Biochemistry in healthy and neoplastic human tissues: metabolic alteration revealed by HR-MAS nuclear magnetic resonance spectroscopy

This thesis is focused on the metabolomic study of human cancer tissues by ex vivo High Resolution-Magic Angle Spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy. This new technique allows for the acquisition of spectra directly on intact tissues (biopsy or surgery), and it has become very important for integrated metabonomics studies. The objective is to identify metabolites that can be used as markers for the discrimination of the different types of cancer, for the grading, and for the assessment of the evolution of the tumour. Furthermore, an attempt to recognize metabolites, that although involved in the metabolism of tumoral tissues in low concentration, can be important modulators of neoplastic proliferation, was performed. In addition, NMR data was integrated with statistical techniques in order to obtain semi-quantitative information about the metabolite markers. In the case of gliomas, the NMR study was correlated with gene expression of neoplastic tissues. Chapter 1 begins with a general description of a new “omics” study, the metabolomics. The study of metabolism can contribute significantly to biomedical research and, ultimately, to clinical medical practice. This rapidly developing discipline involves the study of the metabolome: the total repertoire of small molecules present in cells, tissues, organs, and biological fluids. Metabolomic approaches are becoming increasingly popular in disease diagnosis and will play an important role on improving our understanding of cancer mechanism. Chapter 2 addresses in more detail the basis of NMR Spectroscopy, presenting the new HR-MAS NMR tool, that is gaining importance in the examination of tumour tissues, and in the assessment of tumour grade. Some advanced chemometric methods were used in an attempt to enhance the interpretation and quantitative information of the HR-MAS NMR data are and presented in chapter 3. Chemometric methods seem to have a high potential in the study of human diseases, as it permits the extraction of new and relevant information from spectroscopic data, allowing a better interpretation of the results. Chapter 4 reports results obtained from HR-MAS NMR analyses performed on different brain tumours: medulloblastoma, meningioms and gliomas. The medulloblastoma study is a case report of primitive neuroectodermal tumor (PNET) localised in the cerebellar region by Magnetic Resonance Imaging (MRI) in a 3-year-old child. In vivo single voxel 1H MRS shows high specificity in detecting the main metabolic alterations in the primitive cerebellar lesion; which consist of very high amounts of the choline-containing compounds and of very low levels of creatine derivatives and N-acetylaspartate. Ex vivo HR-MAS NMR, performed at 9.4 Tesla on the neoplastic specimen collected during surgery, allows the unambiguous identification of several metabolites giving a more in-depth evaluation of the metabolic pattern of the lesion. The ex vivo HR-MAS NMR spectra show higher detail than that obtained in vivo. In addition, the spectroscopic data appear to correlate with some morphological features of the medulloblastoma. The present study shows that ex vivo HR-MAS 1H NMR is able to strongly improve the clinical possibility of in vivo MRS and can be used in conjunction with in vivo spectroscopy for clinical purposes. Three histological subtypes of meningiomas (meningothelial, fibrous and oncocytic) were analysed both by in vivo and ex vivo MRS experiments. The ex vivo HR-MAS investigations are very helpful for the assignment of the in vivo resonances of human meningiomas and for the validation of the quantification procedure of in vivo MR spectra. By using one- and two dimensional experiments, several metabolites in different histological subtypes of meningiomas, were identified. The spectroscopic data confirmed the presence of the typical metabolites of these benign neoplasms and, at the same time, that meningomas with different morphological characteristics have different metabolic profiles, particularly regarding macromolecules and lipids. The profile of total choline metabolites (tCho) and the expression of the Kennedy pathway genes in biopsies of human gliomas were also investigated using HR-MAS NMR, and microfluidic genomic cards. 1H HR-MAS spectra, allowed the resolution and relative quantification by LCModel of the resonances from choline (Cho), phosphorylcholine (PC) and glycerolphorylcholine (GPC), the three main components of the combined tCho peak observed in gliomas by in vivo 1H MRS spectroscopy. All glioma biopsies depicted an increase in tCho as calculated from the addition of Cho, PC and GPC HR-MAS resonances. However, the increase was constantly derived from augmented GPC in low grade NMR gliomas or increased PC content in the high grade gliomas, respectively. This circumstance allowed the unambiguous discrimination of high and low grade gliomas by 1H HR-MAS, which could not be achieved by calculating the tCho/Cr ratio commonly used by in vivo 1H MR spectroscopy. The expression of the genes involved in choline metabolism was investigated in the same biopsies. The present findings offer a convenient procedure to classify accurately glioma grade using 1H HR-MAS, providing in addition the genetic background for the alterations of choline metabolism observed in high and low gliomas grade. Chapter 5 reports the study on human gastrointestinal tract (stomach and colon) neoplasms. The human healthy gastric mucosa, and the characteristics of the biochemical profile of human gastric adenocarcinoma in comparison with that of healthy gastric mucosa were analyzed using ex vivo HR-MAS NMR. Healthy human mucosa is mainly characterized by the presence of small metabolites (more than 50 identified) and macromolecules. The adenocarcinoma spectra were dominated by the presence of signals due to triglycerides, that are usually very low in healthy gastric mucosa. The use of spin-echo experiments enable us to detect some metabolites in the unhealthy tissues and to determine their variation with respect to the healthy ones. Then, the ex vivo HR-MAS NMR analysis was applied to human gastric tissue, to obtain information on the molecular steps involved in the gastric carcinogenesis. A microscopic investigation was also carried out in order to identify and locate the lipids in the cellular and extra-cellular environments. Correlation of the morphological changes detected by transmission (TEM) and scanning (SEM) electron microscopy, with the metabolic profile of gastric mucosa in healthy, gastric atrophy autoimmune diseases (AAG), Helicobacter pylori-related gastritis and adenocarcinoma subjects, were obtained. These ultrastructural studies of AAG and gastric adenocarcinoma revealed lipid intra- and extra-cellularly accumulation associated with a severe prenecrotic hypoxia and mitochondrial degeneration. A deep insight into the metabolic profile of human healthy and neoplastic colon tissues was gained using ex vivo HR-MAS NMR spectroscopy in combination with multivariate methods: Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA). The NMR spectra of healthy tissues highlight different metabolic profiles with respect to those of neoplastic and microscopically normal colon specimens (these last obtained at least 15 cm far from the adenocarcinoma). Furthermore, metabolic variations are detected not only for neoplastic tissues with different histological diagnosis, but also for those classified identical by histological analysis. These findings suggest that the same subclass of colon carcinoma is characterized, at a certain degree, by metabolic heterogeneity. The statistical multivariate approach applied to the NMR data is crucial in order to find metabolic markers of the neoplastic state of colon tissues, and to correctly classify the samples. Significant different levels of choline containing compounds, taurine and myoinositol, were observed. Chapter 6 deals with the metabolic profile of normal and tumoral renal human tissues obtained by ex vivo HR-MAS NMR. The spectra of human normal cortex and medulla show the presence of differently distributed osmolytes as markers of physiological renal condition. The marked decrease or disappearance of these metabolites and the high lipid content (triglycerides and cholesteryl esters) is typical of clear cell renal carcinoma (RCC), while papillary RCC is characterized by the absence of lipids and very high amounts of taurine. This research is a contribution to the biochemical classification of renal neoplastic pathologies, especially for RCCs, which can be evaluated by in vivo MRS for clinical purposes. Moreover, these data help to gain a better knowledge of the molecular processes envolved in the onset of renal carcinogenesis.

Polyelectrolytes and their counterions studied by EPR spectroscopy

In this thesis methods of EPR spectroscopy were used to investigate polyion-counterion interactions in polyelectrolyte solutions. The fact that EPR techniques are local methods is exploited and by employing spin-carrying (i.e., EPR-active) probe ions it is possible to examine polyelectrolytes from the counterions’ point of view. It was possible to gain insight into i) the dynamics and local geometry of counterion attachment, ii) conformations and dynamics of local segments of the polyion in an indirect manner, and iii) the spatial distribution of spin probe ions that surround polyions in solution. Analysis of CW EPR spectra of dianion nitroxide spin probe Fremy’s salt (FS, potassium nitrosodisulfonate) in solutions of cationic PDADMAC polyelectrolyte revealed that FS ions and PDADMAC form transient ion pairs with a lifetime of less than 1 ns. This effect was termed as dynamic electrostatic attachment (DEA). By spectral simulation taking into account the rotational dynamics as a uniaxial Brownian reorientation, also the geometry of the attached state could be characterized. By variation of solvent, the effect of solvent viscosity and permittivity were investigated and indirect information of the polyelectrolyte chain motion was obtained. Furthermore, analysis of CW EPR data also indicates that in mixtures of organic solvent/water PDADMAC chains are preferentially solvated by the organic solvent molecules, while in purely aqueous mixtures the PDADMAC chain segments were found in different conformations depending on the concentration ratio R of FS counterions to PDADMAC repeat units.Broadenings in CW EPR spectra of FS ions were assigned to spin-exchange interaction and hence contain information on the local concentrations and distributions of the counterions. From analysis of these broadenings in terms of a modified cylindrical cell approach of polyelectrolyte theory, radial distribution functions for the FS ions in the different solvents were obtained. This approach breaks down in water above a threshold value of R, which again indicates that PDADMAC chain conformations are altered as a function of R. Double electron-electron resonance (DEER) measurements of FS ions were carried out to probe the distribution of attached counterions along polyelectrolyte chains. For a significant fraction of FS spin probes in solution with a rigid-rod model polyelectrolyte containing charged Ru2+-centers, a bimodal distance distribution was found that nicely reproduced the spacings of direct and next-neighbor Ru2+-centers along the polyelectrolyte: 2.35 and 4.7 nm. For the system of FS/PDADMAC, DEER data could be simulated by assuming a two-state distribution of spin probes, one state corresponding to a homogeneous (3-dimensional) distribution of spin probes in the polyelectrolyte bulk and the other to a linear (1-dimensional) distribution of spin probes that are electrostatically condensed along locally extended PDADMAC chain segments. From this analysis it is suggested that the PDADMAC chains form locally elongated structures of a size of at least ~5 nm.

Mode coupling for precise measurements of the electronic g-factor of hydrogen-like ions in Penning traps

The g-factor is a constant which connects the magnetic moment $vec{mu}$ of a charged particle, of charge q and mass m, with its angular momentum $vec{J}$. Thus, the magnetic moment can be writen $ vec{mu}_J=g_Jfrac{q}{2m}vec{J}$. The g-factor for a free particle of spin s=1/2 should take the value g=2. But due to quantum electro-dynamical effects it deviates from this value by a small amount, the so called g-factor anomaly $a_e$, which is of the order of $10^{-3}$ for the free electron. This deviation is even bigger if the electron is exposed to high electric fields. Therefore highly charged ions, where electric field strength gets values on the order of $10^{13}-10^{16}$V/cm at the position of the bound electron, are an interesting field of investigations to test QED-calculations. In previous experiments [H"aff00,Ver04] using a single hydrogen-like ion confined in a Penning trap an accuracy of few parts in $10^{-9}$ was obtained. In the present work a new method for precise measurement of magnetic the electronic g-factor of hydrogen-like ions is discussed. Due to the unavoidable magnetic field inhomogeneity in a Penning trap, a very important contribution to the systematic uncertainty in the previous measurements arose from the elevated energy of the ion required for the measurement of its motional frequencies. Then it was necessary to extrapolate the result to vanishing energies. In the new method the energy in the cyclotron degree of freedom is reduced to the minimum attainable energy. This method consist in measuring the reduced cyclotron frequency $nu_{+}$ indirectly by coupling the axial to the reduced cyclotron motion by irradiation of the radio frequency $nu_{coup}=nu_{+}-nu_{ax}+delta$ where $delta$ is, in principle, an unknown detuning that can be obtained from the knowledge of the coupling process. Then the only unknown parameter is the desired value of $nu_+$. As a test, a measurement with, for simplicity, artificially increased axial energy was performed yielding the result $g_{exp}=2.000~047~020~8(24)(44)$. This is in perfect agreement with both the theoretical result $g_{theo}=2.000~047~020~2(6)$ and the previous experimental result $g_{exp1}=2.000~047~025~4(15)(44).$ In the experimental results the second error-bar is due to the uncertainty in the accepted value for the electron's mass. Thus, with the new method a higher accuracy in the g-factor could lead by comparison to the theoretical value to an improved value of the electron's mass. [H"af00] H. H"affner et al., Phys. Rev. Lett. 85 (2000) 5308 [Ver04] J. Verd'u et al., Phys. Rev. Lett. 92 (2004) 093002-1

Time-resolved surface enhanced resonance Raman spectro-electrochemistry of heme proteins

The membrane protein Cytochrome c Oxidase (CcO) is one of the most important functional bio-molecules. It appears in almost every eukaryotic cell and many bacteria. Although the different species differ in the number of subunits, the functional differences are merely marginal. CcO is the terminal link in the electron transfer pathway of the mitochondrial respiratory chain. Electrons transferred to the catalytic center of the enzyme conduce to the reduction of molecular oxygen to water. Oxygen reduction is coupled to the pumping of protons into the inter-membrane space and hence generates a difference in electrochemical potential of protons across the inner mitochondrial membrane. This potential difference drives the synthesis of adenosine triphosphate (ATP), which is the universal energy carrier within all biological cells. rnrnThe goal of the present work is to contribute to a better understanding of the functional mechanism of CcO by using time-resolved surface enhanced resonance Raman spectroscopy (TR-SERRS). Despite intensive research effort within the last decades, the functional mechanism of CcO is still subject to controversial discussions. It was the primary goal of this dissertation to initiate electron transfer to the redox centers CuA, heme a, heme a3 and CuB electrochemically and to observe the corresponding redox transitions in-situ with a focus on the two heme structures by using SERRS. A measuring cell was developed, which allowed combination of electrochemical excitation with Raman spectroscopy for the purpose of performing the accordant measurements. Cytochrome c was used as a benchmark system to test the new measuring cell and to prove the feasibility of appropriate Raman measurements. In contrast to CcO the heme protein cc contains only a single heme structure. Nevertheless, characteristic Raman bands of the hemes can be observed for both proteins.rnrnIn order to investigate CcO it was immobilized on top of a silver substrate and embedded into an artificial membrane. The catalytic activity of CcO and therefore the complete functional capability of the enzyme within the biomimetic membrane architecture was verified using cyclic voltammetry. Raman spectroscopy was performed using a special nano-structured silver surface, which was developed within the scope of the present work. This new substrate combined two fundamental properties. It facilitated the formation of a protein tethered bilayer lipid membrane (ptBLM) and it allowed obtaining Raman spectra with sufficient high signal-to-noise ratios.rnSpectro-electrochemical investigations showed that at open circuit potential the enzyme exists in a mixed-valence state, with heme a and and heme a3 in the reduced and oxidized state, respectively. This was considered as an intermediate state between the non-activated and the fully activated state of CcO. Time-resolved SERRS measurements revealed that a hampered electron transfer to the redox center heme a3 characterizes this intermediate state.rn

Photokathoden mit internem DBR-Reflektor als Quellen hochintensiver spinpolarisierter Elektronenstrahlen

Die Erzeugung von Elektronenstrahlen hoher Intensität (I$geq$2,mA) und hoher Spinpolarisation (P$geq$85%) ist für die Experimente an den geplanten glqq Linac Ringgrqq Electron--Ion--Collidern (z.B. eRHIC am Brookhaven National Laboratory) unabdingbar, stellt aber zugleich eine enorme Herausforderung dar. Die Photoemission aus ce{GaAs}--basierten Halbleitern wie z.B. den in dieser Arbeit untersuchten GaAlAs/InGaAlAs Quanten--Übergittern zeichnet sich zwar durch eine hohe Brillanz aus, die geringe Quantenausbeute von nur ca. 1% im Bereich maximaler Polarisation erfordert jedoch hohe Laserintensitäten von mehreren Watt pro $text{cm}^{2}$, was erhebliche thermische Probleme verursacht. rnrnIn dieser Arbeit konnte zunächst gezeigt werden, dass die Lebensdauer einer Photokathode mit steigender Laserleistung bzw. Temperatur exponentiell abnimmt. Durch Einbringen eines DBR--Spiegels zwischen die aktive Zone der Photokathode und ihr Substrat wird ein Großteil des ungenutzten Laserlichts wieder aus dem Kristall herausreflektiert und trägt somit nicht zur Erwärmung bei. Gleichzeitig bildet der Spiegel zusammen mit der Grenzfläche zum Vakuum eine Resonator--Struktur aus, die die aktive Zone umschließt. Dadurch kommt es für bestimmte Wellenlängen zu konstruktiver Interferenz und die Absorption in der aktiven Zone erhöht sich. Beide Effekte konnten durch vergleichenden Messungen an Kathoden mit und ohne DBR--Spiegel nachgewiesen werden. Dabei ergibt sich eine gute Übereinstimmung mit der Vorhersage eines Modells, das auf der dielektrischen Funktion der einzelnen Halbleiterstrukturen beruht. Von besonderer praktischer Bedeutung ist, dass die DBR--Kathode für einen gegebenen Photoemissions-strom eine um einen Faktor $geq$,3{,}5 kleinere Erwärmung aufweist. Dies gilt über den gesamten Wellenlängenbereich in dem die Kathode eine hohe Strahlpolarisation (P$>$80%) produzieren kann, auch im Bereich der Resonanz.rnAus zeitaufgelösten Messungen der Ladungsverteilung und Polarisation lassen sich sowohl Rückschlüsse über die Transportmechanismen im Inneren einer Kathode als auch über die Beschaffenheit ihrer Oberfläche ziehen. Im Rahmen dieser Dissertation konnte die Messgeschwindigkeit der verwendeten Apparatur durch den Einbau eines schnelleren Detektors und durch eine Automatisierung der Messprozedur entscheidend vergrößert und die resultierende Zeitauflösung mit jetzt 1{,}2 Pikosekunden annähernd verdoppelt werden.rnrnDie mit diesen Verbesserungen erhaltenen Ergebnisse zeigen, dass sich der Transport der Elektronen in Superlattice--Strukturen stark vom Transport in den bisher untersuchten Bulk--Kristallen unterscheidet. Der Charakter der Bewegung folgt nicht dem Diffusionsmodell, sondern gibt Hinweise auf lokalisierte Zustände, die nahe der Leitungsbandunterkante liegen und Elektronen für kurze Zeit einfangen können. Dadurch hat die Impulsantwort einer Kathode neben einem schnellen Abfall des Signals auch eine größere Zeitkonstante, die selbst nach 30,ps noch ein Signal in der Größenordnung von ca. 5textperthousand der Maximalintensität erzeugt.

Measurement of the forward-backward asymmetry of Z boson decays in electron-positron pairs with the ATLAS detector in proton-proton collisions at root out s = 7TeV at the LHC

In this thesis the measurement of the effective weak mixing angle wma in proton-proton collisions is described. The results are extracted from the forward-backward asymmetry (AFB) in electron-positron final states at the ATLAS experiment at the LHC. The AFB is defined upon the distribution of the polar angle between the incoming quark and outgoing lepton. The signal process used in this study is the reaction pp to zgamma + X to ee + X taking a total integrated luminosity of 4.8\,fb^(-1) of data into account. The data was recorded at a proton-proton center-of-mass energy of sqrt(s)=7TeV. The weak mixing angle is a central parameter of the electroweak theory of the Standard Model (SM) and relates the neutral current interactions of electromagnetism and weak force. The higher order corrections on wma are related to other SM parameters like the mass of the Higgs boson.rnrnBecause of the symmetric initial state constellation of colliding protons, there is no favoured forward or backward direction in the experimental setup. The reference axis used in the definition of the polar angle is therefore chosen with respect to the longitudinal boost of the electron-positron final state. This leads to events with low absolute rapidity have a higher chance of being assigned to the opposite direction of the reference axis. This effect called dilution is reduced when events at higher rapidities are used. It can be studied including electrons and positrons in the forward regions of the ATLAS calorimeters. Electrons and positrons are further referred to as electrons. To include the electrons from the forward region, the energy calibration for the forward calorimeters had to be redone. This calibration is performed by inter-calibrating the forward electron energy scale using pairs of a central and a forward electron and the previously derived central electron energy calibration. The uncertainty is shown to be dominated by the systematic variations.rnrnThe extraction of wma is performed using chi^2 tests, comparing the measured distribution of AFB in data to a set of template distributions with varied values of wma. The templates are built in a forward folding technique using modified generator level samples and the official fully simulated signal sample with full detector simulation and particle reconstruction and identification. The analysis is performed in two different channels: pairs of central electrons or one central and one forward electron. The results of the two channels are in good agreement and are the first measurements of wma at the Z resonance using electron final states at proton-proton collisions at sqrt(s)=7TeV. The precision of the measurement is already systematically limited mostly by the uncertainties resulting from the knowledge of the parton distribution functions (PDF) and the systematic uncertainties of the energy calibration.rnrnThe extracted results of wma are combined and yield a value of wma_comb = 0.2288 +- 0.0004 (stat.) +- 0.0009 (syst.) = 0.2288 +- 0.0010 (tot.). The measurements are compared to the results of previous measurements at the Z boson resonance. The deviation with respect to the combined result provided by the LEP and SLC experiments is up to 2.7 standard deviations.

Probing the decay characteristics of the Pygmy Dipole Resonance in the semi-magic nucleus 140 Ce with gamma-gamma coincidence measurements

Im Rahmen dieser Arbeit wurde ein neuartiger Experimentaufbau -- das γ3 Experiment -- zur Messung von photoneninduzierten Kern-Dipolanregungen in stabilen Isotopen konzipiert und an der High Intensity γ-Ray Source (HIγS) an der Duke University installiert.rnDie hohe Energieauflösung und die hohe Nachweiseffizienz des Detektoraufbaus, welcher aus einer Kombination von LaBr Szintillatoren und hochreinen Germanium-Detektoren besteht, erlaubt erstmals die effiziente Messung von γ-γ-Koinzidenzen in Verbindung mit der Methode der Kernresonanzfluoreszenz.rnDiese Methode eröffnet den Zugang zum Zerfallsverhalten der angeregten Dipolzustände als zusätzlicher Observablen, die ein detaillierteres Verständnis der zugrunde liegenden Struktur dieser Anregungen ermöglicht.rnDer Detektoraufbau wurde bereits erfolgreich im Rahmen von zwei Experimentkampagnen in 2012 und 2013 für die Untersuchung von 13 verschiedenen Isotopen verwendet. Im Fokus dieser Arbeit stand die Analyse der Pygmy-Dipolresonanz (PDR) im Kern 140Ce im Energiebereich von 5,2 MeV bis 8,3 MeV basierend auf den mit dem γ3 Experimentaufbau gemessenen Daten. Insbesondere das Zerfallsverhalten der Zustände, die an der PDR beteiligt sind, wurde untersucht. Der Experimentaufbau, die Details der Analyse sowie die Resultate werden in der vorliegenden Arbeit präsentiert. Desweiteren erlaubt ein Vergleich der Ergebnisse mit theoretischen Rechnungen im quasi-particle phonon model (QPM) eine Interpretation des beobachteten Zerfallsverhaltens.

Imaging spin-filter efficiency of W(001) and Ir(001) single crystals

Während der letzten Jahre wurde für Spinfilter-Detektoren ein wesentlicher Schritt in Richtung stark erhöhter Effizienz vollzogen. Das ist eine wichtige Voraussetzung für spinaufgelöste Messungen mit Hilfe von modernen Elektronensp ektrometern und Impulsmikroskopen. In dieser Doktorarbeit wurden bisherige Arbeiten der parallel abbildenden Technik weiterentwickelt, die darauf beruht, dass ein elektronenoptisches Bild unter Ausnutzung der k-parallel Erhaltung in der Niedrigenergie-Elektronenbeugung auch nach einer Reflektion an einer kristallinen Oberfläche erhalten bleibt. Frühere Messungen basierend auf der spekularen Reflexion an einerrnW(001) Oberfläche [Kolbe et al., 2011; Tusche et al., 2011] wurden auf einenrnviel größeren Parameterbereich erweitert und mit Ir(001) wurde ein neues System untersucht, welches eine sehr viel längere Lebensdauer der gereinigten Kristalloberfläche im UHV aufweist. Die Streuenergie- und Einfallswinkel-“Landschaft” der Spinempfindlichkeit S und der Reflektivität I/I0 von gestreuten Elektronen wurde im Bereich von 13.7 - 36.7 eV Streuenergie und 30◦ - 60◦ Streuwinkel gemessen. Die dazu neu aufgebaute Messanordnung umfasst eine spinpolarisierte GaAs Elektronenquellernund einen drehbaren Elektronendetektor (Delayline Detektor) zur ortsauflösenden Detektion der gestreuten Elektronen. Die Ergebnisse zeigen mehrere Regionen mit hoher Asymmetrie und großem Gütefaktor (figure of merit FoM), definiert als S2 · I/I0. Diese Regionen eröffnen einen Weg für eine deutliche Verbesserung der Vielkanal-Spinfiltertechnik für die Elektronenspektroskopie und Impulsmikroskopie. Im praktischen Einsatz erwies sich die Ir(001)-Einkristalloberfläche in Bezug auf längere Lebensdauer im UHV (ca. 1 Messtag), verbunden mit hoher FOM als sehr vielversprechend. Der Ir(001)-Detektor wurde in Verbindung mit einem Halbkugelanalysator bei einem zeitaufgelösten Experiment im Femtosekunden-Bereich am Freie-Elektronen-Laser FLASH bei DESY eingesetzt. Als gute Arbeitspunkte erwiesen sich 45◦ Streuwinkel und 39 eV Streuenergie, mit einer nutzbaren Energiebreite von 5 eV, sowie 10 eV Streuenergie mit einem schmaleren Profil von < 1 eV aber etwa 10× größerer Gütefunktion. Die Spinasymmetrie erreicht Werte bis 70 %, was den Einfluss von apparativen Asymmetrien deutlich reduziert. Die resultierende Messungen und Energie-Winkel-Landschaft zeigt recht gute Übereinstimmung mit der Theorie (relativistic layer-KKR SPLEED code [Braun et al., 2013; Feder et al.,rn2012])

Feasibility of texture analysis for the assessment of biochemical changes in meniscal tissue on T1 maps calculated from delayed gadolinium-enhanced magnetic resonance imaging of cartilage data: comparison with conventional relaxation time measurements

To (1) establish the feasibility of texture analysis for the in vivo assessment of biochemical changes in meniscal tissue on delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC), and (2) compare textural with conventional T1 relaxation time measurements calculated from dGEMRIC data ("T1(Gd) relaxation times").

Comparison of arterial and venous coronary artery bypass flow measurements using 3-T magnetic resonance phase contrast imaging

Comparison of arterial and venous coronary artery bypass flow measurements using 3-T magnetic resonance (MR) phase contrast in correlation with intraoperative Doppler flow measurements.

Advanced morphological 3D magnetic resonance observation of cartilage repair tissue (MOCART) scoring using a new isotropic 3D proton-density, turbo spin echo sequence with variable flip angle distribution (PD-SPACE) compared to an isotropic 3D steady-state free precession sequence (True-FISP) and standard 2D sequences

To evaluate a new isotropic 3D proton-density, turbo-spin-echo sequence with variable flip-angle distribution (PD-SPACE) sequence compared to an isotropic 3D true-fast-imaging with steady-state-precession (True-FISP) sequence and 2D standard MR sequences with regard to the new 3D magnetic resonance observation of cartilage repair tissue (MOCART) score.

Comparison of spatial and temporal pattern for fMRI obtained with BOLD and arterial spin labeling

Functional magnetic resonance imaging (fMRI) is presently either performed using blood oxygenation level-dependent (BOLD) contrast or using cerebral blood flow (CBF), measured with arterial spin labeling (ASL) technique. The present fMRI study aimed to provide practical hints to favour one method over the other. It involved three different acquisition methods during visual checkerboard stimulation on nine healthy subjects: 1) CBF contrast obtained from ASL, 2) BOLD contrast extracted from ASL and 3) BOLD contrast from Echo planar imaging. Previous findings were replicated; i) no differences between the three measurements were found in the location of the activated region; ii) differences were found in the temporal characteristics of the signals and iii) BOLD has significantly higher sensitivity than ASL perfusion. ASL fMRI was favoured when the investigation demands for perfusion and task related signal changes. BOLD fMRI is more suitable in conjunction with fast event related design.

Effect of multislice acquisition on T1 and T2 measurements of articular cartilage at 3T

PURPOSE: The aim of this study was to investigate the effect of magnetization transfer on multislice T(1) and T(2) measurements of articular cartilage. MATERIALS AND METHODS: A set of phantoms with different concentrations of collagen and contrast agent (Gd-DTPA(2-)) were used for the in vitro study. A total of 20 healthy knees were used for the in vivo study. T(1) and T(2) measurements were performed using fast-spin-echo inversion-recovery (FSE-IR) sequence and multi-spin-echo (MSE) sequence, respectively, in both in vitro and in vivo studies. We investigated the difference in T(1) and T(2) values between that measured by single-slice acquisition and that measured by multislice acquisition. RESULTS: Regarding T(1) measurement, a large drop of T(1) in all slices and also a large interslice variation in T(1) were observed when multislice acquisition was used. Regarding T(2) measurement, a substantial drop of T(2) in all slices was observed; however, there was no apparent interslice variation when multislice acquisition was used. CONCLUSION: This study demonstrated that the adaptation of multislice acquisition technique for T(1) measurement using FSE-IR methodology is difficult and its use for clinical evaluation is problematic. In contrast, multislice acquisition for T(2) measurement using MSE was clinically applicable if inaccuracies caused by multislice acquisition were taken into account. J. Magn. Reson. Imaging 2007;26:109-117. (c) 2007 Wiley-Liss, Inc.