Modeling of intensity-modulated focused ultrasound in pediatric brain tumors using acoustic holograms

Targeted drug delivery to enhance chemotherapy treatments in brain tumors can be achieved by opening the blood-brain barrier in a non-invasive, transient, localized, safe manner by using focused ultrasound (FUS) and microbubbles. However, as brain tumors are large and irregular structures, conventional single-element FUS methods are inefficient because they do not allow large covering. In this study, we numerically showed how 3D-printed acoustic holograms allow to correct the skull aberrations and to produce a large and localized focusing along a pediatric brain tumor. Several targeting configurations were numerically studied aiming to increase the covered tumor volume while reducing the off-target coverage. Fluid-like tissue simulations were performed using the k-space method. We used a 250-kHz single-element device in different configurations (ROC=110 mm, OD=110 or 132 mm, ID=0 or 44 mm), where the optimal setup with lens (OD=132 mm, ID=0 mm) provided a 16 % of tumor coverage compared to the 5 % obtained using the transducer without lens (OD=110 mm, ID=44 mm), while keeping a reduced 0.06 % of off-target coverage. The focal amplitude decreases 1.6 times accordingly to the focus spread. The estimated sonication duration and the number of microbubble injections can be reduced by 3.2 times, defining a time- and cost-efficient approach. The reported approach is simple, low-cost, and feasible to offering personalized, tumor-directed precision FUS treatment, to improve drug delivery for pediatric patients with brain tumors.