E-Dissertationen

Calibration-free parallel-transmit RF pulse design for 7 T-MRI of the brain

2026-07-03T05:16:34Z

Calibration-free parallel-transmit RF pulse design for 7 T-MRI of the brain Löwen, Daniel Magnetic resonance imaging (MRI) is a versatile imaging modality that has substantially advanced clinical diagnostics by enabling early and accurate detection of disease. However, the inherently low signal-to-noise ratio (SNR) of MRI remains a fundamental limitation and continues to motivate methodological developments.
An established strategy to increase SNR is the use of higher static magnetic field strengths, which enhance thermal equilibrium spin polarization and thereby improve signal levels. Nevertheless, operation at ultra-high field (UHF) strengths (≥ 7T) introduces additional challenges, most notably spatial inhomogeneities of the radiofrequency (RF) excitation field caused by wave interference effects at high frequencies. These effects result in spatially varying flip angles, signal non-uniformity, and local signal dropouts.
Parallel transmission (pTx) has emerged as an effective technique to mitigate RF field inhomogeneities by enabling spatially tailored RF excitation through multiple independently driven transmit channels. Despite its technical advantages, the routine use of pTx remains limited due to the requirement for time-consuming subject-specific calibration measurements prior to each imaging session. Such calibrations increase workflow complexity, require expert supervision, and are not guaranteed to yield robust results.
This thesis advances the concept of universal pulses (UPs), which are calibration-free ("plug-and-play") pTx RF pulses designed to operate reliably across subjects without subject-specific calibration. By eliminating subject-specific calibration, UPs improve the robustness, efficiency, and accessibility of UHF MRI. Application-specific UPs were developed for clinically relevant sequences, including chemical exchange saturation transfer (CEST) imaging and 3D single-slab variable flip angle turbo spin echo (TSE) imaging. In addition, UPs were designed for more general application enabling homogeneous slice- or slab-selective excitation or simultaneous water excitation with fat suppression.
Furthermore, the Gradient Ascent Pulse Engineering (GRAPE) algorithm was systematically adapted for applications that previously suffered from limited homogenization performance, sensitivity to static field inhomogeneities, or long durations due to limited flexibility in the design of parameterized RF pulses. Short, unparameterized GRAPE pulses were developed to improve excitation homogeneity, robustness to field inhomogeneities, and time-efficiency for both spatially and spectrally selective RF excitation.

Multi-Extended Object Tracking with Generalized Physical Models

2026-07-03T05:10:37Z

Multi-Extended Object Tracking with Generalized Physical Models Hoher, Patrick The objective of sensor data processing is to extract the most informative knowledge possible by fusing prior information with imperfect sensor measurements. This dissertation focuses on model-based approaches for multiple extended object tracking that represent sensor and object characteristics as accurately as possible based on physical principles.
In the first part, a novel approach for extended object tracking is presented. First, the measurement spread and center of gravity are estimated using a known approach from the literature. Subsequently, synthetic data are generated for a hypothetical estimate based on Virtual Measurement Models (VMMs), and the center of gravity and spread of these synthetic measurements are compared with those of the real measurements. Based on the resulting error, the test estimate is adaptively adjusted. The stability and convergence of this adaptation algorithm are proven in this dissertation. Virtual measurement models can represent arbitrary sensor and shape characteristics, enabling, for example, the accurate modeling of lidar sensors through a combination of contour and interior measurements. Assumptions that measurements are uniformly distributed over the contour or volume of an object are therefore not required.
If it is unknown which shape best represents the object, or whether the measurements originate from the contour, the interior, or a combination of both, multiple virtual measurement models can be applied in parallel. The resulting artificial measurements can then be used for classification purposes.
To evaluate the proposed VMM approach, extensive simulations are conducted and real recorded lidar data are analyzed, primarily originating from maritime scenarios. The VMM approach is particularly suitable for such environments because the objects encountered can be described very well by basic geometric shapes. For example, the shape of a motorboat resembles an ellipsoid, whereas a sailboat can be approximated effectively by an elliptical cone.
The second part of this dissertation addresses the birth densities of tracking algorithms and the initialization required when an object is detected for the first time. Existing approaches place birth densities wherever measurements were observed in the previous time step. In scenarios with many false measurements, however, this leads to high computational costs and increases the risk of false detections. Therefore, the birth density is modeled here based on physical properties: the sensing range of a sensor is limited, and under unobstructed visibility, newly appearing objects must enter the surveillance area through its boundary; otherwise, they would already have been detected earlier and would therefore not be new. However, the exact location and width of this surveillance boundary must be determined adaptively. For this purpose, information about the initial positions of previously detected objects can be exploited. Since point symmetry can be assumed, particularly for lidar sensors with 360° coverage, a circular birth density in polar coordinates is introduced. The adaptive birth densities are evaluated extensively in simulation studies, and their relevance in real-world environments is demonstrated using a maritime scenario.

Chemogenetic G Protein-Ligand Pairs for Causal Investigation of Cellular Biology In Vitro and In Vivo

2026-07-02T12:11:18Z

Chemogenetic G Protein-Ligand Pairs for Causal Investigation of Cellular Biology In Vitro and In Vivo Alenfelder, Judith The targeted pharmacological inhibition of signaling pathways is an appealing experimental approach for deconvoluting signal transduction downstream of G protein-coupled receptors (GPCRs). A powerful and broadly used molecule to pharmacologically inhibit Gq, G11, and G14 heterotrimers with remarkable specificity is the natural depsipeptide FR900359 (FR). FR prevents nucleotide exchange on the Gα subunit and, consequently, its activation, and can, therefore, be used as a tool to study the contribution of Gq family proteins to complex cellular processes. Similar specific inhibitors for other G protein families are urgently needed, as their availability would tremendously advance the field. Despite extensive efforts, developing such molecules has proven extremely challenging, and no suitable cell-permeable compounds have been identified to date.
To overcome this lack of specific inhibitors, we suggest harnessing the specificity of FR by placing the remaining G protein families under its direct pharmacological control. This strategy involves creating artificial FR binding sites to construct a modular "chemogenetics-like" toolkit, from which engineered FR-sensitive G protein subtypes can selectively be chosen. In this thesis, as a first step towards such a toolbox, we aimed to design and validate FR-resistant Gαq isoforms that remain fully functional and can be employed in vivo.
We selected the fruit fly, Drosophila melanogaster, as our experimental model due to its genetical tractability and potential for the detailed dissection of signaling circuits in vivo. We rationally designed Drosophila Gαq (DGq) variants that retain wildtype-like signaling properties and display markedly reduced FR sensitivity. These mutants were characterized in HEK293 cells using a suite of assays covering G protein dissociation, downstream signaling, and whole-cell activation. Several mutants were excluded from further studies due to poor expression, aberrant subcellular localization or residual FR sensitivity. Ultimately, we succeeded in developing DGq proteins combining wild type-like behavior with robust resistance to FR that qualified for proof-of-concept experiments in vivo.
FR exhibits dose-dependent oral lethality in insects, an effect that we exploited to investigate whether lethality is causally linked to Gq inhibition. By ubiquitously overexpressing our DGαq variants, we rescued the FR-induced lethality in Drosophila without any obvious adverse effects, providing direct experimental proof that FR lethality in this model is mediated by Gq inhibition. Encouraged by these results, we introduced analogous mutations to murine Gαq, generating functional mGαq variants refractory to FR inhibition and suited for future application in live mice.
We envision our engineered Drosophila and mouse Gq protein-ligand pairs to serve as versatile chemogenetics-like tools for noninvasive, cell type-specific manipulation of Gq-mediated and -modulated signaling, enabling causal exploration of these pathways in vitro and in vivo.

Darstellung von Mehrfachbindungen zwischen Kobalt und den schweren Elementen der Tetrele

2026-07-02T12:08:00Z

Darstellung von Mehrfachbindungen zwischen Kobalt und den schweren Elementen der Tetrele Deckstein, Tobias Die Carbin-Komplexe stellen eine zentrale Klasse organometallischer Verbindungen dar und besitzen, wie ihre schweren Homologe, die Tetrelylidin-Komplexe, eine nahezu lineare M–E–R-Struktur mit sehr kurzen M–E-Bindungslängen (E = Si–Pb, M = Übergangsmetall, R = Substituent). Der metathetische Austausch von M≡C-Bindungen in Carbin‑Komplexen mit Alkine ist ein grundlegendes Prinzip der Alkinmetathese und verläuft über metallacyclobutadienartige Zwischenstufen. Die Dreifachbindungsspaltung von Ditetrelinen RE≡ER (E = Si–Pb, R = Substituent) an Metallzentren ist jedoch deutlich weniger erforscht. Bedingt durch das umgekehrte Verhältnis der Bindungsdissoziationsenergien bei schwereren Tetrel-Elementen |ΔH°(M≡E)| > |ΔH°(E≡E)|) im Vergleich zu Kohlenstoff (|ΔH°(C≡C)| > |ΔH°(M≡C)|), eröffnen sich neue Synthesewege für Tetrelylidin-Komplexe und bietet einen alternativen Zugang zur Synthese von Tetrelylidin-Komplexen jenseits klassischer Synthesemöglichkeiten. Ein bedeutender Fortschritt war die metathetische Austausch von [Mo(⁵-C₅H₅)₂(CO)₂]₂ mit Ditetrelinen RE≡ER (E = Ge–Pb, R = ArDipp; ArDipp = C₆H₃-2,6-(C₆H₃-2,6-ⁱPr₂)) zur Darstellung des Komplexes [Cp(CO)₂Mo≡ER]. In dieser Arbeit wird ein systematischer Ansatz zur effizienten Synthese des kationischen Bis-Germylidin-Komplexes [Co(GeMind)₂(PMe₃)₂][B(ArF)₄] durch die gezielte Spaltung der Ge≡Ge-Bindung mit dem Komplex [Co(PMe₃)₄][B(ArF)₄] vorgestellt. Die Vervollständigung der homologen Reihe von Kobalt-Tetrelylidin-Komplexen gelang zum einem durch eine Kobalt-zentrierte Spaltung der E≡E-Bindung der Ditetreline Ge₂Tbb₂ bzw. Sn₂ArDipp₂ mit [Co(PMe₃)₄]. Zusätzlich wird die Darstellung von Tetrelylidin-Komplexen mittels der klassischen Salz-Eliminierungsmethode durch Reaktionen von Tetrel(II)-Halogeniden mit K[Co(PMe₃)₄] beschrieben. Besonders erwähnenswert ist die Synthese des Silylidyne-Komplexes [Co(SiTbb)(PMe₃)₃], der durch eine bisher einzigartige metathetische Austauschreaktion zwischen Co≡Sn/Co≡Si- oder Co≡Pb/Co≡Si-Bindungen dargestellt wurde. Diese Ergebnisse demonstrieren erstmals einen neuartigen, nicht-Katz-basierten Mechanismus zur gezielten Umwandlung von M≡E-Bindungen. Die vorgestellte Methodik erweitert die Synthesemöglichkeiten für Tetrelylidin-Komplexe des Übergangsmetalls Kobalt mit den schweren Tetrel-Elementen und liefert zudem neue Einblicke in das Reaktionsverhalten und die Bindungseigenschaften von schweren Tetrelylidin-Komplexen des Übergangmetalls Kobalt.