Non-invasive Blood-Brain Barrier Disruption using Acoustic Holography with a Clinical Focused Ultrasound System

Non-invasive Blood-Brain Barrier Disruption using Acoustic Holography with a Clinical Focused Ultrasound System

Non-invasive Blood-Brain Barrier Disruption using Acoustic Holography with a Clinical Focused Ultrasound System 789 444 IEEE Transactions on Biomedical Engineering (TBME)
Author(s): Nathan McDannold, Yongzhi Zhang, Stecia-Marie Fletcher, Patrick Y. Wen, David A. Reardon, Alexandra J. Golby, and Margaret Livingstone

Holographic methods can be used with phased array transducers to shape an ultrasound field. We tested a simple method to create holograms with a hemispherical 1024-element phased array transducer tested clinically to enhance drug delivery via blood-brain barrier (BBB) disruption.

With this method, we loaded 1024 individual acoustic simulations for each element of the transducer into computer memory. We systematically modulated each element’s phase until the combined field matched a desired pattern. We evaluated the holograms with MR temperature imaging in a tissue-mimicking phantom and in vivo in experiments disrupting the BBB in rats and in a macaque. The results suggest that this approach can tailor the focal volume in a patient-specific manner and could reduce the number of sonication targets needed to disrupt large volumes, improve the homogeneity of the disruption, and improve our ability to detect microbubble activity in tissues with low vascular density.

We also explored whether this approach could improve focusing in clinical treatments with this device. We simulated transcranial focusing in patients where we disrupted the BBB to enhance chemotherapy delivery. The results suggest that this holographic method could mitigate secondary reflections during transcranial sonication when the focus was close to the skull.

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