Development and evaluation of quantitative imaging for improved estimation of radiopharmaceutical bio-distribution in small animal imaging

Quantitative imaging techniques like Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) are an essential part of the treatment planning based on dosimetry in targeted radiation therapy. Apart from Fluorine-18 (18F), the potential of various other radionuclides with respect to the development of new radiopharmaceuticals which can be used for both diagnostic and therapeutic applications are increasingly under investigation. Three such radionuclides that are attractive for further research are Gallium-68 (68Ga), Copper-64 (64Cu) and Zirconium-89 (89Zr). To determine the performance of a PET or a SPECT, the National Electrical Manufacturing Association (NEMA) has published a standard set of protocols. However, there are limitations with the NEMA method with respect to the determination of the spatial resolution. Firstly, it does not take into account the overall behavior of the point spread function (PSF). Secondly, it has a very limited scope for a validation or a quality check criterion and thus the error of the calculated full width at half maximum (FWHM) cannot be determined. In the first part of this work, the aim was to quantitatively develop, evaluate and improve the performance characteristics of the PET and SPECT subsystem of the Albira II pre-clinical tri-modal system (Bruker BioSpin MRI GmbH, Ettlingen, Germany) for the radionuclides 18F, 68Ga, 64Cu and 89Zr (PET) and 99mT (SPECT). In this study, the sensitivity and spatial resolution characteristics of the systems based on a developed point source phantom were furthermore investigated for each of the radionuclides and compared with the NEMA protocol results based on measurements with a 22Na point source. In addition, a new set of protocols was developed for quantitative image reconstruction with the respective systems. In the second part of this work, an alternative method to accurately determine the PSF of an imaging system was developed to improve quantification accuracy in dosimetry. The developed method is based on 3-dimensional Gaussian fit functions taking into account the correction for the pixel size and the source dimension. Additionally, the effect of inaccurate determination of the PSF on the partial volume correction and hence the quantification of small structures in a diagnostic image was investigated. The ability of quantitative image reconstructions was determined based on the recovery coefficients that showed that upto 95% and 60% activity values could be recovered with the PET and SPECT systems, respectively. Overall the system performed satisfactory with respect to the linearity for the activity range (8-10) MBq generally used for pre-clinical imaging for all the investigated radionuclides. With respect to the determination of the system PSF, the method includes fitting of 3-dimensional functions, validation of fitting quality and choosing the best fit function based on the Akaike information criterion (AIC). The proposed method has advantages that it can better take into account the 3D distribution of the data and additionally yields an estimate for the error of the FWHM calculated from the estimated PSF. Furthermore, the investigation demonstrated that the PSF determined using the NEMA or another inadequate fit function can lead to a relative deviation of more than 40% for the recovery correction of small structures. Thus, the general method developed here can be used for obtaining robust and better reproducible PSFs for performing recovery corrections in PET/SPECT quantification studies and thus is a prerequisite for optimal evaluation of biokinetics in small animal studies

Extensions of Positive Definite Functions: Applications and Their Harmonic Analysis

We study two classes of extension problems, and their interconnections: (i) Extension of positive definite (p.d.) continuous functions defined on subsets in locally compact groups $G$; (ii) In case of Lie groups, representations of the associated Lie algebras $La\left(G\right)$ by unbounded skew-Hermitian operators acting in a reproducing kernel Hilbert space (RKHS) $\mathscr{H}_{F}$. Why extensions? In science, experimentalists frequently gather spectral data in cases when the observed data is limited, for example limited by the precision of instruments; or on account of a variety of other limiting external factors. Given this fact of life, it is both an art and a science to still produce solid conclusions from restricted or limited data. In a general sense, our monograph deals with the mathematics of extending some such given partial data-sets obtained from experiments. More specifically, we are concerned with the problems of extending available partial information, obtained, for example, from sampling. In our case, the limited information is a restriction, and the extension in turn is the full positive definite function (in a dual variable); so an extension if available will be an everywhere defined generating function for the exact probability distribution which reflects the data; if it were fully available. Such extensions of local information (in the form of positive definite functions) will in turn furnish us with spectral information. In this form, the problem becomes an operator extension problem, referring to operators in a suitable reproducing kernel Hilbert spaces (RKHS). In our presentation we have stressed hands-on-examples. Extensions are almost never unique, and so we deal with both the question of existence, and if there are extensions, how they relate back to the initial completion problem.Comment: 235 pages, 42 figures, 7 tables. arXiv admin note: substantial text overlap with arXiv:1401.478

The origin of dwarf carbon stars

Dwarf carbon (dC) stars are low-mass, main-sequence stars that exhibit spectra analogous to carbon-rich giants found along the asymptotic giant branch. An almost half a century old hypothesis postulates that the peculiar atmospheric chemistry of dC stars is owed to mass transfer from an evolved companion. Speci cally, while the former primary ascended the asymptotic giant branch, triple- -processed material was dredged to the surface before the stellar wind liberated the carbon-enhanced outer layers. The liberated material is then transferred to the main-sequence companion, polluting its atmosphere, and forming a dC star, while the original primary becomes a white dwarf. In this thesis, I present the results of a decade-long spectroscopic survey of 37 dC stars to test this binary evolution hypothesis. Using MCMC simulations to analyse the radial-velocity variations of all 37 dC stars in this sample, it has been possible to show that the population is consistent with a 100 per cent binary fraction and are thus likely the product of mass transfer. Furthermore, the orbital parameters of nine dC stars are reported for the rst time, increasing the number of known dC binaries by 220 per cent. Interestingly, eight of these newly constrained dC binaries exhibit emission features in their optical spectrum. Moreover, the orbital periods of these emission-line dC stars are all shorter than 12 d, implying that these stars have evolved through a common envelope. Thus, the discovery of eight short-orbital period dC stars indicates that low-mass, metal-weak or metal-poor stars can accrete substantial material before entering the common-envelope phase. Finally, a kinematical study of 1200 candidate dC stars is presented, with the analysis indicating that as much as 70 per cent of the population may possess Galactic orbits that are inconsistent with thin disc membership. This result, therefore, suggests that dC stars are generally old and likely metal-poor

Learning and memory systems supporting decision making in the human brain

We successfully navigate the world by making decisions based on what we have learned. In the brain, two prominent learning systems have been identified and each is likely to guide decisions in different ways. Research on decision making has primarily focused on a reward learning system in the striatum. These studies have illuminated the how repeated choices and rewards build representations that guide choices and actions when encountering the same situation again. However, in a constantly changing environment, choices may not repeat themselves. Further, the environment may have more structure than simple reward learning can navigate. In these situations, decisions may be guided by a different learning system, namely a flexible learning system in the hippocampus which encodes episodes, or more broadly, relations between stimuli. However, investigations into the role of a reward learning system and a relational learning system in decision making have developed largely independently of each other. In the studies described below, I explore the function of these learning systems in value-guided decision making. Complementarily, I also explore how ongoing reward learning may modulate memory formation in the hippocampal system. In these studies, I demonstrate that reward learning and decision making is influenced by relational learning, and that these effects are predicted by hippocampal-striatal connectivity during learning. Separately, I establish that episodic memory is, in turn, influenced by ongoing reward learning. Successful memory is predicted by modulations of reward and memory regions including the striatum and hippocampus. Overall, these results provide novel insights into the learning systems encoding memories for future adaptive behavior

Reconstruction of moving surfaces of revolution from sparse 3-D measurements using a stereo camera and structured light

Das Ziel dieser Arbeit ist die Entwicklung und Analyse der algorithmischen Methodik zur Rekonstruktion eines parametrischen Oberflächenmodells für ein rotationssymmetrisches Objekt aus einer Sequenz von dünnen 3D-Punktwolken. Dabei kommt ein neuartiges Messsystem mit großem Sichtfeld zum Einsatz, das auch in schwierigen Bedingungen eingesetzt werden kann. Das zu vermessende Objekt kann während der Aufnahme der Sequenz einer als analytisches Modell formulierbaren Bewegung unterliegen. Das Verfahren wird anhand einer praktischen Anwendung zur Oberflächenrückgewinnung eines Rades analysiert und entwickelt. Es wird gezeigt, dass die durch Fit eines einfachen Models für jede Einzelmessung erzielbare Genauigkeit durch Anpassung eines globalen Modells unter gleichzeitiger Einbeziehung aller Einzelmessungen und unter Berücksichtigung eines geeigneten Bewegungsmodells erheblich verbessert werden kann. Die Gewinnung der dreidimensionalen Punktdaten erfolgt mit einem Stereokamerasystem in Verbindung mit aktiver Beleuchtung in Form eines Punktmusters. Eine relativ hohe Punktdichte im gesamten Sichtfeld des Stereokamerasystems wird durch Verbindung mehrerer Laserprojektoren zu einer Projektionseinheit erzielt. Durch exakte Kalibrierung des Kamerasystems und der Projektionseinheit wird trotz großer Streuung der Laserpunkte im Kamerabild unter Ausnutzung der trifokalen geometrischen Bedingungen eine hohe Genauigkeit in den dreidimensionalen Punktdaten erzielt

Control Over Cadmium Chalcogenide Nanocrystal Heterostructures via Precursor Conversion Kinetics

Semiconductor nanocrystals have immense potential to make an impact in consumer products due to their narrow, tunable emission linewidths. One factor limiting their use is the ease and reproducibility of core/shell nanocrystal syntheses. This thesis aims to address this issue by providing chemical control over the formation of core/shell nanostructures by replacing engineering controls with kinetic controls. Chapter 1 contextualizes our study on nanoparticle synthesis with a brief discussion on the physics of quantum confinement and the importance of narrow size dispersities, core/shell band alignments, and low lattice mismatches and strain at core/shell nanocrystal interfaces. Next, the evolution of cadmium chalcogenide nanocrystal reagents is described, ranging from the original organometallic reagents used in the 1980s to modern approaches involving cadmium phosphonates and carboxylates. This is followed by a description of chalcogen precursors, highlighting the recent introduction of molecules whose well-controlled and tunable reaction rates allow for the size tuning of nanocrystals at 100% yield, and accompanying theories on nanocrystal nucleation. Chapter 2 covers work to expand the library of available sulfur precursors to a wider range of molecules relevant for the synthesis of cadmium sulfide nanocrystals. Using thioureas alone, only very fast or very slow precursor conversion rates can be accessed. This limits the accessible sizes of cadmium sulfide nanocrystals using a single hot injection of precursor at standardized reaction conditions. We observe that thiocarbonate and thiocarbamate precursors with varying electronic substituents allow access to intermediate precursor conversion rates and cadmium sulfide nanocrystal sizes. Interestingly, we note that these new precursor classes nucleate particles with higher monodispersity than ones synthesized from thioureas. These results indicate that in addition to precursor structure controlling precursor conversion rate, precursor structure additionally impacts nanocrystal monodispersity. Chapter 3 expands the library of sulfur and selenium precursors to include cyclic thiones and selenones which extends chemical control of precursor conversion kinetics to cover five orders of magnitude. This unprecedented breadth of rate control allows for the simultaneous hot injection of multiple precursors to generate core/shell or alloyed nanoparticles using precursor reactivity. Using this new synthetic strategy, we observe that kinetic control runs into several issues which we partially attribute to differences in cadmium sulfide and cadmium selenide critical concentrations and growth rates. Nevertheless, combined with a syringe pump shelling method, we are able to access core/shell and alloyed nanocrystals with photoluminescence quantum yields of 67-81%. Chapter 4 applies the concept of nanostructure control via precursor conversion kinetics to a better model system: two-dimensional nanoplatelets. Cadmium chalcogenide nanoplatelets are highly desirable materials due to their exceptionally narrow emission full width half max (FWHM) values which make them pure emitters relative to quantum dots or organic dyes. We synthesize 3 monolayer thick nanoplatelets whose lateral dimensions vary from 10 nm x 10 nm to 186 x 100 nm and demonstrate compositional control on the smallest platelet sizes with STEM EELS

Developing Tools For Probing Stellar Interiors With Asteroseismology

Asteroseismology is the study of stellar oscillations. Recent space missions, such as CoRoT, Kepler, and TESS, are rapidly revolutionising the field by collecting vast amounts of data. These data have enabled accurate characterisation of stellar oscillations for a wide range of stars, leading to improved understanding of stellar physics and knowledge of Galactic and planetary populations. This thesis builds on existing tools and develops new techniques to advance our understanding of stars using their oscillations. Firstly, we investigate 36 subgiants observed by Kepler, measuring their oscillation parameters and extracting their frequencies, amplitudes and linewidths. They are used as modelling input to derive accurate stellar parameters. Secondly, we measure the core and envelope rotation rates for these subgiants, and study them as a function of stellar properties. We find near solid-body rotation in early subgiants and differential rotation in later stages. Thirdly, we evaluate the intrinsic scatter of the asteroseismic scaling relations, using the sharpness of population-level features that are naturally formed by stars. We constrain the intrinsic scatter to be a few percent. Fourthly, we propose a new method to correct the stellar surface effect, which involves prescribing the surface effect as a function of stellar surface parameters. This method reduces the scatter of model-derived stellar properties and provides a revised correction for the Dnu scaling relation. Fifthly, we test the numax scaling relation by comparing observed numax with model-inferred scaling numax constrained by individual frequencies. We conclude no noticeable deviation of the numax scaling relation and a lack of metallicity dependency. Lastly, we construct a mass-radius diagram for red clump stars, leading to the discovery of two new types of post-mass-transfer stars. The new finding offers exciting opportunities to study binary evolution using asteroseismology

Mechatronics design of a robot society : a case study of minimalist underwater robots for distributed perception and task execution

This thesis describes the mechatronics design of a cooperative multi-robot system, including systems level design, practical implementation, and testing. Two main subjects are integrated in this research work: the generic concept of a Robot Society as an engineering framework to control an autonomously operating distributed multi-robot system, and the constructed prototype society consisting of several sensor/actuator robots for submerged use in a liquid environment. These novel types of prototype robots, SUBMARs, are targeted for distributed autonomous perception and task execution in the internal, three-dimensional on-line monitoring of various flow-through processes. The Robot Society control architecture implemented into SUBMAR robots supports such features as the autonomous cooperation of the robots, multi-tasking, self-organization, and selfoptimization in task execution. The mechatronics design of the robots has followed a minimalist approach, where the structure of the robot is maximally simplified. As a solution to compensate the obvious limitations derived from minimalism, the multiplicity and the cooperation of the robots have been exploited. On a systems level, this produces fault tolerant, flexible, and cost-effective engineering solutions for application. Altogether over 90 logged experiment runs with physical robots have been completed to elucidate the functioning and reveal the factors affecting the performance of the system. The testing has been performed in a laboratory environment in a special demonstration process. In these experiment series, the searching and destroying of distributed dynamic targets were tested. Furthermore, the meaning of communication in the development of robot consciousness during the mission has also been analyzed. As a result of the research work and systems development, profound knowledge has been gained and new solutions presented for the required technology for a minimalist mobile robot operating in a liquid process environment. SUBMAR Robot Society forms a technological basis for the development of real-world applications in the future.reviewe

Dynamical and topological tools for (modern) music analysis

Is it possible to represent the horizontal motions of the melodic strands of a contrapuntal composition, or the main ideas of a jazz standard as mathematical entities? In this work, we suggest a collection of novel models for the representation of music that are endowed with two main features. First, they originate from a topological and geometrical inspiration; second, their low dimensionality allows to build simple and informative visualisations. Here, we tackle the problem of music representation following three non-orthogonal directions. We suggest a formalisation of the concept of voice leading (the assignment of an instrument to each voice in a sequence of chords) suggesting a horizontal viewpoint on music, constituted by the simultaneous motions of superposed melodies. This formalisation naturally leads to the interpretation of counterpoint as a multivariate time series of partial permutation matrices, whose observations are characterised by a degree of complexity. After providing both a static and a dynamic representation of counterpoint, voice leadings are reinterpreted as a special class of partial singular braids (paths in the Euclidean space), and their main features are visualised as geometric configurations of collections of 3-dimensional strands. Thereafter, we neglect this time-related information, in order to reduce the problem to the study of vertical musical entities. The model we propose is derived from a topological interpretation of the Tonnetz (a graph commonly used in computational musicology) and the deformation of its vertices induced by a harmonic and a consonance-oriented function, respectively. The 3-dimensional shapes derived from these deformations are classified using the formalism of persistent homology. This powerful topological technique allows to compute a fingerprint of a shape, that reflects its persistent geometrical and topological properties. Furthermore, it is possible to compute a distance between these fingerprints and hence study their hierarchical organisation. This particular feature allows us to tackle the problem of automatic classification of music in an innovative way. Thus, this novel representation of music is evaluated on a collection of heterogenous musical datasets. Finally, a combination of the two aforementioned approaches is proposed. A model at the crossroad between the signal and symbolic analysis of music uses multiple sequences alignment to provide an encompassing, novel viewpoint on the musical inspiration transfer among compositions belonging to different artists, genres and time. To conclude, we shall represent music as a time series of topological fingerprints, whose metric nature allows to compare pairs of time-varying shapes in both topological and in musical terms. In particular the dissimilarity scores computed by aligning such sequences shall be applied both to the analysis and classification of music

A semiotic evaluation of musical meaning in the works of Igor Stravinsky : decoding syntax and markedness and prototypicality theory.

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