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Imperial College, Waters, Bruker, Developing Real-Time Metabolic Profiling of Surgical Patients


By Adam Bonislawski

Researchers at Imperial College London are partnering with Waters and Bruker Biospin on a Surgical Metabonomics Laboratory designed to provide surgeons with real-time patient information.

The laboratory, part of a broad effort led by Imperial College professor and surgeon Ara Darzi and Jeremy Nicholson, head of the college's Department of Surgery and Cancer, is being developed to have a patient's metabonomic data available to the surgeon throughout the procedure.

The expectation is that such data will help surgeons make better decisions regarding, for instance, what tissue to resect when operating on diseases such as cancer.

The initiative aims to take metabonomics techniques "that have been developed for experimental purposes and implement them in a way that will benefit patient care," Nicholson told ProteoMonitor. "I'm a professor of chemistry, but for the last year and a half I've been in charge of the Department of Surgery and Cancer, and part of my role is to ensure proper translational medicine."

To that end, Nicholson and his colleagues have begun moving metabonomics research instruments out of the lab and into the clinic. The project, he said, marks one of the first efforts to broadly integrate such tools into a point-of-care environment.

Earlier this month, the college installed a Bruker Biospin high-resolution solid-state nuclear magnetic resonance machine, allowing doctors at its St. Mary's Hospital to analyze patient tissue samples for real-time diagnostic information during operations.

In addition, the college is currently working with Waters to identify in-surgery applications for its MALDI-TOF mass spec.

Nicholson said he hopes the lab will enable doctors to make better decisions regarding what tissue to leave and what to remove during surgery for conditions like cancer or intestinal infarctions.

In the case of "an infarcted gut, literally what the surgeon does is looks at how blue it is, cuts out the blue bits, and then joins the rest together," he said. "If they make a mistake on that, the ligature in the sutures will break down in about 24 hours and [the patient] will have to go back into the operating theater and they may die. So if we could take some chemical information from a piece of tissue and say, 'This is viable or this is non-viable,' we might be able to improve the decision making about how much to cut."

By the end of 2011, Nicholson said, the team hopes to have in use what he calls an "intelligent knife," a device that would capture and rapidly analyze the smoke and vapor generated by surgical lasers and ultrasound knives via NMR and mass spec to determine if the cells being cut are healthy or not.

"The smoke [from the cauterized tissue] carries a chemical signature that in principle can tell you what you're cutting through," he said. "So if we process the data fast enough it would be possible to give feedback on what the surgeon was cutting through. We're doing a work-up right now on what's the optimal knife temperature, what's the optimal type of knife, what's the optimal type of mass spectrometry, before we put it in the operating theater itself."

Surgeons could use the device as a probe for testing areas of tissue that they aren't certain are viable with, perhaps, a simple traffic light-style readout telling them to either cut or not cut, Nicholson said.

Such profiling systems could by and large use existing mass spec and NMR instrumentation, said Waters vice president of worldwide marketing Rohit Khanna, who has been working with Nicholson on the project. The primary challenge in terms of technology development is building software to integrate mass spec and NMR data in a useful way, he said.

"The development that really needs to be done is from a software perspective to enhance having the NMR and mass-spec [data] together," he told ProteoMonitor. "You can profile by NMR and you can profile by mass spec, but you're going to have more knowledge of the metabolic profile if we can put all that together. So we're working with Imperial and Bruker to see if we can pull that together and better display that information from the two technologies for the surgeons."

The Imperial College researchers are currently building databases of metabolic information that physicians will use in making surgical decisions, Nicholson said, concentrating on areas like cancer and intestinal infarction, where there is the most "unmet medical need."

In addition to developing tools to provide real-time metabonomic information during surgery, the college this year plans to begin monitoring patients' metabonomic profiles throughout their entire hospital stay in hopes of improving outcomes.

"Patients come in for an operation and there will be a work-up to characterize them," Nicholson said. "Then they go on the operating table where we apply these technologies. Then they come out, and they could come out very well or they might come out septic. Then they might end up in intensive care.

"So one of the things we're trying to do is model people through that journey and use [metabonomic] diagnostics to feed back information to clinicians at a regular rate to monitor if a patient is getting better or worse and to predict what their outcome might be," he added.

In particular, such data would be useful in critical-care units, he added, noting that currently around 30 percent of patients that enter critical care end up dying.

"You've got a very high morbidity rate of patients in critical care, and they're also changing very quickly," he said. "Somebody may go into intensive care with one particular problem, but because they're very ill you get systemic failure and sequential organ shutdown.

"When it's multiple organ failure a person has a very good chance of dying, so anything you can do to understand the collapse of the system and feed that back to the doctor so they can make an intervention a little bit earlier will really help save lives," he added.

In the next year, each of the three critical care units under his purview will receive either an NMR or mass-spec machine for metabolic profiling, Nicholson said.

"If we can do the right thing and save lives, especially in critical care, that will be an exciting and important contribution," he said. "The big picture is trying to make systems medicine real rather than just something people write about in Nature. Nothing is wrong with writing about it in Nature … but making it happen is another order of magnitude."

Have topics you'd like to see covered in ProteoMonitor? Contact the editor at abonislawski [at] genomeweb [.] com.

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