The surgical intelligent knife distinguishes normal, borderline and malignant gynaecological tissues using rapid evaporative ionisation mass spectrometry (REIMS)

Abstract

BackgroundSurvival from ovarian cancer (OC) is improved with surgery, but surgery can be complex and tumour identification, especially for borderline ovarian tumours (BOT), is challenging. The Rapid Evaporative Ionisation Mass Spectrometric (REIMS) technique reports tissue histology in real-time by analysing aerosolised tissue during electrosurgical dissection.MethodsAerosol produced during diathermy of tissues was sampled with the REIMS interface. Histological diagnosis and mass spectra featuring complex lipid species populated a reference database on which principal component, linear discriminant and leave-one-patient-out cross-validation analyses were performed.ResultsA total of 198 patients provided 335 tissue samples, yielding 3384 spectra. Cross-validated OC classification vs separate normal tissues was high (97·4% sensitivity, 100% specificity). BOT were readily distinguishable from OC (sensitivity 90.5%, specificity 89.7%). Validation with fresh tissue lead to excellent OC detection (100% accuracy). Histological agreement between iKnife and histopathologist was very good (kappa 0.84, P < 0.001, z = 3.3). Five predominantly phosphatidic acid (PA(36:2)) and phosphatidyl-ethanolamine (PE(34:2)) lipid species were identified as being significantly more abundant in OC compared to normal tissue or BOT (P < 0.001, q < 0.001).ConclusionsThe REIMS iKnife distinguishes gynaecological tissues by analysing mass-spectrometry-derived lipidomes from tissue diathermy aerosols. Rapid intra-operative gynaecological tissue diagnosis may improve surgical care when histology is unknown, leading to personalised operations tailored to the individual.

The intelligent knife (iKnife) and its intraoperative diagnostic advantage for the treatment of cervical disease

“…Despite encouraging findings, translation of the technique to clinical settings may be limited by current size and cost considerations, which would necessitate its use in centralized locations within hospitals and operating theaters with controlled temperature due to the limited mobility of the equipment. The current iKnife apparatus occupies a substantial footprint similar to that required for robot-assisted surgery (19,(23)(24)(25)(26); however, future refinement of the technology toward a smaller, more user-friendly apparatus is achievable.…”

“…Dysregulation of lipid metabolism is associated with many cancers (21) and has been readily detected by REIMS in a number of tissue types (22). The iKnife technology robustly (100% accuracy) discriminates cancer from normal tissue in different tumor sites including the brain, breast, ovaries, and colon (19,(23)(24)(25)(26)(27).…”

The coming 15 years in gynaecological pathology: digitisation, artificial intelligence, and new technologies

“…Recently, mass spectrometry has been applied to detect cancer at the surgeon's cauterised margin . The same concept has also been applied to provide a diagnostic support tool at the time of frozen sectioning . Similarly to how an airport security attendant swabs your luggage and rapidly analyses it for the presence of forbidden chemicals, it is foreseeable that pathologists may one day be able to swab/incinerate a small piece of tumour at the time of frozen sectioning to aid in rapid diagnosis.…”

“…27 The same concept has also been applied to provide a diagnostic support tool at the time of frozen sectioning. 28 Similarly to how an airport security attendant swabs your luggage and rapidly analyses it for the presence of forbidden chemicals, it is foreseeable that pathologists may one day be able to swab/incinerate a small piece of tumour at the time of frozen sectioning to aid in rapid diagnosis. An example could be the distinction of high-grade serous carcinoma from clear cell carcinoma from high-grade endometrioid carcinoma at the time of frozen sectioning.…”

Proteomics in Pathology: The Special Issue

“…In addition to the methods presented in this special issue that will find diagnostic applications in institutes of pathology, new sampling and atmospheric pressure ionization technologies have been developed for intraoperative molecular profiling/imaging. Desorption/electrospray ionization, MasSpec Pen, SpiderMass, and rapid evaporative ionization mass spectrometry represent concrete alternatives for another possible evolution of MS‐based patient monitoring, within the surgery block.…”