In silico Study of Low-Frequency Transcranial Ultrasound Fields in Acute Ischemic Stroke Patients

Abstract

Ultrasound in the sub-megahertz range enhances thrombolysis and may be applied transcranially to ischemic stroke patients. The consistency of transcranial insonification needs to be evaluated. Acoustic and thermal simulations based on computed-tomography (CT) scans of 20 patients were performed. An unfocused 120-kHz transducer allowed homogeneous insonification of the thrombus, and positioning based on external landmarks performed similarly to an optimized placement based on CT data. With a weakly focused 500-kHz transducer, the landmark-based positioning underperformed. The predicted inter-patient variation of in situ acoustic pressure was similar with both transducers for the optimized placement (18.0–26.4% relative standard deviation). The simulated maximum acoustic pressure in intervening tissues was 2.6±0.6 and 2.0±0.7 times the pressure in the thrombus for the 120-kHz and 500-kHz transducers, respectively. A 1 W/cm2 insonification of the thrombus caused a 3.8±2.2°C temperature increase in the bone for the 120-kHz transducer, and a 13.4±3.3°C increase for the 500-kHz transducer. Contralateral local maxima up to 1.1 times the pressure amplitude in the targeted zone were predicted for the 120-kHz transducer. We established two transducer placement approaches, one based on analysis of a head CT and the other using simple external, visible landmarks. Both approaches allowed consistent insonification of the thrombus.

Sonothrombolysis

“…However, several studies have shown negligible thermal effects in bench-top (Francis et al 1992; Shaw et al 2006; Damianou et al 2014) or clinical studies (Barlinn and Alexandrov 2013). Numerical computations confirm a negligible temperature rise in clots due to 0.12–3.5 MHz insonations during thrombolysis (Nahirnyak et al 2007; Bouchoux et al 2014). In contrast, Sakharov et al (2000) attributed increased thrombolytic efficacy from 1-MHz insonation in-vitro due to the combined effect of heating and acoustic streaming.…”

“…The transcranial ultrasound field produced by this device was evaluated in-vitro and the safety of this approach was demonstrated in a healthy primate model (Shimizu et al 2012). Bouchoux et al (2014) simulated 120 and 500-kHz transcranial ultrasound fields from the head CT scans of 20 ischemic stroke patients using a validated acoustic propagation numerical model (Bouchoux et al 2012). Consistent and homogeneous insonation of the Ml segment of the MCA was achieved at both 120 and 500 kHz.…”

“…Future TCD studies employing user-free devices may help decrease the patient-to-patient variability (Barlinn et al 2013). The means to obtain reproducible and predictable transcranial sub-megahertz ultrasound fields have been devised (Bouchoux et al 2014), and the approach appears safe in large primate models (Shimizu et al 2012). …”

“…The Ml segment of the MCA is shown in green and the transducer in red. The orange contour indicates the regions where the acoustic pressure is larger than half the maximum pressure in the Ml region of interest (Bouchoux et al 2014). ( d ) MR-Guided Focused Ultrasound .…”

Microfluidic manufacture of rt-PA -loaded echogenic liposomes

“…It is noteworthy that this frequency may not be able to penetrate the skull for nearly 15 % of patients (Wijnhoud et al 2008). For such patients, sub-megahertz frequencies may be employed (Bouchoux et al 2012, 2014) at which microbubbles in the 20–50 µm range are resonant. However, microbubbles larger 7 µm are filtered by the lungs and thus for cavitation nucleation for enhancement of rt-PA thrombolysis.…”