Characterization of Bone and its Microstructure using High-resolution 3D-MRI

Neue Therapieansätze durch Tissue Engineering erfordern gleichzeitig angepasste Diagnosemöglichkeiten und nicht-invasive Erfolgskontrollen. Speziell die 3D-MR-Bildgebung ist ein vielversprechendes Instrument, um Parameter mit hoher räumlicher Präzision zu quantifizieren. Vor diesem Hintergrund wurden im Rahmen dieser Arbeit neue Ansätze für die hochauflösende 3D-MRT in vivo entwickelt und deren Eignung im Bereich des Tissue Engineerings gezeigt. Welchen Vorteil die Quantifizierung von Parametern bietet, konnte im Rahmen einer prä-klinischen Studie an einem Modell der Hüftkopfnekrose gezeigt werden. Der Therapieverlauf wurde zu verschiedenen Zeitpunkten kontrolliert. Trotz der niedrigen räumlichen Auflösung, konnten durch eine systematische Auswertung der Signalintensitäten von T1- und T2-FS-gewichteten Aufnahmen Rückschlüsse über Veränderungen in der Mikrostruktur gezogen werden, die darüber hinaus in guter Übereinstimmung mit Ergebnissen von ex vivo µCT-Aufnahmen waren. Dort konnte eine Verdickung der Trabekelstruktur nachgewiesen werden, welche sehr gut mit einer Signalabnahme in den T1-gewichteten Aufnahmen korrelierte. Die radiale Auswertung der Daten erlaubte dabei eine komprimierte Darstellung der Ergebnisse. Dadurch wurde eine effiziente Auswertung der umfangreichen Daten (verschiedene Tiere an mehreren Zeitpunkten mit einer Vielzahl an Einzelaufnahmen) ermöglicht und eine unabhängige Bewertung erreicht. Um die Limitationen der begrenzten Auflösung von 2D-Multi-Schichtaufnahmen aufzuheben, wurden neue Ansätze für eine hochaufgelöste 3D-Aufnahme entwickelt. Hierfür wurden Spin-Echo-basierte Sequenzen gewählt, da diese eine genauere Abbildung der Knochenmikrostruktur erlauben als Gradienten-Echo-basierte Methoden. Zum einen wurde eine eigene 3D-FLASE-Sequenz entwickelt und zum anderen eine modifizierte 3D-TSE-Sequenz. Damit an Patienten Aufnahmen bei klinischer Feldstärke von 1,5 T mit einer hohen räumlichen Auflösung innerhalb einer vertretbaren Zeit erzielt werden können, muss eine schnelle und signalstarke Sequenz verwendet werden. Eine theoretische Betrachtung bescheinigte der TSE-Sequenz eine um 25 % höhere Signaleffizienz verglichen mit einer FLASE-Sequenz mit identischer Messzeit. Dieser Unterschied konnte auch im Experiment nachgewiesen werden. Ein in vivo Vergleich der beiden Sequenzen am Schienbein zeigte eine vergleichbare Darstellung der Spongiosa mit einer Auflösung von 160 × 160 × 400 µm. Für die Bildgebung des Hüftkopfs mit der neuen Sequenz waren jedoch aufgrund der unterschiedlichen Anatomie weitere Modifikationen notwendig. Um längere Messzeiten durch ein unnötig großes Field-of-View zu vermeiden, mussten Einfaltungsartefakte unterdrückt werden. Dies wurde durch die orthogonale Anwendung der Anregungs- und Refokussierungspulse in der TSE-Sequenz effizient gelöst. Technisch bedingt konnte jedoch nicht eine vergleichbare Auflösung wie am Schienbein realisiert werden. Der Vorteil der 3D-Bildgebung, dass Schichtdicken von deutlich weniger als 1 mm erreicht werden können, konnte jedoch erfolgreich auf den Unterkiefer übertragen werden. Der dort verlaufende Nervus Mandibularis ist dabei eine wichtige Struktur, deren Verlauf im Vorfeld von verschiedenen operativen Eingriffen bekannt sein muss. Er ist durch eine dünne knöcherne Wand vom umgebenden Gewebe getrennt. Im Vergleich mit einer 3D-VIBE-Sequenz zeigte die entwickelte 3D-TSE-Sequenz mit integrierter Unterdrückung von Einfaltungsartefakten eine ähnlich gute Lokalisierung des Nervenkanals über die gesamte Länge der Struktur. Dies konnte in einer Studie an gesunden Probanden mit verschiedenen Beobachtern nachgewiesen werden. Durch die neue Aufnahmetechnik konnte darüber hinaus die Auflösung im Vergleich zu bisherigen Studien deutlich erhöht werden, was insgesamt eine präzisere Lokalisierung des Nervenkanals erlaubt. Ein Baustein des Tissue Engineerings sind bio-resorbierbare Materialien, deren Abbau- und Einwachsverhalten noch untersucht werden muss, bevor diese für die klinische Anwendung zugelassen werden. Die durchgeführten in vitro µMR-Untersuchungen an Polymerscaffolds zeigten die reproduzierbare Quantifizierung der Porengröße und Wandstärke. Darüber hinaus wurde eine inhomogene Verteilung der Strukturparameter beobachtet. Die Ergebnisse waren in guter Übereinstimmung mit µCT-Aufnahmen als Goldstandard. Unterschiedliche Varianten der Scaffolds konnten identifiziert werden. Dabei bewies sich die MR-Bildgebung als zuverlässige Alternative. Insgesamt zeigen die Ergebnisse dieser Arbeit, welche Vorteile und Anwendungsmöglichkeiten die 3D-MRT-Bildgebung bietet, und dass auch mit klinischer Feldstärke in vivo Voxelgrößen im Submillimeterbereich für alle Raumrichtungen erreichbar sind. Die erzielten Verbesserungen in der räumlichen Auflösung erhöhen die Genauigkeit der verschiedenen Anwendungen und ermöglichen eine bessere Identifikation von kleinen Abweichungen, was eine frühere und zuverlässigere Diagnose für Patienten verspricht.New tissue engineering based therapies require adjusted diagnostic methods as well as non-invasive therapy monitoring. Especially 3D MR imaging is a promising tool for parameter quantification at high spatial precision. To serve that need new approaches for high resolution in vivo 3D MRI were developed and their applications in combination with tissue engineering have been demonstrated. The advantages of parameter quantification have been demonstrated in a preclinical study of a femoral heck necrosis model in a large animal. Therapy progress has been monitored at different time points. Despite a commonly used 2D imaging protocol a systematic evaluation of signal intensities from T1 and T2-FS weighted images allowed to draw conclusions about changes in bone microstructure. These results were in good agreement with ex vivo µCT images. The observed increase of trabecular thickness were highly correlated with a signal decrease in the T1 weighted images. The radial evaluation of the data allowed a compressed representation of the results. This lead to an efficient evaluation of numerous data (different animals at various time points with huge number of images each) and allowed an observer independent evaluation. To overcome the limitations from the limited spatial resolution in 2D multi slice images, new approaches for a high-resolution 3D imaging were developed. The focus was on spin echo based sequences due to their better representation of bone microstructure compared to gradient echo based sequences. On one hand a 3D FLASE sequence was developed and on the other hand a modified 3D TSE sequence. To achieve a high resolution in vivo at clinical field strength of 1.5 T within a reasonable scan time, a fast and signal intense sequence is strongly required. A theoretical evaluation of signal equations attributed an increase of 25 % to the TSE sequence compared to the FLASE sequence at identical scan time and resolution. This difference was also observed in experimental results. An in vivo comparison of both sequences at the distal tibia showed a comparable depiction of bone microstructure at a resolution of 160 × 160 × 400 µm. To apply this sequence for high resolution imaging of the femoral head, further modifications were necessary due to the different anatomy. A large field of view had to be avoided to reduce the overall scan time, thus aliasing artifacts had to be suppressed. This was achieved by orthogonal application of excitation and refocusing pulses in the TSE sequence. However, due to technical limitations the achievable resolution was lower than at the distal tibia. A slice thickness much smaller than 1 mm is one of the biggest advantages of 3D MRI and this sequence was successfully applied to imaging of the mandible. The course of the mandibular canal must be known before many surgeries, in order to avoid damaging this structure. The canal is separated from the surrounding only by a small bony wall. In comparison to a 3D VIBE sequence the developed 3D TSE sequence with incorporated aliasing suppression showed a comparable good localization of the canal across the full length of the structure. This was demonstrated in a study with various healthy volunteers and different observers. In comparison to previous results the new imaging technique allowed an increase of spatial resolution to a isotropic voxel size of 0.5 mm, which in total provides a higher precision for localizing the nerve canal. One important element in tissue engineering are bio resorbable materials. Their degradation and ingrowth process must be evaluated before they can be approved for clinical application. The performed in vitro µMRstudies at polymer scaffolds showed a reproducible quantification of pore size and wall thickness for different samples. Additionally, an inhomogeneous distribution of parameters in some samples was observed. The results were in good agreement with data based on µCT images, which are considered to be gold standard for this evaluation and showed significant differences between different groups of scaffolds. The results of this work demonstrate the advantages and possible applications of 3D MRI in clinical applications. Even at clinical field strength it is possible to achieve submillimeter resolution for all three spatial dimension within reasonable scan time. The achieved improvements in spatial resolution allow for an improved precision of the different applications as well as a better identification of small local deviations, which promises an earlier and more reliable diagnosis for patients

Development and evaluation of a numerical simulation approach to predict metal artifacts from passive implants in MRI

Objective!#!This study presents the development and evaluation of a numerical approach to simulate artifacts of metallic implants in an MR environment that can be applied to improve the testing procedure for MR image artifacts in medical implants according to ASTM F2119.!##!Methods!#!The numerical approach is validated by comparing simulations and measurements of two metallic test objects made of titanium and stainless steel at three different field strengths (1.5T, 3T and 7T). The difference in artifact size and shape between the simulated and measured artifacts were evaluated. A trend analysis of the artifact sizes in relation to the field strength was performed.!##!Results!#!The numerical simulation approach shows high similarity (between 75% and 84%) of simulated and measured artifact sizes of metallic implants. Simulated and measured artifact sizes in relation to the field strength resulted in a calculation guideline to determine and predict the artifact size at one field strength (e.g., 3T or 7T) based on a measurement that was obtained at another field strength only (e.g. 1.5T).!##!Conclusion!#!This work presents a novel tool to improve the MR image artifact testing procedure of passive medical implants. With the help of this tool detailed artifact investigations can be performed, which would otherwise only be possible with substantial measurement effort on different MRI systems and field strengths

High resolution MRI of the mandibular canal at 1.5T: A comparison of gradient and spin echo sequences

Objectives: The precision of localizing the mandibular canal prior to surgical intervention depends on the achievable resolution, while identification of the nerve depends on the image contrast. In our study we developed new protocols based on gradient and spin echo sequences. The results from both sequences were quantitatively compared for their agreement to identify the most suitable approach. Methods: By limiting the field of view to one side of the mandible, 3D acquisitions with T1-weighted gradient and spin echo sequences were performed with 0.5x0.5x0.5mm³ resolution within 6.5min covering the mandibular canal from the mandibular to the mental foramen. Aliasing artifacts were suppressed by different techniques. A manual segmentation of the mandibular canal from seven healthy volunteers was performed on this section by three different observers. Surface distance of the segmented volumes was computed between both sequences as well as between the different observers as a measure of equality. Results: The quantitative comparison of the segmentation resulted in an average surface distance of (0.26±0.05) mm between both sequences and an inter-observer difference of (0.26±0.08) mm for gradient and (0.29±0.07) mm for spin echo data. By repeated evaluation a difference of (0.15±0.02) mm for gradient and (0.18±0.03) mm for spin echo data was observed, indicating a slightly higher variability for spin echo images. Conclusion: Both sequences can be used to achieve high resolution images with good contrast and can be used for precise localization of the mandibular canal. Despite a slightly increased difference for the spin echo data, the advantage of an easy and robust setup remains

Troubled Formations Sexuality and the Irish Catholic Bildungsroman, 1916-1965

Summary This dissertation studies the historical development of the Irish Catholic bildungsroman from James Joyce to Edna O ’Brien and John McGahern. Specifically, this study is focused on the construction of sexuality in this genre. The novels are therefore read in conjunction with those d iscourses of sexuality that were circulating in Irish Catholic culture between the First World W a r and the Second Vatican Council. The first chapter reconsiders the concentration on issues of public morality that characterised Irish Catholicism in the early twentieth century, and most acutely in the two decades after independence. In the second chapter, I discuss the epistemic shift in the understanding of modern sexuality that was occasioned by the historical emergence of sexology and psychoanalysis, before moving on to develop a close reading of Joyce’s A Po rtra it o f the A rtis t A s a Young Man (1916). The third chapter contains close readings of two novels by Kate O ’Brien, and locates O ’Brien’s narrative aesthetic, and the conception of sexuality that informs that aesthetic, within the broader historical context of Irish intellectual and political culture in the 1930s and 1940s. The next chapter analyses advice literature produced for Irish teenag ers between the 1940s and 1960s and I argue that this literature exemplifies a significant shift in Irish Catholic thinking on sexuality. The writings of Maura Laverty and Patrick Kavanagh are discussed in Chapter Five. Their rural bildung sromane are read as innovative permutations within the development of this genre and as complex interventions into mid-century debates about sexuality and Irish underdevelopment. Finally, Chapter Six offers close readings of Edna O 'B rie n ’s The Country Girls trilogy (1960-64) and John McGahern’s The Dark (1965). This chapter locates the distinctive narrative aesthetic and plotting of these bildung sromane within the history of the genre, and also reconsiders the critical consensus about the relationship between these novels and Irish modernisation

Animal assignments and comparisons of MR and histology for all sets of animals investigated.

<p>Animal assignments and comparisons of MR and histology for all sets of animals investigated.</p

Long axis (row A) and short axis (row B) T2* weighted (TE = 3 ms, 100 μm isotropic resolution) images of <i>ex vivo</i> hearts from CVB3-infected ABY/SnJ mice during acute myocarditis.

<p>Corresponding Masson's trichrome stained heart tissue sections (short axis) from (1) non-infected control mouse, (2) mild acute myocarditis (9 d p.i.), (3) severe acute myocarditis (9 d p.i.), (4) mild subacute myocarditis (14 d p.i.) and (5) subacute severe myocarditis (14 d p.i.). The extent and location of of hypointense regions seen in T2* weighted MRI images (row B) agree well with patterns of cardiac of lesions as visualized by Masson's trichrome staining (row C, x5 magnification).</p

Correlation of T2* w contrast <i>in vivo</i> (A1, B1: TE = 2.6ms) and <i>ex vivo</i> (A2, B2 TE = 2.6/6ms) in chronic myocarditis in ABY/SnJ mice (8 weeks p.i., row A) and SWR/J mice (8 months p.i., row B).

<p>The location of the T2* hypointense regions correlates very well with virus induced lesions as observed in Masson's trichrome staining (A4, B4) and Prussian blue staining (iron deposits, A5, B5). An increase in T2* blooming effect in <i>ex vivo</i> images is found at longer echo times. Note severe dilation of the left ventricle 8 months p.i. indicating DCM and heart failure in the SWR/J mouse 8 months p.i. (B).</p