Franziska Werner

Magnetic Particle / Magnetic Resonance Imaging: In-Vitro MPI-Guided Real Time Catheter Tracking and 4D Angioplasty Using a Road Map and Blood Pool Tracer Approach.

Purpose In-vitro evaluation of the feasibility of 4D real time tracking of endovascular devices and stenosis treatment with a magnetic particle imaging (MPI) / magnetic resonance imaging (MRI) road map approach and an MPI-guided approach using a blood pool tracer. Materials and Methods A guide wire and angioplasty-catheter were labeled with a thin layer of magnetic lacquer. For real time MPI a custom made software framework was developed. A stenotic vessel phantom filled with saline or superparamagnetic iron oxide nanoparticles (MM4) was equipped with bimodal fiducial markers for co-registration in preclinical 7T MRI and MPI. In-vitro angioplasty was performed inflating the balloon with saline or MM4. MPI data were acquired using a field of view of 37.3×37.3×18.6 mm3 and a frame rate of 46 volumes/sec. Analysis of the magnetic lacquer-marks on the devices were performed with electron microscopy, atomic absorption spectrometry and micro-computed tomography. Results Magnetic marks allowed for MPI/MRI guidance of interventional devices. Bimodal fiducial markers enable MPI/MRI image fusion for MRI based roadmapping. MRI roadmapping and the blood pool tracer approach facilitate MPI real time monitoring of in-vitro angioplasty. Successful angioplasty was verified with MPI and MRI. Magnetic marks consist of micrometer sized ferromagnetic plates mainly composed of iron and iron oxide. Conclusions 4D real time MP imaging, tracking and guiding of endovascular instruments and in-vitro angioplasty is feasible. In addition to an approach that requires a blood pool tracer, MRI based roadmapping might emerge as a promising tool for radiation free 4D MPI-guided interventions.

Current European Labyrinthula zosterae Are Not Virulent and Modulate Seagrass (Zostera marina) Defense Gene Expression

Pro- and eukaryotic microbes associated with multi-cellular organisms are receiving increasing attention as a driving factor in ecosystems. Endophytes in plants can change host performance by altering nutrient uptake, secondary metabolite production or defense mechanisms. Recent studies detected widespread prevalence of Labyrinthula zosterae in European Zostera marina meadows, a protist that allegedly caused a massive amphi-Atlantic seagrass die-off event in the 1930s, while showing only limited virulence today. As a limiting factor for pathogenicity, we investigated genotype×genotype interactions of host and pathogen from different regions (10–100 km-scale) through reciprocal infection. Although the endophyte rapidly infected Z. marina, we found little evidence that Z. marina was negatively impacted by L. zosterae. Instead Z. marina showed enhanced leaf growth and kept endophyte abundance low. Moreover, we found almost no interaction of protist×eelgrass-origin on different parameters of L. zosterae virulence/Z. marina performance, and also no increase in mortality after experimental infection. In a target gene approach, we identified a significant down-regulation in the expression of 6/11 genes from the defense cascade of Z. marina after real-time quantitative PCR, revealing strong immune modulation of the hosts defense by a potential parasite for the first time in a marine plant. Nevertheless, one gene involved in phenol synthesis was strongly up-regulated, indicating that Z. marina plants were probably able to control the level of infection. There was no change in expression in a general stress indicator gene (HSP70). Mean L. zosterae abundances decreased below 10% after 16 days of experimental runtime. We conclude that under non-stress conditions L. zosterae infection in the study region is not associated with substantial virulence.

Activation of AMPKα2 is not crucial for mitochondrial uncoupling-induced metabolic effects but required to maintain skeletal muscle integrity.

Transgenic (UCP1-TG) mice with ectopic expression of UCP1 in skeletal muscle (SM) show a phenotype of increased energy expenditure, improved glucose tolerance and increase substrate metabolism in SM. To investigate the potential role of skeletal muscle AMPKα2 activation in the metabolic phenotype of UCP1-TG mice we generated double transgenic (DTG) mice, by crossing of UCP1-TG mice with DN-AMPKα2 mice overexpressing a dominant negative α2 subunit of AMPK in SM which resulted in an impaired AMPKα2 activity by 90±9% in SM of DTG mice. Biometric analysis of young male mice showed decreased body weight, lean and fat mass for both UCP1-TG and DTG compared to WT and DN-AMPKα2 mice. Energy intake and weight-specific total energy expenditure were increased, both in UCP1-TG and DTG mice. Moreover, glucose tolerance, insulin sensitivity and fatty acid oxidation were not altered in DTG compared to UCP1-TG. Also uncoupling induced induction and secretion of fibroblast growth factor 21 (FGF21) from SM was preserved in DTG mice. However, voluntary physical cage activity as well as ad libitum running wheel access during night uncovered a severe activity intolerance of DTG mice. Histological analysis showed a progressive degenerative morphology in SM of DTG mice which was not observed in SM of UCP1-TG mice. Moreover, ATP-depletion related cellular stress response via heat shock protein 70 was highly induced, whereas capillarization regulator VEGF was suppressed in DTG muscle. In addition, AMPKα2-mediated induction of mitophagy regulator ULK1 was suppressed in DTG mice, as well as mitochondrial respiratory capacity and content. In conclusion, we demonstrate that AMPKα2 is dispensable for SM mitochondrial uncoupling induced metabolic effects on whole body energy balance, glucose homeostasis and insulin sensitivity. But strikingly, activation of AMPKα2 seems crucial for maintaining SM function, integrity and the ability to compensate chronic metabolic stress induced by SM mitochondrial uncoupling.

Sensitivity Enhancement in Magnetic Particle Imaging by Background Subtraction

Biomedical applications such as cell tracking and angiography require the detection of low concentrations of superparamagnetic iron oxide nanoparticles (SPIOs) for imaging purposes. Magnetic particle imaging (MPI) is a new technology which enables the quantitative and time-resolved localization of SPIO distributions. However, the minimum concentration at which the SPIOs can be reconstructed with a suitable quality still remains to be investigated. In this work we examine the background signals in raw data that were measured without any SPIOs in the scanner tube. We show that a background subtraction in combination with a frequency cutoff for the dynamic part of the background signal lowers the detection limit for SPIOs in MPI up to a factor of ten. In-vivo mouse experiments show that for early time points from when the tracer enters the vena cava a reconstructed image of sufficient quality can only be obtained when a background subtraction is performed.

Artifact free reconstruction with the system matrix approach by overscanning the field-free-point trajectory in magnetic particle imaging.

Magnetic particle imaging is a tracer-based imaging method that utilizes the non-linear magnetization response of iron-oxide for determining their spatial distribution. The method is based on a sampling scheme where a sensitive spot is moved along a trajectory that captured a predefined field-of-view (FOV). However, particles outside the FOV also contribute to the measurement signal due to their rotation and the non-sharpness of the sensitive spot. In the present work we investigate artifacts that are induced by particles not covered by the FOV and show that the artifacts can be mitigated by using a system matrix that covers not only the region of interest but also a certain area around the FOV. The findings are especially relevant when using a multi-patch acquisition scheme where the boundaries of neighboring patches have to be handled.

Magnetic Particle Imaging for High Temporal Resolution Assessment of Aneurysm Hemodynamics

Purpose The purpose of this work was to demonstrate the capability of magnetic particle imaging (MPI) to assess the hemodynamics in a realistic 3D aneurysm model obtained by additive manufacturing. MPI was compared with magnetic resonance imaging (MRI) and dynamic digital subtraction angiography (DSA). Materials and Methods The aneurysm model was of saccular morphology (7 mm dome height, 5 mm cross-section, 3–4 mm neck, 3.5 mm parent artery diameter) and connected to a peristaltic pump delivering a physiological flow (250 mL/min) and pulsation rate (70/min). High-resolution (4 h long) 4D phase contrast flow quantification (4D pc-fq) MRI was used to directly assess the hemodynamics of the model. Dynamic MPI, MRI, and DSA were performed with contrast agent injections (3 mL volume in 3 s) through a proximally placed catheter. Results and Discussion 4D pc-fq measurements showed distinct pulsatile flow velocities (20–80 cm/s) as well as lower flow velocities and a vortex inside the aneurysm. All three dynamic methods (MPI, MRI, and DSA) also showed a clear pulsation pattern as well as delayed contrast agent dynamics within the aneurysm, which is most likely caused by the vortex within the aneurysm. Due to the high temporal resolution of MPI and DSA, it was possible to track the contrast agent bolus through the model and to estimate the average flow velocity (about 60 cm/s), which is in accordance with the 4D pc-fq measurements. Conclusions The ionizing radiation free, 4D high resolution MPI method is a very promising tool for imaging and characterization of hemodynamics in human. It carries the possibility of overcoming certain disadvantages of other modalities like considerably lower temporal resolution of dynamic MRI and limited 2D characteristics of DSA. Furthermore, additive manufacturing is the key for translating powerful pre-clinical techniques into the clinic.

First experimental comparison between the Cartesian and the Lissajous trajectory for magnetic particle imaging

Magnetic particle imaging (MPI) is a quantitative imaging modality that allows us to determine the distribution of superparamagnetic nanoparticles. Sampling is achieved by moving a field-free point (FFP) along a specific trajectory through the volume of interest. The magnetic material that lies along the path or in the close vicinity of the FFP changes its magnetization and induces a voltage in the surrounding receiver coils. Various trajectories for the FFP are conceivable, but most experimental MPI scanners either use a Cartesian or a Lissajous sampling trajectory. For the first time, this study compares both sampling methods experimentally using an MPI scanner that allows us to implement both sampling patterns. By default, the scanner is capable of scanning 2D and 3D field of views using a Lissajous trajectory. But since it also has a 1D mode, it is possible to perform Cartesian measurements by shifting the 1D scan line in a perpendicular direction to the FFP movement using the focus field. These line scans are jointly reconstructed to obtain a 2D image. In a further step, the unidirectional Cartesian trajectory is improved by interchanging the excitation and the focus-field direction leading to a bidirectional Cartesian trajectory. Our findings reveal similar results for the bidirectional Cartesian and Lissajous trajectory concerning the overall image quality and sensitivity. In a more detailed view, the bidirectional Cartesian trajectory achieves a slightly higher spatial center resolution, whereas the Lissajous trajectory is more efficient regarding the temporal resolution since less acquisition time is needed to reach an adequate image quality.

Geometrieplanung und Bildregistrierung mittels bimodaler Fiducial-Marker für Magnetic Particle Imaging

Magnetic Particle Imaging (MPI) ist ein Bildgebungsverfahren, welches die Visualisierung der raumlichen Verteilung superparamagnetischer Nanopartikel ermoglicht. Im Gegensatz zu anderen Bildgebungsmodalit aten liefert MPI keine morphologische Information, was die Positionierung des darzustellenden Objektes im Magnetfeldzentrum und die Interpretation von MPI-Bildern erschwert. Daher werden zusatzlich Daten einer morphologischen Bildgebungsmodalitat akquiriert und mit den MPI-Daten uberlagert. Um die Bildregistrierung beider Modalit aten automatisieren zu konnen, werden in dieser Arbeit bimodale Fiducial-Marker entwickelt. Die Marker ermoglichen im MPI zusatzlich eine prazise Positionierung.