Early Stage squareStroke, defined as the rapid loss of brain function resulting from a disrupted blood supply to the brain, can result in permanent neurologic damage or death. Strokes can be classified as either Hemorrhagic or Ischemic. Ischemic strokes, which are caused by blockages of blood vessels, (e.g. by blood clots), account for almost 90% of strokes. Hemorrhagic strokes, which are caused by ruptured blood vessels and hemorrhage, account for about 10%.

Symptoms range from the inability to move limbs on one side of the body to impaired speech and vision. Important risk factors include age, high blood pressure and cholesterol, and diabetes. Almost 800,000 Americans experience a stroke each year, and it is also the fourth leading cause of death among Americans. 

Current Treatment

Treatment for stroke can vary depending on whether the stroke is Ischemic or Hemorrhagic.

Treatment for Ischemic stroke focuses on restoring blood flow to the brain by dissolving existing blood clots. This can be done with medications administered intravenously within approximately 4-5 hours of the onset of the stroke. Microcatheters can also be used to administer medications directly to the blocked artery or to mechanically break apart the clot.

Treatment for Hemorrhagic stroke focuses on both controlling bleeding and reducing pressure in the brain. Different medications can be given to counteract the effects of blood thinners or lower intracranial pressure and prevent vasospasm and seizure. Most intracerebral hemorrhages are caused by high blood pressure. Treatment involves controlling the blood pressure and in some cases invasive surgery to remove the blood clot from the brain. Intracerebral hemorrhage from other causes such as ruptured aneurysms and arteriovenous malformations involves treatment of the offending pathology.

Focused Ultrasound Therapy

Preclinical research is exploring the ability of focused ultrasound to dissolve blood clots by directing ultrasound energy to cause vibrations that can either break the clot apart directly or make it more susceptible to the effects of thrombolytic agents.  Researchers have shown the feasibility of treating both ischemic and hemorrhagic stroke as well as inducing reperfusion of occluded blood vessels in other organs of the body.  More work is needed to optimize the parameters of focused ultrasound before research can reach the clinic.

Notable Papers

Ischemic Stroke
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.

Suo D, Guo S, Lin W, Jiang X, Jing Y. Thrombolysis using multi-frequency high intensity focused ultrasound at MHz range: an in vitro study. Phys Med Biol. 2015 Sep 21;60(18):7403-18. doi: 10.1088/0031-9155/60/18/7403.

Durst C, Monteith S, Sheehan J, Moldovan K, Snell J, Eames M, Huerta T, Walker W, Viola F, Kassell N, Wintermark M. Optimal imaging of in vitro clot sonothrombolysis by MR-guided focused ultrasound. J Neuroimaging. 2013 Apr;23(2):187-91.

Hölscher T, Ahadi G, Fisher D, Zadicario E, Voie A. MR-guided focused ultrasound for acute stroke: a rabbit model. Stroke. 2013;44(6 Suppl 1):S58-60.

Hemorrhagic Stroke
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.

Monteith SJ, Harnof S, Medel R, Popp B, Wintermark M, Lopes MB, Kassell NF, Elias WJ, Snell J, Eames M, Zadicario E, Moldovan K, Sheehan J. Minimally invasive treatment of intracerebral hemorrhage with magnetic resonance-guided focused ultrasound. Neurosurgery. 2013;118(5):1035-45

Monteith SJ, Kassell NF, Goren O, Harnof S. Transcranial MR-guided focused ultrasound sonothrombolysis in the treatment of intracerebral hemorrhage. Neurosurgery Focus. 2013 May;34(5):E14.

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