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

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 x 5 x 2.5 cm3 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.