Introduction: Ultrasound nonthermal ablation is an emerging noninvasive technique to perform functional neurosurgery. To achieve enough cavitation for ablation purpose, microbubbles (MBs) are introduced through intravenous injection which could enhance ultrasound energy deposition. However, MBs are existed systemically after injection and could prevent the ultrasound wave to reach the focus. This would result in unwanted pre-focal damage at eloquent brain regions like cortex. We proposed to use an ultrasound activatable agent – perfluorobutane phase shift nanoemulsions (PFB PSNE) that would only be activated at the focus of ultrasound and thus prevent pre-focal damage. Materials and Methods: The PFB PSNE were synthesized by compressing (~45 psi) the MBs under dry ice bath (-10~-15 oC). Sonications were performed using two high intensity focused ultrasound (HIFU) transducers operating at 837 kHz. In each sonication, we started with a ramping pressure pulses (pressure ranging from 0.9 to 2.1 MPa) to determine the cavitation threshold. The peak negative pressures were fixed at the determined threshold (~2.1 MPa for PSNE and ~0.8 MPa for MBs) to sonicate for another 90 seconds. Two rats were sonicated with PFB PSNE and the other two served as control. The tumors were sonicated 8 days after the implantation and animals were sacrificed at day 13 to harvest the brains. The tumor growth was evaluated with magnetic resonance imaging (MRI) and hematoxylin and eosin stain and the result indicated localized microhemorrhage at targeted region Results and Discussion: The PFB PSNE facilitated ablation generated a well-defined round-shape lesion at targeted area that was more compact than MBs facilitated ablation. After 3D reconstruction from stack of 2D images , it appeared that the lesion from PSNE group was more localized than MBs group (3x3x4 mm of PFB PSNE VS 5x9x7 mm for MBs). On contrary, MBs group showed apparent damages in the cortex region (Figure 1D). Interestingly, the damage of PFB PSNE ablation appears to be much more significant in tumors than in healthy rats which indicates an enhanced tumor killing capability.

Perfluorobutane nanoemulsions facilitated transcranial ablation

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.