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Franz Wegner,1 Thomas Friedrich,2 Maximilian Wattenberg,2 Justin Ackers,2 Malte Maria Sieren,1,3 Roman Kloeckner,1 Joerg Barkhausen,3 Thorsten M Buzug,2,4 Matthias Graeser,2,4 Anselm von Gladiss5 1Institute for Interventional Radiology, University of Luebeck, Luebeck, Germany; 2Fraunhofer Research Institution for Individualized and Cell-Based Medical Engineering IMTE, Luebeck, Germany; 3Department of Radiology and Nuclear Medicine, University of Luebeck, Luebeck, Germany; 4Institute of Medical Engineering, University of Lubeck, Luebeck, Germany; 5Institute for Computer Science, University of Koblenz, Koblenz, GermanyCorrespondence: Franz Wegner, University of Luebeck, Institute for Interventional Radiology, Ratzeburger Allee 160, Luebeck, 23538, Germany, Tel +4945150072388, Fax +4945150017004, Email franz.wegner@uksh.dePurpose: Magnetic particle imaging (MPI) is an emerging medical imaging modality that is on the verge of clinical use. In recent years, cardiovascular applications have shown huge potential like, e.g., intraprocedural imaging guidance of stent placement through MPI. Due to the lack of signal generation, nano-modifications have been necessary to visualize commercial medical instruments until now. In this work, it is investigated if commercial interventional devices can be tracked with MPI without any nano-modification.Material and Methods: Potential MPI signal generation of nine endovascular metal stents was tested in a commercial MPI scanner. Two of the stents revealed sufficient MPI signal. Because one of the two stents showed relevant heating, the imaging experiments were carried out with a single stent model (Boston Scientific/Wallstent-Uni Endoprothesis, diameter: 16 mm, length: 60 mm). The nitinol stent and its delivery system were investigated in seven different scenarios. Therefore, the samples were placed at 49 defined spatial positions by a robot in a meandering pattern during MPI scans. Image reconstruction was performed, and the mean absolute errors (MAE) between the signals’ centers of mass (COM) and ground truth positions were calculated. The stent material was investigated by magnetic particle spectroscopy (MPS) and vibrating sample magnetometry (VSM). To detect metallic components within the delivery system, nondestructive testing via computed tomography was performed.Results: The tracking of the stent and its delivery system was possible without any nano-modification. The MAE of the COM were 1.49 mm for the stent mounted on the delivery system, 3.70 mm for the expanded stent and 1.46 mm for the delivery system without the stent. The results of the MPS and VSM measurements indicate that besides material properties eddy currents seem to be responsible for signal generation.Conclusion: It is possible to image medical instruments with dedicated designs without modifications by means of MPI. This enables a variety of applications without compromising the mechanical and biocompatible properties of the instruments.Keywords: magnetic particle imaging, instrument tracking, interventional instruments, stent, medical imaging

Nikolaos Panagiotopoulos,1 Robert L Duschka,1 Mandy Ahlborg,2 Gael Bringout,2 Christina Debbeler,2 Matthias Graeser,2 Christian Kaethner,2 Kerstin Lüdtke-Buzug,2 Hanne Medimagh,2 Jan Stelzner,2 Thorsten M Buzug,2 Jörg Barkhausen,1 Florian M Vogt,1 Julian Haegele1 1Clinic for Radiology and Nuclear Medicine, University Hospital Schleswig Holstein, Campus Lübeck, 2Institute of Medical Engineering, University of Lübeck, Lübeck, Germany Abstract: Magnetic particle imaging (MPI) is a novel imaging method that was first proposed by Gleich and Weizenecker in 2005. Applying static and dynamic magnetic fields, MPI exploits the unique characteristics of superparamagnetic iron oxide nanoparticles (SPIONs). The SPIONs’ response allows a three-dimensional visualization of their distribution in space with a superb contrast, a very high temporal and good spatial resolution. Essentially, it is the SPIONs’ superparamagnetic characteristics, the fact that they are magnetically saturable, and the harmonic composition of the SPIONs’ response that make MPI possible at all. As SPIONs are the essential element of MPI, the development of customized nanoparticles is pursued with the greatest effort by many groups. Their objective is the creation of a SPION or a conglomerate of particles that will feature a much higher MPI performance than nanoparticles currently available commercially. A particle’s MPI performance and suitability is characterized by parameters such as the strength of its MPI signal, its biocompatibility, or its pharmacokinetics. Some of the most important adjuster bolts to tune them are the particles’ iron core and hydrodynamic diameter, their anisotropy, the composition of the particles’ suspension, and their coating. As a three-dimensional, real-time imaging modality that is free of ionizing radiation, MPI appears ideally suited for applications such as vascular imaging and interventions as well as cellular and targeted imaging. A number of different theories and technical approaches on the way to the actual implementation of the basic concept of MPI have been seen in the last few years. Research groups around the world are working on different scanner geometries, from closed bore systems to single-sided scanners, and use reconstruction methods that are either based on actual calibration measurements or on theoretical models. This review aims at giving an overview of current developments and future directions in MPI about a decade after its first appearance. Keywords: magnetic particle imaging, superparamagnetic iron oxide nanoparticles, magnetic particle spectrometer, peripheral nerve stimulation, cardiovascular interventions

Julian Haegele,1 Robert L Duschka,1 Matthias Graeser,2 Catharina Schaecke,1 Nikolaos Panagiotopoulos,1 Kerstin Lüdtke-Buzug,2 Thorsten M Buzug,2 Jörg Barkhausen,1 Florian M Vogt1 1Clinic for Radiology and Nuclear Medicine, 2Institute of Medical Engineering, University Hospital Schleswig Holstein, Lübeck, Schleswig-Holstein, Germany Background: Magnetic particle imaging (MPI) uses magnetic fields to visualize superparamagnetic iron oxide nanoparticles (SPIO). Today, Resovist® is still the reference SPIO for MPI. The objective of this study was to evaluate the in vivo blood half-life of two different types of Resovist (one from Bayer Pharma AG, and one from I’rom Pharmaceutical Co Ltd) in MPI. Methods: A Resovist concentration of 50 µmol/kg was injected into the ear artery of ten New Zealand White rabbits. Five animals received Resovist distributed by I’rom Pharmaceutical Co Ltd and five received Resovist by Bayer Pharma AG. Blood samples were drawn before and directly after injection of Resovist, at 5, 10, and 15 minutes, and then every 15 ­minutes until 120 minutes after the injection. The MPI signal of the blood samples was evaluated using magnetic particle spectroscopy. Results: The average decline of the blood MPI signal from the two distributions differed significantly (P=0.0056). Resovist distributed by Bayer Pharma AG showed a slower decline of the MPI signal (39.7% after 5 minutes, 20.5% after 10 minutes, and 12.1% after 15 minutes) compared with Resovist produced by I’rom Pharmaceutical Co Ltd (20.4% after 5 minutes, 7.8% after 10 minutes, no signal above noise level after 15 minutes). Conclusion: In MPI, the blood half-life of an SPIO tracer cannot be equalized to the blood half-life of its MPI signal. Resovist shows a very rapid decline of blood MPI signal and is thus not suitable as a long circulating tracer. For cardiovascular applications in MPI, it may be used as a bolus tracer. Keywords: magnetic particle imaging, superparamagnetic iron oxide nanoparticles, magnetic particle spectroscopy, blood half-life time, Resovist®

Abstract Background The presence of tumor-infiltrating lymphocytes has been associated with prognosis and chemotherapy response, particularly in high-risk breast cancer subtypes. There is limited data so far as to (i) how tumor-infiltrating lymphocyte (TIL) measurements correlate with genomic measurements such as the Oncotype DX Recurrence Score® and (ii) whether the survival impact of TIL measurements varies according to different adjuvant systemic therapies. Methods The WSG PlanB trial compared an anthracycline-free chemotherapy regimen (6x docetaxel/cyclophosphamide, TC) to an anthracycline-taxane sequence (4xEC followed by 4x docetaxel) in patients with intermediate-risk, HER2-negative early breast cancer (EBC). Patients with HR-positive HER2-negative EBC were further stratified to receive endocrine therapy alone vs. chemotherapy followed by endocrine therapy based on Recurrence Score results and nodal status. In this analysis, three independent observers quantified and categorized the presence of TILs among tumor samples from patients in PlanB. TIL measurements were correlated with clinical/pathological parameters and treatment outcome overall and according to the treatment arm. Results Disease-free survival (DFS) rates were significantly better (p = .04) in HR-negative patients with high vs. intermediate TIL levels and were higher in low vs. intermediate TIL patients, however with borderline significance only (p = .06). There were no significant differences among TIL categories in HR+ patients. High RS categories, HR-negative status, and high KI67 were independently and significantly associated with high TIL categories. There was no significant impact of TIL category on DFS in patients treated by endocrine therapy only; however, in patients receiving chemotherapy, DFS in the intermediate TIL category was lower than that in the other categories. Conclusion Although the presence of high TILs is associated with negative prognostic parameters such as high KI67 and HR-negative status among patients with HR-positive HER2-negative EBC, patients with high TILs show a favorable 5-year DFS in both HR-positive/HER2-negative and triple-negative breast cancer.