Abstract 10748: Quantitative Improvements in Cerebral Blood Flow Detected with Magnetic Resonance Imaging Following Transtemporal Ultrasound and Microbubbles in Pigs with Acute Stroke

Abstract

Background. Transtemporal Ultrasound (TTU) and intravenous (IV) microbubbles (MB) have been explored as a method of enhancing the effectiveness of fibrinolytic therapy in acute stroke. However, it is unclear what effect TTU and IV MB have on the ability to improve cerebral blood flow (CBF) in this setting. The purpose of this study was to quantify the CBF changes induced by TTU and IV MB in a large animal model, using magnetic resonance imaging (MRI).

Methods. In seven pigs, an acute stroke was induced by bilateral embolization of both internal carotids with >4 hour old venous thrombi. All pigs received aspirin (160 mg), followed by 30 minutes of therapeutic impulses from either diagnostic TTU alone (2.4 mechanical index (MI); 5 usec pulse duration) or the same therapeutic impulses given during an IV MB infusion (3% Definity; Lantheus Medical). In this setting, the therapeutic impulses were given only when low MI imaging detected MB within the temporal-parietal region. Magnetic resonance imaging (MRI) was performed with intravenous gadolinium contrast to quantify CBF, mean transit time (MTT), and cerebral blood volume changes before randomized treatment, immediately after treatment, and at 24 hours post stroke. A transverse T2*-weighted sequence with three-dimensional echo-planar principles of echo shifting with a train of observations (PRESTO) was applied for all perfusion studies. Echo-planar diffusion weighted imaging was performed with a b-value of 1000. Phase-contrast MRA utilized a velocity encoding of 20 cm/sec. CBF and MTT changes were measured within the temporal, parietal, and frontal regions ipsilateral to the applied TTU.

Results. Following treatment with guided TTU and IV MB, CBF increased and MTT decreased (p=0.004 for CBF; p=0.003 for MTT), while no change occurred in pigs treated with TTU alone (p=0.59 for CBF and 0.62 for MTT). Immediate increases in CBF were seen even in the absence of phase contrast MRA evidence of recanalization. Conclusions. Guided TTU impulses from a modified diagnostic ultrasound system can be utilized with commercially available IV MB to immediately improve CBF in acute stroke, even when large vessel recanalization does not occur. This may be a method of immediately preserving cerebral blood flow in acute stroke.