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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®

Objectives: Multi-station contrast-enhanced magnetic resonance angiography (MRA) is considered as the imaging investigation of first choice in patients suffering from peripheral arterial occlusive disease. In order to overcome venous overlay and to gain dynamic flow information as provided by digital subtraction angiography (DSA), we developed a triple injection protocol for high-resolution MRA of the entire peripheral vascular system, applying time-resolved (TR) four-dimensional (4D) MRA sequences.Methods: Ten patients underwent three-station TR-MRA of the pelvis and lower extremities with DSA as reference standard. Both investigations were compared concerning stenosis on a segment-by-segment basis. Furthermore, 28 consecutive patients underwent the same MR-only imaging protocol. All images were evaluated concerning image quality (1 = non-diagnostic, 4 = excellent), venous overlay (from none up to substantial) and time to venous enhancement (very early/early/normal/late).Results: Three-station TR-MRA proved feasible and was comparable with DSA in 282 vessel segments, with underestimation grade of stenosis in four segments and overestimation in four segments, respectively. In 32/38 patients no venous overlay was noted; in six patients there was mild venous overlay. Image quality was rated excellent or good in most cases.Conclusions: TR-MRA provides morphological and functional information without any timing issues due to optimal arterial enhancement at high spatial resolution without venous overlay. [ABSTRACT FROM AUTHOR]

Background and Purpose: Combination therapies are becoming increasingly important for the treatment of high blood pressure. Little is known about whether double blockade of angiotensin II (AT(1) ) receptors and angiotensin-converting enzyme (ACE) exert synergistic metabolic effects.Experimental Approach: Spontaneously hypertensive rats were allowed to choose between palatable chocolate bars and standard chow and were simultaneously treated with the AT(1) blocker telmisartan (8 mg·kg(bw) (-1) ·day(-1) ), the ACE inhibitor ramipril (4 mg·kg(bw) (-1) ·day(-1) ) or a combination of the two (8 + 4 mg·kg(bw) (-1) ·day(-1) ) for 12 weeks.Key Results: Although food-dependent energy intake was increased by telmisartan and telmisartan + ramipril compared with ramipril or controls, body weight gain, abundance of fat and plasma leptin levels were decreased. Increased insulin levels in response to an oral glucose tolerance test were comparably attenuated by telmisartan and telmisartan + ramipril, but not by ramipril. During an insulin tolerance test, glucose utilization was equally as effectively improved by telmisartan and telmisartan + ramipril. In response to a stress test, ACTH, corticosterone and glucose increased in controls. These stress reactions were attenuated by telmisartan and telmisartan + ramipril.Conclusions and Implications: The combination of telmisartan + ramipril was no more efficacious in regulating body weight and glucose homeostasis than telmisartan alone. However, telmisartan was more effective than ramipril in improving metabolic parameters and in reducing body weight. The association between the decrease in stress responses and the diminished glucose levels after stress supports our hypothesis that the ability of telmisartan, as an AT(1) receptor blocker, to alleviate stress reactions may contribute to its hypoglycaemic actions. [ABSTRACT FROM AUTHOR]

The objective was to assess the feasibility of a combined arterial and venous whole-body three-dimensional magnetic resonance (MR) angiography, together with a cardiac MR examination, in patients with arterial thromboembolism. Ten patients with arterial thromboembolism underwent a contrast-enhanced whole-body MR examination of the arterial and venous vessels, followed by a cardiac MR examination on a separate occasion within 24 h. All examinations were performed on a 1.5-T MR scanner. For both arterial and venous MR angiography only one injection of contrast agent was necessary. The cardiac imaging protocol included dark-blood-prepared half-Fourier acquisition single-shot turbo-spin-echo sequences, fast steady-state free precession cine sequences, T2-weighted turbo-spin-echo sequences and inversion recovery gradient-echo fast low-angle-shot sequences after injection of contrast agent. MR imaging revealed additional clinically unknown arterial thromboembolisms in four patients. The thoracic aorta was depicted as embolic source in four patients, while deep vein thrombosis (DVT) was found in one patient as the underlying disease. Unsuspected infarction of parenchymal organs was detected by MRI in two patients. An unknown additional DVT was found in one patient. Four patients were considered to have arterial emboli of cardiac origin. In conclusion, acquisition of arterial and venous MR angiograms of the entire vascular system combined with cardiac MR imaging is a most comprehensive and valuable strategy in patients with arterial thromboembolism. [ABSTRACT FROM AUTHOR]

RATIONALE: Partial neuromuscular transmission failure by acetylcholine receptor blockade (neuromuscular blockade) or antibody-mediated functional loss (myasthenia gravis), even with a magnitude of muscle weakness that does not evoke respiratory symptoms, can evoke dysphagia and decreased inspiratory airflow, and increases the risk of susceptible patients to develop severe pulmonary complications. OBJECTIVES: To assess whether impaired neuromuscular transmission predisposes individuals to inspiratory upper airway collapse, we assessed supraglottic airway diameter and volume by respiratory-gated magnetic resonance imaging, upper airway dilator muscle function (genioglossus force and EMG), and changes in lung volume, respiratory timing, and peripheral muscle function before, during, and after partial neuromuscular blockade in healthy, awake volunteers. MEASUREMENTS AND MAIN RESULTS: Partial neuromuscular blockade (train-of-four [TOF] ratio: 0.5 and 0.8) was associated with the following: (1) a decrease of inspiratory retropalatal and retroglossal upper airway volume to 66 +/- 22 and 82 +/- 12% of baseline, which was significantly more intense in the retropalatal area; (2) an attenuation of the normal increase in anteroposterior upper airway diameter during forced inspiration to 74 +/- 18% of baseline; (3) a decrease in genioglossus activity during maximum voluntary tongue protrusion to 39 +/- 19% (TOF, 0.5) and 73 +/- 29% (TOF, 0.8) of baseline; and (4) no effects on upper airway size during expiration, lung volume, and respiratory timing. CONCLUSIONS: Thus, impaired neuromuscular transmission, even to a degree insufficient to evoke respiratory symptoms, markedly impairs upper airway dimensions and function. This may be explained by an impairment of the balance between upper airway dilating forces and negative intraluminal pressure generated during inspiration by respiratory 'pump' muscles. [ABSTRACT FROM AUTHOR]

Conclusions. Whole-body MRI is feasible for the tumor staging of patients with malignant head and neck tumors and appears to be a quick, reliable and proven alternative in general and for patients with contraindications to CT. This examination minimizes the logistical effort required compared to multimodality strategies. Its economic impact remains to be determined. Objective. To assess the performance of whole-body MRI for staging patients with squamous cell carcinoma of the head and neck region. Material and methods. This was a randomized, prospective clinical study. For tumor staging, 21 patients (mean age 56.7 years; range 43-80 years) with advanced malignant head and neck tumors underwent whole-body MRI in addition to routinely performed imaging investigations, including sonography, chest X-ray, CTof the head, neck and thorax and endoscopy. All investigations were accomplished within a period of 10±3 days in a random order. A randomized, blinded, consensus assessment of all the whole-body MRI examinations was performed by two radiologists. The localization and extent of the primary tumor and metastases were documented for whole-body MRI and compared to the standard of reference (all other imaging modalities as well as histology). Point estimates of the diagnostic accuracy of whole-body MRI were calculated. Results. In accordance with the standard of reference, the overall TNM category was correctly determined with whole-body MRI in all 21 patients. However, four patients were classified as having carcinoma of unknown primary, as the primary tumor was not found with any imaging modality. Two patients had mediastinal, pulmonary and hepatic metastases. [ABSTRACT FROM AUTHOR]