The structures in the centre of the brain (often referred to as the deep grey matter structures) are vitally important to our ability to perform everyday tasks. This includes processing and passing on information from our senses, regulating consciousness and sleep, and the control of voluntary movement and coordination. Abnormalities in the deep grey matter structures can lead to a wide range of neurological disorders. Some examples are Parkinson's disease, Huntington's disease, chronic pain, and essential tremor. These disorders are extremely debilitating, and have a significant impact on quality of life for patients and their carers. Neurological conditions are also very common, and form the largest single cause of morbidity in the EU in terms of disability adjusted life years. In the UK alone, approximately 10 million people are affected, with 350,000 needing some form of full time care.
Currently, most neurological disorders are treated by the prescription of drugs that cause alterations in brain function. These drugs act on the structures that transmit electrical and chemical signals in the brain. For many patients, this causes a reduction in their symptoms. However, long-term treatment is often not very effective, and there can be many side-effects. For some patients with advanced or drug-resistant disorders, a surgical procedure known as deep brain stimulation may also be offered. This involves putting a small wire into the brain via holes drilled through the skull. This can be very effective, but is highly invasive, and only available to a small number of patients.
An exciting alternative to drugs and surgery is brain stimulation using ultrasound. Ultrasound is well known as a diagnostic imaging tool, particularly during pregnancy. In recent years, a growing number of therapeutic applications of ultrasound have also been demonstrated, including for stimulating the brain. This is possible because the mechanical vibrations caused by ultrasound waves can generate internal forces that act on the brain cells. Depending on the pattern of the ultrasound pulses, this can cause the generation or suppression of electrical signals in the brain, which in turn can be used to restore normal brain function. However, until now, ultrasound brain stimulation has only been demonstrated on small animals and in superficial areas of the human brain.
The aim of this proposal is to develop a new type of ultrasound device to deliver ultrasound waves non-invasively into the deep grey matter structures of the brain to treat neurological disorders. The device will contain hundreds of individual ultrasound transmitters distributed in a ring array positioned on the patient's head. The arrangement of the transmitters will be optimised to ensure ultrasound can be focused into the deep brain without affecting other areas of brain circuitry. The ultrasound device will be coupled with a computer planning system that uses a detailed mathematical model of how ultrasound waves propagate through the skull and brain. This will be used to position the ultrasound beam precisely based on images of the patient's anatomy. After development, the system will be rigorously tested in the laboratory using 3D printed skull phantoms, before being tested on adult human volunteers.
Success in this project will be a major breakthrough in the treatment of neurological disorders. The developed system will be completely non-invasive, and allow the stimulation, suppression, and modulation of the neural circuitry in deep grey matter structures with unprecedented accuracy and flexibility. This will ultimately improve our understanding of deep brain function and associated neurodegenerative diseases, as well as underpin the development of ground-breaking new clinical treatments. The low-cost and scalable nature of the technology also means it could be widely deployed, greatly increasing the number of patients that have access to non-pharmacological treatments.
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