Stroke, Thromboembolic

Last Updated:

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 thromboembolic stroke. This novel technology focuses beams of ultrasound energy precisely and accurately on targets deep in the brain without damaging surrounding normal tissue.

How it Works
Where the beams converge, focused ultrasound produces several therapeutic effects that are being evaluated. One mechanism is the disruption of blood clots, which allows reperfusion of ischemic tissue. Another mechanism is the temporary opening of the blood-brain barrier, which enables entry of stem cells into the area of the stroke. A third mechanism is neuromodulation, which can increase regional blood flow to ischemic areas. All are still in the early stage, and more work is needed before this research can reach the clinic. Please note that there is another major cause of stroke, listed separately under “Stroke, intracellular hemorrhage.” 

Advantages
The primary options for treatment of stroke include medications with the possible inclusion of surgery.

For certain patients, focused ultrasound could provide a noninvasive alternative to surgery with less risk of complications – such as surgical wound healing or infection – at a lower cost. It can reach the desired target without damaging surrounding tissue and is repeatable, if necessary.

Clinical Trials

There is a clinical trial ongoing in North Carolina using low intensity focused ultrasound to help with upper extremity motor deficits after a stroke.

Regulatory Approval and Reimbursement

Focused ultrasound treatment for thromboembolic stroke is not yet approved by regulatory bodies or covered by medical insurance companies.

Notable Papers

Shen QR, Hu MT, Feng W, Li KP, Wang W. Narrative Review of Noninvasive Brain Stimulation in Stroke Rehabilitation. Med Sci Monit. 2022 Dec 2;28:e938298. doi: 10.12659/MSM.938298.

Deng LD, Qi L, Suo Q, Wu SJ, Mamtilahun M, Shi RB, Liu Z, Sun JF, Tang YH, Zhang ZJ, Yang GY, Wang JX. Transcranial focused ultrasound stimulation reduces vasogenic edema after middle cerebral artery occlusion in mice. Neural Regen Res. 2022 Sep;17(9):2058-2063. doi: 10.4103/1673-5374.335158.

Raghuram H, Looi T, Pichardo S, Waspe AC, Drake JM. A robotic MR-guided high-intensity focused ultrasound platform for intraventricular hemorrhage: assessment of clot lysis efficacy in a brain phantom. J Neurosurg Pediatr. 2022 Sep 16:1-9. doi: 10.3171/2022.8.PEDS22144.

Alptekin A, Khan MB, Ara R, Rashid MH, Kong F, Parvin M, Frank JA, Chopra R, Dhandapani K, Arbab AS. Pulsed Focal Ultrasound as a Non-Invasive Method to Deliver Exosomes in the Brain/Stroke. J Biomed Nanotechnol. 2021 Jun 1;17(6):1170-1183. doi: 10.1166/jbn.2021.3091.

Wang J, Li G, Deng L, Mamtilahun M, Jiang L, Qiu W, Zheng H, Sun J, Xie Q, Yang GY. Transcranial Focused Ultrasound Stimulation Improves Neurorehabilitation after Middle Cerebral Artery Occlusion in Mice. Aging Dis. 2021 Feb 1;12(1):50-60. doi: 10.14336/AD.2020.0623. eCollection 2021 Feb.

Hoque MM, Abdelazim H, Jenkins-Houk C, Wright D, Patel BM, Chappell JC. The Cerebral Microvasculature: Basic and Clinical Perspectives on Stroke and Glioma. Microcirculation. 2020 Nov 10:e12671. doi: 10.1111/micc.12671.

Baek H, Sariev A, Lee S, Dong SY, Royer S, Kim H. Deep Cerebellar Low-intensity Focused Ultrasound Stimulation Restores Interhemispheric Balance after Ischemic Stroke in Mice. IEEE Trans Neural Syst Rehabil Eng. 2020 Jun 15;PP. doi: 10.1109/TNSRE.2020.3002207.

Lee J, Chang WS, Shin J, Seo Y, Kong C, Song BW, Na YC, Kim BS, Chang JW. Non-invasively enhanced intracranial transplantation of mesenchymal stem cells using focused ultrasound mediated by overexpression of cell-adhesion molecules. Stem Cell Res. 2020 Jan 30;43:101726. doi: 10.1016/j.scr.2020.101726.

Guo S, Guo X, Wang X, Zhou D, Du X, Han M, Zong Y, Wan M. Reduced clot debris size in sonothrombolysis assisted with phase-change nanodroplets. Ultrason Sonochem. 2019 Jun;54:183-191. doi: 10.1016/j.ultsonch.2019.02.001. Epub 2019 Feb 2.

Gerhardson T, Sukovich JR, Chaudhary N, Chenevert TL, Ives K, Hall TL, Camelo-Piragua S, Xu Z, Pandey AS. Histotripsy Clot Liquefaction in a Porcine Intracerebral Hemorrhage Model. Neurosurgery. 2019 Mar 29. pii: nyz089. doi: 10.1093/neuros/nyz089.

Juratli MA, Menyaev YA, Sarimollaoglu M, Melerzanov AV, Nedosekin DA, Culp WC, Suen JY, Galanzha EI, Zharov VP. Noninvasive label-free detection of circulating white and red blood clots in deep vessels with a focused photoacoustic probe. Biomed Opt Express. 2018 Oct 23;9(11):5667-5677. doi: 10.1364/BOE.9.005667. eCollection 2018 Nov 1.

Baek H, Sariev A, Kim MJ, Lee H, Kim J, Kim H. A neuroprotective brain stimulation for vulnerable cerebellar Purkinje cell after ischemic stroke: a study with low-intensity focused ultrasound. Conf Proc IEEE Eng Med Biol Soc. 2018 Jul;2018:4744-4747. doi: 10.1109/EMBC.2018.8513138.

Zafar A, Quadri SA, Farooqui M, Ortega-Gutiérrez S, Hariri OR, Zulfiqar M, Ikram A, Khan MA, Suriya SS, Nunez-Gonzalez JR, Posse S, Mortazavi MM, Yonas H. MRI-Guided High-Intensity Focused Ultrasound as an Emerging Therapy for Stroke: A Review. J Neuroimaging. 2018 Oct 8. doi: 10.1111/jon.12568.

Baek H, Pahk KJ, Kim MJ, Youn I, Kim H. Modulation of Cerebellar Cortical Plasticity Using Low-Intensity Focused Ultrasound for Poststroke Sensorimotor Function Recovery. Neurorehabil Neural Repair. 2018 Sep;32(9):777-787. doi: 10.1177/1545968318790022. Epub 2018 Aug 29.

Ilyas A, Chen CJ, Ding D, Romeo A, Buell TJ, Wang TR, Kalani MYS, Park MS. Magnetic resonance-guided, high-intensity focused ultrasound sonolysis: potential applications for stroke. Neurosurg Focus. 2018 Feb;44(2):E12. doi: 10.3171/2017.11.FOCUS17608.

Li H, Sun J, Zhang D, Omire-Mayor D, Lewin PA, Tong S. Low-intensity (400 mW/cm2, 500 kHz) pulsed transcranial ultrasound preconditioning may mitigate focal cerebral ischemia in rats. Brain Stimul. 2017 Feb 27. pii: S1935-861X(17)30615-0. doi: 10.1016/j.brs.2017.02.008.

Yang W, Zhou Y. Effect of pulse repetition frequency of high-intensity focused ultrasound on in vitro thrombolysis. Ultrason Sonochem. 2017 Mar;35(Pt A):152-160. doi: 10.1016/j.ultsonch.2016.09.014.

Papadopoulos N, Yiallouras C, Damianou C. The Enhancing Effect of Focused Ultrasound on TNK-Tissue Plasminogen Activator-Induced Thrombolysis Using an In Vitro Circulating Flow Model. J Stroke Cerebrovasc Dis. 2016 Sep 2. pii: S1052-3057(16)30270-1. doi: 10.1016/j.jstrokecerebrovasdis.2016.07.052.

Papadopoulos N, Damianou C. In Vitro Evaluation of Focused Ultrasound-Enhanced TNK-Tissue Plasminogen Activator-Mediated Thrombolysis. J Stroke Cerebrovasc Dis. 2016 Aug;25(8):1864-77. doi: 10.1016/j.jstrokecerebrovasdis.2016.03.051.

Click here for additional references from PubMed.

Clinical Trials