The blood-brain barrier (BBB) is a specialized vascular system that prevents the diffusion of agents larger than 400 Daltons into the brain. The BBB excludes not only bacteria and antibodies but many therapeutic agents as well. It has been demonstrated that focused ultrasound (FUS) increases the permeability of targeted sites in the BBB and that the use of precise microbubble concentrations, pulse lengths and pulse repetition frequencies can control the size of the opening. Current methods of employing FUS and microbubble technology involve expensive multi-element transducers and real-time magnetic resonance (MR) guidance. This technology outlines a method for calculating the orientation and position of a single element ultrasound transducer to target and open the BBB without the need for real-time MR.
Planning system enables low cost, non-invasive, simple method to open blood brain barrier
Using a brain atlas or previous MR scans, the optimal orientation and positioning of a single element ultrasound transducer can be determined, offering a less expensive alternative to current multi-element, MR guided techniques. Low frequencies (500-800 kHz) are used to ensure that skull aberrations are minimized to allow formation of a uniform focus. It is envisioned that this technology could ease the implementation of BBB opening for recurrent drug delivery in Alzheimer’s, Parkinson’s, and other central nervous system diseases.
The capability of this technology to induce a localized BBB opening at the center of a targeted region has been demonstrated on both primate and human skulls.
Lead Inventor:
Elisa E. Konofagou, Ph.D.
Applications:
- Recurrent drug delivery in Alzheimer’s, Parkinson’s and other central nervous system diseases.
- Localized delivery of toxic drugs to a tissue site of interest.
- Research tool for finely controlled membrane manipulation.
- High throughput drug screening in vivo.
Advantages:
- Minimally invasive due to transient creation of small BBB opening.
- Safe and quick relative to techniques such as cranial surgery.
- Non-toxic compared to drug-based methods for BBB disruption.
- Highly localized and cost-effective for access to specific regions of the brain.
- Enables single element transducer, MR guidance-free procedures.
Patent information:
Patent Pending (WO/2011/079177)
Tech Ventures Reference: IR 2687
Related Publications:
Y.S. Tung, F. Vlachos, J.J. Choi, T. Deffieux, K. Selert, E.E. Konofagou. In vivo transcranial cavitation threshold detection during ultrasound-induced blood-brain barrier opening in mice. Phys Med Biol, Vol. 55, Issue 20, Oct 2010, pp. 6141-55.
T.Deffieux, E.E.Konofagou. Numerical study of a simple transcranial focused ultrasound system applied to blood-brain barrier opening. IEEE Trans Ultrason Ferroelectr Freq Control, Vol. 57, Issue 12, Dec 2010, pp.2637-53.
B. Baseri, J.J. Choi, T. Deffieux, M. Samiotaki, Y, Tung, O, Olumolade, S.A. Small, B. Morrison, E.E.Konofagou. Activation of signaling pathways following localized delivery of systemically-administered neurotrophic factors across the blood-brain barrier using focused ultrasound and
microbubbles. Phys Med Biol, Vol. 57, Issue 7, April 2012, pp. N65-N81.
