Rapid evaporative ionisation mass spectrometry of electrosurgical vapours for the identification of breast pathology: towards an intelligent knife for breast cancer surgery

Abstract

BackgroundRe-operation for positive resection margins following breast-conserving surgery occurs frequently (average = 20–25%), is cost-inefficient, and leads to physical and psychological morbidity. Current margin assessment techniques are slow and labour intensive. Rapid evaporative ionisation mass spectrometry (REIMS) rapidly identifies dissected tissues by determination of tissue structural lipid profiles through on-line chemical analysis of electrosurgical aerosol toward real-time margin assessment.MethodsElectrosurgical aerosol produced from ex-vivo and in-vivo breast samples was aspirated into a mass spectrometer (MS) using a monopolar hand-piece. Tissue identification results obtained by multivariate statistical analysis of MS data were validated by histopathology. Ex-vivo classification models were constructed from a mass spectral database of normal and tumour breast samples. Univariate and tandem MS analysis of significant peaks was conducted to identify biochemical differences between normal and cancerous tissues. An ex-vivo classification model was used in combination with bespoke recognition software, as an intelligent knife (iKnife), to predict the diagnosis for an ex-vivo validation set. Intraoperative REIMS data were acquired during breast surgery and time-synchronized to operative videos.ResultsA classification model using histologically validated spectral data acquired from 932 sampling points in normal tissue and 226 in tumour tissue provided 93.4% sensitivity and 94.9% specificity. Tandem MS identified 63 phospholipids and 6 triglyceride species responsible for 24 spectral differences between tissue types. iKnife recognition accuracy with 260 newly acquired fresh and frozen breast tissue specimens (normal n = 161, tumour n = 99) provided sensitivity of 90.9% and specificity of 98.8%. The ex-vivo and intra-operative method produced visually comparable high intensity spectra. iKnife interpretation of intra-operative electrosurgical vapours, including data acquisition and analysis was possible within a mean of 1.80 seconds (SD ±0.40).ConclusionsThe REIMS method has been optimised for real-time iKnife analysis of heterogeneous breast tissues based on subtle changes in lipid metabolism, and the results suggest spectral analysis is both accurate and rapid. Proof-of-concept data demonstrate the iKnife method is capable of online intraoperative data collection and analysis. Further validation studies are required to determine the accuracy of intra-operative REIMS for oncological margin assessment.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-017-0845-2) contains supplementary material, which is available to authorized users.

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.…”

“…For iKnife processing, frozen samples were thawed in batches of eight samples at a time to room temperature. The samples were processed with iKnife as previously described (20,26,55). A Covidien ForceTriad generator at 20 W was used with a modified electrosurgical hand-piece (iKnife) to diathermize the samples in cut mode.…”

“…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).…”

Patient-level costs in margin re-excision for breast-conserving surgery

“…The iKnife (Waters Corporation, Milford, Massachusetts, USA), is a novel mass spectrometric method that allows intraoperative analysis of breast tissue types and thus resection margin status in vivo by interpretation of cellular chemical components. Despite good sensitivity (94·1 per cent), the iKnife was noted to have modest specificity (87·3 per cent) in analysing solid benign lesions (fibroadenoma) compared with tumour in a subset analysis. Moreover, adoption is potentially hampered by device costs, associated consumables and maintenance costs.…”

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.…”