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Title: “Phase shift nanoemulsions facilitated transcranial high intensity focused ultrasound ablation”
Committee:
Tyrone Porter, PhD – BU ME, BME (Research Co-Advisor)
Nathan McDannold, PhD – BWH Radiology (Research Co-Advisor)
Joyce Wong, PhD – BU BME (Chair)
David Boas, PhD – BU BME
Glynn Holt, PhD – BU ME
Abstract:
Glioblastoma (GBM) is one of the most devastating tumor type and 5-year survival is a disheartening 5%. Surgery is the most crucial part of the standard of care of GBM and there is a strong correlation between the extent of tumor removal and the length of survival. However, due to the invasiveness of brain surgery, only ~24% of the recurrent patients decide to do a second surgery. This creates a huge unmet medical need for a less invasive or noninvasive alternative to debulk brain tumors. Therefore, in this thesis, the feasibility of using PFB PSNE, a novel ultrasound activable contrast agent, to facilitate focused ultrasound transcranial noninvasive ablation of GBM was tested.
PFB PSNE is an emerging cavitation nucleus that can be acoustically vaporized at much lower acoustic pressure compared to its predecessors (PFP and PFH PSNE). Because of the lower vaporization threshold, PFB PSNE is a more appropriate cavitation nucleus for transcranial application due to the presence of the skull. In our results, PFB PSNE can be activated at 1.5-2.5 MPa which is readily achievable for clinical focused ultrasound system. Compared with commercial ultrasound contrast agents, PFB PSNE is shown to increase the focusing and localization of this ablation therapy. PFB PSNE-facilitated ablation also demonstrated a higher short-term efficacy against GBM indicated with a higher percentage of tumor death after ablation (89.4% vs 11.1% for PFB PSNE and MBs). PFB PSNE-facilitated ablation also prolonged the survival of glioma rats with an increase of median survival (27 vs 25 days) and overall survival (12.5% vs 0%) in 32 days. These results suggested that PFB PSNE-facilitated ablation is a promising alternative to facilitate the brain tumor ablation with an improved localization.
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