Improved Healing by combining Optical and Electrical Stimulation of Nerves (HOpES)

Electrical nerve stimulation is increasingly being considered over the last few years for the treatment of otherwise untreatable neurogenic medical conditions. An example is the stimulation of the Vagus nerve, one of the longest nerves, that connects the brain to some of the most vital organs including the heart, the lungs and the gut. Vagus nerve stimulation (VNS) is effected with approved implanted devices using electrodes at the neck to apply electrical pulses which activate nerve fibres that connect to the brain. VNS has proved very beneficial for addressing conditions like treatment-resistant epilepsy, depression and several more.
The use of nerve implants is not yet widespread, mainly because in their present form they are not sufficiently selective, in particular in the direction of the induced nervous signal. For example, VNS aims at stimulating nerve signals which should propagate towards the Vagus roots in the brain in order to affect structures involved in seizures. The induced nerve signals propagate, however, also in the opposite direction, thus affecting critical organs like the larynx, the lungs and the heart and often cause unwanted voice hoarseness and pain.
The inability of neurostimulation to selectively stimulate targets towards only one end of a nerve while leaving the other end unaffected is one of the main reasons why the method is not being more widely used, despite its vast potential in a great number of medical applications. It is therefore desirable to achieve a directionally selective, or "unidirectional", neurostimulation method.
Several studies have attempted to achieve unidirectionality through different stimulation waveforms or electrode topologies, however these methods have had limited success. An alternative approach, based on relevant published research including a pilot study published recently by the applicant and his co-researchers is to combine electrical with optical stimuli in order to improve the selectivity (or specificity) of the resulting therapeutic effect. The aforementioned research did not address directionally selective stimulation.
The proposed project aims at improving neurostimulation as a therapeutic method by making its effects unidirectional, i.e. allowing the therapeutic effect to be directed solely towards the central nervous system or solely towards the periphery but not towards both of them. Future application of the proposed methodology in VNS and other implantable stimulators will ultimately endow them with much more targeted therapeutic capabilities with minimal side-effects and render them suitable for mainstream healthcare practice.
This project will build on the results of the pilot study mentioned above by using nerve tissue spectrophotometry to accurately measure relevant optical properties of the tissue layers of a nerve and then use them as input for in-depth simulations of light-tissue interactions. The effect of different light wavelengths and intensities and other optical parameters of the tissue itself will be examined in the simulation in order to estimate the optimum optical stimulus parameters. Finally, using the simulation outcome, in-vitro measurements on amphibian nerves will be carried out in order to determine the degree of directional selectivity as a function of the combinations of electrical and optical stimuli applied. The effectiveness of the method will be assessed by two neural recording electrodes on either side of the optical and electrical stimulation site.

The impact of the proposed research will ultimately be achieved when the method developed is eventually incorporated in a prototype device, preferably miniaturised and implantable. It can then be used by:

- The Biomedical Technology Industry, to form a basis for new therapeutic neuroprosthetic devices. With the neuroprosthetics industry market expected to reach approximately $15 Billion by 2020, it is very timely to sell or license any intellectual property stemming from this project to established biomedical technology companies like Medtronics, Cyberonics or GE Healthcare.

- Pharmaceutical Companies, in conjunction with medicinal therapies either for increased effectiveness (as is the case with several current applications) or to minimise drug side effects. Moreover, such companies will have a direct interest in a potential prototype stemming from this research as they are lately increasing their direct involvement in the development of neuroprosthetics, dubbed "electronic medicine" or "electroceuticals". Such companies will also have the facilities to carry out clinical trials and to obtain ethical approval for such a product.

- The National Health System (NHS) will potentially adopt the resulting therapeutic devices and develop policies and procedures to adopt their various embodiments in clinical practice. The NHS will benefit from more effective therapies with reduced side-effects and thus will provide better service and potentially tackle new medical conditions. Implantable devices will offer chronic therapy with less or no dependence on drugs and their eventual mass production will offer substantial financial benefits.

- The Patients, who will see significant improvements in their health and their quality of life. Through the use of potential outcomes of this research in the devices and practices mentioned above, they will receive better, efficient and personalised therapy, with reduced side-effects. Long term implantable devices will also reduce the need for frequent hospital visits, making the therapy less disruptive and in some cases minimising social stigma and the associated psychological impacts.

Following intellectual property protection through City University, publications in biomedical engineering conferences will disseminate the knowledge to the companies mentioned above. A workshop will be organised at the end of the project which will include seminars for clinicians.