Advanced interfaces for biomedical engineering applications in high- and low field NMR/MRI

Das zentrale Thema dieser Dissertation ist die Magnetresonanz(MR)-Sicherheit und MR-Kompatibilität von Bauelementen. Der Öffentlichkeit bekannt ist diese Thematik im Zusammenhang mit kommerziellen Implantaten. Die Gefahren, die sich aus den Wechselwirkungen zwischen dem MR-Tomografen (MRT) und dem Implantat ergeben, hindern viele Patienten daran, eine Untersuchung mittels MRT durchführen zu lassen. MR-Kompatibilität spielt jedoch nicht nur beim Design und der Kennzeichnung von Implantaten eine wichtige Rolle, sondern auch bei der Entwicklung von Bauelementen für die MR-Hardware. Beide Themen, Implantatinteraktionen und Hardware-Design, bilden fundamentale Aspekte dieser Arbeit. Der erste Teil befasst sich mit MRT-Wechselwirkungen von Implantaten. Die Ergebnisse einer umfangreichen Literaturrecherche zeigen, dass dringend belastbare Daten benötigt werden, um die durch MRT ausgelösten Schwingungen von Implantaten besser verstehen zu können. Dies gilt insbesondere für Vibrationen in viskoelastischen Umgebungen wie dem Gehirn. Im Rahmen dieser Arbeit wird ein neuartiges Messsystem vorgestellt, mit dem sich Schwingungen bei Standard-MRT-Aufnahmen und mit hoher Genauigkeit quantitativ messen lassen. Durch die Verwendung einer amplituden- und frequenzgesteuerten externen Stromversorgung werden die Übertragungsfunktionen implantatartiger Strukturen in viskoelastischen Umgebungen präzise bestimmt. Basierend auf den erfassten Daten wird eine Korrelation zwischen den resultierenden Schwingungsamplituden und den Zeitparametern der Aufnahmesequenz hergestellt und experimentell verifiziert. Eine wichtige Erkenntnis ist, dass die untersuchten Strukturen ein unterdämpftes Verhalten zeigen und damit resonant schwingen können. Darüber hinaus wird eine neue Kennzahl eingeführt, anhand derer die Wechselwirkung des Implantats auf Vibrationen klassifiziert werden können. Die Kennzahl gibt das normierte induzierte Drehmoment an, und ermöglicht eine einfache Berechnung des maximal zu erwartenden Drehmomoments auf jedem MRT-System. Somit können die zu erwartenden Maximalamplituden unkompliziert und für jedes System direkt ermittelt werden. Eine anderes Forschungsgebiet, die in-situ-Kernspinspektroskopie und -MRT von biologischen Untersuchungsobjekten im Hochfeld, erfordert eine neuartige MR-Messsonde sowie verbesserte MR-kompatible Substrate für die Zellkultivierung. Eine MR-Sonde mit flexibler Schnittstelle wurde entwickelt. Die endgültige Version ist mit zwei HF-Kanälen und einer Gradientenschnittstelle für flüssiggekühlte Gradienten ausgestattet. Ein Leistungsbewertung wurde mittels Standard-NMR/MRT-Experimenten durchgeführt, die eine Linienbreite von 0,5 Hz und ein mit kommerziellen Messsystem vergleichbares Signal-Rausch-Verhältnis ergaben. Der Vorteil liegt in dem integrierten Durchführungssystem innerhalb des mechanischen Rahmens. Dies bietet eine einfache Methode, zur spezifischen Erweiterung der Messsonde unter Verwendung zusätzlicher elektrischer, optischer und fluidischer Versorgungsleitungen. Auf dieser Basis können spezifische, komplexe experimentelle Hochfeld-NMR/MRT-Aufbauten in kurzer Zeit realisiert werden, ohne Bedarf nach maßgeschneiderten, teuren Sonden. Als Referenz werden zwei Messaufbauen präsentiert, bei ersterem wird die Sonde für ein Öl-Wasser-Fluidikexperiment und bei dem zweitem, in einem wasserstoffbasierten Hyperpolarisationsexperiment eingesetzt. Darüber hinaus wird ein neuartiges, MR-kompatibles 3D-Zellsubstrat basierend auf Kohlenstoff vorgestellt, das erfolgreich auf Zellwachstum und MR-Bildgebung getestet wurde. Die MRT dient des Weiteren als Analysewerkzeug, um die Erhaltung der Morphologie während der Pyrolyse zu untersuchen und zu bestätigen. Das Herstellungsprotokoll ist auf andere Vorläuferpolymere anwendbar, die den Weg zu einer Vielzahl von lithografisch strukturierten 3D-Gerüsten ebnen

Motion prediction enables simulated MR-imaging of freely moving model organisms

Magnetic resonance tomography typically applies the Fourier transform to k-space signals repeatedly acquired from a frequency encoded spatial region of interest, therefore requiring a stationary object during scanning. Any movement of the object results in phase errors in the recorded signal, leading to deformed images, phantoms, and artifacts, since the encoded information does not originate from the intended region of the object. However, if the type and magnitude of movement is known instantaneously, the scanner or the reconstruction algorithm could be adjusted to compensate for the movement, directly allowing high quality imaging with non-stationary objects. This would be an enormous boon to studies that tie cell metabolomics to spontaneous organism behaviour, eliminating the stress otherwise necessitated by restraining measures such as anesthesia or clamping. In the present theoretical study, we use a phantom of the animal model C. elegans to examine the feasibility to automatically predict its movement and position, and to evaluate the impact of movement prediction, within a sufficiently long time horizon, on image reconstruction. For this purpose, we use automated image processing to annotate body parts in freely moving C. elegans, and predict their path of movement. We further introduce an MRI simulation platform based on bright field videos of the moving worm, combined with a stack of high resolution transmission electron microscope (TEM) slice images as virtual high resolution phantoms. A phantom provides an indication of the spatial distribution of signal-generating nuclei on a particular imaging slice. We show that adjustment of the scanning to the predicted movements strongly reduces distortions in the resulting image, opening the door for implementation in a high-resolution NMR scanner.ISSN:1553-734XISSN:1553-735

Should patients with brain implants undergo MRI?

Patients suffering from neuronal degenerative diseases are increasingly being equipped with neural implants to treat symptoms or restore functions and increase their quality of life. Magnetic resonance imaging (MRI) would be the modality of choice for diagnosis and compulsory post-operative monitoring of such patients. However, interactions between the MR environment and implants pose severe health risks to the patient. Nevertheless, neural implant recipients regularly underwent MRI examinations, and adverse events were reported rarely. This should not imply that the procedures are safe. More than 300.000 cochlear implant recipients are excluded from MRI unless the indication outweighs excruciating pain. For 75.000 DBS recipients quite the opposite holds: MRI is considered essential part of the implantation procedure and some medical centres deliberately exceed safety regulations which they referred to as crucially impractical. MRI related permanent neurological dysfunctions in DBS recipients have occurred in the past when manufacturer recommendations were exceeded. Within the last decades extensive effort has been invested to identify, characterise, and quantify the occurring interactions. Today we are far from a satisfying solution to achieve a safe and beneficial MR procedure for all implant recipients. To contribute, we intend to raise awareness of a growing concern and want to summon the community to stop absurdities and instead improve the situation for the increasing number of patients. Therefore, we review implant safety in the MRI literature from an engineering point of view, with a focus on cochlear and DBS implants as success stories in clinical practice. We briefly explain fundamental phenomena which can lead to patient harm, and point out breakthroughs and errors made. We end with conclusions and strategies to avoid future implants from being contraindicated to MR examinations. We believe that implant recipients should enter MRI, but before doing so, we should make sure that the procedure is reasonable

Polysaccharide-Based Theranostic Systems for Combined Imaging and Cancer Therapy: Recent Advances and Challenges

Designing novel systems for efficient cancer treatment and improving the quality of life for patients is a prime requirement in the healthcare sector. In this regard, theranostics have recently emerged as a unique platform, which combines the benefits of both diagnosis and therapeutics delivery. Theranostics have the desired contrast agent and the drugs combined in a single carrier, thus providing the opportunity for real-time imaging to monitor the therapy results. This helps in reducing the hazards related to treatment overdose or underdose and gives the possibility of personalized therapy. Polysaccharides, as natural biomolecules, have been widely explored to develop theranostics, as they act as a matrix for simultaneously loading both contrast agents and drugs for their utility in drug delivery and imaging. Additionally, their remarkable physicochemical attributes (biodegradability, satisfactory safety profile, abundance, and diversity in functionality and charge) can be tuned via postmodification, which offers numerous possibilities to develop theranostics with desired characteristics. Hence, we provide an overview of recent advances in polysaccharide matrix-based theranostics for drug delivery combined with magnetic resonance imaging, computed tomography, positron emission tomography, single photon emission computed tomography, and ultrasound imaging. Herein, we also summarize the toxicity assessment of polysaccharides, associated contrast agents, and nanotoxicity along with the challenges and future research directions. Accepted Author ManuscriptBT/Biocatalysi

Motion prediction enables simulated MR-imaging of freely moving model organisms

Magnetic resonance tomography typically applies the Fourier transform to k-space signals repeatedly acquired from a frequency encoded spatial region of interest, therefore requiring a stationary object during scanning. Any movement of the object results in phase errors in the recorded signal, leading to deformed images, phantoms, and artifacts, since the encoded information does not originate from the intended region of the object. However, if the type and magnitude of movement is known instantaneously, the scanner or the reconstruction algorithm could be adjusted to compensate for the movement, directly allowing high quality imaging with non-stationary objects. This would be an enormous boon to studies that tie cell metabolomics to spontaneous organism behaviour, eliminating the stress otherwise necessitated by restraining measures such as anesthesia or clamping. In the present theoretical study, we use a phantom of the animal model C. elegans to examine the feasibility to automatically predict its movement and position, and to evaluate the impact of movement prediction, within a sufficiently long time horizon, on image reconstruction. For this purpose, we use automated image processing to annotate body parts in freely moving C. elegans, and predict their path of movement. We further introduce an MRI simulation platform based on bright field videos of the moving worm, combined with a stack of high resolution transmission electron microscope (TEM) slice images as virtual high resolution phantoms. A phantom provides an indication of the spatial distribution of signal-generating nuclei on a particular imaging slice. We show that adjustment of the scanning to the predicted movements strongly reduces distortions in the resulting image, opening the door for implementation in a high-resolution NMR scanner.ISSN:1553-734XISSN:1553-735

Single Photon Ionization Orthogonal Acceleration Time-of-Flight Mass Spectrometry and Resonance Enhanced Multiphoton Ionization Time-of-Flight Mass Spectrometry for Evolved Gas Analysis in Thermogravimetry: Comparative Analysis of Crude Oils

Coupling thermal analysis (TA) with a subsequent analytical method in order to investigate evolved gaseous products from the thermal analysis is a well established method. A popular practice to analyze the gaseous products evolving from thermal analysis is mass spectrometry using electron impact ionization (EI).(1-4) As the kinetic energy of the electrons thereby is typically far beyond the ionization energies of the assayed samples, the electron impact effects fragmentation particularly of organic compounds, hampering the correlation of the ion signals to the gaseous compounds. This applies for complex mixtures in particular. Fragmentation can be reduced using so-called soft ionization techniques. In the course of the presented setup, single photon ionization (SPI) using electron beam pumped excimer lamps (EBEL) emitting vacuum ultraviolet (VUV) light (lambda = 126 nm) is employed. For the instrumentation, a TA system has been coupled to an EBEL-SPI-oaTOFMS (oaTOFMS: orthogonal acceleration time-of-flight mass spectrometry) system using a heated transfer capillary in order to detect semivolatile organic substances from the gas flow of a thermobalance with high temporal resolution. Presented measurements focus on crude oils of different origins. In-depth analysis demonstrates that it is possible to tell apart different crude oil samples on the basis of temperature resolved mass spectra gained from the described setup. TA allows for the assay of crude oils without sample preparation via a distillation process which precedes the thermal decomposition of nonvolatile oil components, i.e., resins and asphaltenes. The gases that evolve during thermal analysis are a complex mixture of organic compounds. These can be analyzed without losing molecular information using mass spectrometry with a soft ionization technique, such as SPI