Application of 1H HR-MAS-NMR spectroscopy in spatial tissue metabolic profiling

HR-MAS-NMR of intact tissue biopsies is a well-established method resulting in one NMR spectrum per whole biopsy showing all detectable metabolites at once. The aim of this project was to explore the possibility and usefulness of monitoring specific locations within the biopsy using HR-MAS-NMR. Firstly, the method was applied to a classic toxicology situation. Many drug development compounds fail because of preclinical animal liver toxicity conventionally detected using histology. Usually, only one of the murine liver lobes is used for this and is assumed to be representative of the whole organ. In this work, a metabolic variation across murine liver lobes has been investigated via a set of biopsies across all lobes. Using HR-MAS-NMR spectra analysed by various types of multivariate analysis, no lobe-specific metabolic variation could be found, confirming the general validity of the representative lobe approach. To increase location specificity, a spatially-resolved NMR pulse sequence (slice local- ized spectroscopy (SLS)) was modified and its respective effectiveness was explored. The pulse sequence was first validated using artificially created samples (phantoms), and practical examples were layered fruit separated by paraffin film and milled phantoms produced from materials which were magnetic-susceptibility-matched to the HR-MAS rotor. The HR-MAS SLS sequence was then applied to a mixed mouse renal tissue biopsy, and renal cortex and medulla successfully assigned to individual slices from spatially-resolved spectra using pure cortex and medulla reference HR-MAS-NMR spectra and orthogonal projection to latent structures discriminant analysis (OPLS-DA) to establish metabolic markers differentiating the two. Together, this work shows the potential of HR-MAS-NMR as applied to tissue biopsies. Particularly, spatially-resolved methods hold potential for improved biochemical and mechanistic understanding and the methodology could be expanded to applications in many areas of biomedical relevance.Open Acces

Neuroinformatics in Functional Neuroimaging

This Ph.D. thesis proposes methods for information retrieval in functional neuroimaging through automatic computerized authority identification, and searching and cleaning in a neuroscience database. Authorities are found through cocitation analysis of the citation pattern among scientific articles. Based on data from a single scientific journal it is shown that multivariate analyses are able to determine group structure that is interpretable as particular “known ” subgroups in functional neuroimaging. Methods for text analysis are suggested that use a combination of content and links, in the form of the terms in scientific documents and scientific citations, respectively. These included context sensitive author ranking and automatic labeling of axes and groups in connection with multivariate analyses of link data. Talairach foci from the BrainMap ™ database are modeled with conditional probability density models useful for exploratory functional volumes modeling. A further application is shown with conditional outlier detection where abnormal entries in the BrainMap ™ database are spotted using kernel density modeling and the redundancy between anatomical labels and spatial Talairach coordinates. This represents a combination of simple term and spatial modeling. The specific outliers that were found in the BrainMap ™ database constituted among others: Entry errors, errors in the article and unusual terminology

Complexity Reduction in Image-Based Breast Cancer Care

The diversity of malignancies of the breast requires personalized diagnostic and therapeutic decision making in a complex situation. This thesis contributes in three clinical areas: (1) For clinical diagnostic image evaluation, computer-aided detection and diagnosis of mass and non-mass lesions in breast MRI is developed. 4D texture features characterize mass lesions. For non-mass lesions, a combined detection/characterisation method utilizes the bilateral symmetry of the breast s contrast agent uptake. (2) To improve clinical workflows, a breast MRI reading paradigm is proposed, exemplified by a breast MRI reading workstation prototype. Instead of mouse and keyboard, it is operated using multi-touch gestures. The concept is extended to mammography screening, introducing efficient navigation aids. (3) Contributions to finite element modeling of breast tissue deformations tackle two clinical problems: surgery planning and the prediction of the breast deformation in a MRI biopsy device

TECHNART 2017. Non-destructive and microanalytical techniques in art and cultural heritage. Book of abstracts

440 p.TECHNART2017 is the international biannual congress on the application of Analytical Techniques in Art and Cultural Heritage. The aim of this European conference is to provide a scientific forum to present and promote the use of analytical spectroscopic techniques in cultural heritage on a worldwide scale to stimulate contacts and exchange experiences, making a bridge between science and art. This conference builds on the momentum of the previous TECHNART editions of Lisbon, Athens, Berlin, Amsterdam and Catania, offering an outstanding and unique opportunity for exchanging knowledge on leading edge developments. Cultural heritage studies are interpreted in a broad sense, including pigments, stones, metal, glass, ceramics, chemometrics on artwork studies, resins, fibers, forensic applications in art, history, archaeology and conservation science. The meeting is focused in different aspects: - X-ray analysis (XRF, PIXE, XRD, SEM-EDX). - Confocal X-ray microscopy (3D Micro-XRF, 3D Micro-PIXE). - Synchrotron, ion beam and neutron based techniques/instrumentation. - FT-IR and Raman spectroscopy. - UV-Vis and NIR absorption/reflectance and fluorescence. - Laser-based analytical techniques (LIBS, etc.). - Magnetic resonance techniques. - Chromatography (GC, HPLC) and mass spectrometry. - Optical imaging and coherence techniques. - Mobile spectrometry and remote sensing

SPICA:revealing the hearts of galaxies and forming planetary systems : approach and US contributions

How did the diversity of galaxies we see in the modern Universe come to be? When and where did stars within them forge the heavy elements that give rise to the complex chemistry of life? How do planetary systems, the Universe's home for life, emerge from interstellar material? Answering these questions requires techniques that penetrate dust to reveal the detailed contents and processes in obscured regions. The ESA-JAXA Space Infrared Telescope for Cosmology and Astrophysics (SPICA) mission is designed for this, with a focus on sensitive spectroscopy in the 12 to 230 micron range. SPICA offers massive sensitivity improvements with its 2.5-meter primary mirror actively cooled to below 8 K. SPICA one of 3 candidates for the ESA's Cosmic Visions M5 mission, and JAXA has is committed to their portion of the collaboration. ESA will provide the silicon-carbide telescope, science instrument assembly, satellite integration and testing, and the spacecraft bus. JAXA will provide the passive and active cooling system (supporting the

The Apertif Surveys:The First Six Months

Apertif is a new phased-array feed for the Westerbork Synthesis Radio Telescope (WSRT), greatly increasing its field of view and turning it into a natural survey instrument. In July 2019, the Apertif legacy surveys commenced; these are a time-domain survey and a two-tiered imaging survey, with a shallow and medium-deep component. The time-domain survey searches for new (millisecond) pulsars and fast radio bursts (FRBs). The imaging surveys provide neutral hydrogen (HI), radio continuum and polarization data products. With a bandwidth of 300 MHz, Apertif can detect HI out to a redshift of 0.26. The key science goals to be accomplished by Apertif include localization of FRBs (including real-time public alerts), the role of environment and interaction on galaxy properties and gas removal, finding the smallest galaxies, connecting cold gas to AGN, understanding the faint radio population, and studying magnetic fields in galaxies. After a proprietary period, survey data products will be publicly available through the Apertif Long Term Archive (ALTA, https://alta.astron.nl). I will review the progress of the surveys and present the first results from the Apertif surveys, including highlighting the currently available public data