This file was created by the Typo3 extension sevenpack version 0.7.16 --- Timezone: CET Creation date: 2024-11-01 Creation time: 06-27-06 --- Number of references 12 phdthesis hoehl2011 2011 Die Suche nach einem Einfluss von Ultraschall auf das Kernspinsystem in weicher Materie ist eine spannende Aufgabe. Nachdem in den 50er Jahren gezeigt werden konnte, dass in homogenen Flüssigkeiten die hohe Moleküldynamik eine effektive Kopplung zwischen Ultraschall und Spinsystem verhindert, wurden Messungen dazu weitgehend eingestellt. Einige theoretische Arbeiten deuten mittlerweile darauf hin, dass es Wechselwirkungsmechanismen gibt, die trotzdem eine Kopplung ermöglichen, wenn komplexe Moleküle oder kolloidal gelöste Partikel mit magnetischen Eigenschaften in der Flüssigkeit vorhanden sind. Doch im Vergleich zu typischen Experimenten an Festkörpern, wird in Flüssigkeiten nur eine schwache Beeinflussung des Spinsystems erwartet. Experimente dazu liefern bislang widersprüchliche Ergebnisse. In dieser Arbeit wird untersucht, warum keine eindeutigen experimentellen Daten vorliegen und gezeigt, dass bei Messungen an Flüssigkeiten eine Reihe von Einflüssen auftreten, die in Konkurrenz zur Ultraschall induzierten Relaxation oder Sättigung des Kernspinsystems stehen. Es werden Lösungen vorgeschlagen, wie man in einer empfindlichen NMR-Messapparatur den Ultraschalleinfluss bestimmen kann und wie man Resonanzexperimente am Magnetresonanztomographen durchführen kann. Erste Messungen mit den vorgestellten Aufbauten werden präsentiert und es wird nachgewiesen, dass magnetische Nanopartikel Ultraschall an das Proton-Kernspinsystem koppeln können nmr http://nbn-resolving.org/urn:nbn:de:hbz:5N-24386 Universität Bonn Dissertation C.Höhl phdthesis elmiladidiss2010 2010 nmr http://nbn-resolving.org/urn:nbn:de:hbz:5N-22404 Universität Bonn Dissertation N. M.Elmiladi mastersthesis jahanbakhsh 2010 4 nmr Universität Bonn Diplomarbeit F.Jahanbakhsh mastersthesis wolf 2010 3 nmr https://agmaier.hiskp.uni-bonn.de/fileadmin/publications/2010_Diplom_Wolf.pdf Universität Bonn Diplomarbeit P. J.Wolf conference hoeismrm10 2010 5 <em>Purpose</em> MRI has become a powerful tool to distinguish between adjacent tissues by taking into account a variety of chemical, physical and biological properties of living tissue. By use of magnetic contrast agents in MRI one can even gain insight into some metabolic functions of a host. Conclusion on the metabolism, however, can only be drawn if (a) the metabolic function of interest locally affects the concentration of the contrast agent, and (b) the contrast agent leads to a clearly observable change in MRI signal within the region of interest. We present a contrast mechanism which aims to distinguish between magnetic contrast agents which are conjugated to cells or macromolecules and those which are not, independent on their spatial distribution. which is expected to picture the mobility of labeled macromolecules. The mobility might be changed, e.g., by the viscosity of the MNPs surroundings or by the macromolecules reactions to cells or other objects. which instantaneously can be switched on and off and thus provide specific information by immediate comparison between pictures taken with this contrast and those taken without it. The high specificity to chemical reactions of the here proposed contrast mechanism might become basis of a new method for functional imaging. <em>Method</em> The spin-lattice relaxation time T1 of a sample volume decreases if magnetic nanoparticles (MNP) which are connected to mesoscopic objects are subjected to an ultrasonic wave at MRI Larmor frequency. This effect can be interpreted as a change in relaxivity of the MNPs under the influence of resonant ultrasound (US). MNPs subjected to an ultrasonic wave are accelerated periodically with US frequency, which now is assumed to match the Larmor frequency. It is well known that the induced translational movement of the MNPs does not lead to a pronounced change in the MRI relaxation times. If a MNP is connected to a organic macromolecule, however, the compound bends and to tilts periodically in the ultrasonic wave because its center of mass differs from its center of geometry (Fig. to right). Consequently these MNPs act as radio frequency near field antennas, inducing additional relaxation to nuclei in the vicinity of the MNPs. <em>Results</em> We measured the proton spin-lattice relaxation time of a colloidal solution of MNPs (Ø = 50 nm) connected to a macromolecule (chicken IgG) by means of an inversion recovery sequence (TI = 550 ms, TR = 20,000 ms) and analyzed the spectral composition of the 90° FID (cf. Fig. to left). The abscissa denotes the frequency match between Larmor frequencies and US frequency (fUS = 18.32 MHz). When US was applied during the recovery process we could observe a change in signal amplitudes for spectral components matching the US frequency (upper curves). This we interpreted as a gain in relaxivity of the MNP-macromolecule compounds (lower curves). No changes in the FIDs' spectral amplitudes under the influence of resonant US were observed for a comparable solution of standard MNPs. We observed a gain in relaxivity of more than 15 % at US intensities of P = 10-3 W/cm². <em>Conclusion</em> Experiments for observing this contrast in a low field MRI device are underway. Due to the possibility to distinguish between bound an unbound MNPs independent on their spatial distribution and due to the improved contrast reliability by immediate comparison with not-contrast-enhanced pictures we expect this contrast method to fundamentally improve functional MRI. nmr Konferenz Joint Annual Meeting ISMRM and ESMRMB, Stockholm - Sweden C.Hoehl N.Elmiladi F.Jahanbakhsh F.Repp P.Wolf K.Maier conference jahdpg10 2010 3 Der Einsatz von Kontrastmittel erlaubt der Magnetresonanztomographie (MRT) bestimmte Stoffwechselprozesse abzubilden. Vorraussetzung dafür ist stets, dass die Stoffwechselprozesse zu einer lokalen Anreicherung des Kontrastmittels führen. Eine wichtige Klasse von Kontrastmitteln sind magnetische Nanopartikel (MNP), deren Oberfläche praktische beliebig funktionalisiert werden kann. Die Reaktion von Makromolekülen mit der Oberfläche der MNPs kann unabhängig von deren lokaler Anreicherung in H-NMR Experimenten beobachtet werden, wenn die Probe während der Messung resonantem Ultraschall ausgesetzt ist. Dieser Effekt wurde in Wasser entdeckt, die Anwendbarkeit der Methode in Gewebephantomen wird diskutiert. Dabei wird auch der Einfluss auf die Querrelaxationszeit nmr Konferenz DPG Frühjahrstagung des Arbeitskreises Festkörperphysik, Regensburg F.Jahanbakhsh C.Höhl F.Repp P.Wolf K.Maier conference wodpg10 2010 3 Magnetische Nanopartikel (NMPs) sind in der NMR Relaxationszentren und werden deshalb in der Magnetresonanztomographie (MRT) als Kontrastmittel eingesetzt. Sie bestehen aus einem oder mehreren magnetischen Kernen und einer nichtmagnetischen Hülle die nahezu beliebig chemisch funktionalisiert und mit Makro molekülen beschichtet werden kann. In MMR-Experimenten konnte gezeigt werden, dass durch resonanten Ultraschall (US) mit NMR Lamorfrequenz zwischen einseitig beschichteten und nicht beschichteten NMPs unterschieden werden kann. Dies birgt interessant Eigenschaften für ortsaufgelöste Messungen an einem MRT. Allerdings ist resonanter Ultraschall dort schwerlich anwendbar, da elektromagnetische Übersprecher der USApparatur mit Lamorfrequenz den MRT-Empfangskreis empfindlich stören. Außerdem beträgt bei üblichen Lamorfrequenzen die Eindringtiefe in Gewebe nur Zentimeter. Deshalb schlagen wir das Konzept der Frequenzverdopplung vor. Der Energietransfer ins Gewebe erfolgt mit einem Ultraschallemitter mit einer niedrigen Grundfrequenz. Im Fokus eines Ultraschallemitters erzeugt man aufgrund von Nichtlinearitäten des Gewebes höhere Harmonische der Schallwelle. Erste Messungen und Experimente werden vorgestellt. nmr Konferenz DPG Frühjahrstagung des Arbeitskreises Festkörperphysik, Regensburg P.Wolf C.Höhl F.Jahanbakhsh F.Repp K.Maier conference hoeismrm09 2009 5 <em>Purpose</em> MRI has become a powerful tool to distinguish between adjacent tissues by taking into account a variety of chemical, physical and biological properties of living tissue. By use of magnetic contrast agents in MRI one can even gain insight into some of the tissue's metabolic functions. Conclusions on the metabolism, however, can only be drawn if (a) the metabolic function in question locally affects the concentration of the contrast agent, and if (b) the contrast agent leads to a clearly observable change of the MRI signal within the region under consideration. First observations of a contrast mechanism which addresses these limitation have been presented during last ISMRM conference, and a more complete presentation and discussion has been submitted to Phys. Rev. Let. recently. Questions remained open, however, whether the technical requirements for the contrast mechanism may become compatible with in vivo measurements in a standard MRI device. Current research promises to solve the technical difficulties and first observations of the contrast in a low field MRI device are underway. <em>Method</em> Contrast agents based on magnetic nanoparticles (MNPs) affect the transverse relaxation times of nuclei of the solvent (e. g. protons) in their vicinity due to their magnetic stray field. MNP also affect the longitudinal relaxation time T1 if the thermal motion of the MNPs happens to lead to local field fluctuations at nuclei Larmor frequency. It was shown, that ultrasound at Larmor frequency increased the influence of specially prepared MNPs on T1 considerably if ultrasound (US) matches Larmor frequency. These experiments were carried out using an NMR spectrometer where shielding of the receiving coils can be realized easily. In an MRI device, however, US radiation at MRI Larmor frequency would lead to disturbance of the MRI device. <em>Results</em> Picture1 presents the pressure evolution over time at a given position in a US wave (fUS = 2.5 MHz) in a water sample (measurement with hydrophone with bandwith of 60 MHz). Deviations from the sinusoidal wave-form originate from the strong nonlinear behavior of the water sample. Exploiting frequency doubling effects in tissue not only avoids electromagnetic cross-coupling between the US device and the MRI device, but also provides us with the higher penetration depth of the fundamental wave. <em>Conclusion</em> The contrast mechanism allows to distinguish between bound and unbound MNPs independent on their spatial distribution. The strong nonlinearities of tissue exposed to an ultrasonic wave promise this contrast mechanism to become compatible with standard MRI devices. Experiments exploiting ultrasound frequency doubling to activate the contrast mechanism in a low field MRI device (open tomography system) are underway. nmr Konferenz ISMRM Seventeenth Scientific Meeting and Exhibition, Honolulu - Hawaii N.Elmiladi C.Hoehl K.Maier conference elmdpg09 2009 3 We have developed a method involving the application of ultrasound (US) in magnetic resonance imaging (MRI) in the presence of antibody coated magnetic nanoparticles to generate contrast. Similar magnetic nanoparticles are already used as contrast agents. It is interesting to control their effect by additional parameters, which can be switched on and off externally, and depend on the properties of the surrounding tissue. In performing proton nuclear magnetic resonance spectroscopy, US is applied to an aqueous sample containing magnetic nanoparticles coated with antibodies from one side only. Therefore, while the asymmetric magnetic nanoparticles in the sample are subjected to an US wave, a torque is initiated along the vibrational motion and will cause the particles to tilt periodically. The asymmetric magnetic nanoparticles will act as an US driven radio frequency antenna, leading to an increase in the spectral density function at the US frequency. If the US frequency matches the Larmor frequency, protons in the near field region of the particle are stimulated to lose energy, and the T1 of the aqueous solution decreases. A significant increase of the longitudinal proton relaxation rate is experimentally observed when using a colloidal aqueous solution of asymmetric magnetic nanoparticles. nmr Konferenz DPG Frühjahrstagung des Fachverbandes Strahlen- und Medizinphysik, München N.Elmiladi C.Höhl K.Maier conference hoeismrm08 2008 5 <strong>Purpose</strong> MRI provides images with excellent anatomical details based on soft-tissue contrast and functional information in a non-invasive and real-time monitoring manner. MRI has been further advanced by the development of contrast agents such as Gadolinium compounds that enable more specific and clearer images and enlargement of detectable organs and systems. Magnetic nanometer-sized, colloidal particles (nanoparticles) are well known and extensively used in MRI as contrast agent, too. Due to their influence on the relaxation processes, they offer a possibility to label organic macro molecules. It is interesting to control their effect on MRI by additional parameters, which may be switched on and off externally or may depend on the properties of the surrounding tissue. We develop such a new contrast method with nanoparticles, by applying ultrasound (US) while performing proton magnetic resonance spectroscopy. <strong>Method</strong> The basic process involved in the relaxation in MRI is coupling between the magnetic moments of the spin and photons with the corresponding larmor frequency - which can lead to stimulated emission or absorbtion. This results in an energy transfer out of the spin system to the lattice (longitudinal relaxation process) or transfer within the spin system (transversal relaxation process). To gain higher sensitivity with a contrast agent in MRI, the contrast agent has to have a greater effect on the relaxation times. Especially prepared nanoparticles work as a radio frequency transmitter. For this, we are using two completely different kinds of nanoparticles: a) Superparamagnetic of Iron Oxide (SPIO) To increase the spectral density of photons with a special frequency, SPIO should work as an antenna. The SPIOs are prepared such that the center of geometry differs from the center of mass. This is done by sedimentation of the SPIOs, so that we can add macromolecules from one side only. Due to the particle velocity in the US-wave, SPIOs are accelerated and due to their asymmetric shape they tilt periodically. This produces additional photons with US-frequency. b) Piezoelectric Nanoparticles Piezoelectric particles have the ability to generate an electric potential in response to applied mechanical stress. In combination with the periodic pressure variation in an US-wave, these particles function as a transmitter (displacement current). To achieve this, a powder consisting of 100nm sized particles is prepared into a colloid in water by coating with PAA. The HF-fields emitted by nanoparticles are not coherent and therefore unable to rotate the net-magnetization. <strong>Results</strong> Influence of the US on NMR measurements for the SPIO was examined. Early measurements showed a change of the relaxation times T1 and T2* in water when using piezoelectric particles. Furthermore, measurements on SPIO indicates the influence of the US at the resonance frequency. The figure to the right compares the amplitude of the FID after a 90° puls in an inversion recovery sequence with and without US. These measurements were taken before getting the SPIO in the final shape. Sedimentation process of the SPIO have been achieved by applying a combination of centrifugal force and magnetic force. Conclusion Using nanoparticles as local antenna in combination with US promises new contrast methods which image properties of the tissue. Even without any special preparation of the nanoparticles, an effect of the US on the MRI-Signal has been seen. nmr Konferenz ISMRM Sixteenth Scientific Meeting and Exhibition, Toronto - Canada C.Hoehl N.Elmiladi J.Mende K.Maier conference elmdpg08 2008 2 Magnetic resonance imaging (MRI) is one of the most powerful imaging techniques for living organisms. Magnetic nanoparticles such as superparamagnetic iron oxide (SPIO) have been applied as contrast enhancement agents for MRI. We develop a new contrast method for SPIO with the application of ultrasound (US) while performing proton magnetic resonance spectroscopy. Especially prepared SPIO should work as radio frequency transmitters. The nanoparticles are prepared such that the center of geometry differs from the center of mass. This is done by the magnetic oriented sedimentation of the SPIOs so that we can add macro molecules from one side only. Sedimentation process of the SPIO have been achieved by applying a combination of centrifugal force and magnetic force. Due to the particle velocity in the resonant US wave, SPIOs are accelerated and due to their asymmetric shape, they tilt periodically. This produces additional photons with the US frequency that affect the relaxation times. Using nanopariticles as local antenna in combination with US promises new contrast methods to visualize additional properties of the tissue. Even without any special preparation of the nanoparticles, an effect of the US on the MRI signal has already been seen. nmr Konferenz DPG Frühjahrstagung des Arbeitskreises Festkörperphysik, Berlin N.Elmiladi C.Höhl J.Mende M.Schlichtenmayer B.Habenstein K.Maier mastersthesis hoehl 2007 3 nmr https://agmaier.hiskp.uni-bonn.de/fileadmin/publications/2007_Diplom_Hoehl.pdf Universität Bonn Diplomarbeit C.Höhl