Metabolic profiling of tissue samples could transform the way surgeons make decisions in the operating theatre, say researchers at a new laboratory. Scientists at Imperial College London, in partnership with clinicians at Imperial College Healthcare NHS Trust, have installed a high resolution solid state nuclear magnetic resonance (NMR) spectrometer in St Mary’s Hospital. Researchers will use the machine to analyse intact tissue samples from patients taking part in studies, to investigate whether it can ultimately give surgeons detailed diagnostic information while their patients are under the knife.
The Surgical Metabonomics Laboratory will be led by the surgical innovator Professor Lord Ara Darzi and Professor Jeremy Nicholson, a leading researcher in biomolecular medicine and Head of the Department of Surgery and Cancer.
The science of metabonomics, which involves comprehensively measuring the metabolic changes in a person’s body, has been pioneered by the Imperial team over the last 20 years. Techniques from analytical chemistry, such as NMR spectroscopy and mass spectrometry, can allow researchers to measure simultaneously all of the chemicals produced by the body’s metabolism. With knowledge of which molecules correspond to which conditions in the body, this “metabolic fingerprint” can provide a wealth of information about the state of a person’s health.
Metabonomics has previously been applied to samples of bodily fluids such as blood and urine to look for indicators of disease or of how a person might respond to a particular drug. Now the Imperial team have acquired an NMR spectrometer—the first to be installed in a hospital setting—that will analyse solid tissue samples from patients undergoing surgery with Imperial College Healthcare.
The research projects are funded by Imperial’s Comprehensive Biomedical Research Centre. Imperial’s is one of five Comprehensive Biomedical Research Centres in the UK; it was awarded to Imperial College Healthcare NHS Trust by the National Institute for Health Research following a national competition. The new laboratory forms part of the Academic Health Science Centre, a unique partnership between the Trust and Imperial College London, which aims to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies as quickly as possible.
Professor Darzi, Chairman of the Institute of Global Health Innovation at Imperial College London and an Honorary Consultant Surgeon with Imperial College Healthcare NHS Trust, said: “People respond differently to the physical trauma of surgery, but currently the tools we have to measure how they respond are very limited. Blood tests are slow and they can only measure one chemical component at a time; the doctor simply looks at whether a particular measure has gone up or down. Using NMR, we can simultaneously measure all of the chemicals that the body is producing, and analyse those data to give the surgeon real-time information about the patient’s condition which will help him make decisions.”
Surgeons will be able to take tissue samples and have them loaded straight into the NMR machine without the need to prepare them. The research team think it will be possible to give the surgeon a readily interpretable readout from the analysis within 20 minutes, which would provide information such as whether the tissue is infected or how good its blood supply is. Surgeons might also use the technology to determine exactly which areas of tissue are cancerous.
One project that the team will undertake at the new laboratory is to develop an “intelligent knife”. Surgeons commonly use a technique called electrocautery in operations to seal blood vessels by burning them with a hot iron. By sucking up the smoke produced in this procedure into a mass spectrometer, researchers believe they will be able to tell the surgeon whether the tissue they are burning is healthy, cancerous or infected.
Professor Nicholson, Head of the Department of Surgery and Cancer at Imperial College London, said: “This is a radical change of approach that doesn’t just apply to surgery. We want to be able to provide a metabolic map of the entire patient journey. Before surgery, metabonomics could tell the doctor how risky surgery might be for that patient, or how best to prepare him for surgery. After the operation, metabonomics might help the doctor to monitor the patient's recovery and prescribe the most suitable drugs or diet. Ultimately we hope to apply this approach to every area of medicine.”
“It’s no small task. The analytical chemistry and mathematical modelling involved are challenging, and not everything we try will work. But we hope that within two to three years, we'll have robust evidence that metabolic profiling can be a really useful tool in surgery.”
Dr James Kinross, a Clinical Lecturer in the Division of Surgery at Imperial College London, said: “People have been talking about personalised medicine for many years now, but so far there have been few meaningful steps towards delivering on that promise. Genome sequencing is currently quite slow and expensive, and it can only tell you so much. Metabonomics takes into account not only what genes somebody has, but also all of the environmental factors that influence their biology, such as their diet, what drugs they're taking, and what bacteria they have in their body.”
“Because of the world class expertise we have here and the close links between surgeons and biomolecular scientists, Imperial is uniquely placed to be able to make major advances in this field. Almost no other institution is in a position to take on the challenges involved.”
To help realise the vision of the new centre to enhance surgical safety and patient care, Imperial has partnered with Bruker BioSpin and Waters, who will help to develop, optimise and implement NMR and mass spectrometric technologies for real time diagnostics and prognostic modelling.
“By combining bioinformatics and surgical expertise with advanced mass spectrometry technology, Imperial College London is setting a powerful vision for innovative new techniques in the operating room,” said Rohit Khanna PhD, Vice President of Worldwide Marketing for Waters. “At Waters, our success is based upon the ability and imagination of scientists to apply advances in analytical technology to solve their most difficult challenges. Bringing metabolic profiling to the surgical suite is a great example of how a disruptive innovation can potentially improve patient care with a radical new approach. On behalf of all Waters employees, we congratulate Imperial on the launch of the Surgical Metabonomics Laboratory. We look forward to working together on tomorrow’s innovations.”