Stroke, Intracerebral Hemorrhage 

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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 intracerebral hemorrhage. 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
The mechanisms of action are that 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 temporarily opening the blood-brain barrier which enables entry of stem cells into the area of the stroke that can repopulate the area. 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, thromboembolic.”

Advantages
The primary options for treatment of intracerebral hemorrhage 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.

There is a clinical trial in China using neuromodulation to help deliver brain derived neurotrophic factor to patients after hemorrhagic stroke.  

Regulatory Approval and Reimbursement

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

Notable Papers

Li KP, Wu JJ, Zhou ZL, Xu DS, Zheng MX, Hua XY, Xu JG. Noninvasive Brain Stimulation for Neurorehabilitation in Post-Stroke Patients. Brain Sci. 2023 Mar 6;13(3):451. doi: 10.3390/brainsci13030451.

Wang T, Lei H, Li X, Yang N, Ma C, Li G, Gao X, Ge J, Liu Z, Cheng L, Chen G. Magnetic Targeting Nanocarriers Combined with Focusing Ultrasound for Enhanced Intracerebral Hemorrhage Therapy. Small. 2023 Apr;19(17):e2206982. doi: 10.1002/smll.202206982. Epub 2023 Jan 26.

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.

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 Dec 1;30(6):586-594. doi: 10.3171/2022.8.PEDS22144.

He Y, Yang J, Hu F, Liao M, Nie Y, Zhu X, Zhang T, Song K, Li Q, Li X, Mei C, Wu Z, Lu Q, Zhong Z. A new method for preparing a rat intracerebral hemorrhage model by combining focused ultrasound and microbubbles. Animal Model Exp Med. 2023 Jan 17. doi: 10.1002/ame2.12303.

Wang T, Lei H, Li X, Yang N, Ma C, Li G, Gao X, Ge J, Liu Z, Cheng L, Chen G. Magnetic Targeting Nanocarriers Combined with Focusing Ultrasound for Enhanced Intracerebral Hemorrhage Therapy. Small. 2023 Jan 26:e2206982. doi: 10.1002/smll.202206982.

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.

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.

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.

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.

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. 2019 Jan;29(1):5-13. doi: 10.1111/jon.12568. Epub 2018 Oct 8.

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.

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.

Harnof S, Zibly Z, Hananel A, Monteith S, Grinfeld J, Schiff G, Kulbatski I, Kassell N. Potential of Magnetic Resonance-guided Focused Ultrasound for Intracranial Hemorrhage: An In Vivo Feasibility Study. J Stroke Cerebrovasc Dis. 2014 Jul;23(6):1585-91.

Click here for additional references from PubMed.

Clinical Trials