title: Towards use of MRI-guided ultrasound for treating cerebral vasospasm.
abstract: Cerebral vasospasm is a major cause of morbidity and mortality in patients with subarachnoid hemorrhage (SAH), causing delayed neurological deficits in as many as one third of cases. Existing therapy targets induction of cerebral vasodilation through use of various drugs and mechanical means, with a range of observed efficacy. Here, we perform a literature review supporting our hypothesis that transcranially delivered ultrasound may have the ability to induce therapeutic cerebral vasodilation and, thus, may one day be used therapeutically in the context of SAH. Prior studies demonstrate that ultrasound can induce vasodilation in both normal and vasoconstricted blood vessels in peripheral tissues, leading to reduced ischemia and cell damage. Among the proposed mechanisms is alteration of several nitric oxide (NO) pathways, where NO is a known vasodilator. While in vivo studies do not point to a specific physical mechanism, results of in vitro studies favor cavitation induction by ultrasound, where the associated shear stresses likely induce NO production. Two papers discussed the effects of ultrasound on the cerebral vasculature. One study applied clinical transcranial Doppler ultrasound to a rodent complete middle cerebral artery occlusion model and found reduced infarct size. A second involved the application of pulsed ultrasound in vitro to murine brain endothelial cells and showed production of a variety of vasodilatory chemicals, including by-products of arachidonic acid metabolism. In sum, nine reviewed studies demonstrated evidence of either cerebrovascular dilation or elaboration of vasodilatory compounds. Of particular interest, all of the reviewed studies used ultrasound capable of transcranial application: pulsed ultrasound, with carrier frequencies ranging between 0.5 and 2.0 MHz, and intensities not substantially above FDA-approved intensity values. We close by discussing potential specific treatment paradigms of SAH and other cerebral ischemic disorders based on MRI-guided transcranial ultrasound.
authors.affiliation: Department of Neurological Surgery, University of Washington, 325 9th Ave, Box 359924, Seattle, WA 98104 USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Bonow
authors.affiliation: Department of Neurological Surgery, University of Washington, 325 9th Ave, Box 359924, Seattle, WA 98104 USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Silber
authors.affiliation: Department of Radiology, University of California Los Angeles, 924 Westwood Blvd. Suite 805, Los Angeles, CA 90024 USA.
authors.forename: Dieter R
authors.initials: DR
authors.lastname: Enzmann
authors.affiliation: Department of Radiology, University of Washington, RR-218 Health Science Building, 1959 NE Pacific St, Seattle, WA 98195 USA.
authors.forename: Norman J
authors.initials: NJ
authors.lastname: Beauchamp
authors.affiliation: Department of Neurological Surgery, University of Washington, 325 9th Ave, Box 359924, Seattle, WA 98104 USA.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Ellenbogen
authors.affiliation: Department of Neurological Surgery, University of Washington, 325 9th Ave, Box 359924, Seattle, WA 98104 USA ; Department of Radiology, University of Washington, RR-218 Health Science Building, 1959 NE Pacific St, Seattle, WA 98195 USA ; Division of Engineering, University of Washington, 18115 Campus Way NE, Bothell, WA 98011 USA.
authors.forename: Pierre D
authors.initials: PD
authors.lastname: Mourad
keywords: Brain; Cerebral vasospasm; Subarachnoid hemorrhage; Therapeutic ultrasound; Vasoconstriction