Bau und Entwicklung eines Applikators zur Verabreichung hyperpolarisierter Gase in der MRT der Lunge

Im Rahmen meiner Dissertation habe ich gemäß dem Medizinproduktegesetz ein MR-kompatibles Verabreichungsgerät entwickelt, um Patienten hyperpolarisierte Gas Boli (He-3, Xe-129) als Kontrasgas zur MRT der Lunge zu applizieren. Das Gerät wurde dazu optimiert, die Gase oder Gasmischungen (z. B. HP Gas + N2) in definierten Mengen und zu definierten Zeitpunkten während der Inspiration mit hoher Reproduzierbarkeit und Zuverlässigkeit zu verabreichen, ohne dabei die MR-Qualität zu beeinträchtigen. Aus Sicherheitsgründen und zur späteren Datenanalyse werden die Atemflusskurven der Patienten kontinuierlich angezeigt und aufgezeichnet. Ein Kolbenkompressor ist integriert, um die gesamte gespeicherte He-3-Menge nutzen zu können. Weiterhin ist es möglich, die Polarisation vor Ort zu bestimmen und das abgeatmete He-3 zur späteren Rückgewinnung aufzufangen. Diese Auffangeffizienz konnte durch Untersuchungen mit He-4 (als He-3-Ersatz) gesteigert werden.rnDie ersten MR-Aufnahmen von 10 gesunden Probanden wurden mit diesem Aufbau imrnRahmen einer klinischen Studie durchgeführt. Die Analyse der bestimmten MR-Parameter Signal-Rausch-Verhältnis (SNR), Sauerstoffpartialdruck (pO2), Scheinbarer Diffusionskoeffizient (ADC=apparent diffusion coefficient) sowie die Signalanstiegszeit (rise-time) zeigt eine deutlich bessere Reproduzierbarkeit bei der Verabreichung des He-3 mit dem Applikators anstelle eines Tedlarbags (= kleine heliumdichte Plastiktüte).

Neuartige kryogene Penning-Falle für den Nachweis von Spin-Übergängen eines Protons und Bestimmung seines g-Faktors

In dieser Arbeit wird der Entwurf, der Aufbau, die Inbetriebnahme und die Charakterisierung einer neuartigen Penning-Falle im Rahmen des Experiments zur Bestimmung des g-Faktors des Protons präsentiert. Diese Falle zeichnet sich dadurch aus, dass die Magnetfeldlinien eines äußeren homogenen Magnetfeldes durch eine ferromagnetische Ringelektrode im Zentrum der Falle verzerrt werden. Der inhomogene Anteil des resultierenden Magnetfeldes, die sogenannte magnetische Flasche, lässt sich durch den Koeffizient B2 = 297(10) mT/mm2 des Terms zweiter Ordnung der Ortsabhängigkeit des Feldes quantifizieren. Eine solche ungewöhnlich starke Feldinhomogenität ist Grundvoraussetzung für den Nachweis der Spinausrichtung des Protons mittels des kontinuierlichen Stern-Gerlach-Effektes. Dieser Effekt basiert auf der im inhomogenen Magnetfeld entstehenden Kopplung des Spin-Freiheitsgrades des gefangenen Protons an eine seiner Eigenfrequenzen. Ein Spin-Übergang lässt sich so über einen Frequenzsprung detektieren. Dabei ist die nachzuweisende Änderung der Frequenz proportional zu B2 und zum im Fall des Protons extrem kleinen Verhältnis zwischen seinem magnetischen Moment nund seiner Masse. Die durch die benötigte hohe Inhomogenität des Magnetfeldes bedingten technischen Herausforderungen erfordern eine fundierte Kenntnis und Kontrolle der Eigenschaften der Penning-Falle sowie der experimentellen Bedingungen. Die in der vorliegenden Arbeit entwickelte Penning-Falle ermöglichte den erstmaligen zerstörungsfreien Nachweis von Spin-Quantensprüngen eines einzelnen gefangenen Protons, was einen Durchbruch für das Experiment zur direkten Bestimmung des g-Faktors mit der angestrebten relativen Genauigkeit von 10−9 darstellte. Mithilfe eines statistischen Verfahrens ließen sich die Larmor- und die Zyklotronfrequenz des Protons im inhomogenen Magnetfeld der Falle ermitteln. Daraus wurde der g-Faktor mit einer relativen Genauigkeit von 8,9 × 10−6 bestimmt. Die hier vorgestellten Messverfahren und der experimentelle Aufbau können auf ein äquivalentes Experiment zur Bestimmung des g-Faktors des Antiprotons zum Erreichen der gleichen Messgenauigkeit übertragen werden, womit der erste Schritt auf dem Weg zu einem neuen zwingenden Test der CPT-Symmetrie im baryonischen Sektor gemacht wäre.

Non-parametric estimation of the diffusion coefficient of a branching diffusion with immigration

Wir betrachten Systeme von endlich vielen Partikeln, wobei die Partikel sich unabhängig voneinander gemäß eindimensionaler Diffusionen [dX_t = b(X_t),dt + sigma(X_t),dW_t] bewegen. Die Partikel sterben mit positionsabhängigen Raten und hinterlassen eine zufällige Anzahl an Nachkommen, die sich gemäß eines Übergangskerns im Raum verteilen. Zudem immigrieren neue Partikel mit einer konstanten Rate. Ein Prozess mit diesen Eigenschaften wird Verzweigungsprozess mit Immigration genannt. Beobachten wir einen solchen Prozess zu diskreten Zeitpunkten, so ist zunächst nicht offensichtlich, welche diskret beobachteten Punkte zu welchem Pfad gehören. Daher entwickeln wir einen Algorithmus, um den zugrundeliegenden Pfad zu rekonstruieren. Mit Hilfe dieses Algorithmus konstruieren wir einen nichtparametrischen Schätzer für den quadrierten Diffusionskoeffizienten $sigma^2(cdot),$ wobei die Konstruktion im Wesentlichen auf dem Auffüllen eines klassischen Regressionsschemas beruht. Wir beweisen Konsistenz und einen zentralen Grenzwertsatz.

Climate change in Libya and desertification of Jifara Plain

The study was arranged to manifest its objectives through preceding it with an intro-duction. Particular attention was paid in the second part to detect the physical settings of the study area, together with an attempt to show the climatic characteristics in Libya. In the third part, observed temporal and spatial climate change in Libya was investigated through the trends of temperature, precipitation, relative humidity and cloud amount over the peri-ods (1946-2000), (1946-1975), and (1976-2000), comparing the results with the global scales. The forth part detected the natural and human causes of climate change concentrat-ing on the greenhouse effect. The potential impacts of climate change on Libya were ex-amined in the fifth chapter. As a case study, desertification of Jifara Plain was studied in the sixth part. In the seventh chapter, projections and mitigations of climate change and desertification were discussed. Ultimately, the main results and recommendations of the study were summarized. In order to carry through the objectives outlined above, the following methods and approaches were used: a simple linear regression analysis was computed to detect the trends of climatic parameters over time; a trend test based on a trend-to-noise-ratio was applied for detecting linear or non-linear trends; the non-parametric Mann-Kendall test for trend was used to reveal the behavior of the trends and their significance; PCA was applied to construct the all-Libya climatic parameters trends; aridity index after Walter-Lieth was shown for computing humid respectively arid months in Libya; correlation coefficient, (after Pearson) for detecting the teleconnection between sun spot numbers, NAOI, SOI, GHGs, and global warming, climate changes in Libya; aridity index, after De Martonne, to elaborate the trends of aridity in Jifara Plain; Geographical Information System and Re-mote Sensing techniques were applied to clarify the illustrations and to monitor desertifi-cation of Jifara Plain using the available satellite images MSS, TM, ETM+ and Shuttle Radar Topography Mission (SRTM). The results are explained by 88 tables, 96 figures and 10 photos. Temporal and spatial temperature changes in Libya indicated remarkably different an-nual and seasonal trends over the long observation period 1946-2000 and the short obser-vation periods 1946-1975 and 1976-2000. Trends of mean annual temperature were posi-tive at all study stations except at one from 1946-2000, negative trends prevailed at most stations from 1946-1975, while strongly positive trends were computed at all study stations from 1976-2000 corresponding with the global warming trend. Positive trends of mean minimum temperatures were observed at all reference stations from 1946-2000 and 1976-2000, while negative trends prevailed at most stations over the period 1946-1975. For mean maximum temperature, positive trends were shown from 1946-2000 and from 1976-2000 at most stations, while most trends were negative from 1946-1975. Minimum tem-peratures increased at nearly more than twice the rate of maximum temperatures at most stations. In respect of seasonal temperature, warming mostly occurred in summer and au-tumn in contrast to the global observations identifying warming mostly in winter and spring in both study periods. Precipitation across Libya is characterized by scanty and sporadically totals, as well as high intensities and very high spatial and temporal variabilities. From 1946-2000, large inter-annual and intra-annual variabilities were observed. Positive trends of annual precipi-tation totals have been observed from 1946-2000, negative trends from 1976-2000 at most stations. Variabilities of seasonal precipitation over Libya are more strikingly experienced from 1976-2000 than from 1951-1975 indicating a growing magnitude of climate change in more recent times. Negative trends of mean annual relative humidity were computed at eight stations, while positive trends prevailed at seven stations from 1946-2000. For the short observation period 1976-2000, positive trends were computed at most stations. Annual cloud amount totals decreased at most study stations in Libya over both long and short periods. Re-markably large spatial variations of climate changes were observed from north to south over Libya. Causes of climate change were discussed showing high correlation between tempera-ture increasing over Libya and CO2 emissions; weakly positive correlation between pre-cipitation and North Atlantic Oscillation index; negative correlation between temperature and sunspot numbers; negative correlation between precipitation over Libya and Southern Oscillation Index. The years 1992 and 1993 were shown as the coldest in the 1990s result-ing from the eruption of Mount Pinatubo, 1991. Libya is affected by climate change in many ways, in particular, crop production and food security, water resources, human health, population settlement and biodiversity. But the effects of climate change depend on its magnitude and the rate with which it occurs. Jifara Plain, located in northwestern Libya, has been seriously exposed to desertifica-tion as a result of climate change, landforms, overgrazing, over-cultivation and population growth. Soils have been degraded, vegetation cover disappeared and the groundwater wells were getting dry in many parts. The effect of desertification on Jifara Plain appears through reducing soil fertility and crop productivity, leading to long-term declines in agri-cultural yields, livestock yields, plant standing biomass, and plant biodiversity. Desertifi-cation has also significant implications on livestock industry and the national economy. Desertification accelerates migration from rural and nomadic areas to urban areas as the land cannot support the original inhabitants. In the absence of major shifts in policy, economic growth, energy prices, and con-sumer trends, climate change in Libya and desertification of Jifara Plain are expected to continue in the future. Libya cooperated with United Nations and other international organizations. It has signed and ratified a number of international and regional agreements which effectively established a policy framework for actions to mitigate climate change and combat deserti-fication. Libya has implemented several laws and legislative acts, with a number of ancil-lary and supplementary rules to regulate. Despite the current efforts and ongoing projects being undertaken in Libya in the field of climate change and desertification, urgent actions and projects are needed to mitigate climate change and combat desertification in the near future.

Ventilation-perfusion ratio in perflubron during partial liquid ventilation

BACKGROUND: Functional magnetic resonance imaging (fMRI) of fluorine-19 allows for the mapping of oxygen partial pressure within perfluorocarbons in the alveolar space (Pao(2)). Theoretically, fMRI-detected Pao(2) can be combined with the Fick principle approach, i.e., a mass balance of oxygen uptake by ventilation and delivery by perfusion, to quantify the ventilation-perfusion ratio (Va/Q) of a lung region: The mixed venous blood and the inspiratory oxygen fraction, which are equal for all lung regions, are measured. In addition, the local expiratory oxygen fraction and the end capillary oxygen content, both of which may differ between the lung regions, are calculated using the fMRI-detected Pao(2). We investigated this approach by numerical simulations and applied it to quantify local Va/Q in the perfluorocarbons during partial liquid ventilation. METHODS: Numerical simulations were performed to analyze the sensitivity of the Va/Q calculation and to compare this approach with another one proposed by Rizi et al. in 2004 (Magn Reson Med 2004;52:65-72). Experimentally, the method was used during partial liquid ventilation in 7 anesthetized pigs. The Pao(2) distribution in intraalveolar perflubron was measured by fluorine-19 MRI. Respiratory gas fractions together with arterial and mixed venous blood samples were taken to quantify oxygen partial pressure and content. Using the Fick principle, the local Va/Q was estimated. The impact of gravity (nondependent versus dependent) of perflubron dose (10 vs 20 mL/kg body weight) and of inspired oxygen fraction (Fio(2)) (0.4-1.0) on Va/Q was examined. RESULTS: In numerical simulations, the Fick principle proved to be appropriate over the Va/Q range from 0.02 to 2.5. Va/Q values were in acceptable agreement with the method published by Rizi et al. In the experimental setting, low mean Va/Q values were found in perflubron (confidence interval [CI] 0.08-0.29 with 20 mL/kg perflubron). At this dose, Va/Q in the nondependent lung was higher (CI 0.18-0.39) than in the dependent lung regions (CI 0.06-0.16; P = 0.006; Student t test). Differences depending on Fio(2) or perflubron dose were, however, small. CONCLUSION: The results show that derivation of Va/Q from local Po(2) measurements using fMRI in perflubron is feasible. The low detected Va/Q suggests that oxygen transport into the perflubron-filled alveolar space is significantly restrained.

The relationship between extravascular lung water and oxygenation in three patients with influenza A (H1N1)-induced respiratory failure

This case series reports the correlation between extravascular lung water (EVLW) and the partial arterial oxygen pressure/fractional inspiratory oxygen (PaO(2)/FiO(2)) ratio in three patients with severe influenza A (H1N1)-induced respiratory failure. All patients suffered from grave hypoxia (PaO(2), 26-42 mmHg) and were mechanically ventilated using biphasic airway pressure (PEEP, 12-15 mmHg; FiO(2), 0.8-1) in combination with prone positioning at 12 hourly intervals. All patients were monitored using the PICCO system for 8-11 days. During mechanical ventilation, a total of 62 simultaneous determinations of the PaO(2)/FiO(2) ratio and EVLW were performed. A significant correlation between EVLW and the PaO(2)/FiO(2) ratio (Spearman-rho correlation coefficient, -0.852; p < 0.001) was observed. In all patients, a decrease in EVLW was accompanied by an improvement in oxygenation. Serum lactate dehydrogenase levels were elevated in all patients and significantly correlated with EVLW during the intensive care unit stay (Spearman-rho correlation coefficient, 0.786; p < 0.001). In conclusion, EVLW seems increased in patients with severe H1N1-induced respiratory failure and appears to be closely correlated with impairments of oxygenatory function.