delivery of anti-amyloid antibodies to the brain. Studies suggest that this method can reduce the number of plaques and improve cognition in Alzheimer’s disease models. Furthermore, focused ultrasound and microbubbles alone (no antibodies) have had similar effects in two different Alzheimer’s models. There is also work looking at using genetic therapy, where adeno-associated virus (AAV) could be used to as a one-time treatment.
Potential advantages
- Focused ultrasound is noninvasive – no incisions, holes in the skull, electrodes in the brain – and therefore has reduced risk for infection and blood clots.
- Precise targeting minimizes damage to non-targeted healthy brain.
- Treatment can be a complement to drug therapy, enabling enhanced delivery of disease-modifying therapies into the brain via temporary opening of the blood-brain barrier.
Clinical Trials
A clinical trial in Utah is treating patients with Alzheimer’s Disease with low intensity focused ultrasound.
A clinical trial in West Virginia is combining opening of the BBB with Aducanumab in patients with early cognitive disability or Alzheimer’s disease.
A second clinical trial in West Virginia is using low intensity focused ultrasound neuromodulation in the treatment of patients with mild cognitive impairment due to Alzheimer’s disease.
A Phase II trial at Sunnybrook Health Sciences Centre in Toronto, Canada, is investigating the use of focused ultrasound to temporarily open the BBB in multiple regions of the brain.
A clinical trial in the US is opening the BBB with MR-guided focused ultrasound in patients with Alzheimer’s disease.
A clinical trial with low intensity focused ultrasound treatment is being used for treatment of early cognitive disability or Alzheimer’s disease in Los Angeles.
A clinical trial in Japan is using Low Intensity Pulsed UltraSound (LIPUS) to treat patients with early Alzheimer’s disease.
See a list of treatment sites >
See a list of clinical trials sites >
See a list of laboratory research sites >
The Foundation updates these pages regularly, but with the increasing number of clinical trials, we want to be sure that our audience has the latest information available. Therefore, we also added the website search information for the above trials. If you click here, it will take you to the latest information available from https://www.clinicaltrials.gov/.
Preclinical Laboratory Studies
Preclinical studies suggest focused ultrasound’s potential to reduce amyloid plaques and improve cognition in Alzheimer’s models. Active studies are assessing focused ultrasound-induced BBB opening to improve the delivery of:
- Anti-amyloid antibodies and other disease modifying drugs (Sunnybrook Health Sciences Centre; Columbia University; Queensland University – Australia; Brigham and Women’s Hospital)
- Anti-tau antibodies (Queensland University – Australia).
Additional Information
Alzheimer’s Association
ExAblate Neuro by Insightec LTD
Notable Papers
Suggested Reading: Focused Ultrasound: Transforming treatment of Neurodegenerative Diseases. August 2022
Suggested Reading: Focused Ultrasound for Alzheimer’s Disease. January 2022.
Cai Q, Meng L, Quan M, Wang L, Ren J, Zheng C, Yang J, Ming D. Progress of research in the application of ultrasound technology for the treatment of Alzheimer’s disease. Neural Regen Res. 2025 Oct 1;20(10):2823-2837. doi: 10.4103/NRR.NRR-D-24-00539. Epub 2024 Sep 24. PMID: 39314155
Koch G, Altomare D, Benussi A, Bréchet L, Casula EP, Dodich A, Pievani M, Santarnecchi E, Frisoni GB. The emerging field of non-invasive brain stimulation in Alzheimer’s disease. Brain. 2024 Nov 20:awae292. doi: 10.1093/brain/awae292. PMID: 39562009
Strohman A, Isaac G, Payne B, Verdonk C, Khalsa SS, Legon W. Low-intensity focused ultrasound to the insula differentially modulates the heartbeat-evoked potential: A proof-of-concept study. Clin Neurophysiol. 2024 Nov;167:267-281. doi: 10.1016/j.clinph.2024.09.006. Epub 2024 Sep 19. PMID: 39366795
Ye BS, Chang KW, Kang S, Jeon S, Chang JW. Repetitive and extensive focused ultrasound-mediated bilateral frontal blood-brain barrier opening for Alzheimer’s disease. J Neurosurg. 2025 Jan 10:1-8. doi: 10.3171/2024.8.JNS24989. Online ahead of print. PMID: 39793012
Jimenez-Gambin S, Bae S, Ji R, Tsitsos F, Konofagou EE. Feasibility of Hologram-assisted Bilateral Blood-Brain Barrier Opening in Non-Human Primates. IEEE Trans Ultrason Ferroelectr Freq Control. 2024 Aug 28;PP. doi: 10.1109/TUFFC.2024.3451289. PMID: 39196737
Scott K, Klaus SP. Focused ultrasound therapy for Alzheimer’s disease: exploring the potential for targeted amyloid disaggregation. Front Neurol. 2024 Aug 6;15:1426075. doi: 10.3389/fneur.2024.1426075. eCollection 2024. PMID: 39165269
Ye D, Chukwu C, Yang Y, Hu Z, Chen H. Adeno-associated virus vector delivery to the brain: Technology advancements and clinical applications. Adv Drug Deliv Rev. 2024 Aug;211:115363. doi: 10.1016/j.addr.2024.115363. Epub 2024 Jun 19. PMID: 38906479
Wang R, Li J. Noninvasive focused ultrasound-mediated delivery of rAAV9-EGFP vectors for neuronal targeting in rats. Neuroimage. 2024 Jul 1;294:120630. doi: 10.1016/j.neuroimage.2024.120630. Epub 2024 May 11. PMID: 38740226
Leinenga G, Padmanabhan P, Götz J. Improving Cognition Without Clearing Amyloid: Effects of Tau and Ultrasound Neuromodulation. J Alzheimers Dis. 2024 Jul 22. doi: 10.3233/JAD-240616. PMID: 39058447
Zhao P, Wu T, Tian Y, You J, Cui X. Recent advances of focused ultrasound induced blood-brain barrier opening for clinical applications of neurodegenerative diseases. Adv Drug Deliv Rev. 2024 Jun;209:115323. doi: 10.1016/j.addr.2024.115323. Epub 2024 Apr 21. PMID: 38653402
Götz J, Padmanabhan P. Ultrasound and antibodies - a potentially powerful combination for Alzheimer disease therapy. Nat Rev Neurol. 2024 Feb 20. doi: 10.1038/s41582-024-00943-1. Online ahead of print.PMID: 38378999
Rezai AR, D’Haese PF, Finomore V, Carpenter J, Ranjan M, Wilhelmsen K, Mehta RI, Wang P, Najib U, Vieira Ligo Teixeira C, Arsiwala T, Tarabishy A, Tirumalai P, Claassen DO, Hodder S, Haut MW. Ultrasound Blood Brain Barrier Opening and Aducanumab in Alzheimer’s Disease. N Engl J Med. 2024 Jan 4;390(1):55-62. doi: 10.1056/NEJMoa2308719. PMID: 38169490
Hynynen K. Sounding Out the Blood-Brain Barrier. N Engl J Med. 2024 Jan 4;390(1):82-85. doi: 10.1056/NEJMe2311358. PMID: 38169495
Song G, Plumlee P, Ahn JY, Wong ST, Zhao H. Translational strategies and systems biology insights for blood-brain barrier opening and delivery in brain tumors and Alzheimer’s disease. Biomed Pharmacother. 2023 Sep 11;167:115450. doi: 10.1016/j.biopha.2023.115450.
Géraudie A, Riche M, Lestra T, Trotier A, Dupuis L, Mathon B, Carpentier A, Delatour B. Effects of Low-Intensity Pulsed Ultrasound-Induced Blood-Brain Barrier Opening in P301S Mice Modeling Alzheimer’s Disease Tauopathies. Int J Mol Sci. 2023 Aug 3;24(15):12411. doi: 10.3390/ijms241512411.
Fernández-Castaño R, Fernández-Blázquez MÁ, Echevarría-Fernández I, Cabrera-Freitag M, Freitag K. Effect of Transcranial Pulse Stimulation for the Treatment of Alzheimer´s Disease and its Related Symptoms. Curr Alzheimer Res. 2023 Jul 27. doi: 10.2174/1567205020666230727102025.
Antoniou A, Stavrou M, Evripidou N, Georgiou E, Kousiappa I, Koupparis A, Papacostas SS, Kleopa KA, Damianou C. FUS-mediated blood-brain barrier disruption for delivering anti-Aβ antibodies in 5XFAD Alzheimer’s disease mice. J Ultrasound. 2023 Jul 29. doi: 10.1007/s40477-023-00805-4.
Yoo SS, Kim E, Kowsari K, Van Reet J, Kim HC, Yoon K. Non-invasive enhancement of intracortical solute clearance using transcranial focused ultrasound. Sci Rep. 2023 Jul 31;13(1):12339. doi: 10.1038/s41598-023-39640-2.
Rezai AR, Ranjan M, Haut MW, Carpenter J, D’Haese PF, Mehta RI, Najib U, Wang P, Claassen DO, Chazen JL, Krishna V, Deib G, Zibly Z, Hodder SL, Wilhelmsen KC, Finomore V, Konrad PE, Kaplitt M, Kaplitt M. Focused ultrasound-mediated blood-brain barrier opening in Alzheimer’s disease: long-term safety, imaging, and cognitive outcomes. J Neurosurg. 2023 Jul 1;139(1):275-283. doi: 10.3171/2022.9.JNS221565.
Mehta RI, Carpenter JS, Mehta RI, Haut MW, Wang P, Ranjan M, Najib U, D’Haese PF, Rezai AR. Ultrasound-mediated blood-brain barrier opening uncovers an intracerebral perivenous fluid network in persons with Alzheimer’s disease. Fluids Barriers CNS. 2023 Jun 16;20(1):46. doi: 10.1186/s12987-023-00447-y.
Kuo YY, Chen WT, Lin GB, Chen YM, Liu HH, Chao CY. Thermal cycling-hyperthermia ameliorates Aβ25-35-induced cognitive impairment in C57BL/6 mice. Neurosci Lett. 2023 Jun 12;810:137337. doi: 10.1016/j.neulet.2023.137337.
Ye D, Chen S, Liu Y, Weixel C, Hu Z, Yuan J, Chen H. Mechanically manipulating glymphatic transport by ultrasound combined with microbubbles. Proc Natl Acad Sci U S A. 2023 May 23;120(21):e2212933120. doi: 10.1073/pnas.2212933120. Epub 2023 May 15.
Kong C, Ahn JW, Kim S, Park JY, Na YC, Chang JW, Chung S, Chang WS. Long-lasting restoration of memory function and hippocampal synaptic plasticity by focused ultrasound in Alzheimer’s disease. Brain Stimul. 2023 May 19;16(3):857-866. doi: 10.1016/j.brs.2023.05.014.
Gouveia FV, Lea-Banks H, Aubert I, Lipsman N, Hynynen K, Hamani C. Anesthetic-loaded nanodroplets with focused ultrasound reduces agitation in Alzheimer’s mice. Ann Clin Transl Neurol. 2023 Apr;10(4):507-519. doi: 10.1002/acn3.51737. Epub 2023 Jan 30.
Pacia CP, Yuan J, Yue Y, Leuthardt EC, Benzinger TLS, Nazeri A, Chen H. Focused Ultrasound-mediated Liquid Biopsy in a Tauopathy Mouse Model. Radiology. 2023 Apr;307(2):e220869. doi: 10.1148/radiol.220869. Epub 2023 Jan 31.
Meng Y, Goubran M, Rabin JS, McSweeney M, Ottoy J, Pople CB, Huang Y, Storace A, Ozzoude M, Bethune A, Lam B, Swardfager W, Heyn C, Abrahao A, Davidson B, Hamani C, Aubert I, Zetterberg H, Ashton NJ, Karikari TK, Blennow K, Black SE, Hynynen K, Lipsman N. Blood-brain barrier opening of the default mode network in Alzheimer’s disease with magnetic resonance-guided focused ultrasound. Brain. 2023 Jan 25:awac459. doi: 10.1093/brain/awac459. PMID: 36694943
Gouveia FV, Lea-Banks H, Aubert I, Lipsman N, Hynynen K, Hamani C. Anesthetic-loaded nanodroplets with focused ultrasound reduces agitation in Alzheimer’s mice. Ann Clin Transl Neurol. 2023 Jan 30. doi: 10.1002/acn3.51737. PMID: 36715553
Pacia CP, Yuan J, Yue Y, Leuthardt EC, Benzinger TLS, Nazeri A, Chen H. Focused Ultrasound-mediated Liquid Biopsy in a Tauopathy Mouse Model. Radiology. 2023 Jan 31:220869. doi: 10.1148/radiol.220869.
Click here for additional references from PubMed.