Brustkrebs stellt eine der am häufigsten vorkommenden Krebserkrankungen bei Frauen weltweit dar. Jährlich erkranken in Deutschland ca. 47.000 Frauen neu an Brustkrebs, ca. 18.000 fallen dieser Krankheit im gleichen Zeitraum zum Opfer. Die Brustkrebsdiagnostik basiert auf klinische und verschiedene bildgebende Methoden, die Magnetresonanztomographie (MRT) weist dabei die höchste Sensitivität speziell bei der Erkennung kleiner Tumore unter 5 mm auf. Im Hinblick auf zukünftige Verbesserungen der MR-Bildgebung wird bereits vermutet, dass im Jahr 2010 ca. 50% der neudetektierten Brustkrebse kleiner als 10 mm sein werden. Zur Erhöhung der Diagnosesicherheit werden suspekte Läsionen sowie unklare bildgestützte Befunde zusätzlich mittels Biopsie abgeklärt. In Bezug auf den Stand der Technik ist die sichere Biopsie von Tumoren unter 10 mm Größe jedoch schwierig. Mit dem Ziel, die MR-gestützte Biopsie im Hinblick auf eine höhere Effizienz und Präzision zu verbessern, wurde ein neuer Prototyp für minimal invasive Biopsien speziell in geschlossenen MR-Tomographen entwickelt. Dieses MR-kompatible System basiert auf verschiedene Neukonzeptionen, mit einem automatischen Positioniersystem und Biopsieinstrument zur Ausführung der Intervention. Die extrem hohen Anforderungen an dieses System konnten nur durch spezielle Konstruktionen und Kinematiken, sowie durch MR-kompatible Materialien, Aktoren und Sensoren gelöst werden. Das System ist modular aufgebaut und unterstützt Brustbiopsien sowohl von cranial oder caudal im direkten Anschluss an die Tumorerkennung mit einer neuen doppelseitigen MR-Brustspule. Ein großer Vorteil dieses neuen Ansatzes liegt in der hohen Präzision und der Möglichkeit, sowohl die bildgebende Diagnostik als auch die Biopsie während eines Untersuchungstermines durchzuführen. Die vorklinische Erprobung in einem 1,5 T Hochfeld-MRT zeigte, dass die Zielabweichungen des Instrumentes geringer als 1 mm waren, so dass Interventionen mit hoher Genauigkeit und Reproduzierbarkeit durchführbar wären. Das System implementiert benutzerfreundliche Oberflächen für die Interventionsplanung und für die Gerätesteuerung. Das vorliegende Dissertation stellt die Konzepte und Ergebnisse dieser neuen Biopsieeinrichtung vor und nimmt Bezug auf zahlreiche wissenschaftliche Untersuchungen, insbesondere im Hinblick auf die Anwendung von Materialien und Aktoren im MRT-Magnetfeld. / Breast cancer is one of the most common cancer diseases which women suffer world wide. The incidence rate of breast cancer in Germany goes along with about 47.000 women per year, 18.000 fatal casualties were ascertained in the same period. The breast cancer diagnostic is based on clinical and different imaging methods, whereas Magnetic Resonance Imaging (MRI) is the most sensitive imaging modality in the detection of especially small lesions under 5 mm. Due to improvements of breast imaging - especially MRI - it has been predicted that by the year 2010 about 50% of newly diagnosed breast cancers will be less than 10 mm in size. However, to assure the image based breast cancer diagnosis, biopsies of tumor tissue are often necessary in order to avoid false specified results. With reference to the state of the art, it is still difficult to achieve sufficient accurate MRI-supported biopsies for tumor sizes of under 10 mm. To improve the MR-controlled diagnostic in respect of increasing the efficiency and precision of the biopsy method, a new apparatus for minimal invasive breast biopsies particularly for the use inside closed bore MRI-scanner was developed. This MR-compatible device is based on new concepts which meet the extremely high requirements on interventions in strong magnetic fields through special designs and kinematic concepts and the application of MR-compatible materials, actors and sensor systems. It is of a modular structure and consists mainly of an automated positioning unit and an integrated intervention tool. This new system makes it possible to do the breast interventions either from the cranial or the caudal position directly after tumor detecting with the use of a new double breast coil. A major advantage of this approach is the high accuracy and the possibility to realize image diagnostic and biopsy in one session. As the preclinical evaluation with a 1.5 T MRI-scanner showed, the deviation of the intervention device regarding instrument positioning to a located target was less than 1mm, so that interventions could be carried out precisely and reproducible. Furthermore there were no image interferences due to the additional materials in the MRI-isocenter. The system implements a user-interface for intervention planning on up-to-date MR images and device control. Besides the concepts and results of the new biopsy device, the present dissertation refers to numerous scientific investigations with a focus on material and actuator application in the magnetic field of a MRI-scanner.

No description available.

Background: Prophylactic mastectomies in carriers of mutations in BRCA1 or BRCA2 are becoming increasingly more accepted. We investigated the outcome after prophylactic mastectomy, especially regarding satisfaction with the procedure, in a monocenter study. Methods: BRCA1/2 mutation carriers and non-carriers with elevated pedigree-based cancer risk were followed prospectively in a structured surveillance program between 2000 and 2017. A retrospective telephone survey was conducted among all patients with documented prophylactic mastectomy. Complications and satisfaction with the decision for prophylactic mastectomy were recorded. Results: 39 patients who opted for a prophylactic mastectomy (38 BRCA1/2 mutation carriers and 1 noncarrier) were interviewed. Mostly nipple-sparing mastectomy with reconstruction was performed (87%). Half of the patients (22/39; 56.4%) had a history of unilateral breast cancer. The median time since prophylactic mastectomy was 5.6 years. While 61.5% did not report any complications, flap loss was seen in 15% (3/20) and moderate limitations in everyday life were present in 20% (7/35). An improvement in quality of life was noticed by 82% after prophylactic mastectomy and no patient expressed regret with regard to the decision. Conclusions: Prophylactic mastectomy is a procedure with risk for long-term complications in some cases. Our results confirm high satisfaction with the decision and improved quality of life.

No description available.

Determination of cell signalling behaviour is crucial for understanding the physiological response to a specific stimulus or drug treatment. Current approaches for large-scale data analysis do not effectively incorporate critical topological information provided by the signalling network. We herein describe a novel model- and data-driven hybrid approach, or signal transduction score flow algorithm, which allows quantitative visualization of cyclic cell signalling pathways that lead to ultimate cell responses such as survival, migration or death. This score flow algorithm translates signalling pathways as a directed graph and maps experimental data, including negative and positive feedbacks, onto gene nodes as scores, which then computationally traverse the signalling pathway until a pre-defined biological target response is attained. Initially, experimental data-driven enrichment scores of the genes were computed in a pathway, then a heuristic approach was applied using the gene score partition as a solution for protein node stoichiometry during dynamic scoring of the pathway of interest. Incorporation of a score partition during the signal flow and cyclic feedback loops in the signalling pathway significantly improves the usefulness of this model, as compared to other approaches. Evaluation of the score flow algorithm using both transcriptome and ChIP-seq data-generated signalling pathways showed good correlation with expected cellular behaviour on both KEGG and manually generated pathways. Implementation of the algorithm as a Cytoscape plug-in allows interactive visualization and analysis of KEGG pathways as well as user-generated and curated Cytoscape pathways. Moreover, the algorithm accurately predicts gene-level and global impacts of single or multiple in silico gene knockouts. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Determination of cell signalling behaviour is crucial for understanding the physiological response to a specific stimulus or drug treatment. Current approaches for large-scale data analysis do not effectively incorporate critical topological information provided by the signalling network. We herein describe a novel model- and data-driven hybrid approach, or signal transduction score flow algorithm, which allows quantitative visualization of cyclic cell signalling pathways that lead to ultimate cell responses such as survival, migration or death. This score flow algorithm translates signalling pathways as a directed graph and maps experimental data, including negative and positive feedbacks, onto gene nodes as scores, which then computationally traverse the signalling pathway until a pre-defined biological target response is attained. Initially, experimental data-driven enrichment scores of the genes were computed in a pathway, then a heuristic approach was applied using the gene score partition as a solution for protein node stoichiometry during dynamic scoring of the pathway of interest. Incorporation of a score partition during the signal flow and cyclic feedback loops in the signalling pathway significantly improves the usefulness of this model, as compared to other approaches. Evaluation of the score flow algorithm using both transcriptome and ChIP-seq data-generated signalling pathways showed good correlation with expected cellular behaviour on both KEGG and manually generated pathways. Implementation of the algorithm as a Cytoscape plug-in allows interactive visualization and analysis of KEGG pathways as well as user-generated and curated Cytoscape pathways. Moreover, the algorithm accurately predicts gene-level and global impacts of single or multiple in silico gene knockouts. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.