Photoacoustic staging of nodal metastases using SPIOs: Comparison between in vivo, in toto and ex vivo imaging in a rat model

Article type: Research Article

Authors: Grootendorst, Diederik J.^{a; *} | Fratila, Raluca M.^b | Pouw, Joost^b | Ten Haken, Bennie^b | Van Wezel, Richard J.A.^c | Rottenberg, Sven^d | Steenbergen, Wiendelt^{a; **} | Manohar, Srirang^{a; **} | Ruers, Theo J.M.^{d; e}

Affiliations: [a] Biomedical Photonic Imaging Group, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands | [b] Neuro IMaging Group, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands | [c] Neurophysiology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, P.O. Box 9104, 6500 HE Nijmegen, The Netherlands | [d] Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital (NKI-AVL), The Netherlands | [e] Nanobiophysics Group, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands

Correspondence: [*] Corresponding author. E-mail: d.j.grootendorst@gmail.com.

Note: [**] Dr. Steenbergen and Dr. Manohar do have a minority share in PA Imaging BV, which however was not associated with this work and did not finance the research.

Abstract: Background and objectives:To determine prognosis and treatment, accurate nodal staging is essential in many tumor types. After injection of clinical grade superparamagnetic iron oxide (SPIO) nanoparticles, it has been shown that metastatic lymph nodes can be distinguished from benign specimens using MR imaging. However, MR does not benefit per-operative nodal staging which requires a non-ionizing, small volume, high resolution, fast imaging technique. In vivo non-invasive photoacoustic (PA) imaging of lymph nodes might facilitate nodal staging during surgery, thereby benefiting both surgeon and patient. Materials and methods:In order to investigate the feasibility of an in vivo nodal staging approach using photoacoustics, six Mat-lylu inoculated Copenhagen rats were photo-acoustically imaged after injection of a new Class IIa medical device SPIO magnetic tracer (Sienna+). Lymph nodes were imaged in vivo, in toto (after euthanization) and ex vivo using multiple wavelength illumination. Results were compared with MRI, immunohistochemistry and photographs of the sectioned nodes. Results:These experiments demonstrate that in an ex vivo setting, the PA contrast of Sienna+ is able to facilitate a distinction between metastatic and benign nodes. A non-invasive distinction between both groups is partially impeded by the low amount of PA contrast generated by the SPIO particles compared to that of endogenous absorbers such as hemoglobins. Conclusions:This comparison between in vivo, in toto and ex vivo PA imaging of lymph nodes after SPIO injection demonstrates that the clinical potential of combined PA/SPIO staging should initially be exploited in an ex vivo setting. Improved distinction between chromophores by for example multi-spectral unmixing might in the near future enable non-invasive assessment of nodal involvement.

Keywords: Photoacoustic, non-invasive, sentinel lymph nodes (SLN), SPIONS, in vivo and in toto, optoacoustic

DOI: 10.3233/BSI-150127

Journal: Biomedical Spectroscopy and Imaging, vol. 5, no. 1, pp. 71-87, 2016