Professor Nick Stone
Chair of biomedical imaging and bio sensing, University of Exeter
Honorary NHS consultant clinical scientist
Nick started the talk with a brief description of his early work as a sandwich student designing a novel probe for radiofrequency ablation to treat uterine bleeding. He then concentrated on optical frequencies as diagnostic and potential therapeutic tools.
The clinical need for better diagnosis and treatment is clear, he told us; one in two of us currently will get cancer, and one in three will die from it. There is a strong incentive to improve early diagnosis, but it is not always clear how we select and apply appropriate treatments, and we always have to ask who actually does need treatment.
Nick introduced us gently to optical diagnosis: at the simplest level we recognise that the yellowing of skin is associated with jaundice and the blue of cyanosis with a shortage of oxygen. At a slightly more sophisticated level, pulse oximeters use differential absorption between two adjacent red wavelengths to determine blood oxygenation. The science then stepped up a little, with a simple description of Raman spectroscopy. This technique relies on inelastic scattering of light from atoms and molecules: the molecule absorbs a little of the incident light energy, which means that what is scattered is a slightly lower energy and therefore slightly shifted in wavelength. This wavelength shift is extremely sensitive to the physical and chemical environment of the atom or molecule, and provides a way to use light to interrogate that atom or molecule and get it to tell us something about its environment. In particular, small changes in the Raman fingerprint can be seen when tissue is diseased or in some other way pathological. These wavelength shifts are very small and the techniques used to determine them can be quite sophisticated. Raman spectroscopy is rapid, safe, non-destructive and reproducible across different systems, patients, centres and users. It can match or exceed the analytical performance of independent pathologists. Whilst most biomedical analyses are laboratory based, and Raman spectroscopy certainly has its place there, perhaps its greatest strength is its applicability to immediate patient assessment. The aim has been to develop tools which allow medical practitioners to make immediate on-the-spot diagnoses.
Raman spectroscopy has other advantages. Nick illustrated this with reference to a condition known as Barrett’s Oesophagus, in which changes to the wall of the oesophagus increase cancer risk by up to 125 times. Conventionally, diagnosis is done via biopsy but for obvious reasons the number of biopsy samples cannot be infinite, and the areas affected can be quite small, meaning there is a reasonable chance that affected cells may be missed. Raman spectroscopy allows large areas of the oesophagus wall to be scanned in real time. Biopsies generate a lot of false negative tests, particularly when used in routine screening, which represents a significant burden on histology laboratories. Nick informed us at this point that trained pigeons performed at least as well as pathologists in recognising diseased tissues; the problem comes down to pattern recognition rather than expertise. It also can be difficult for humans to make a clear decision on unclear data against a background of unnecessary treatment risk, versus leaving intervention too late. Algorithms based on physical measurement can remove this human uncertainty.
One important concept in cancer biopsy is surgical targeting or margin. A suitable sample must include enough, but not too much, of the surrounding healthy tissue. If this is done even slightly incorrectly another biopsy would be needed. Tumour boundaries can be hard to identify by eye under surgical conditions, but because tumour tissue is highly vascularised it has a higher water content than normal tissue and easily can be differentiated in real time using Raman spectroscopy.
Raman spectroscopy is also can be used to check the sentinel lymph node after cancer surgery to assess the presence of any metastases, although this is used less now because sentinel node excision at the time of surgery is no longer usual: biopsies are taken and post surgery radiotherapy is used if necessary.
Nick ended his talk with a project under development. The Raman interaction is via only about one in a million of the target atoms or molecules, but gold nanoparticles can increase this by several orders of magnitude. A promising new technique uses monoclonal antibodies to attach gold nanoparticles to specific tumours; Raman spectroscopy is used to identify and interrogate the tumour sites in real time; a high-powered laser can be targeted on the tumour from outside the body, and via the gold nanoparticle/light interactions the tumour is destroyed by heating. The thermal environment of the tumour is interrogated in real time using spectroscopy so that therapy can be precisely calibrated. The gold is safely excreted after the tumour is destroyed.
Phil Chadwick
