The extent of clot lysis was automatically measured by means of light absorbance at a wavelength of 412 nm using a spectrometer before and after thrombolytic treatment. This method allowed the

researchers to measure automatically a total of 200 positions within minutes, representing a throughput about 100 times as large as that of conventional methods. Magnetic resonance-guided focused ultrasound (MRgFUS) is a novel method for optimizing US treatment. In general, magnetic resonance imaging (MRI) enables the adjustment of the US beam, based on differences in temperature measurements in the targeted parenchyma. For the purpose of sonothrombolysis, preliminary steps have involved using in vitro models with human skull and porcine brain. In future, it may be possible to detect the thrombus within the vessel, to focus the US beam on this Selleck Cyclopamine target, and make corrections to the US beam

so as to avoid side effects of US caused by distortion and shifting of the human skull [29] and [30]. Another way of enhancing the effect of sonothrombolysis involves the use of microspheres. Commercially manufactured ultrasonic contrast amplifiers have been used in several studies: SonoVue®, which consists of sulfur hexafluoride-filled microbubbles of phospholipids, and Levovist®, a granulate of galactose and palmitic acid, which binds to micrometer-sized air bubbles. Following IV injection, they Inhibitor Library solubility dmso take energy on under influence of US, and by oscillation or rupture, this energy is released again, which reinforces the US effectiveness. Various experiments have shown the effectiveness of this method without an increase in the intracranial bleeding rate, which has been demonstrated in vivo. Molina et al. [31] showed an improvement by intermittent bolus injection of Levovist® in addition to tPA treatment plus 2-h insonation with TCD monitoring. A similar study was conducted

by Perren et al. [32] in which patients who had suffered from an MCA stroke underwent IV rtPA thrombolysis and 2-MHz TCCS monitoring for 1 h with SonoVue®, resulting in clinical improvement in these patients. No additional intracranial bleedings were noted in these studies. In the transcranial ultrasound in clinical sonothrombolysis Niclosamide (TUCSON) randomized clinical trial, intravenously applied microspheres, which had been developed for the purpose of strengthening the effect of sonothrombolysis, were clinically tested [5]. This dose-escalation study of microspheres showed increased bleeding in the second dose tier, prompting the sponsor of the study to discontinue this approach. In vivo molecular imaging of the human thrombus can be carried out with microspheres conjugated with abciximab, a glycoprotein IIb/IIIa receptor inhibitor that is involved in ligand targeting of the thrombus. In vitro experiments have shown that improved binding of microspheres to the clot enhances sonothrombolysis [33] and [34]. In their 2011 study, Shimizu et al.