From ultrahigh to extreme field magnetic resonance: where physics, biology and medicine meet

International audienc

Beta-Untereinheiten abhängige Modulation von GABAA Rezeptoren durch einen Naturstoff

Gamma-Aminobuttersäure (GABA) ist der wichtigste inhibitorische Neurotransmitter im ZNS bei einer Vielzahl an physiologischen Prozessen beteiligt. Durch Modulation der GABAergen Transmission können therapeutische Effekte erzielt werden. GABAA Rezeptor Modulatoren werden klinisch als Anxiolytika, Antiepileptika, Anästhetika und Hypnotika angewendet. GABAA Rezeptoren bestehen aus fünf transmembranären Untereinheiten. Sie vermitteln schnelle synaptische Neurotransmission und gehören zur Familie der Liganden gesteuerten Ionenkanäle. Bis heute wurden 19 menschliche GABAA Untereinheiten gefunden: alpha1-6, beta1-3, gamma1-3, delta, epsilon, pi, rho1-3 und theta. All diese Untereinheiten können den heteromeren GABAA Rezeptor formen. Aus diesem Grund ist die Zahl der möglichen GABAA Rezeptor Kombinationen groß. Im Rahmen dieser Diplomarbeit wurde die Modulation von IGABA durch den Naturstoff SG-C 1 untersucht. Verschiedene GABAA Untereinheiten wurden in Xenopus laevis Oozyten exprimiert und IGABA mit der Zwei-Mikroelektroden Spannungsklemmtechnik gemessen. SG-C 1 zeigte als GABAA Rezeptor Modulator Beta-Spezifität. Beta2 und Beta3 Rezeptoren wurden durch SG-C 1 stimuliert, Beta1 inkorporierende Rezeptoren hingegen wiesen ein signifikant verminderte Sensibilität auf. Von Alpha1Beta1 zu Alpha1Beta1N290S mutierte Rezeptoren zeigten eine mit Alpha1Beta2 vergleichbare Sensibilität, interessanterweise verminderte die Punktmutation des korrespondierenden Rests von Alpha1Beta2 zu Alpha1Beta2S265N Rezeptoren nicht die Modulierbarkeit durch SG-C 1. Die Modulation von IGABA durch SG-C 1 war nicht vom Vorhandensein einer spezifischen Gamma-Untereinheiten abhängig. Eine weitere interessante Eigenschaft von SG-C 1 ist, dass sie auch in Abwesenheit des Agonisten GABA den Kanal direkt aktiviert. Zusammenfassend wurde ein weiterer Naturstoff als selektiver GABAA Rezeptor Ligand identifiziert, der partiell agonistischen Eigenschaften besitzt und mit einer vermutlich bisher unbeschriebene Bindungsstelle interagiert.Gamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. GABA is involved many physiological processes, and therapeutic intervention in GABAergic neurotransmission is beneficial in numerous diseases. Drugs increasing GABAA receptor signalling such as anxiolytics, anti-epileptics, anaesthetics and hypnotics are widely used. GABAA receptors transmembrane assemblies of five subunits. They mediate fast synaptic responses to GABA and belong to the superfamily of ligand-gated ion channels. So far 19 human GABAA subunits have been identified: alpha1-6, beta1-3, gamma1-3, delta, epsilon, pi, rho1-3 and theta. These subunits form the heteromeric GABAA receptor complexes. As a consequence a large number of GABAA receptor combinations can be formed. Within this project the modulation of IGABA by the natural compound SG-C 1 was examined. Different GABAA receptor subunit compositions were expressed in Xenopus laevis oocytes and IGABA was measured using the two-microelectrodes voltage clamp technique. A beta-subunit dependent stimulation of IGABA was established. SG-C 1 modulated channels containing beta2 or beta3 subunits whereas receptors incorporating beta1 subunits showed a significantly reduced sensitivity. After mutating the alpha1beta1 to alpha1beta1N290S receptors they rebuild SG-C 1 sensitivity, comparable to alpha1beta2 receptors. Interestingly the pointmutation of the corresponding residue in alpha1beta2 to alpha1beta2S265N receptors did not exert influence on the receptors sensitivity to SG-C 1. Modulation of IGABA by SG-C 1 was not gamma-subunit dependent. Moreover SG-C 1 directly activates the GABAA channel in absence of the agonist GABA. In summary the natural compound SG-C 1 was identified as a subunit dependent allosteric modulator of GABAA receptors that possibly interacts with a so far undescribed binding site

A cost-effective cell- and matrix-based minimally invasive single-stage chondroregenerative technique developed with validated vertical translation methodology.

Introduction: The morbidity and significant health economic impact associated with the chondral lesion has led to a large number of strategies for therapeutic neochondrogenesis. The challenge has been to develop techniques that are cost effective single-stage procedures with minimal surgical trauma that have undergone rigorous preclinical scrutiny and robust reproducible assessment of effectiveness. A biological repair requires the generation of a cellular and matrix composite with appropriate signalling for chondrogenic differentiation. Methods and Results: A technique was developed that allowed chondrogenic primary (uncultured) cells from bone marrow aspirate concentrate, combined with a composite hydrophilic and fibrillar matrix to be applied arthroscopically to a site of a chondral lesion. The construct was tested in vitro and in animal experiments before clinical trials. Clinical trials involved 60 patients in a prospective study. Symptomatic International Cartilage Repair Society grade 3 and 4a lesions were mapped and treated. Pre- and postoperative clinical assessments showed statistically significant improved outcomes; Lysholm Knee Scoring Scale (mean 52.8 to > 76.4; P 79 P 89.2 P < 0.05). Postoperative magnetic resonance imaging was evaluated morphologically (magnetic resonance observation of cartilage repair tissue, average MOCART score 72) and qualitatively; the regenerate was comparable to native cartilage. Conclusions: This technique is effective, affordable, requires no complex tools and delivers a single-stage treatment that is potentially accessible to any centre capable of performing arthroscopic surgery. Good clinical results were found to be sustained at five years of follow-up with a regenerate that appears hyaline like using multiple magnetic resonance measures

School violence in young adult fiction

Schulgewalt ist kein neues Phänomen. Heutzutage existiert es jedoch noch immer an vielen Schulen und deshalb müssen Lösungen gefunden werden, um diesem ernstzunehmenden Problem entgegenzuwirken. Eine Möglichkeit wie man mit diesem sensiblen Thema im Fremdsprachenunterricht umgehen könnte, wäre der Gebrauch eines literarischen Werkes, welches einen großen Einfluss auf die Leser hat: es ermöglicht ihnen ihre persönlichen Ansichten und Ideen in die Welt des Textes einzubringen. Dadurch werden die Schüler hoffentlich begreifen, dass es falsch ist, andere Schüler zu quälen, um Macht über sie zu gewinnen. Was das Unterrichten von Literatur anbelangt, gibt es viele Argumente, die für den Einsatz literarischer Werke in Situationen in denen Englisch als Fremdsprache unterrichtet wird sprechen, insbesondere jene Werke, die für Heranwachsende verfasst sind, weil „Literatur ist ein Bereich für die Anwendung mentaler Kraft, es ist ein Bereich für Kreativität, es ist ein Bereich, der Platz für all die persönlichen Elemente von Interaktion, Mitwirkung, Anliegen und Persönlichkeit bieten kann“ (McRae, 1991: 6). Demzufolge erzieht Literatur die gesamte Person. Um dies zu erreichen, müssen Lehrer nicht nur ein literarisches Werk auswählen, welches am ehesten deren Absichten und Lernzielen entspricht, sondern sie müssen sich auch für eine geeignete Herangehensweise entscheiden, welche ihren Lernzielvorstellungen gerecht wird, um den Literatur- und Sprachlernprozess der Schüler zu steigern. Zusätzlich könnten sich in diesem Prozess auch die Lehrerrollen ändern. Dies hängt von den Lehrmethoden und den Herangehensweisen ab, die im Unterricht verwendet werden. In diesem Zusammenhang würde ich gerne hervorheben, dass das Hauptziel der Lehrer jenes sein sollte, die Schüler zu ermutigen und motivieren, literarische Werke mit Freude und Vergnügen zu lesen. Persönlich denke ich, dass der Umgang mit Literatur im Fremdsprachenunterricht mehr bedeutet, als nur das Lesen von Texten: es sollte den Schülern ermöglichen, die Welt des Textes auf einer persönlichen Erfahrungsebene zu erforschen. Demzufolge sollte dies zur persönlichen Entwicklung des Schülers führen, welches auch eines der Hauptziele der Unterrichtseinheit in dieser Diplomarbeit darstellt. Weiters habe ich mich in Bezug auf die Unterrichtseinheit dazu entschlossen das Lernzirkel-Modell („Stationenlernen“) zu verwenden, welches den Schülern ermöglicht verschiedene Aktivitäten unabhängig vom Lehrer zu bearbeiten, entweder alleine, zu zweit oder in Gruppen (vgl. Dickinson, 1987: 59). Auf diese Weise richtet sich diese schülerorientierte Lehrmethode auf die Entwicklung von Schülerkompetenzen für das lebensbegleitende autonome Lernen. Zusätzlich habe ich Aktivitäten für das Stationenlernen entworfen, welche auch die persönliche Entwicklung der Schüler fördern sollen, indem man den Schülern erlaubt, ihre persönlichen Gedanken und Gefühle in den Prozess der Meinungsbildung über ein spezielles literarisches Werk einzubringen. Nachdem die Schüler letztendlich zahlreiche verschiedene Aktivitäten („Stationen“) bearbeitet haben, werden sie hoffentlich verstehen, dass es besser ist ihren Verstand zu benutzen anstatt ihrer Fäuste, um Konflikte in der Schule zu lösen.School violence is not a new phenomenon. Nowadays, however, it still exists at many schools and therefore solutions have to be found in order to encounter this serious problem. One possible way of dealing with such a sensitive topic in the foreign language classroom might be to use a literary work which has a strong impact on readers: it enables them to bring their own views and ideas into the world of the text they enter. Thus, the students will hopefully realize that it is wrong to tantalize other students in order to gain power over them. As far as literature teaching is concerned, there are many arguments for using literary works, in particular those written for young adults, in EFL settings since “literature is a space for the exercise of mental energy; it is a space for creativity; it is a space where the personal elements of interaction, involvement, concern and personality can all be accommodated” (McRae, 1991: 6). As a consequence, literature educates the whole person. Therefore, teachers do not only have to select a literary work that is most suitable for their teaching purposes and aims, but they also have to decide upon an appropriate approach which embraces their learning objectives in order to make the students’ literature as well as language learning process become successful. In addition, the roles of the teachers might also change during this process depending on the teaching methods and approaches that are used in class. In this context, I would like to point out that the teacher’s primary aim should be to encourage and motivate students to read literary works with enjoyment and pleasure. Personally, I think that dealing with literature in the foreign language classroom is more than just reading texts: it should enable the students to explore the world of a literary text on a personal level of experience. As a consequence, this should lead to the students’ personal growth which is also one of the major aims that should be achieved in the teaching unit of this diploma thesis. Furthermore, with regard to this teaching unit, I have decided to use the Circle Model which enables students to work on different activities independently of the teacher, either alone, in pairs or in groups (cf. Dickinson, 1987: 59). Thus, this student-centred teaching method aims at developing the students’ competences for autonomous life-long learning. In addition, I have designed activities arranged within the Circle Model that should also foster the students’ personal development by allowing them to bring in their personal thoughts and feelings in the process of meaning creation of a specific literary work. Finally, after having completed several different activities within the Circle Model, the students may hopefully understand that it is better to use their brain instead of their fists to solve conflicts at school

Optimized spectrally selective steady-state free precession sequences for cartilage imaging at ultra-high fields

Object: Fat suppressed 3D steady-state free precession (SSFP) sequences are of special interest in cartilage imaging due to their short repetition time in combination with high signal-to-noise ratio. At low-to-high fields (1.5-2.0T), spectral spatial (spsp) radio frequency (RF) pulses perform superiorly over conventional saturation of the fat signal (FATSAT pulses). However, ultra-high fields (7.0T and more) may offer alternative fat suppression techniques as a result of the increased chemical shift. Materials and methods: Application of a single, frequency selective, RF pulse is compared to spsp excitation for water (or fat) selective imaging at 7.0T. Results: For SSFP, application of a single frequency selective RF pulse for selective water or fat excitation performs beneficially over the commonly applied spsp RF pulses. In addition to the overall improved fat suppression, the application of single RF pulses leads to decreased power depositions, still representing one of the major restrictions in the design and application of many pulse sequences at ultra-high fields. Conclusion: The ease of applicability and implementation of single frequency selective RF pulses at ultra-high-fields might be of great benefit for a vast number of applications where fat suppression is desirable or fat-water separation is needed for quantification purpose

Phase unwrapping with a rapid opensource minimum spanning tree algorithm (ROMEO)

PURPOSE: To develop a rapid and accurate MRI phase-unwrapping technique for challenging phase topographies encountered at high magnetic fields, around metal implants, or postoperative cavities, which is sufficiently fast to be applied to large-group studies including Quantitative Susceptibility Mapping and functional MRI (with phase-based distortion correction). METHODS: The proposed path-following phase-unwrapping algorithm, ROMEO, estimates the coherence of the signal both in space-using MRI magnitude and phase information-and over time, assuming approximately linear temporal phase evolution. This information is combined to form a quality map that guides the unwrapping along a 3D path through the object using a computationally efficient minimum spanning tree algorithm. ROMEO was tested against the two most commonly used exact phase-unwrapping methods, PRELUDE and BEST PATH, in simulated topographies and at several field strengths: in 3T and 7T in vivo human head images and 9.4T ex vivo rat head images. RESULTS: ROMEO was more reliable than PRELUDE and BEST PATH, yielding unwrapping results with excellent temporal stability for multi-echo or multi-time-point data. It does not require image masking and delivers results within seconds, even in large, highly wrapped multi-echo data sets (eg, 9 seconds for a 7T head data set with 31 echoes and a 208 × 208 × 96 matrix size). CONCLUSION: Overall, ROMEO was both faster and more accurate than PRELUDE and BEST PATH, delivering exact results within seconds, which is well below typical image acquisition times, enabling potential on-console application

Radiologische Diagnose des femoroazetabulären Impingements

Zusammenfassung: Beim femoroazetabulären Impingement (FAI) bewirkt ein anatomisches Missverhältnis zwischen proximalem Femur und Azetabulum eine frühzeitige Abnützung der Gelenkflächen. Um Symptome wie eingeschränkte Beweglichkeit und Schmerzen zu beheben, aber auch um dem degenerativen Prozess vorzubeugen oder ihn zu verlangsamen, ist häufig eine Operation notwendig. Dabei hängt das Resultat vom präoperativen Gelenkstatus ab - mit schlechten Ergebnissen bei bereits fortgeschrittener Hüftgelenkarthrose. Dies erklärt die Notwendigkeit einer akkuraten Diagnostik, um Frühstadien der Gelenkschädigung erkennen zu können. Die Diagnostik des FAI beinhaltet klinische Untersuchung, Röntgendiagnostik und Magnetresonanztomographie (MRT). Die Standardröntgen-radiologische Untersuchung beim FAI wird anhand von 2 Röntgenaufnahmen durchgeführt, der a.p.-Beckenaufnahme sowie einer seitlichen Aufnahme des proximalen Femurs wie z.B. der"lateralen cross-table”- oder der Lauenstein-Aufnahme. Hierbei müssen Positionskriterien eingehalten werden, um Verzerrungsartefakte auszuschließen. Die MRT-Bildgebung ermöglicht eine Untersuchung der Hüfte in 3 Ebenen und sollte zudem radial geplante Sequenzen für eine verbesserte Darstellung der randnahen Strukturen wie Labrum und peripherem Knorpel beinhalten. Die Verwendung von Kontrastmittel für ein direktes MR-Arthrogramm (MRA) hat sich insbesondere für die Darstellung von Labrumschäden als vorteilhaft erwiesen. Die Datenlage in Hinblick auf die Knorpelbildgebung ist noch unklar. Weiterentwicklungen der Techniken werden in naher Zukunft die Diagnostik der Hüfte verbessern können. Hierzu zählen u.a. biochemisch sensitive MRT-Anwendunge

Coil combination of multichannel MRSI data at 7 T: MUSICAL

The goal of this study was to evaluate a new method of combining multi-channel 1H MRSI data by direct use of a matching imaging scan as a reference, rather than computing sensitivity maps. Seven healthy volunteers were measured on a 7-T MR scanner using a head coil with a 32-channel array coil for receive-only and a volume coil for receive/transmit. The accuracy of prediction of the phase of the 1H MRSI data with a fast imaging pre-scan was investigated with the volume coil. The array coil 1H MRSI data were combined using matching imaging data as coil combination weights. The signal-to-noise ratio (SNR), spectral quality, metabolic map quality and Cramér–Rao lower bounds were then compared with the data obtained by two standard methods, i.e. using sensitivity maps and the first free induction decay (FID) data point. Additional noise decorrelation was performed to further optimize the SNR gain. The new combination method improved significantly the SNR (+29%), overall spectral quality and visual appearance of metabolic maps, and lowered the Cramér–Rao lower bounds (−34%), compared with the combination method based on the first FID data point. The results were similar to those obtained by the combination method using sensitivity maps, but the new method increased the SNR slightly (+1.7%), decreased the algorithm complexity, required no reference coil and pre-phased all spectra correctly prior to spectral processing. Noise decorrelation further increased the SNR by 13%. The proposed method is a fast, robust and simple way to improve the coil combination in 1H MRSI of the human brain at 7 T, and could be extended to other 1H MRSI techniques. © 2013 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd

Kinematic biomechanical assessment of human articular cartilage transplants in the knee using 3-T MRI: an in vivo reproducibility study

The aims of this study were to examine the clinical feasibility and reproducibility of kinematic MR imaging with respect to changes in T (2) in the femoral condyle articular cartilage. We used a flexible knee coil, which allows acquisition of data in different positions from 40 degrees flexion to full extension during MR examinations. The reproducibility of T (2) measurements was evaluated for inter-rater and inter-individual variability and determined as a coefficient of variation (CV) for each volunteer and rater. Three different volunteers were measured twice and regions of interest (ROIs) were selected by three raters at different time points. To prove the clinical feasibility of this method, 20 subjects (10 patients and 10 age- and sex-matched volunteers) were enrolled in the study. Inter-rater variability ranged from 2 to 9 and from 2 to 10% in the deep and superficial zones, respectively. Mean inter-individual variability was 7% for both zones. Different T (2) values were observed in the superficial cartilage zone of patients compared with volunteers. Since repair tissue showed a different behavior in the contact zone compared with healthy cartilage, a possible marker for improved evaluation of repair tissue quality after matrix-associated autologous chondrocyte transplantation (MACT) may be available and may allow biomechanical assessment of cartilage transplants