[2020; already taken] Stent with ultrasound transmitters for high spatial resolution brain stimulation and opening of the blood brain barrier

For the past decades, neuronal electrophysiology have helped neuroscientists to study and decode the neural circuits in the brain. Traditional electrophysiology devices consist on electrodes implanted in the brain region under study, which are used to stimulate and record neuronal activity. When translating these devices from neuroscience into clinical applications, one of the main hurdles is the fact that implanting electrical devices in the brain requires risky and expensive surgery, which may cause brain lesions during insertion, inflammation and even rejection of the implant. These drawbacks become even more limitative when targeting deep regions in the brain. Therefore, there is a need to provide high-resolution interfaces with the brain, both at the surface and in depth, while being minimally invasive to avoid the risks of surgically implanted devices.

A non-invasive alternative method to interface with brain circuits consists on using low intensity focused ultrasound (LIFU) [1]. It uses ultrasound energy levels below thermal ablation, thus providing a targeted and safe way of stimulating neurons without requiring surgery. However, the limitation of this technology is the need to transmit ultrasound waves through the skull, which has a very high absorption coefficient, thus only sub-MHz ultrasound waves can go through the skull while still providing high enough energy at the focal spot to stimulate neurons. Since sub-MHz ultrasound waves have wavelengths in the millimeter range, this leads to a poor spatial resolution when compared with implantable electrodes.

The aim of this project is to develop an ultrasound transmitter system integrated in a stent to use the brain vasculature as a path to bypass the skull and delivery high frequency (MHz range) ultrasound waves to the brain. Insertion of stents in the vasculature has been a common practice for several years, typically to restore normal blood flow in narrowed arteries, and is minimally invasive, only requiring percutaneous insertion. Several veins the brain have diameters of several millimeters, such has the superior sagittal sinus, thus representing good candidates for stent insertion with ultrasound transmitters. By bypassing the skull, ultrasound waves can be transmitted with frequencies of several MHz, potentially increasing the spatial resolution from existing ultrasound stimulators by one order of magnitude, and with much higher depth of stimulation than existing stents with electrode-based stimulators [2]. This technology can be used not only for brain stimulation, but also for selective opening of the blood brain barrier for drug delivery in the brain [3].

References:

1. Tufail, Y. et al. Transcranial pulsed ultrasound stimulates intact brain circuits. Neuron 66, 681–94 (2010).

2. Oxley, T. J. et al. Minimally invasive endovascular stent-electrode array for high-fidelity, chronic recordings of cortical neural activity. Nat. Biotechnol. 34, 320–327 (2016).

3. Madsen, S. J. & Hirschberg, H. Site-specific opening of the blood-brain barrier. J. Biophotonics 3, 356–367 (2010).

Assignment

1st part: Literature review of stents ultrasound interfaces with the brain, for both stimulation and opening of blood brain barrier:

1. What ultrasound pressure levels are required?

2. What is duration of sonication and pulse repetition frequency?

3. What transducer materials and configurations are typically used?

4. What type of stent materials are preferred?

Finite element analysis and ultrasound propagation simulations might be required to help answer this questions.

2nd part: Implementation of the ultrasonic stent prototype according with the specifications derived in the 1st part. This will involve fabrication of both the stent and the ultrasound transmitters, which can also consist on modifying commercially available solutions. A simple printed circuit board might be required to control the transmitters. Characterization of the prototype will require the fabrication of an ultrasound test phantom to mimic both the stent insertion and to monitor the transmitted ultrasound waves.

At the end of the project, the student should have a bench-top validated prototype with performance compatible with both neuronal stimulation and opening of the blood brain barrier. Depending on the performance metrics, this work could lead to conference paper submissions.

Contact

dr. Tiago Costa

Bioelectronics Group

Department of Microelectronics

Last modified: 2021-02-10