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Techn. University, Diss., 2003--Freiberg (Sachsen).

Techn. Universiẗat, Diss., 2003--Berlin.

Techn. Universiẗat, Diss., 2002--Darmstadt.

Universiẗat, Diss., 2004--Kiel.

University, Diss., 2002--Kiel.

Techn. Universiẗat, Diss., 2004--Berlin.

University, Diss., 2005--Frankfurt (Main). / Zsfassung in engl. und dt. Sprache.

Today tumour diseases are the second most cause of death in Western countries. But only 45 percent of the patients can be cured by the established treatment methods. The further improvement of the these forms of therapy and the development of new therapeutical approaches is urgent. A substantial proportion of the patients could benefit from particle therapy with heavy ions. Beams of accelerated heavy ions (e.g. carbon, nitrogen or oxygen) with an energy between 70 and 500 AMeV are characterised by physical and biological properties superior to the radiation used in conventional radiotherapy (photons, electrons, neutrons). They form a sharp dose maximum (Bragg peak) shortly before coming to rest and are scarcely scattered while penetrating tissue. Because of the increased relative biological efficiency of these ions in the Bragg peak region they are suitable for precision therapy of deeply seated, compact, radioresistant tumours near to organs at risk. For a safe application of heavy ions close to radiosensitive structures (brain stem, optical nerves, eyes) an in situ monitoring of the therapy is desirable. This can be accomplished by positron emission tomography (PET), since fragmentation reactions between the stable ions of the therapy beam and the atomic nuclei of the tissue generate a dynamic spatial distribution of positron emitters (ß+-emitters) that can be observed by a positron camera. At the Gesellschaft für Schwerionenforschung in Darmstadt a medical treatment site for heavy ion therapy has been established in co-operation with the Radiologische Universitätsklinik Heidelberg, the Deutsches Krebsforschungszentrum Heidelberg and the Forschungszentrum Rossendorf. The fast variation of the beam energy in conjunction with the vertical and horizontal beam deflection by dipole magnets (raster scanning) allows the three-dimensional, strictly tumour shape conformed irradiations. The dual head positron camera BASTEI has been installed at the treatment place in order to measure the decay of the ß+-emitters during the irradiation and a few minutes after. Two ways to verify the treatment plan by PET are possible. # In critical situations when the beam has to pass very heterogeneous structures and radiosensitive organs are situated in the direction of the beam behind the Bragg peak, a monoenergetic low dose beam pulse can be applied to the patient. The range of the particles can be derived from the simultaneous PET scan, so that the correct range calculation of the treatment plan is ensured before the therapeutical irradiations are started. # During each fraction of the heavy ion therapy the ß+-activity distributions are measured routinely. Based on the time course of every individual therapy fraction the expected ß+-emitter distribution is computed. By comparing the simulated with the measured data the precision of the dose deposition of this single therapy fraction is assessed. If a considerable disagreement between these two distributions is revealed by this comparison the treatment plan has to be modified before proceeding with the following therapy fraction. The PET data are recorded in list mode, together with a protocol of important accelerator parameters of the irradiation. Because of the half-lives of the most abundant ß+-emitters 11C and 15O it is on principle impossible to obtain the precise position of the 12C therapy beam by PET during the irradiation. …

Cardiovascular disease is one of the leading causes of death worldwide and, so far, echocardiography, nuclear cardiology, and catheterization are the gold standard techniques used for its detection. Cardiac magnetic resonance (CMR) can replace the invasive imaging modalities and provide a "one-stop shop" characterization of the cardiovascular system by measuring myocardial tissue structure, function and perfusion of the heart, as well as anatomy of and flow in the coronary arteries. In contrast to standard clinical magnetic resonance imaging (MRI) scanners, which are often operated at a field strength of 1.5 or 3 Tesla (T), a higher resolution and subsequent cardiac parameter quantification could potentially be achieved at ultra-high field, i.e., 7 T and above. Unique insights into the pathophysiology of the heart are expected from ultra-high field MRI, which offers enhanced image quality in combination with novel contrast mechanisms, but suffers from spatio-temporal B0 magnetic field variations. Due to the resulting spatial misregistration and intra-voxel dephasing, these B0-field inhomogeneities generate a variety of undesired image artifacts, e.g., artificial image deformation. The resulting macroscopic field gradients lead to signal loss, because the effective transverse relaxation time T2* is shortened. This affects the accuracy of T2* measurements, which are essential for myocardial tissue characterization. When steady state free precession-based pulse sequences are employed for image acquisition, certain off-resonance frequencies cause signal voids. These banding artifacts complicate the proper marking of the myocardium and, subsequently, systematic errors in cardiac function measurements are inevitable. Clinical MR scanners are equipped with basic shim systems to correct for occurring B0-field inhomogeneities and resulting image artifacts, however, these are not sufficient for the advanced measurement techniques employed for ultra-high field MRI of the heart. Therefore, this work focused on the development of advanced B0 shimming strategies for CMR imaging applications to correct the spatio-temporal B0 field variations present in the human heart at 7 T. A novel cardiac phase-specific shimming (CPSS) technique was set up, which featured a triggered B0 map acquisition, anatomy-matched selection of the shim-region-of-interest (SROI), and calibration-based B0 field modeling. The influence of technical limitations on the overall spherical harmonics (SH) shim was analyzed. Moreover, benefits as well as pitfalls of dynamic shimming were debated in this study. An advanced B0 shimming strategy was set up and applied in vivo, which was the first implementation of a heart-specific shimming approach in human UHF MRI at the time. The spatial B0-field patterns which were measured in the heart throughout this study contained localized spots of strong inhomogeneities. They fluctuated over the cardiac cycle in both size and strength, and were ideally addressed using anatomy-matched SROIs. Creating a correcting magnetic field with one shim coil, however, generated eddy currents in the surrounding conducting structures and a resulting additional, unintended magnetic field. Taking these shim-to-shim interactions into account via calibration, it was demonstrated for the first time that the non-standard 3rd-order SH terms enhanced B0-field homogeneity in the human heart. However, they were attended by challenges for the shim system hardware employed in the presented work, which was indicated by the currents required to generate the optimal 3rd-order SH terms exceeding the dynamic range of the corresponding shim coils. To facilitate dynamic shimming updated over the cardiac cycle for cine imaging, the benefit of adjusting the oscillating CPSS currents was found to be vital. The first in vivo application of the novel advanced B0 shimming strategy mostly matched the simulations. The presented technical developments are a basic requirement to quantitative and functional CMR imaging of the human heart at 7 T. They pave the way for numerous clinical studies about cardiac diseases, and continuative research on dedicated cardiac B0 shimming, e.g., adapted passive shimming and multi-coil technologies. / Herz-Kreislauf-Erkrankungen zählen zu den häufigsten Todesursachen weltweit und werden bisher in der Regel mittels Echokardiographie, Nuklearkardiologie und Katheterisierung untersucht. Die kardiale Magnetresonanztomographie hat das Potential diese invasiven Bildgebungsmodalitäten zu ersetzen. Dabei können sowohl das kardiovaskuläre System anhand der myokardialen Gewebestruktur sowie der Funktion und Perfusion des Herzens als auch Anatomie und Blutfluss der Koronararterien während einer einzigen Untersuchung charakterisiert werden. Im Gegensatz zu den weit verbreiteten klinischen Magnetresonanztomographie- (MRT) Geräten, welch häufig bei magnetischen Feldstärken zwischen 1.5 und 3T operieren, ermöglichen Feldstärken von 7 Tesla und mehr eine höhere Auflösung und somit eine akkuratere Quantifizierung kardialer Parameter. Die Ultrahochfeld-Magnetresonanztomographie (UHF-MRT) ermöglicht einzigartige Einblicke in die Pathophysiologie des Herzens. Neuartige Kontrastmechanismen und die verbesserte Bildqualität leiden jedoch unter Inhomogenitäten des statischen magnetischen B0-Feldes. Aufgrund der daraus resultierenden falschen räumlichen Registrierung der Voxel und einer Dephasierung des Signals innerhalb eines Voxels erzeugen diese Inhomogenitäten des B0-Feldes eine Vielzahl unerwünschter Bildartefakte, beispielsweise eine künstliche Deformation des Bildes. Die resultierenden makroskopischen Gradienten führen zu Signalverlust und beeinträchtigen die Messung der effektiven transversalen T2*-Relaxationszeit, welche für die Charakterisierung myokardialen Gewebes essentiell ist. Vor allem bei der Bildakquisition mittels der Steady State Free Precession Methode führen Inhomogenitäten des B0-Feldes zu Signalauslöschungen. Die dadurch entstehenden Bildartefakte erschweren die genaue Markierung des Myokards und haben so systematische Fehler bei der Bestimmung der kardialen Funktion zur Folge. Klinische MRT-Geräte sind dabei mit sogenannten Shim-Systemen ausgestattet um die Inhomogenitäten des B0-Feldes zu korrigieren. Für die kardiale UHF-MRT des Herzens sind diese standardisierten Shim-Systeme allerdings nicht mehr ausreichend. Im Fokus stand deshalb die Entwicklung moderner Methoden zur räumlichen und zeitlichen Korrektur der B0-Inhomogenitäten, welche als „Shimming“ bezeichnet wird, für die kardiale UHF-MRT. Es wurde eine neue, herzphasen-spezifische Shimming-Strategie untersucht, welche auf der getriggerten Datenaufnahme, der Optimierung für die Anatomie des Herzens, sowie der kalibrierungsbasierten Modellierung des korrigierenden Magnetfeldes basierte. Zudem wurde der Einfluss technischer Limitationen der Hardware auf das Shimming, insbesondere das dynamische Shimming, in dieser Studie erörtert. Schließlich wurde die entwickelte neuartige Shimming-Strategie in vivo evaluiert, welche zu diesem Zeitpunkt die erste Implementierung einer herzspezifischen Shimming-Strategie in der humanen kardialen UHF-MRT darstellte. Räumlich wies das B0-Feld, welches im Rahmen dieser Studie im Herzen gemessen wurde, lokalisierte Inhomogenitäten im Myokardium auf. Diese variierten zudem in ihrer Größe sowie der Stärke der B0-Inhomogenität zeitlich über den Herzzyklus hinweg und ließen sich mittels anatomisch angepasstem, kalibrierungsbasiertem Shimming deutlich reduzieren. Erzeugt man ein korrigierendes Magnetfeld mittels einer Shim-Spule, so werden jedoch Wirbelströme in nahen leitenden Strukturen und weiterhin ein zusätzliches, unerwünschtes Magnetfeld erzeugt. Berücksichtigt man diese Wechselwirkungen zwischen den verschiedenen Shim-Spulen, konnte erstmalig der Vorteil von korrigierenden Magnetfeldern in der Form von Kugelflächenfunktionen der dritten Ordnung für die kardiale UHF-MRT gezeigt werden. Hierbei waren jedoch die erforderlichen, besonders starken Ströme in den Shim-Spulen zu berücksichtigen, welche über den Herzzyklus hinweg oszillierten und für dynamisches Shimming angepasst werden sollten. Die erste in vivo Anwendung der neu entwickelten Shim-Strategie stimmte gut mit den vorigen Simulationen überein. Die vorgestellten technischen Entwicklungen stellen grundlegende Anforderungen an die quantitative und funktionelle kardialer UHF-MRT dar. Klinische Studien zu kardialen Erkrankungen wie der Herzinsuffizienz erscheinen nun ebenso in Reichweite wie weitere Forschung zu kardialem B0-Shimming basierend auf angepasstem passiven Shimming sowie Multikanal-Spulen.