In the hope of helping oncologists remove every piece of tumor tissue during surgery, researchers are developing new imaging tools that work in real time in the operating room. European researchers have now demonstrated that a chemical analysis instrument called a mass spectrometer can be coupled with an electroscalpel to create a molecular profile of tissue during surgery. The researchers have shown that the method can be used to map out different tissue types and distinguish cancerous tissue. The device will begin clinical trials next month.
“When a surgeon is performing cancer surgery, he doesn’t have any direct information on where the tumor is,” says Zoltán Takáts, a professor at Justus-Liebig University in Giessen, Germany. Instead, surgeons rely on preoperative imaging scans and on feedback from pathologists examining tissue biopsies under a microscope. “We want to provide a tool that’s right in their hands, so that if they think a structure looks suspicious, they can just test it,” says Takáts.
Mass spectrometry, a very precise method for identifying molecules by analyzing the ratio between their mass and charge, is already being used by a handful of research groups to study biological samples. Researchers have known for many years that tumor tissue and healthy tissue have different molecular profiles and that this can be used to tell them apart, or even to determine how aggressive a particular tumor is. Other research groups have used mass spectrometry to analyze biopsied tissue and have shown that it can make these differentiations. The problem with using mass spectrometry in the operating room is sample collection. Before molecules can be analyzed, they have to be ionized and sucked up into the machine. Creating ions requires bombarding a sample with a stream of charged particles, often a gas, and these methods aren’t suitable for the operating room. “A high-voltage nitrogen jet is not compatible with the human body,” says Takáts.
Takáts realized that some surgical cutting tools, including electroscalpels, produce gaseous ions as a kind of waste product that are suitable for analysis with mass spectrometry. And these fumes, often called “surgical smoke,” are already collected during surgery because they’re harmful to the lungs. Takáts and his collaborators found that mass spectrometry of surgical smoke can be used to make a molecular map of a tumor. After the fumes are sucked into the mass spectrometer, the chemicals in the sample are identified and checked against a database to give the surgeon a readout. Gathering and analyzing a chemical sample takes a few hundred milliseconds. “We can draw a map and say this part is healthy liver, that is connective tissue, this is adipose tissue, that is cancer,” says Takáts.
“This work represents a milestone in the application of mass spectrometry to medicine,” says R. Graham Cooks, a professor of chemistry at Purdue University who was not involved with the research.
Mass spectrometry is just one of many imaging techniques being evaluated for use during surgery. Another approach is to inject a patient with fluorescent dyes that bind to tumor molecules and are visible under infrared light. But mass spectrometry can provide more comprehensive information about tissues’ molecular profiles. The new system not only provides real-time information, but also produces an image of the tumor, using chemical information, which could also help guide postoperative care. The imager could, for example, reveal a particularly aggressive form of cancer, and this information could guide oncologists in prescribing the right drug.
Cooks is developing a different type of mass-spectrometry system for tissue analysis. His system, called DESI, requires spraying a mist of charged particles onto the tissue, but it can analyze a wider range of molecules and might provide more detailed information. Takáts’s technique mostly samples the fatty molecules called lipids that make up cell membranes.
So far, the German researchers have tested the surgical mass-spectrometry system in several animals, including rodents, with cancer. The group is also working with veterinarians to use the scalpel during tumor-removal surgeries in dogs with naturally occurring tumors. Next month the device will go into human clinical trials, and Takáts is working with Meyer-Haake, a German electrosurgical device company, to develop the machinery.
The most important remaining hurdle to getting mass spectrometry into the operating room may be the expense. An electrosurgery system typically costs $8,000, while a commercial mass-spectrometry system starts at $120,000. Takáts notes that the market for mass spectrometry is currently very small, but opening up the surgical market may help bring costs down. By using instruments tailored to the kind of analysis relevant to biological tissue, which doesn’t need to be as high-performance as that in chemistry labs, Takáts hopes to make a machine that costs about $20,000.
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