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

Br J Radiol. 2020 May 1;93(1109):20190214. doi: 10.1259/bjr.20190214. Epub 2020 Feb 5.

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.

MeSH terms

  • Animals
  • Blood-Brain Barrier / radiation effects*
  • Brain / blood supply
  • Magnetic Resonance Angiography
  • Male
  • Mice, Inbred C57BL
  • Permeability
  • Phantoms, Imaging
  • Radiation Dosage
  • Radiosurgery*
  • Ultrasonic Therapy / methods*