Voxel-wise comparisons of cellular microstructure and diffusion-MRI in mouse hippocampus using 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND)

A key challenge in medical imaging is determining a precise correspondence between image properties and tissue microstructure. This comparison is hindered by disparate scales and resolutions between medical imaging and histology. We present a new technique, 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND), for registering medical images with 3D histology to overcome these limitations. Ex vivo 120 × 120 × 200 μm resolution diffusion-MRI (dMRI) data was acquired at 7 T from adult C57Bl/6 mouse hippocampus. Tissue was then optically cleared using CLARITY and stained with cellular markers and confocal microscopy used to produce high-resolution images of the 3D-tissue microstructure. For each sample, a dense array of hippocampal landmarks was used to drive registration between upsampled dMRI data and the corresponding confocal images. The cell population in each MRI voxel was determined within hippocampal subregions and compared to MRI-derived metrics. 3D-BOND provided robust voxel-wise, cellular correlates of dMRI data. CA1 pyramidal and dentate gyrus granular layers had significantly different mean diffusivity (p > 0.001), which was related to microstructural features. Overall, mean and radial diffusivity correlated with cell and axon density and fractional anisotropy with astrocyte density, while apparent fibre density correlated negatively with axon density. Astrocytes, axons and blood vessels correlated to tensor orientation

Measurement of migration of a humeral head resurfacing prosthesis using radiostereometry without implant marking: An experimental study

Today, the shoulder joint is the third most commonly replaced joint after the hip and knee joints and the incidence is increasing. In Sweden, 1863 primary Shoulder Arthroplasties and 195 revisions were performed in 2017. The most common diagnoses are Osteoarthritis and irreparable tears of the rotator cuff, with or without arthropathy, often referred to as cuff tear arthropathy. Different Shoulder Arthroplasty (SA) concepts include anatomical total shoulder arthroplasty (TSA), hemiarthroplasty (HSA) and reversed shoulder arthroplasty, but also humeral head resurfacing (HHR) and stemless arthroplasties. All concepts offer pain relief, improvement of function and in quality of life for the different diagnoses. Unfortunately, there are sometimes complications after SA. They involve periprosthetic joint infection, humeral and glenoid fractures, stress shielding, loosening of the glenoid and humeral component but also glenoid erosion and cuff rupture. Some of these complications are most common within 1 year after operation, some after several years, both may lead to a revision. This, together with the fact that new designs of implants and methods of fixation of SA continues to develop, stresses the importance of continuous monitoring of implant survival and follow-up. The overall aim of this thesis was to describe clinical examples of different methods to assess the outcome after Shoulder Arthroplasty. The most common methods are clinical examination, radiographic assessment, Patient Reported Outcome Measure (PROM), National Joint registries, where revisions are an important outcome, but also Clinical Trials. All of these methods are used in one or more of the 4 papers in this thesis and shows the complexity of the topic and the practical work. In paper I we used Radio Stereometric Analysis (RSA) in an experimental set-up and concluded that marker-free RSA can be used for a humeral head resurfacing arthroplasty. In paper II we used data from the Swedish Shoulder Arthroplasty Registry (SSAR) with PROM and revisions to conclude that age is the only factor that affects revision when comparing HSA and HHR. Paper III is a long-time follow-up of a Randomized controlled study where we used radiological assessment, PROM and revisions. The conclusion was that both TSA and HSA develop severe radiological changes 10 year after primary operation. Paper IV is a prospective RSA cohort study where we also evaluated PROM and revisions. The conclusion is that HHR seems to obtain a secure fixation in the humerus, after an initial migration. But also that the prostheses shows continuous glenoid wear. The main conclusion of this thesis is that patient’s operated with SA needs continuous monitoring and several methods may be used to evaluate the outcome

Application of a two-step approach for mapping ice thickness to various glacier types on Svalbard

The basal topography is largely unknown beneath most glaciers and ice caps, and many attempts have been made to estimate a thickness field from other more accessible information at the surface. Here, we present a two-step reconstruction approach for ice thickness that solves mass conservation over single or several connected drainage basins. The approach is applied to a variety of test geometries with abundant thickness measurements including marine- and land-terminating glaciers as well as a 2400-km2 ice cap on Svalbard. The input requirements are kept to a minimum for the first step. In this step, a geometrically controlled, non-local flux solution is converted into thickness values relying on the shallow ice approximation (SIA). In a second step, the thickness field is updated along fast-flowing glacier trunks on the basis of velocity observations. Both steps account for available thickness measurements. Each thickness field is presented together with an error-estimate map based on a formal propagation of input uncertainties. These error estimates point out that the thickness field is least constrained near ice divides or in other stagnant areas. Withholding a share of the thickness measurements, error estimates tend to overestimate mismatch values in a median sense. We also have to accept an aggregate uncertainty of at least 25-% in the reconstructed thickness field for glaciers with very sparse or no observations. For Vestfonna ice cap (VIC), a previous ice volume estimate based on the same measurement record as used here has to be corrected upward by 22-%. We also find that a 13-% area fraction of the ice cap is in fact grounded below sea level. The former 5-% estimate from a direct measurement interpolation exceeds an aggregate maximum range of 6-23-% as inferred from the error estimates here.This study received primary funding from the German Research Foundation (DFG) under grant number FU1032/1-1. Results presented in this publication are based on numerical simulations conducted at the high-performance computing centre of the Regionales Rechenzentrum Erlangen (RRZE) of the University of Erlangen-Nuremberg. The reconstruction approach also benefits from co-development work of the Elmer/Ice team at the CSC-IT Center for Science Ltd. (Finland). The velocity analysis on Svalbard was funded by DFG within the priority programme 1158 Antarctic Research with Comparable Investigations in Arctic Sea Ice Areas under contract number BR2105/9-1 and received financial support from the Helmholtz Association of the German Research Centres (HGF) Alliance on Remote Sensing and Earth System Dynamics. Thickness data collection in Wedel Jarlsberg Land was funded by the Spanish R&D projects C11093001 and C150954001, NCBiR/PolarCLIMATE-2009/2-2/2010 from the Polish National Centre for R&D, by IPY/269/2006 from the Polish Ministry of Science and Higher Education, by Polish-Norwegian funding through the AWAKE (PNRF-22-AI-1/07) project, by the EU FP7 ice2sea programme (grant number 226375) and by funds of the Leading National Research Centre (KNOW) received by the Centre for Polar Studies of the University of Silesia, Poland. The DEM generation inWedel Jarlsberg Land received financial support from the European Research Council (grant 320816) and from ESA (project Glaciers CCI, 4000109873/14/I-NB). TanDEM-X data were provided under AO XTIGLAC6770. The WRF-SMB field was produced within the PERMANOR project funded by the Norwegian Research Council (255331)

Whole-body tissue stabilization and selective extractions via tissue-hydrogel hybrids for high-resolution intact circuit mapping and phenotyping

To facilitate fine-scale phenotyping of whole specimens, we describe here a set of tissue fixation-embedding, detergent-clearing and staining protocols that can be used to transform excised organs and whole organisms into optically transparent samples within 1–2 weeks without compromising their cellular architecture or endogenous fluorescence. PACT (passive CLARITY technique) and PARS (perfusion-assisted agent release in situ) use tissue-hydrogel hybrids to stabilize tissue biomolecules during selective lipid extraction, resulting in enhanced clearing efficiency and sample integrity. Furthermore, the macromolecule permeability of PACT- and PARS-processed tissue hybrids supports the diffusion of immunolabels throughout intact tissue, whereas RIMS (refractive index matching solution) grants high-resolution imaging at depth by further reducing light scattering in cleared and uncleared samples alike. These methods are adaptable to difficult-to-image tissues, such as bone (PACT-deCAL), and to magnified single-cell visualization (ePACT). Together, these protocols and solutions enable phenotyping of subcellular components and tracing cellular connectivity in intact biological networks

Korrelation der Saugspannungs-/Sättigungskurve mit der Wärmeleitfähigkeit von Lockergesteinen

Für die meisten Lockergesteine sind in der Literatur nur Richtwerte der möglichen geothermischen Entzugsleistungen im feuchten und trockenen Zustand angegeben. Die individuellen in-situ Bedingungen sind jedoch starken jahreszeitlichen Schwankungen unterworfen. Deswegen ist es für die exakte Charakterisierung, Modellierung und spätere Nutzung eines geothermischen Reservoirs notwendig, den Zusammenhang zwischen Wassergehalt, Saugspannung und Wärmeleitfähigkeit zu untersuchen. Es werden mehrere tausend Messungen mit dem Messgerät TK 04 mit den Sonden nach dem Halbraumlinienquellen- und Vollraumlinienquellenverfahren durchgeführt und mit Literaturwerten und Berechnungsmodellen verglichen. Die Messungen der Wärmeleitfähigkeit im teilgesättigten Zustand werden in einem Säulenversuch an einem definierten Versuchssand mit unterschiedlichen Wassergehalten durchgeführt. In der Säule werden parallel zueinander Wassergehalt, Wasserspannung und Wärmeleitfähigkeit der Proben bestimmt. Es zeigt sich, dass der Zusammenhang zwischen Wassergehalt und Wärmeleitfähigkeit nicht linear verläuft. Jedoch bestehen zwischen der Form der Saugspannungs-/ Sättigungskurve und der Form der Saugspannungs-/ Wärmeleitfähigkeitskurve signifikante Übereinstimmungen. Die Überführung der Messwerte der Saugspannungs-/ Sättigungskurve in eine stetige Funktion geschieht mittels der van Genuchten Parameter. Es wird - entsprechend dem Beispiel der van Genuchten Funktion - in weiterführenden Arbeiten geprüft, ob eine Funktion für die Saugspannungs-/Wärmeleitfähigkeitskurve ermittelt und ob dementsprechende Parameter gefunden werden können