Magnetic iron oxide nanoparticles as potential contrast agents for magnetic resonance imaging

This thesis presents the development of novel formulations on the basis of magnetic iron oxide nanoparticles. Optimization of the synthesis route resulted in the development of particles meeting general requirements for eventual applications. Furthermore, the selection of appropriate stabilizing agents imparted the nanoparticles with beneficial features, making an in vivo application possible. In doing so, the formulations seem to be especially promising for the application as contrast agents in magnetic resonance imaging. Chapter 1 gives a brief insight into current research in the field of magnetic nanoparticles. While the originally promoted idea of dragging nanoparticles to the site of action by a massive external field is becoming less important, the use of magnetic carriers as single and multifunctional imaging agents is gaining in importance. Chapter 2 describes the synthesis of magnetic iron oxide nanoparticles with optimal properties for MRI contrast enhancement and the comparative assessment of polymeric macromolecules as stabilizers for such nanoparticles. It was revealed that particles covered by poly(ethylene imine)-g-poly(ethylene glycol) performed better than their poly(ethylene imine) counterparts, in terms of stability and cytotoxicity. The systems containing the former polymer showed pronounced colloidal stability even in protein-rich cell media. In addition, cytotoxicity was reduced by more than an order of magnitude. In this respect, the assumptions made in the run-up to the studies have found confirmation. Indeed, the introduction of hydrophilic poly(ethylene glycol) moieties to the polymer backbone positively manipulated the above properties. In addition, the physicochemical properties of the generated iron oxide nanoparticles were found to be excellent, despite the simplicity of the synthesis procedure. The iron oxide cores displayed high crystallinity, high saturation magnetization and superparamagnetic features. The polymer-coated nanoparticles were narrowly distributed around an average diameter of 40 nm and showed relaxation parameters comparable to presently marketed products. Given these results, the established magnetic ferrofluids appear to be interesting for an intracorporal application as an MRI contrast agent. The assumption that the configuration of magnetic nanoparticles affects cell uptake (mechanisms) and localization, and subsequently cellular MRI signaling, provided a basis for further studies. Chapter 3 includes the evaluation of oppositely charged iron oxide nanoparticle systems with regard to physicochemical properties, cell interaction and cell-constrained relaxometry. The findings of this section confirm that surface potential is the key factor controlling cell internalization of magnetic iron oxide nanoparticles. Particles with a positive zeta potential were taken up to an almost tenfold extent after 24 hours, and with faster kinetics than the negatively charged counterparts. Basically, these results confirm the preliminary assumptions that electrostatic attractive forces between the cell membrane and the nanoparticles favor an enhanced internalization of positive carriers. However, the clear discrepancy in overall uptake led to the conclusion that synergistic effects, such as colloidal stability, also influence the rate of particle accumulation in cells. Both systems were found to be compartmentalized in endosomes after their uptake into cells by a correspondent endocytotic pathway. This cellular confinement caused the relaxation parameters to change in comparison to freely dispersed nanosuspensions, in such a way that the signal contrast in T2-weighted MRI sequences degraded. Nevertheless, phantoms of cells incubated with positively charged nanoparticles still revealed effective signal darkening in these MRI sequences. The results suggest the suspensions examined as promising agents for cell tracking purposes, as here high iron uptake in combination with pronounced relaxivity is required

„…des Volkes, des man niht enaht…“: soziale Randgruppen und Außenseiter im Spiegel der österreichischen Chronistik des späten Mittelalters unter besonderer Berücksichtigung der Überlieferungen zur Sozialstruktur in Kärnten

1000 Worte Forschung: Laufende Dissertation (Mittelalterliche Geschichte), Alpen-Adria-Universität Klagenfur

Detection of metastable electronic states by Penning trap mass spectrometry

State-of-the-art optical clocks achieve fractional precisions of $10^{-18}$ and below using ensembles of atoms in optical lattices or individual ions in radio-frequency traps. Promising candidates for novel clocks are highly charged ions (HCIs) and nuclear transitions, which are largely insensitive to external perturbations and reach wavelengths beyond the optical range, now becoming accessible to frequency combs. However, insufficiently accurate atomic structure calculations still hinder the identification of suitable transitions in HCIs. Here, we report on the discovery of a long-lived metastable electronic state in a HCI by measuring the mass difference of the ground and the excited state in Re, the first non-destructive, direct determination of an electronic excitation energy. This result agrees with our advanced calculations, and we confirmed them with an Os ion with the same electronic configuration. We used the high-precision Penning-trap mass spectrometer PENTATRAP, unique in its synchronous use of five individual traps for simultaneous mass measurements. The cyclotron frequency ratio $R$ of the ion in the ground state to the metastable state could be determined to a precision of $\delta R=1\cdot 10^{-11}$, unprecedented in the heavy atom regime. With a lifetime of about 130 days, the potential soft x-ray frequency reference at $\nu=4.86\cdot 10^{16}\,\text{Hz}$ has a linewidth of only $\Delta \nu\approx 5\cdot 10^{-8}\,\text{Hz}$, and one of the highest electronic quality factor ($Q=\frac{\nu}{\Delta \nu}\approx 10^{24}$) ever seen in an experiment. Our low uncertainty enables searching for more HCI soft x-ray clock transitions, needed for promising precision studies of fundamental physics in a thus far unexplored frontier

Observation of a low-lying metastable electronic state in highly charged lead by Penning-trap mass spectrometry

Highly charged ions (HCIs) offer many opportunities for next-generation clock research due to the vast landscape of available electronic transitions in different charge states. The development of XUV frequency combs has enabled the search for clock transitions based on shorter wavelengths in HCIs. However, without initial knowledge of the energy of the clock states, these narrow transitions are difficult to be probed by lasers. In this Letter, we provide experimental observation and theoretical calculation of a long-lived electronic state in Nb-like Pb$^{41+}$ which could be used as a clock state. With the mass spectrometer Pentatrap, the excitation energy of this metastable state is directly determined as a mass difference at an energy of 31.2(8) eV, corresponding to one of the most precise relative mass determinations to date with a fractional uncertainty of $4\times10^{-12}$. This experimental result agrees within 1 $\sigma$ with two partially different \textit{ab initio} multi-configuration Dirac-Hartree-Fock calculations of 31.68(13) eV and 31.76(35) eV, respectively. With a calculated lifetime of 26.5(5.3) days, the transition from this metastable state to the ground state bears a quality factor of $1.1\times10^{23}$ and allows for the construction of a HCI clock with a fractional frequency instability of $<10^{-19}/\sqrt{\tau}$

User Perceptions of ROTEM-Guided Haemostatic Resuscitation: A Mixed Qualitative–Quantitative Study

Viscoelastic point-of-care haemostatic resuscitation methods, such as ROTEM or TEG, are crucial in deciding on time-efficient personalised coagulation interventions. International transfusion guidelines emphasise increased patient safety and reduced treatment costs. We analysed care providers’ perceptions of ROTEM to identify perceived strengths and areas for improvement. We conducted a single-centre, mixed qualitative–quantitative study consisting of interviews followed by an online survey. Using a template approach, we first identified themes in the responses given by care providers about ROTEM. Later, the participants rated six statements based on the identified themes on five-point Likert scales in an online questionnaire. Seventy-seven participants were interviewed, and 52 completed the online survey. By analysing user perceptions, we identified ten themes. The most common positive theme was “high accuracy”. The most common negative theme was “need for training”. In the online survey, 94% of participants agreed that monitoring the real-time ROTEM temograms helps to initiate targeted treatment more quickly and 81% agreed that recurrent ROTEM training would be beneficial. Anaesthesia care providers found ROTEM to be accurate and quickly available to support decision-making in dynamic and complex haemostatic situations. However, clinicians identified that interpreting ROTEM is a complex and cognitively demanding task that requires significant training needs

Stromal Expression of Heat-Shock Protein 27 Is Associated with Worse Clinical Outcome in Patients with Colorectal Cancer Lung Metastases

Pulmonary metastases are common in patients with primary colorectal cancer (CRC). Heat- shock protein 27 (Hsp27) is upregulated in activated fibroblasts during wound healing and systemically elevated in various diseases. Cancer-associated fibroblasts (CAFs) are also thought to play a role as prognostic and predictive markers in various malignancies includ- ing CRC. Surprisingly, the expression of Hsp27 has never been assessed in CAFs. There- fore we aimed to investigate the expression level of Hsp27 in CAFs and its clinical implications in patients with CRC lung metastases

Visual Blood, a 3D Animated Computer Model to Optimize the Interpretation of Blood Gas Analysis

Acid–base homeostasis is crucial for all physiological processes in the body and is evaluated using arterial blood gas (ABG) analysis. Screens or printouts of ABG results require the interpretation of many textual elements and numbers, which may delay intuitive comprehension. To optimise the presentation of the results for the specific strengths of human perception, we developed Visual Blood, an animated virtual model of ABG results. In this study, we compared its performance with a conventional result printout. Seventy physicians from three European university hospitals participated in a computer-based simulation study. Initially, after an educational video, we tested the participants’ ability to assign individual Visual Blood visualisations to their corresponding ABG parameters. As the primary outcome, we tested caregivers’ ability to correctly diagnose simulated clinical ABG scenarios with Visual Blood or conventional ABG printouts. For user feedback, participants rated their agreement with statements at the end of the study. Physicians correctly assigned 90% of the individual Visual Blood visualisations. Regarding the primary outcome, the participants made the correct diagnosis 86% of the time when using Visual Blood, compared to 68% when using the conventional ABG printout. A mixed logistic regression model showed an odds ratio for correct diagnosis of 3.4 (95%CI 2.00–5.79, p < 0.001) and an odds ratio for perceived diagnostic confidence of 1.88 (95%CI 1.67–2.11, p < 0.001) in favour of Visual Blood. A linear mixed model showed a coefficient for perceived workload of −3.2 (95%CI −3.77 to −2.64) in favour of Visual Blood. Fifty-one of seventy (73%) participants agreed or strongly agreed that Visual Blood was easy to use, and fifty-five of seventy (79%) agreed that it was fun to use. In conclusion, Visual Blood improved physicians’ ability to diagnose ABG results. It also increased perceived diagnostic confidence and reduced perceived workload. This study adds to the growing body of research showing that decision-support tools developed around human cognitive abilities can streamline caregivers’ decision-making and may improve patient care