Purpose or Case Report: Focused ultrasound (FUS) is a promising non-invasive technique for targeted drug-delivery to the brain through the disruption of the blood-brain barrier (BBB). Preclinical research into FUS-mediated BBB opening is largely limited to dedicated labs as precise imaging and targeting of brain regions is dependent on well-calibrated stereotactic stages. Here, we present a low-cost, portable system that allows for precise and reproducible image-guided FUS using a motorized, consumer-available motion-stage with techniques for calibration.
Methods & Materials: A custom motion stage was designed using a consumer-available 3D printer (Ender 3 V2) which has precision motorized control down to 0.1 mm along three axes and a heated bed for ensuring animal temperature regulation. A stereotactic frame with ear and tooth bars for head stabilization was designed and fabricated using 3D printing. A high-frequency ultrasound imaging probe (L22-14vX LF) and FUS probe (2 MHz, HIFUPlex-003) were co-aligned along one axis using a 3D printed transducer holder. The platform is controlled using a graphical user interface designed in MATLAB. Motion-stage calibration was performed using a thermochromic sheet which co-registered imaging to FUS probe placement through maximizing heat generation and visual confirmation of the focal point. In vivo testing was performed on an adult Balb/C mouse, targeting the right striatum with imaging, translating the stage to FUS probe, injecting a 200 µL bolus of Lumason contrast agent, and treating with FUS for 5 minutes at 2% duty cycle and 0.59 MPa.
Results: Motion-stage calibration using the thermochromic film identified a 1.3 mm Y-axis deviation from the manufactured FUS system to the specifications. After correction for axis deviations, in vivo imaging allowed for identification of the right striatum using anatomical features of the skull-base and digital mouse-brain atlas. FUS treatments showed accurate targeting of the right striatum through Evans blue extravasation.
Conclusions: We have developed a custom precision image-guided focused ultrasound platform for small rodent BBB opening. The high-precision of this system (0.1 mm) potentially allows for BBB opening experiments in neonatal mice as well as adult. This low-cost, portable system allows for researchers of all backgrounds to implement targeted BBB opening using commercially available ultrasound probes.