Design and Validation of a Patient-Specific Stereotactic Frame for Transcranial Ultrasound Therapy

Transcranial-focused ultrasound (tFUS) procedures such as neuromodulation and blood-brain barrier (BBB) opening require precise focus placement within the brain. MRI is currently the most reliable tool for focus localization but can be prohibitive for procedures requiring recurrent therapies. We designed, fabricated, and characterized a patient-specific, 3-D-printed, stereotactic frame for repeated tFUS therapy. The frame is compact, with minimal footprint, can be removed and re-secured between treatments while maintaining sub-mm accuracy, and will allow for precise and repeatable transcranial FUS treatment without the need for MR-guidance following the initial calibration scan. Focus localization and repeatability were assessed via MR-thermometry and MR-acoustic radiation force imaging (ARFI) on an ex vivo skull phantom and in vivo nonhuman primates (NHPs), respectively. Focal localization, registration, steering, and re-steering were accomplished during the initial MRI calibration scan session. Keeping steering coordinates fixed in subsequent therapy and imaging sessions, we found good agreement between steered foci and the intended target, with target registration error (TRE) of $1.2~\pm ~0.3$ ( ${n} =4$ , ex vivo) and $1.0~\pm ~0.5$ ( ${n} =3$ , in vivo) mm. Focus position (steered and non-steered) was consistent, with sub-mm variation in each dimension between studies. Our 3-D-printed, patient-specific stereotactic frame can reliably position and orient the ultrasound transducer for repeated targeting of brain regions using a single MR-based calibration. The compact frame allows for high-precision tFUS to be carried out outside the magnet and could help reduce the cost of tFUS treatments where repeated application of an ultrasound focus is required with high precision.