Professor Brian Brown

Professor Brian BrownBrian Brown, as Professor of Medical Physics and Clinical Engineering at the University of Sheffield, UK has spent the past 20 years pioneering the use of Electrical Impedance Tomography (EIT) and Electrical Impedance Spectroscopy (EIS) as clinical tools. He is the academic founder of Zilico

How was EIT first developed?

We know that the human body conducts electricity pretty well and a key research area for me has been examining the electrical properties of tissue. Around 20 years ago, I began to develop a technique called electrical impedance tomography, where you place electrodes onto a part of the body and produce an image of the impedance distribution in that area.

Different organs have characteristic electrical impedances. For example, lung and muscle tissues have high impedance, whereas blood, that has a lot of extracellular fluid, has a relatively low impedance. Further research showed it was possible to predict the impedance of different tissues once you knew enough about their structure. Tissue impedances change with frequency and it is the impedance spectrum that is characteristic of a particular tissue. Electrical Impedance Spectroscopy (EIS) is the technique for making these measurements.

How did you come to realise the significance of EIS?

I started some discussions with Professor Frank Sharp, Dean of the Faculty of Medicine at the University of Sheffield, about how the structure of the cervical epithelium changes as cancer develops. I used some pathology slides showing these changes to do some crude modelling work to see what the impedance spectra might be in these different tissue samples. The models predicted large differences between normal and pre-malignant tissues.

This work led to a pilot study of about 100 women to find out if the modelling was accurate. Our colleagues in the workshop of the Royal Hallamshire Hospital, in Sheffield,UK,  helped us develop a device that we could use to carry out the tests and the results of the study were published in the Lancet in 2000.

How did this research start to move towards commercialisation?

I started working with John Tidy and his team of research clinicians and our research progressed to the point where it looked as if commercialisation could be a possibility. First, however, there were a number of improvements we wanted to make. We wanted to improve the performance and to work on making the tip of the device either disposable or sterile. We also wanted to make it more practical to use by developing a wireless version.

We were awarded funding through the UK NHS’s New and Emerging Applications of Technology (NEAT) scheme to develop these areas.  Medipex, the NHS Innovation Hub for Yorkshire and the Humber, then filed three patents in 2005. The NEAT project finished in 2006 and at that point Exomedica Ltd and Medipex, with the backing of the University of Sheffield, set up a company called Aperio Diagnostics, which later became Zilico Ltd, to move our device forward into the market place.

Have you made improvements to EIS?

Yes we have.  During the development of the device we realised that the conventional method of analysing the EIS data, using the well-established Cole Equations, could be improved upon by using the technique known as Finite Element Modeling (FEM) to produce mathematical models of the different tissue types found in the cervix.  FEM allows you to build up a model from the individual elements of a system, in this case the cells found in the cervical epithelium, and to take into account features such as the layering of different cell types and the presence of mucus to the surface.  The cervical epithelium and the changes that take place there are well understood so it is possible to develop models for normal and abnormal tissue types which can then allow you to calculate the EIS results that would be expected for each tissue type.  These model spectra are then used as templates against which the patient's own EIS results are compared to determine the likelihood that disease is present at each of the sites where a reading is taken.  This approach provides a more reliable assessment of the cervical tissue.

What do you see as the future for EIS?

My primary aim is to see the results of 20 years of research end in a pioneering device that can be adapted into general clinical use. We’re very confident of its ability in the colposcopy market and I think it has potential for general screening as well.

This technology does have potential for use in the diagnosis of other forms of cancer, particularly anal or oral cancer, where incidences are on the rise. Both these types of cancer are accessible for this type of testing and the particular kinds of cell arrangements involved are likely to give good results for EIS.