An MRI‐compatible system for focused ultrasound experiments in small animal models

Abstract

The development of novel MRI-guided therapeutic ultrasound methods including potentiated drug delivery and targeted thermal ablation requires extensive testing in small animals such as rats and mice due to the widespread use of these species as models of disease. An MRI-compatible, computer-controlled three-axis positioning system was constructed to deliver focused ultrasound exposures precisely to a target anatomy in small animals for high-throughput preclinical drug delivery studies. Each axis was constructed from custom-made nonmagnetic linear ball stages driven by piezoelectric actuators and optical encoders. A range of motion of 5 ϫ 5 ϫ 2.5 cm 3 was achieved, and initial bench top characterization demonstrated the ability to deliver ultrasound to the brain with a spatial accuracy of 0.3 mm. Operation of the positioning system within the bore of a clinical 3 T MR imager was feasible, and simultaneous motion and MR imaging did not result in any mutual interference. The system was evaluated in its ability to deliver precise sonications within the mouse brain, linear scanned exposures in a rat brain for blood barrier disruption, and circular scans for controlled heating under MR temperature feedback. Initial results suggest that this is a robust and precise apparatus for use in the investigation of novel ultrasound-based therapeutic strategies in small animal preclinical models.

Blood-Brain Barrier: Real-time Feedback-controlled Focused Ultrasound Disruption by Using an Acoustic Emissions–based Controller

“…Twelve animals from group 2, which were treated by using only the 50% target level, survived for 8 days after treatment and were imaged prior to sacrifice were placed supine on a three-axis MR imaging-compatible focused ultrasound system (operationally similar to the system described by Chopra et al [21]). The rats' heads were coupled to the ultrasound transducer by means of a water bath, as shown in Figure 1.…”

Focused ultrasound for treatment of bone tumours

“…Over the past decades, there have been numerous external ultrasound array systems for focused heating in the body, [22][23][24][25][26][27] including one system specifically optimized for small animal treatments [28]. At present, there are three commercial non-invasive ultrasound heating systems that have been integrated within either US or MR imaging systems for image-guidance of FUS treatments in humans: the ExAblate system (InSightec Ltd., Tirat Carmel, Israel) based on the General Electric MR platform [29,30]; the Sonalleve FUS system (Koninklijke Philips Electronics NV, Eindhoven, The Netherlands) based on the Phillips MR platform [31,32]; and the Haifu system (Model JC, Chongqing Haifu Medical Technology Co. Ltd., Chongqing, China) coupled with a B-type ultrasonography system [33].…”

Detecting blood–brain barrier disruption within minimal hemorrhage following transcranial focused ultrasound: A correlation study with contrast‐enhanced MRI

“…As shown in the present study, R 1 mapping of the whole brain was acquired using the spin echo sequence, with a scan time of $50 min. To make R 1 mapping more clinically feasible, one could potentially reduce the scan time by using the gradient echo sequence combined with parallel imaging techniques (22,25).…”

“…To minimize brain damage, recent studies have focused on optimizing FUS parameters combined with intravascular preformed microbubbles to minimize sonication-induced hemorrhage (5,6,9,20,21). To ensure safe operation, the role of MRI becomes even more important; MRI not only aids FUS to localize the target region to gauge the BBB disruption but also provides simultaneous monitoring to detect incipient hemorrhage or neuronal dysfunction (18,22).To date, there is no systematic study investigating the ability of various MR methods to detect BBB disruption by FUS operated under safe conditions. Specifically, it is still unknown whether MRI is sensitive enough to indicate the degree of BBB disruption within minimal hemorrhages following FUS sonication using low UCA doses.…”