Design, characterization and evaluation of a laser-guided focused ultrasound system for preclinical investigations

Abstract

Background The clinical applications of transcranial focused ultrasound continue to expand and include ablation as well as drug delivery applications in the brain, where treatments are typically guided by MRI. Although MRI-guided focused ultrasound systems are also preferred for many preclinical investigations, they are expensive to purchase and operate, and require the presence of a nearby imaging center. For many basic mechanistic studies, however, MRI is not required. The purpose of this study was to design, construct, characterize and evaluate a portable, custom, laser-guided focused ultrasound system for noninvasive, transcranial treatments in small rodents. Methods The system comprised an off-the-shelf focused ultrasound transducer and amplifier, with a custom cone fabricated for direct coupling of the transducer to the head region. A laser-guidance apparatus was constructed with a 3D stage for accurate positioning to 1 mm. Pressure field simulations were performed to demonstrate the effects of the coupling cone and the sealing membrane, as well as for determining the location of the focus and acoustic transmission across rat skulls over a range of sizes. Hydrophone measurements and exposures in hydrogels were used to assess the accuracy of the simulations. In vivo treatments were performed in rodents for opening the blood–brain barrier and to assess the performance and accuracy of the system. The effects of varying the acoustic pressure, microbubble dose and animal size were evaluated in terms of efficacy and safety of the treatments. Results The simulation results were validated by the hydrophone measurements and exposures in the hydrogels. The in vivo treatments demonstrated the ability of the system to open the blood–brain barrier. A higher acoustic pressure was required in larger-sized animals, as predicted by the simulations and transmission measurements. In a particular sized animal, the degree of blood–brain barrier opening, and the safety of the treatments were directly associated with the microbubble dose. Conclusion The focused ultrasound system that was developed was found to be a cost-effective alternative to MRI-guided systems as an investigational device that is capable of accurately providing noninvasive, transcranial treatments in rodents.

Beam characterization of a custom, handheld focused ultrasound system using thermochromic liquid crystal films

“…The transducer is attached to a custom, 3D positioning system (Velmex, Bloomfield), with a resolution of 1 mm. Connecting the transducer to the positioning system is achieved using a custom 3D printed component (Anastasiadis et al, 2019). The FUS system is shown in Figure 1.…”

“…Hydrophone measurements of the acoustic pressure field were carried out as previously described (Anastasiadis et al, 2019). In brief, the transducer was operated in continuous mode and placed in a tank (51 ×27 × 32 cm) filled with deionized water.…”

“…This depends both on the complexity of the software and the information used for both the device hardware in question and the medium that is treated (Hancock et al, 2009; Krasovitski et al, 2011; Wang et al, 2011). The most conventional method of experimentally quantifying acoustic fields from a FUS transducer uses hydrophone transducers, which can obtain discrete, high‐resolution 3D quantitative values of localized acoustic pressures (Anastasiadis et al, 2019). While this technique is the most common in preclinical settings, transducer probes and positioning equipment are expensive.…”

“…While this technique is the most common in preclinical settings, transducer probes and positioning equipment are expensive. Needle probes must also be handled carefully due to cavitation-based damage at high acoustic pressures (Anastasiadis et al, 2019;Zanelli & Howard, 2006).…”

Experimental Characterization of A Piezoelectric Transducer Array Taking into Account Crosstalk Phenomenon

“…In several medical applications, therapeutic ultrasounds are based on single transducer and transducer arrays [34][35] with higher powers and mostly lower frequencies. Therefore, the optimal displacement generated by these transducers will play a critical role in terms of the focal area and transferred intensities.…”