Focused ultrasound induced-blood-brain barrier opening in mouse brain receiving radiosurgery dose of radiation enhances local delivery of systemic therapy

聚焦超声诱导小鼠脑血脑屏障开放,从而增强接受放射外科手术剂量辐射的小鼠脑组织对全身治疗的局部吸收。

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Abstract

OBJECTIVE: Investigate the temporal effects of focused ultrasound (FUS)-induced blood-brain barrier (BBB) opening in post-radiotherapy mouse brains. METHODS AND MATERIALS: C57B6 mice without tumors were used to simulate the scenario after gross total resection (GTR) of brain tumor. Radiation dose of 6 Gy x 5 was delivered to one-hemisphere of the mouse brain. FUS-induced BBB-opening was delivered to the irradiated and non-irradiated brain and was confirmed with MRI. Dynamic MRI was performed to evaluate blood vessel permeability. Two time points were selected: acute (2 days after radiation) and chronic (31 days after radiation). RESULTS: BBB opening was achieved after FUS in the irradiated field as compared to the contralateral non-irradiated brain without any decrease in permeability. In the acute group, a trend for higher gadolinium concentration was observed in radiated field. CONCLUSION: Localized BBB-opening can be successfully achieved without loss of efficacy by FUS as early as 2 days after radiotherapy. ADVANCES IN KNOWLEDGE: Adjuvant radiation after GTR is commonly used for brain tumors. Focused ultrasound facilitated BBB-opening can be achieved without loss of efficacy in the post-irradiated brain as early as 2 days after radiation therapy. This allows for further studies on early application of FUS-mediated BBB-opening.

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