Improving Targeting Accuracy and Ultrasound Dose Consistency in FUS procedures using MR-ARFI: A Brain Study in Rats

Introduction: Low-Intensity Focused Ultrasound (LIFU) is a promising non-invasive technique for neuromodulation, but inconsistencies in transducer positioning and skull-induced aberrations can reduce the targeting accuracy and cause inconsistencies in the FUS intensity at the focus. This study aimed to evaluate the use of Magnetic Resonance Acoustic Radiation Force Imaging (MR-ARFI) in improving the targeting accuracy and assessing the variation in ultrasound pressure delivered during transcranial FUS procedures. Method: Experiments were conducted on a 7T small animal MRI scanner equipped with an MR-compatible Focused Ultrasound (FUS) device. The FUS system was calibrated with a hydrophone prior to the animal study to ensure accurate and consistent setting of input ultrasound power. The MR-guided FUS system was then used to bilaterally target the nucleus accumbens (NAc) region of Sprague-Dawley rats. Displacement maps were acquired with MR-ARFI to refine the targeting accuracy by adjusting the focal point position electronically and mechanically as necessary. In addition, the ARFI measurements were used to establish the relationship between the displacement and input power, and to assess intra- and inter-subject variability in FUS pressure. Results: The calibration experiments demonstrated a strong linear relationship between FUS input intensity and measured pressure (r² = 0.994). ARFI displacement was a strong predictor of FUS power (r² = 0.935, p<0.001), with displacements showing quadratic dependence on FUS intensity. In animals, intra-site and intra-subject coefficients of variation (CoV) in ARFI displacement measurements were 9.0% and 18.6%. The CoV in ARFI displacement across animals was 43.4%. Initial MR-guided targeting required secondary adjustments in 21% of cases, highlighting the importance of MR-ARFI in correcting focal point deviations caused by skull aberrations.Conclusion: MR-ARFI proved valuable in enhancing the accuracy of FUS targeting and in estimating and correcting for variations in delivered ultrasound intensity. Despite initial MRI guidance, substantial targeting errors were observed, highlighting the need for advanced imaging techniques like MR-ARFI in neuromodulation procedures. Moreover, ARFI displacements in the target region across subjects varied over 3-fold, indicating very high variation in the delivered acoustic pressure. By improving the precision of FUS targeting and estimating deviations in the FUS pressure, MR-ARFI can contribute to improved therapeutic outcomes and reduced risks in transcranial focused ultrasound stimulation treatments.