James Alexander (Presenter)
Imperial College, London
Bio: James Alexander is a Clinical Research Fellow within the Department of Surgery and Cancer, Imperial College, London. He is studying for a PhD mapping the Microbiome-Metabonome of Colorectal Cancer. Under the supervision of Professor Zoltan Takats, he is developing Rapid Evaporative Ionisation Mass Spectrometry (REIMS) in Endoscopy. He qualified in Medicine at University of Cambridge and Imperial College, London in 2003 and also works as a Gastroenterology Specialist Registrar at Imperial Healthcare NHS Trust,
Authorship: James Alexander (1), Louise Gildea (1), Merja Rossi (1), Julia Balog (2), Steven Pringle (2), Abigail Speller (1), Kirill Veselkov (1), James Kinross (1), Julian Teare (1), Zoltan Takats (1)
(1) Imperial College, London, UK; (2) Waters Corporation, Wilmslow, UK
| Short Abstract Rapid Evaporative Ionisation Mass Spectrometry (REIMS) in endoscopy utilises the aerosol released during electrosurgical tissue dissection through integration with an endoscopic polypectomy snare. A significant barrier to its clinical usefulness is the potential delayed signal transfer and loss of signal intensity resulting from aspiration of aerosol from a closed cavity with a long sampling line. We show experiments comparing a novel direct method for introduction of aerosol to the mass spectrometer. The novel method produced a robust signal comparable to the original Venturi setup, while reducing cut-to-signal time by >50%. It has shown good results in 10 procedures on patients. |
Long Abstract
Introduction
Rapid Evaporative Ionisation Mass Spectrometry (REIMS) is a technique that enables in vivo, in situ, analysis of human tissues through the utilisation of electrosurgical tools as ion sources. Endoscopy is the gold-standard diagnostic modality for pathology in the gastrointestinal tract and it also plays an important role in the therapeutic removal of small tumours and polyps in the colon. The application of REIMS in endoscopy using a modified polypectomy snare has recently been described (1). However, for this technology to be of genuine clinical value technical challenges remain. The information provided to the endoscopist by REIMS must be delivered in near real-time for it to be used to aid lesion recognition and as a safety adjunct during tumour resection. A significant signal delay and loss of signal intensity as a result of aspiration of aerosol from a closed cavity with a long sampling line (>4m) are barriers to this goal. We conducted experiments to optimize the endoscopic REIMS setup and prime it for clinical application.
Methods
A series of bespoke sterile polypectomy snares were developed with commercial partners (Medwork Model No’s POL1-B1-30-23-220-OL and POL1-B7-30-23-220-OL, working length 2300mm, minimum channel size 2.8 mm, opening diameter 10-30 mm). These were equipped with an in-built handle side-port to permit connection of a 1/8′ OD 2 mm PFTE tubing between the tissue evaporation point and the atmospheric inlet of a mass spectrometer (Xevo G2-S Q-TOF, Waters, Manchester, UK, and LTQ Velos linear iontrap mass spectrometer, Thermo Fisher Scientific ltd, San Jose, CA, USA). The electrosurgical aerosol plume generated during the experiments was captured through fenestrations of the snare outer tubing and transferred to the mass spectrometer through the tubing and handle side-port. Three configurations of fenestration in the snare tubing and two different commonly used snare wires (oval braided & convex compact) were tested to ascertain which provided the most robust signal transfer. In addition, three variations of inlet setup were trialled: (i) the original Venturi chamber with 2-propanol (IPA) injection, (ii) direct aerosol introduction to MS capillary without IPA and (iii) aerosol introduction to MS capillary via IPA trifold inlet. Experiments were carried out on porcine tissue and human colonic mucosa. High-resolution mass spectrometry was performed in negative-ion mode in the m/z 150–1500 range. Following optimization of this method, the setup was then employed in vivo during ten colonoscopy procedures on patients at Imperial Healthcare NHS Trust.
Results
High signal intensities were seen for both types of wire snares. Signal intensity for the phospholipid peaks of interest in the 600-1000 m/z region was higher with the oval braided wire snare compared to the convex compact wire snare. Tube fenestration configuration did not significantly affect the signal intensity, and a robust signal was acquired with all three configurations.
The original Venturi chamber with IPA injection method produced a cut-to-signal time delay of approximately six seconds when coupled to the modified snare. With the direct aerosol introduction method without IPA, the delay was reduced to an average of 2.4 seconds. However, in the absence of IPA, signal intensity was 100-fold weaker and reliability of spectral acquisition was reduced. In the third configuration, the direct method was adapted with a trifold inlet to allow mixing of IPA with electrosurgical aerosol. This restored signal intensity and reliability to the level of the Venturi chamber setup, while maintaining the improved cut-to-signal time of 2.4 seconds. In subsequent in vivo tests, the improved system produced comparable results during ten colonoscopy procedures on patients.
Conclusion
There is great potential for Rapid Evaporative Ionisation Mass Spectrometry (REIMS) to be further developed as an adjunct to diagnosis and therapeutics in endoscopy. In addition to the necessary diagnostic accuracy requirements of such a tool, including high sensitivity and specificity of tissue identification, the information provided must also be delivered reliably and in a timely fashion. We have shown that direct introduction of aerosol mixed with IPA to the MS capillary via a trifold inlet reduces cut-to-signal time delay by over 50% while preserving signal intensity. The data presented here demonstrate that our novel REIMS endoscopy setup has overcome technical limitations on signal intensity and cut-to-signal delay, readying it for clinical trials.
References & Acknowledgements:
References
(1) Balog, J., Kumar, S., Alexander, J., Golf, O., Huang, J., Wiggins, T., Abbassi-Ghadi, N., Enyedi, A., Kacska, S., Kinross, J., Hanna, G. B., Nicholson, J. K. and Takats, Z. (2015), In Vivo Endoscopic Tissue Identification by Rapid Evaporative Ionization Mass Spectrometry (REIMS). Angew. Chem. Int. Ed., 54: 11059–11062. doi:10.1002/anie.201502770
Acknowledgements:
This work is funded by Waters Corporation. The first author receives funding from Imperial and Royal Marsden Biomedical Research Centres.
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