We have reacted several derivatives of the anticancer drug cisplatin with N-acetyl-Lcysteine (N-AcCys) and N-acetyl-L-methionine (N-AcMet), which are two of the primary amino acid targets of platinum. NMR spectroscopy was used to monitor the reactions and determine the effect the different ligands would have on the platinum reactivity. Several of the platinum compounds were tested at pH of 4 and 7, and with platinum:amino acid ratios of 1:1, 2:1 and 1:2. Competition reactions between cysteine and methionine were done to confirm which would react with the platinum compound first. [Pt(dien)(NO3)]+ reacts faster with methionine than with cysteine at both pH 4 and 7 at a 1:1:1 ratio. [Pt(N,N,N',N',N"-pentamethyldiethylenetriamine)(NO3)]+ reacts with methionine faster at pH 4 but with cysteine faster at pH 7. This is most likely due to the thiol in the cysteine starting to deprotonate around pH 7. [Pt(Me4en)(NO3)2] (Me4en = N,N,N',N'-tetramethylethylenediamine) forms several products with N-AcCys at both pH 4 and 7, with the amounts of the products varying depending on the ratio of platinum and Cys. Mass spectrometry indicated one product as {[Pt(Me4en)(H2O)]2(N-AcCys)}2+, with two platinum compounds coordinated to a single cysteine. Lastly Pt[(en)(NO3)2] when reacting with N-AcCys at a ratio of 1:1 will coordinate with 2 different Cys molecules. With an excess of Pt the complex prefers to bind to only 1 Cys.

Paramagnetic lanthanide ions have been investigated as possible MIR phantom materials and contrast agents. The aim of this study is to determine if it is possible to apply the well known Solomon-Bloembergen equations to solutions of paramagnetic lanthanide ions that have fast electron spin relaxation times, compared to Gadolinium, the most widely used ion for NMR. Studies of the relaxivity, frequency and temperature dependence, show that there is a considerable difference in those properties over the series. Chelation of the ions to EDTA and DTPA resulted in a decrease in the relaxivity which was directly proportional to the decrease in the number of water molecules in the inner co-ordination sphere. The fit of the Solomon-Bloembergen equations to the variable frequency and temperature relaxation times showed that theory is valid for the fast electron spin ions and allowed the calculation of the electron spin relaxation times. This showed that there is a difference of 5 orders of magnitude between Gadolinium, the ion demonstrated to have a slow electron spin relaxation time, and the remaining ions. The addition of EDTA chelated forms of these ions to agarose gels produced NMR phantom materials with relaxation time characteristics that could be chosen to fulfil a desired application. The biodistribution of Gd-DTPA was investigated using ESR and NMR. The concentration of Gd-DTPA in excised rat tissue, 20 minutes after intraperitoneal injection, was determined, by the change in NMR water proton relaxation time from that of a control tissue, and by ESR from direct measurement of the microwave power absorbed by the sample, which is directly proportional to the number of unpaired electron spins in the sample. The results from these two methods of determining contrast agent concentration agree well with each other both in the order of biodistribution and on the absolute concentrations.

The phase-encoded method of NMR flow imaging is examined in detail. The motion of isochromatic groups in the direction of suitably balanced magnetic field gradients will give a phase change in the NMR signal directly proportional to the velocity, acceleration, or higher derivative of position, dependent upon the form of the field gradient. If a simple bipolar pulse is used then the phase change, for isochromats moving with constant velocity, will be proportional to the velocity. If two such pulses are placed back to back then the phase change is proportional to the acceleration. The motion of isochromats in the magnetic field gradients used for imaging will also cause phase changes. These effects are considered, and simple methods of reducing them presented. Phase errors due to main field inhomogeneity are shown to be eliminated by a simple phase difference technique. In this two image data sets having different flow sensitivities are obtained, and the phase difference between them calculated. Velocity images were obtained using this technique, both by the manipulation of the frequency-encoding and selection gradients, and by the insertion of bipolar pulses in the imaging sequence. Acceleration images were also produced by adding double bipolar pulses to the imaging sequence. Both spin-echo and field-echo sequences were used. Field-echo sequences were shown to be superior for high velocities, particularly when the direction of flow is through the slice, otherwise spin-echo sequences were preferred. The Fourier imaging of velocity is also examined, and images presented. This technique is only considered to be useful for projective imaging, where it is shown to have an SNR advantage over established methods. Using two specially designed phantoms the accuracy of all these techniques is shown to be within 5%.

This thesis describes the study of a series of platinum complexes, with particular emphasis towards hydrosilation. Platinum bis(phosphine) azodicarbonyl complexes Pt(PRI 3)2(R20CNNCOR2) (RI = Ph, Me; R2 = Ph, Me, OEt, Pri) were synthesised and studied. Multinuclear NMR spectroscopy on Pt(PRI3)2(R20CNNCOR2) revealed that the dicarbonyl substituted azo ligand is co-ordinated asymmetrically, consistent with a five membered, Pt-N-N-C-O ring. The crystal structure of Pt(PPh3)2(Pri02CNNC02Pri) shows that the co-ordination sphere of platinum is essentially square planar and co-planar with the five-membered, Pt(1)-0(1)-C(5)-N(2)-N(1) ring. The Pt(PRI 3)lR20CNNCOR2) complexes show sensitivity towards chlorinated solvents (CH2CI2, CHCI3) under photolysis conditions forming the corresponding platinum bis(phosphine) dichloride complexes; the same products are formed in a slower thermal reaction but only for complexes with azodicarboxylate ligands. Complexes with azodicarboxylate ligands also react photochemically with ethylene in ds-THF yielding Pt(PPh3)2(C2H4) but the azodiacyl analogues are inert in this respect. Azodicarboxylate compounds R02CNNC02R (R = Et, Pri, But) are inhibitors of the catalytic activity of [(Pt {174 _(CH2=CHSiMe2hO }h {.u-( CH2=CHSiMe2)20}] for the hydrosilation reaction. The inhibited species can be decomposed thermally or photoch~mically to give active hydrosilation catalysts. It was found that the bulky azo compound But02CNNC02But was the least effective inhibitor of [(Pt{ 174 - '(CH2=CHSiMe2hO} )2(P-( CH2=CHSiMe2)20)]. The photochemistry of platinum bis(phosphine) malonates and phthalates was found to be limited, and their reactivities were much lower compared to the analogous oxalate complexes. Silyl hydride complexes, cis-Pt(PCY3)2(H)(SiR3), were synthesised from the reaction of Pt(PCY3)2 and the corresponding silane. These complexes were undergo dynamic exchange in solution. Two exchange processes were identified; the first involves mutual phosphine exchange, i.e. positional interchange between the hydride and the silyl ligands. The second process occurs at higher temperatures (above 290 K) and involves the elimination and re-addition of the silane ligand HSiR3. Thermodynamic and activation parameters are obtained for cis-Pt(PCY3)2(SiR3) (R = Ph, SiR3 = SiMe2CH2CH=CH2, SiMe2Et). The reaction of Pt(PCY3)2 with the disilane HSiMe2(l,2-C6~)SiMe2H is thought to form a Pt(IV) bis(silyl) dihydride trigonal bipyramidal species of the form, Pt(PCY3)(H)2[SiMe2(1,2-C6~)SiMe2]' where the hydride ligands are in the axial positions. All of the platinum silyl hydride complexes studied degrade thermally to form trans-Pt(PCY3)2(H)2 at, or above, room temperature.

Le paramagnétisme des actinides en solution a été caractérisé par RMN selon deux approches, l'une macroscopique et l'autre moléculaire. Dans la première approche, les susceptibilités magnétiques des ions les plus stables en solution de l'uranium au californium, et ce pour différents degrés d'oxydation (U(IV)-U(VI), Np(IV)-Np(V)-Np(VI), Pu(III)-Pu(IV)-Pu(VI), Am(III), Cm(III) et Cf(III)), ont été mesurées par RMN à l'aide de la méthode d'Evans. En milieu perchlorique, l'étude ducomportement paramagnétique des cations actinide a montré des déviations significatives par rapport à celui des lanthanides, particulièrement pour les ions actinide aux degré d'oxydation +III et +IV. En milieux chlorhydrique et nitrique, il a été observé que les comportements magnétiques des actinides suivaient l'ordre M(IV) > M(VI) > M(III) > M(V), correspondant à l'ordre généralement admis concernant le pouvoir complexant des ions actinide en solution aqueuse. Il a été démontré que la présence d'ions chlorure et nitrate en solution pouvait avoir un impact important sur le comportement magnétique de ces cations. Dans la deuxième approche, les déplacements chimiques des complexes paramagnétiques actinide(IV)-dipicolinate ont été étudiés et analysés en milieu diméthylformamide. Dans ces conditions expérimentales, il a été vérifié que le degré d'oxydation +IV des actinides en solution était stable en présence ou non de ligand ainsi que sur l'échelle de temps des analyses RMN. Les déplacements chimiques paramagnétiques des complexes limites 1 : 3 ont été étudiés à différentes températures. Les méthodes de séparation des contributions de contact et dipolaire habituellement utilisées pour les complexes de lanthanide(III) se sont avérées inapplicables dans le cas des complexes d'actinide(IV). / Paramagnetism of actinides in solution was characterized by NMR according to two approaches, a macroscopic one and a molecular one. In the first approach, magnetic susceptibilities of the most stable ions in solution from uranium to californium, for various oxidation states (U(IV)-U(VI), Np(IV)-Np(V)-Np(VI), Pu(III)-Pu(IV)-Pu(VI), Am(III), Cm(III) et Cf(III)), were measured by NMR by using the Evans' method. In perchloric medium, the paramagnetic behavior of actinide cations showed significant deviations compared with lanthanides, particularly for cations at oxidation state +III and +IV. In hydrochloric and nitric media, it was observed that actinide magnetic behaviors followed the order M(IV) > M(VI) > M(III) > M(V), corresponding to the generally admitted order concerning the complexing power of actinide cations. It was demonstrated that the presence of chloride and nitrate in solution could have an large impact on the magnetic behavior of these cations. In the second approach, chemical shifts of actinide(IV)-dipicolinate paramagnetic complexes were studied and analyzed in dimethylformamide. In these experimental conditions, the only presence of the oxidation state +IV in solution as well as the stability of the latter on the NMR analysis timescale were verified, in presence or not of the ligand. Paramagneticchemical shifts of the 1 : 3 limit complex were studied at various temperatures. Themethod of separation of the contact and dipolar contributions usually used for lanthanide(III) complexes have proved not applicable in the case of actinide(IV) complexes.

<p>Nucleic acids (DNA and RNA) play essential roles in the central dogma of biology for the storage and transfer of genetic information. The unique chemical and conformational structures of nucleic acids – the double helix composed of complementary Watson-Crick base pairs, provide the structural basis to carry out their biological functions. DNA double helix can dynamically accommodate Watson-Crick and Hoogsteen base-pairing, in which the purine base is flipped by ~180° degrees to adopt syn rather than anti conformation as in Watson-Crick base pairs. There is growing evidence that Hoogsteen base pairs play important roles in DNA replication, recognition, damage or mispair accommodation and repair. Here, we constructed a database for existing Hoogsteen base pairs in DNA duplexes by a structure-based survey from the Protein Data Bank, and structural analyses based on the resulted Hoogsteen structures revealed that Hoogsteen base pairs occur in a wide variety of biological contexts and can induce DNA kinking towards the major groove. As there were documented difficulties in modeling Hoogsteen or Watson-Crick by crystallography, we collaborated with the Richardsons’ lab and identified potential Hoogsteen base pairs that were mis-modeled as Watson-Crick base pairs which suggested that Hoogsteen can be more prevalent than it was thought to be. We developed solution NMR method combined with the site-specific isotope labeling to characterize the formation of, or conformational exchange with Hoogsteen base pairs in large DNA-protein complexes under solution conditions, in the absence of the crystal packing force. We showed that there are enhanced chemical exchange, potentially between Watson-Crick and Hoogsteen, at a sharp kink site in the complex formed by DNA and the Integration Host Factor protein. In stark contrast to B-form DNA, we found that Hoogsteen base pairs are strongly disfavored in A-form RNA duplex. Chemical modifications N1-methyl adenosine and N1-methyl guanosine that block Watson-Crick base-pairing, can be absorbed as Hoogsteen base pairs in DNA, but rather potently destabilized A-form RNA and caused helix melting. The intrinsic instability of Hoogsteen base pairs in A-form RNA endows the N1-methylation as a functioning post-transcriptional modification that was known to facilitate RNA folding, translation and potentially play roles in the epitranscriptome. On the other hand, the dynamic property of DNA that can accommodate Hoogsteen base pairs could be critical to maintaining the genome stability.</p> / Dissertation

Signal Amplification by Reversible Exchange (SABRE) is a hyperpolarization technique that utilizes parahydrogen for the NMR signal enhancement of nuclear spins. SABRE is related to Parahydrogen Induced Polarization (PHIP), another means of hyperpolarization using parahydrogen; PHIP achieves hyperpolarization via chemical reduction. Although PHIP and SABRE share many similarities in experimentation, PHIP ultimately requires the presence of an unsaturated chemical bond as well as pairwise-addition of parahydrogen. No permanent chemical change occurs during SABRE, and instead may be considered as a merely physical exchange between molecules with sites on a catalyst. PHIP and SABRE may be compared to Dynamic Nuclear Polarization (DNP), arguably the most well-known and researched method for hyperpolarization; despite all that has been achieved with DNP, PHIP and SABRE offer vastly more-rapid, less-expensive, and more-simplified approaches for achieving hyperpolarization. The focus of this work is experimentation with SABRE processes and methods designed to overcome certain experimental challenges associated with this technique.

Das Hauptziel der vorliegenden Arbeit war es, eine genauere Erkenntnis über die derzeitigen Möglichkeiten der quantitativen Messung der myokardiale Perfusion im Hinblick auf die Beschreibung verschiedener myokardialer Infarkte mittels kardialer MRT zu gewinnen. Die Untersuchungen zur Perfusion im Infarktgebiet ergaben, dass ein visuell festgestellter subendokardialer Infarkt an Hand der Bestimmung der absoluten Perfusion nicht immer nachvollzogen werden konnte. Ein Zusammenhang zwischen dem Auftreten eines no-reflow im Late Enhancement und der Höhe der absoluten Perfusion im Infarktgebiet konnte nicht gezeigt werden. Die Untersuchungen zur Perfusion im Remote Myokard ergaben keinen Zusammenhang zwischen der Perfusion im Remote Myokard und dem transmuralen Ausmaß des no-reflow-Phänomens in der First Pass Perfusion. Auch korrelierte die Perfusion im Remote Myokard nicht mit dem Auftreten eines no-reflow Phänomens im Late Enhancement. Die Perfusion im Remote Myokard unterschied sich zwischen transmuralen und nicht-transmuralen Infarkten. Eine Hyperperfusion im Remote Myokard konnte erst ab einer Infarktausdehnung von 75% im Late Enhancement beobachtet werden, während eine Hypoperfusion im Remote Myokard bei allen Infarktausdehnungen zwischen 0% und 100% auftrat. Die Untersuchungen zur Perfusion bei Vorliegen eines transmuralen Infarktes“ ergaben eine signifikante Korrelation der Perfusionen in Infarktgebiet und Remote Myokard bei transmuralem Infarkten. Die Ergebnisse zur Messung der Perfusion in Abhängigkeit von der relativen Infarktgröße wiesen keinen Zusammenhang zwischen der Perfusion im Infarktgebiet und der relativen Infarktgröße auf. Ebenso konnte keine Beziehung zwischen der Perfusion im Remote Myokard und der relativen Infarktgröße dargelegt werden. Letztendlich wurde das Verhalten der quantitativen Perfusion im Infarktgebiet und im Remote Myokard in Abhängigkeit von der Zeit nach Infarktereignis untersucht. Dabei zeigte sich kein Zusammenhang zwischen dem Auftreten eines no-reflow im Late Enhancement und der Entwicklung der Perfusion im Infarktgebiet zwischen der Erst- und der Spätuntersuchung. Ebenso war kein Zusammenhang zwischen dem Auftreten eines no-reflow im Late Enhancement und der Entwicklung der Perfusion im Remote Myokard zwischen der Erst- und der Spätuntersuchung erkennbar. Die kardiale MRT ist aufgrund der gleichzeitigen Analyse von morphologischen, funktionellen, quantitativen und metabolischen Parametern in einem Untersuchungsgang ein erfolgversprechendes Bildgebungsverfahren der Zukunft, da sie nicht invasiv ist, ohne Einsatz von Röntgenstrahlung auskommt und dabei eine gute räumliche Auflösung bei hohem Gewebekontrast bietet. Studien zeigen, dass die Kombination von Stress-Perfusion und Late-Technik in einem MRT-Protokoll eine höhere Genauigkeit als die Verwendung der SPECT-Untersuchung in der klinischen Beurteilung von Koronargefäßstenosen und im Nachweis subendokardialer Infarkte aufweist. 62 Allerdings erfährt die in vorliegender Arbeit verwendete Technik der Datenverarbeitung in dieser Form ohne Zweifel noch ihre Limitation im klinischen Alltag. Grundsätzlich ist zu sagen, dass die Messung der absoluten Perfusion im Myokard mit der MRT des Herzens zurzeit sicherlich noch nicht ausgereift ist. Dennoch lassen die in dieser Arbeit vorgestellten Ergebnisse und die viel versprechende Weiterentwicklung in der magnetresonanztomographischen Bildgebung weit reichende und interessante Möglichkeiten erahnen. / The aim of this work was to provide a more precise knowledge of the current possibilities for the quantitative measurement of myocardial perfusion in terms of the description of various myocardial infarcts using cardiac MRI. The analysis regarding the determination of a subendokardial infarction using the absolute perfusion in this area showed that the location of the infarction could not always been reproduced. A correlation between the occurrence of a no-reflow in Late Enhancement and the level of absolute perfusion in the area of infarction could not be shown. The analysis on the remote myocardial perfusion showed no coherence between myocardial perfusion in remote and the transmural extent of the no-reflow phenomenon in First-pass perfusion. Also the myocardial perfusion in remote myocardium did not correlate with the occurrence of a no-reflow phenomenon in Late Enhancement. The perfusion in remote myocardium differed between transmural and non-transmural infarctions. A hyperperfusion in remote myocardium was only seen with an extent of infarction of 75% and more in Late Enhancement while a hypoperfusion in remote myocardium occured with all infarction extents between 0% and 100%. The analysis regarding the perfusion when there was a transmural infarction showed a significant correlation of the perfusions in the area of infarcation and the remote myocardium. The results for the measurement of perfusion depending on the relative size of the infarction showed no coherence between the perfusion in the area of the infarction and relative size of it. Also there was no way of showing coherence between the myocardial perfusion in remote myocardium and the relative size of the infarction. Finally the behaviour of quantitative perfusion in the area of infarction and in the remote myocardium was investigated. The results showed no coherence between the occurrence of a no-reflow phenomenon in late enhancement and the development of the perfusion in the area of infarction between the first and the late data ascertainment. Also there was no coherence between the occurrence of a no-reflow in late enhancement and the development of the remote myocardium perfusion in between the first and the late data ascertainment. The cardiac MRI is due to the simultaneous analysis of morphological, functional, quantitative and metabolic parameters during one single investigation a promising imaging procedure of the future, because it is not invasive, without the use of X-rays and requires a good spatial resolution with high tissue contrast. Studies show that the combination of stress perfusion and late-MRI technique provide a higher accuracy in the clinical evaluation of coronary stenosis and subendocardial infarctions than the single use of the SPECT- technique. Without doubt the way of processing data used in this work still comes to its limits in everyday work and the technique of receiving data of the myocardial perfusion using cardiac MRI must still be developed. Nevertheless the results presented in this work and the promising progresses in the field of MRI imaging give a hint to the interesting and far reaching possibilities that are to come.

Die kardiale MRT konnte in dieser Arbeit für die Infarktdiagnostik und Therapiekontrolle erfolgreich eingesetzt werden. Auf Grund einer Vielzahl von Sequenztechniken, dem Vorteil der Nichtinvasivität und dem Fehlen von ionisierenden Strahlen hat sich die MRT zu einem wichtigen Diagnostikwerkzeug zur Bestimmung von Prognoseparametern bei kardialen Erkrankungen entwickelt. / Cardiac MRI could be used successfully for the diagnosis of myocardial infarction and for therapy control. Due to a multiplicity of MRI sequences, the advantage of a non invasive approach and the lack of ionising rays, MRI developed to an important diagnostic tool for the determination of parameters in cardiac diseases

Magnetic Resonance Imaging (MRI) is an imaging modality which provides anatomical or functional images of the human body with variable contrasts in an arbitrarily positioned slice without the need for ionizing radiation. In MRI, data are not acquired directly, but in the reciprocal image space (otherwise known as k-space) through the application of spatially variable magnetic field gradients. The k-space is made up of a grid of data points which are generally acquired in a line-by-line fashion (Cartesian imaging). After the acquisition, the k-space data are transformed into the image domain using the Fast Fourier Transformation (FFT). However, the acquisition of data is not limited to the rectilinear Cartesian sampling scheme described above. Non-Cartesian acquisitions, where the data are collected along exotic trajectories, such as radial and spiral, have been shown to be beneficial in a number of applications. However, despite their additional properties and potential advantages, working with non-Cartesian data can be complicated. The primary difficulty is that non-Cartesian trajectories are made up of points which do not fall on a Cartesian grid, and a simple and fast FFT algorithm cannot be employed to reconstruct images from non-Cartesian data. In order to create an image, the non-Cartesian data are generally resampled on a Cartesian grid, an operation known as gridding, before the FFT is performed. Another challenge for non-Cartesian imaging is the combination of unusual trajectories with parallel imaging. This thesis has presented several new non-Cartesian parallel imaging methods which simplify both gridding and the reconstruction of images from undersampled data. In Chapter 4, a novel approach which uses the concepts of parallel imaging to grid data sampled along a non-Cartesian trajectory called GRAPPA Operator Gridding (GROG) is described. GROG shifts any acquired k-space data point to its nearest Cartesian location, thereby converting non-Cartesian to Cartesian data. The only requirements for GROG are a multi-channel acquisition and a calibration dataset for the determination of the GROG weights. Chapter 5 discusses an extension of GRAPPA Operator Gridding, namely Self-Calibrating GRAPPA Operator Gridding (SC-GROG). SC-GROG is a method by which non-Cartesian data can be gridded using spatial information from a multi-channel coil array without the need for an additional calibration dataset, as required in standard GROG. Although GROG can be used to grid undersampled datasets, it is important to note that this method uses parallel imaging only for gridding, and not to reconstruct artifact-free images from undersampled data. Chapter 6 introduces a simple, novel method for performing modified Cartesian GRAPPA reconstructions on undersampled non-Cartesian k-space data gridded using GROG to arrive at a non-aliased image. Because the undersampled non-Cartesian data cannot be reconstructed using a single GRAPPA kernel, several Cartesian patterns are selected for the reconstruction. Finally, Chapter 7 discusses a novel method of using GROG to mimic the bunched phase encoding acquisition (BPE) scheme. In MRI, it is generally assumed that an artifact-free image can be reconstructed only from sampled points which fulfill the Nyquist criterion. However, the BPE reconstruction is based on the Generalized Sampling Theorem of Papoulis, which states that a continuous signal can be reconstructed from sampled points as long as the points are on average sampled at the Nyquist frequency. A novel method of generating the “bunched” data using GRAPPA Operator Gridding (GROG), which shifts datapoints by small distances in k-space using the GRAPPA Operator instead of employing zig-zag shaped gradients, is presented in this chapter. With the conjugate gradient reconstruction method, these additional “bunched” points can then be used to reconstruct an artifact-free image from undersampled data. This method is referred to as GROG-facilitated Bunched Phase Encoding, or GROG-BPE. / Die Magnetresonanztomographie (MRT) ist ein nichtinvasives bildgebendes Verfahren ohne Strahlenbelastung und eignet sich zur biomedizinischen Darstellung verschiedener Gewebetypen mit hoher räumlicher Auflösung und sehr gutem Kontrastverhalten. In der MRT erfolgt die Datenaufnahme im reziproken Bildraum – auch k-Raum genannt - welcher typischerweise entlang eines diskreten kartesischen Gitters abgetastet wird. Ein Bild erhält man schließlich durch eine schnelle Fouriertransformation der aufgenommenen k-Raum-Daten. Neben den kartesischen Akquisitionsschemata haben sich in den letzten Jahren auch vereinzelt nichtkartesische MRT-Verfahren in der klinischen Routine durchgesetzt. Solche nichtkartesischen Trajektorien erreichen eine hohe Abtasteffizienz, was zu einer Verkürzung der Messzeit führt. Die Schwierigkeit im Umgang mit nichtkartesischen Trajektorien liegt vor allem in der Tatsache begründet, dass nichtkartesisch akquirierte Datensätze vor Anwendung der schnellen Fouriertransformation auf ein kartesisches Gitter transformiert werden müssen („Gridding“). Hierzu gibt es eine Vielzahl von Verfahren, die von zahlreichen Parametern abhängen, womit ein hoher Aufwand und hohe Fehleranfälligkeit verbunden sind. Ein weiterer Nachteil dieser Gridding-Methoden ist, dass sie auf unvollständig aufgenommene Datensätze nicht angewendet werden können. Alternativ zu den konventionellen MR-Verfahren haben sich in den letzten Jahren die sogenannten parallelen Bildgebungsmethoden (beispielsweise SENSE oder GRAPPA) in der klinischen MRT etabliert, die mittlerweile von nahezu allen Herstellerfirmen kommerziell zur Verfügung gestellt werden. Die parallele Bildgebung erlaubt es, die Bildmesszeiten um einen Faktor 2 bis 4 zu verkürzen und lässt sich prinzipiell auf jede beliebige Bilgebungsmethode anwenden ohne dabei das Kontrastverhalten zu beeinflussen. In der klinischen Routine ist diese Technik allerdings lediglich auf kartesische MRT-Verfahren beschränkt, und es ist bisher noch nicht gelungen, die Vorteile der nichtkartesischen MRT-Verfahren optimal mit den Leistungsmerkmalen der parallelen MRT zu verknüpfen. Ziel dieser Arbeit war es, neue und effiziente Strategien zu entwickeln, um die nichtkartesische Magnetresonanztomographie für ein breiteres Anwendungsspektrum in der klinischen Praxis zu etablieren. Neben der Rekonstruktion von herkömmlich aufgenommenen nichtkartesischen Datensätzen sollten auch Verfahren entwickelt werden, die eine Kombination mit Messzeitverkürzungen durch parallele MRT-Verfahren erlauben. In Kapitel 4 wird ein neues paralleles Bildgebungsverfahren zum Gridding nichtkartesischer Datensätze namens „GRAPPA Operator Gridding“ (GROG) vorgestellt. GROG benutzt GRAPPA-ähnliche Gewichtungsfaktoren, um die nichtkartesischen Punkte auf ein kartesisches Gitter zu schieben. Im Gegensatz zu anderen Gridding-Methoden (wie beispielsweise dem „Convolution-Gridding“) werden bei der Anwendung von GROG Parameter wie Faltungskerne, Regularisierungswerte oder Funktionen nicht benötigt. Dies führt nicht nur zu einer erheblichen Vereinfachung des Griddingprozesses, sondern auch zur deutlichen Reduktion der Rechenoperationen. In Kapitel 5 wird eine Erweiterung des GROG-Algorithmus vorgestellt, welche ohne Kalibrierungsdatensätze auskommt („Self-Calibrating GROG“, SC-GROG). Die Gewichtungsfaktoren für die Verschiebungen der Datenpunkte werden in dieser Methode aus den akquirierten Punkten selbst gewonnen. Die erste Anwendung von GROG zur Vereinfachung der Rekonstruktion unvollständig aufgenommener nichtkartesischer Datensätze ist in Kapitel 6 beschrieben. Die Verwendung von GROG zur Transformation der unvollständig aufgenommenen nichtkartesischen Daten auf ein kartesisches Gitter erlaubt es, anschließend einen modifizierten GRAPPA-Algorithmus anzuwenden, und somit nichtkartesische Datensätze aus beschleunigten Experimenten zu rekonstruieren. Schließlich wurde GROG in Kapitel 7 auf die „Bunched Phase Encoding“ (BPE)-Methode angewendet. Bereits zuvor wurde gezeigt, dass das BPE-Verfahren in Verbindung mit einem „Conjugate Gradient“ Rekonstruktionsverfahren eine deutliche Verkürzung der Messzeit gestattet. Basierend auf dem verallgemeinerten Abtasttheorem nach Papoulis werden die Daten bei diesem Verfahren entlang einer extrem schnell oszillierenden Trajektorie aufgenommen. Nach Papoulis ermöglicht die lokal höhere Datendichte eine artefaktfreie Bildrekonstruktion trotz Unterabtastung in anderen k-Raumbereichen. Allerdings werden dabei erhebliche Ansprüche an die Gradienten-Hardware des Tomographen gestellt, wodurch das Konzept auf geringe Beschleunigungsfaktoren beschränkt wird. Im Rahmen dieser Arbeit konnte jedoch gezeigt werden, dass es möglich ist, auf dieses aufwändige Abtastschema zu verzichten, indem lediglich entlang einer regulären nicht-oszillierenden Trajektorie akquiriert wird und die höhere Datendichte nachträglich mittels GROG erreicht wird (GROG-BPE).