Continuous Coagulation Monitoring in Human Blood Samples via Magnetic Particle Spectroscopy

Maria-Josephina Buhné,1,* Justin Ackers,2,* Mandy Ahlborg,2 Matthias Graeser,2,3 Thorsten M Buzug,2,4 Kerstin Luedtke-Buzug,4 Tobias Knopp,2,5,6 Jonas Stroeder,1 Jörg Barkhausen,1 Roman Kloeckner,7 Alex Frydrychowicz,1 Franz Wegner,2,7 Eric Aderhold2 1Institute of Radiology and Nuclear Medicine, University Hospital Schleswig-Holstein, Luebeck, Germany; 2Fraunhofer IMTE, Fraunhofer Research Institution for Individualized Medical Technology and Engineering, Luebeck, Germany; 3Chair of Metrology, University of Rostock, Rostock, Germany; 4Institute of Medical Engineering, University of Luebeck, Luebeck, Germany; 5Section for Biomedical Imaging, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 6Institute for Biomedical Imaging, Hamburg University of Technology, Hamburg, Germany; 7Institute of Interventional Radiology, University Hospital Schleswig-Holstein, Luebeck, Germany*These authors contributed equally to this workCorrespondence: Maria-Josephina Buhné, University Hospital-Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, Lübeck, 23538, Germany, Email [email protected] Justin Ackers, Fraunhofer IMTE, Fraunhofer Research Institution for Individualized Medical Technology and Engineering, Mönkhofer Weg 239a, Lübeck, 23562, Germany, Email [email protected]: Magnetic Particle Imaging (MPI) is a radiation-free imaging modality based on the nonlinear magnetic response of iron oxide nanoparticles, providing high sensitivity and real-time, quantitative, background-free imaging. With the clinical approval of Resotran as an MPI-suitable tracer and the development of first human-scale scanners, clinical applications are within reach. Magnetic Particle Spectroscopy (MPS), the non-imaging counterpart of MPI, enables sensitive analytics by exploiting the signal response of magnetic nanoparticles. In this pilot study, we prove the potential of MPS to continuously monitor blood coagulation in real time.Methods: Blood samples from five volunteers were mixed with the commercial magnetic resonance imaging contrast agent Resotran. The dynamics of the particle signal were assessed in a custom-built MPS-system for a duration of 45 minutes under various conditions, including the presence of anticoagulants (EDTA, Heparin, Citrate) and mechanical stress. The signal amplitude of the fifth harmonic of the MPS was analyzed. To exclude potential thermal effects, the temperature inside the MPS was monitored by using a fiber optic thermometer during the measurements.Results: All Resotran-containing blood samples showed a signal decrease over time. Samples with anticoagulants exhibited no relevant signal decrease (EDTA, Citrate) or a smaller decrease (Heparin) compared to samples without anticoagulants. Additionally, mechanical stress induced a signal decay in all samples, further indicating the link between the observed MPS signal decay and blood coagulation.Conclusion: This study shows that continuous monitoring of human blood coagulation via MPS is feasible, making bedside coagulation monitoring in clinical settings a concrete perspective.Keywords: magnetic particle imaging, blood coagulation, nanoparticles, nanomedicine