Can Rapid Evaporative Ionization Mass Spectrometry (REIMS), the Intelligent Surgical Knife (iKnife) Provide a Point-of-Care Diagnosis for Endometrial Cancer
Diana Marcus (1) Adele Savage (1) Julia Balog (1) Julia Abda (1) Hiromi Kudo (1) Roberto Dina (1) Sadaf Ghaem-Maghami (1) Zoltan Takats (1) (1) Imperial College London, UK
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Diana Marcus (Presenter) Imperial College London
Presenter Bio: I graduated from University College London with a degree in Medicine and BSc In Physiology. I have always been interested in cancer treatment and am currently pursuing a career in gynaecological oncology. I have taken a few years out of training to undertake a PhD in endometrial cancer in Imperial College London, using mass spectrometry to help patients have a faster diagnosis of cancer.
Relevant Financial Disclosures
(within past 24 months)
No relevant financial relationship(s) to disclose.
Abstract
Introduction:
Endometrial cancer is the most common gynaecological cancer in the western world with over 7000 and 88’000 new cases diagnosed per year, in the UK and European Union respectively.
Following pelvic ultrasound imaging the diagnosis of endometrial cancer is confirmed by histological examination of endometrial curetting’s or more commonly outpatient endometrial biopsy e.g. pipelle. Histological examination of the tissue often takes up to two weeks. This wait adds significant anxiety and distress for patients awaiting results. To-date there is no POC diagnosis available. The intelligent surgical knife (‘iKnife’) analyses tissue real-time but has never been used to diagnose endometrial cancer, thus far.
The purpose of this research is to establish whether the iKnife can distinguish between normal and malignant endometrial tissues based on differences in tissue-specific lipidomic profiles.
Methods:
Research pipelle biopsy samples were obtained for women needing biopsies for clinical reasons (samples concurrently sent to conventional histopathology).
A Waters G2-XS Xevo Q-TOF mass spectrometer was used in conjunction with a modified handheld diathermy. The latter converts tissue constituents to gas phase ionic species that are then drawn into the MS-inlet through the REIMS interface. A solution of Isopropyl Alcohol and leucine encephalin was sprayed towards to the REIMS interface.
The resultant surgical aerosol containing ionic species produced during diathermy was then analysed with this technology; producing spectra that are background subtracted, lock mass corrected and in the phospholipid range. Principal component analysis (PCA) and linear discriminant analysis (LDA) were then performed to find the variance in spectral signatures between benign and malignant endometrial tissues. A leave one patient out cross validation was used to obtain diagnostic accuracy.
Results:
134 pipelle biopsy samples (73 normal and 61 malignant) were obtained. Each tissue sample was processed using the technique above using the cutting setting; producing an individual spectrum per burn.
A loading plot was created for the first principle component, in addition to ANOVA. It revealed several key m/z values were associated with the separation between normal and malignant tissue.
PCA score plots were created. The supervised LDA plot separated the results into tissue specific clouds of data. A leave one patient out cross validation was performed. In this validation method the diagnostic accuracy was 80%.
Summary:
This pilot study is the first to use the iKnife as a tool to distinguish between normal and malignant endometrial pipelle samples. These results are promising and suggest that the iKnife could be used as an aide in clinic to provide a POC diagnosis.
= Discovery stage.
= Translation stage.
= Clinically available.
