MSACL 2020 US Abstract

Development of <i>in vivo</i> Real-time Molecular Topological Imaging of Cancer Using SpiderMass

N. Ogrinc1, A. Kruszewski2, Paul Chaillou2, P. Saudemont1, C. Duriez2, M. Salzet1, I. Fournier1
(1) PRISM Inserm U1192, University of Lille, F-59000 Lille, France. (2) UMR 9189 - CRIStAL - Centre de Recherche en Informatique, Signal et Automatique de Lille, University of Lille, INRIA, CNRS, Centrale Lille, Lille, France.

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Isabelle Fournier (Presenter) Université De Lille, Inserm, U1192

Presenter Bio: Distinguished Professor I. Fournier (IF, PRISM, U1192, Lille) is senior member of the University Institute (IUF) with a chair in Clinical Mass Spectrometry. She is currently co-director of PRISM lab INSERM U1192. Prof. Fournier is a specialist of Mass Spectrometry applied to clinics and proteomics. She was pioneer a novel technology in Europe of molecular imaging namely MALDI Mass Spectrometry Imaging in 2002 (Fournier et al., Neuroend. Letters 2003) and in 2007 demonstrated that MALDI MS Imaging could be perform from archived Formalin fixed and Paraffin Embedded hospital tissue samples (Lemaire et al., J. Proteome Res 2007). In 2005, she developed the multiplex targeted imaging, Tag-mass technology (Lemaire J. Proteome Res. 2007; Gagnon et al., Prog Histochem Cytochem 2012). In 2013, she introduced the concept of the spatially-resolved tissue proteomic and applied this technology on different cancers (Longuespee et al., Cancer Metastasis Rev 2012; Quanico et al Chem Com, 2015, Simeone et al., Semin Cancer Biol., 2018). Since 2011, Pr. I. Fournier with Pr. X. Roucou have evidenced the Ghost proteome (Samandi et al., Elife 2017, Delcourt et al., EBioMedicine et al., 2017, Brunet et al., Nucleic. Acid. Res., 2019). In 2014, she performed the development of a novel technology based on mass spectrometry and allowing to realize in vivo real time tissue molecular imaging and for guiding surgery, with an instrument named SpiderMass (Saudemont et al., Cancer cells, 2018; Ogrinc et al., Nature Protocols, 2019).

Relevant Financial Disclosures (within past 24 months) No relevant financial relationship(s) to disclose. Discussing Products? NO, presenter will NOT present educational content related to products/services of the ineligible company(ies) listed above. Conflict mitigation NOT REQUIRED.

INTRODUCTION: Surgery of solid tumors is a difficult process during which surgeons are often “blind” since none of the current advanced tools in used can provide molecular data. Molecular data are only obtained after biopsies are collected which is a long and difficult process compared to the time affordable for the surgery. Getting in vivo molecular data is therefore an unmet need that need to be addressed. A novel mini-invasive technology, called SpiderMass, was developed to perform in vivo real-time MS analysis at the surgery room. The device was demonstrated for manual profiling of tissues. To obtained intraoperative diagnostic and delineation of the resection margins, the device must be automated to enable imaging a defined area of tissue spotted by the surgeon. This can be achieved by integrating SpiderMass onto a robotic system.

OBJECTIVES: The primary objective is to develop a mini-invasive in vivo system which can achieve imaging from non-flat surfaces.

METHODS: The SpiderMass system is composed of a remote laser microprobe, a transfer line and the MS instrument. The laser microprobe is fibered and equipped with a handpiece. It is tuned to 2.94 µm to promote resonant excitation of endogenous water molecules. The desorbed material is further transferred to the MS instrument by aspiration through a tubing of several meters connected to the inlet of the MS instrument using a dedicated interface. MS spectra are recorded in real-time using a QTOF instrument. For combined topological and molecular imaging the handpiece of the laser fibber is mounted on a 6 axis robotic arms through a homemade 3D printed part. A camera is also included in the part. The camera enable to get the topography of the object to be scanned and the molecular data are then plotted back onto the topographic surface.

RESULTS: We programmed the robotic arm so that topographic data could be generated through the camera mounted at the end of the arm. The arm was shown to be able to follow the topography of model objects using 2D motions to generate an image of the topography. Then the arm was programmed to rescan the object while keeping the right focusing distance for the laser to generate the molecular data. Both acquired data were aligned in time and fused enabling to generate a molecular distribution plotted onto a topographic image. First tests were run using 500 µm resolution from a sponge piece which presents a specific topography but only required 2D motion of the arm. Specific signals of the sponge could be followed and monitored. The system was then used on more complex objects requiring a rotation movement of the arm during the scan. Next the system was applied on patient biopsies.

CONCLUSION: SpiderMass MS-based technology was successfully coupled to a robotic arm to get an integration of topographic and molecular images. This developments give a start and open a new way to the technology to get it integrated within the set of conventional surgical tools.