Rapid evaporative Ionization mass spectrometry (REIMS) is an emerging technique that allows near–real-time characterization of human tissue in vivo by analysis of the aerosol (“smoke”) released during electrosurgical dissection. The coupling of REIMS technology with electrosurgery for tissue diagnostics is known as the intelligent knife (iKnife). This study aimed to validate the technique by applying it to the analysis of fresh human tissue samples ex vivo and to demonstrate the translation to real-time use in vivo in a surgical environment. A variety of tissue samples from 302 patients were analyzed in the laboratory, resulting in 1624 cancerous and 1309 noncancerous database entries. The technology was then transferred to the operating theater, where the device was coupled to existing electrosurgical equipment to collect data during a total of 81 resections. Mass spectrometric data were analyzed using multivariate statistical methods, including principal components analysis (PCA) and linear discriminant analysis (LDA), and a spectral identification algorithm using a similar approach was implemented. The REIMS approach differentiated accurately between distinct histological and histopathological tissue types, with malignant tissues yielding chemical characteristics specific to their histopathological subtypes. Tissue identification via intraoperative REIMS matched the postoperative histological diagnosis in 100% (all 81) of the cases studied. The mass spectra reflected lipidomic profiles that varied between distinct histological tumor types and also between primary and metastatic tumors. Thus, in addition to real-time diagnostic information, the spectra provided additional information on divergent tumor biochemistry that may have mechanistic importance in cancer.
Key words: Rapid evaporative ionization mass spectrometry (REIMS), electrosurgery, principal components analysis (PCA), linear discriminant analysis (LDA), histopathological tissue
In the first study to test the invention in the operating theatre, the “iKnife” diagnosed tissue samples from 91 patients with 100 per cent accuracy, instantly providing information that normally takes up to half an hour to reveal using laboratory tests.In cancers involving solid tumours, removal of the cancer in surgery is generally the best hope for treatment. The surgeon normally takes out the tumour with a margin of healthy tissue. However, it is often impossible to tell by sight which tissue is cancerous. One in five breast cancer patients who have surgery require a second operation to fully remove the cancer. In cases of uncertainty, the removed tissue is sent to a lab for examination while the patient remains under general anesthetic.The iKnife is based on electrosurgery, a technology invented in the 1920s that is commonly used today. Electrosurgical knives use an electrical current to rapidly heat tissue, cutting through it while minimising blood loss. In doing so, they vaporise the tissue, creating smoke that is normally sucked away by extraction systems. The inventor of the iKnife, DrZoltanTakats of Imperial College London, realised that this smoke would be a rich source of biological information. To create the iKnife, he connected an electrosurgical knife to a mass spectrometer, an analytical instrument used to identify what chemicals are present in a sample. Different types of cell produce thousands of metabolites in different concentrations, so the profile of chemicals in a biological sample can reveal information about the state of that tissue. In the new study, the researchers first used the iKnife to analyse tissue samples collected from 302 surgery patients, recording the characteristics of thousands of cancerous and non-cancerous tissues, including brain, lung, breast, stomach, colon and liver tumours to create a reference library. The iKnife works by matching its readings during surgery to the reference library to determine what type of tissue is being cut, giving a result in less than three seconds. The technology was then transferred to the operating theatre to perform real-time analysis during surgery. In all 91 tests, the tissue type identified by the iKnife matched the post-operative diagnosis based on traditional methods. While the iKnife was being tested, surgeons were unable to see the results of its readings. The researchers hope to carry out a clinical trial to see whether giving surgeons access to the iKnife’s analysis can improve patients’ outcomes. “These results provide compelling evidence that the iKnife can be applied in a wide range of cancer surgery procedures,” Dr Takats said. “It provides a result almost instantly, allowing surgeons to carry out procedures with a level of accuracy that hasn’t been possible before. We believe it has the potential to reduce tumour recurrence rates and enable more patients to survive.”Although the current study focused on cancer diagnosis, Dr Takats says the iKnife can identify many other features, such as tissue with an inadequate blood supply, or types of bacteria present in the tissue. He has also carried out experiments using it to distinguish horsemeat from beef. “The iKnife is one manifestation of several advanced chemical profiling technologies developed in our labs that are contributing to surgical decision-making and real-time diagnostics. These methods are part of a new framework of patient journey optimization that we are building at Imperial to help doctors diagnose disease, select the best treatments, and monitor individual patients’ progress as part our personalized healthcare plan.” Lord Darzi, Professor of Surgery at Imperial College London, who also co-authored the study, said: “In cancer surgery, you want to take out as little healthy tissue as possible, but you have to ensure that you remove all of the cancer. There is a real need for technology that can help the surgeon determine which tissue to cut out and which to leave in. This study shows that the iKnife has the potential to do this, and the impact on cancer surgery could be enormous. Lord Howe, Health Minister, said: “We want to be among the best countries in the world at treating cancer and know that new technologies have the potential to save lives. The iKnife could reduce the need for people needing secondary operations for cancer and improve accuracy, and I’m delighted we could support the work of researchers at Imperial College London. This project shows once again how Government funding is putting the UK at the forefront of world-leading health research.”
When the technique was transferred to the operating theatre and applied in real time, it proved to be 100% accurate, matching the post-operative conclusions that were based on conventional analyses. The accuracy should help to reduce those cases where patients need further surgery at a later date because all of the cancerous tissue was not removed at the first attempt.“We believe it has the potential to reduce tumor recurrence rates and enable more patients to survive.”
J. Balog et al. ‘Intraoperative tissue identification using rapid evaporative ionization mass spectrometry.’ Sci. Transl. Med. 5, 194ra93 (2013).
A Review on “Intelligent Knife” tells Surgeon if Tissue is Cancerous