Biophysically motivated efficient estimation of the spatially isotropic R*2 component from a single gradient‐recalled echo measurement

Purpose To propose and validate an efficient method, based on a biophysically motivated signal model, for removing the orientation‐dependent part of R*2 using a single gradient‐recalled echo (GRE) measurement. Methods The proposed method utilized a temporal second‐order approximation of the hollow‐cylinder‐fiber model, in which the parameter describing the linear signal decay corresponded to the orientation‐independent part of R*2. The estimated parameters were compared to the classical, mono‐exponential decay model for R*2 in a sample of an ex vivo human optic chiasm (OC). The OC was measured at 16 distinct orientations relative to the external magnetic field using GRE at 7T. To show that the proposed signal model can remove the orientation dependence of R*2, it was compared to the established phenomenological method for separating R*2 into orientation‐dependent and ‐independent parts. Results Using the phenomenological method on the classical signal model, the well‐known separation of R*2 into orientation‐dependent and ‐independent parts was verified. For the proposed model, no significant orientation dependence in the linear signal decay parameter was observed. Conclusions Since the proposed second‐order model features orientation‐dependent and ‐independent components at distinct temporal orders, it can be used to remove the orientation dependence of R*2 using only a single GRE measurement

Research on properties of multi-core superconducting wires made from materials based on magnesium and boron (MgB2)

The article presents the results of laboratory research on the production of multi-core superconducting wires. Multicore wires containing boron and magnesium powders in a copper matrix were obtained in the drawing process combined with intermediate heat treatment. The wires contains powder cores were sintered under high isostatic pressure to produce the MgB2 superconducting phase. The critical temperature for the composite’s superconducting state was determined. The macrostructure and energy dispersion (EDX) analysis of multi-core wires was also presented

More then simply iron: Macro- to microscopic cellular iron distribution in the brain determines MR contrast

Myelin and iron are the major source of MR contrast in the brain. Iron dominates R2*, R2 and QSM in the cortex as well as in subcortical areas and contributes to white matter contrast. To exploit this contrast for cortical parcellation, myeloarchitecture mapping, or iron quantification, significant theoretical and experimental efforts were devoted to the understanding of iron-induced contrast. However, the impact of the cellular and subcellular iron distribution is not well understood. Frequently, it is described by a simple linear dependence of the MRI contrast parameters on iron concentration, largely disregarding the inhomogeneous distribution of iron in the brain. A major reason for this simplification is a lack of quantitative knowledge on the cellular iron distribution. Moreover, the interplay between the microscopic iron distribution and diffusion in creating MR contrast in static de-phasing, motional narrowing or intermediate regime is not fully understood. We set out to address this lack in knowledge and modelling by combining state of the art quantitative 7T MRI with cutting-edge quantitative iron and myelin mapping on post mortem brain samples. Quantitative R2*, R2, R1 and QSM maps were obtained for the human cortex, the subcortical and the deep white matter as well as for brain nuclei before and after de-ironing. Laser Ablation Inductively Coupled Plasma Mass Spectroscopic Imaging (LA ICP MSI) yielded quantitative iron maps with a mesoscopic resolution of 60x120μm. Proton Induced X-ray Emission (PIXE) provided quantitative iron maps with a cellular resolution down to 1μm. MSI and PIXE demonstrated the inhomogenous distribution of iron in both grey and white matter at different spatial scales. In grey matter iron rich fibers, and small (1-3μm) micro-, astro- and oligodendroglia contained most of the iron and were sparsely distributed. In superficial and deep white matter, however, oligodendrocytes somas with the sizes of 5±1.5μm (distance between cells of 20±5μm) and iron rich fibers contained most of the iron. In addition, patches of enhanced iron concentration around small vessels with a typical size of 100-200μm contribute to up to 20% of R2* and QSM and their orientation dependence in white matter. A different contrast mechanism prevailed in brain nuclei where densely packed 20μm large iron loaded neurons dominated the MR contrast. These results provide an important basis for understanding the iron induced MR-contrast and its microstructural underpinnings. Based on these measured microscopic iron distributions and a Gaussian diffusion model we are now in the process of simulating the MR contrast mechanisms in different tissue types

Iron-induced relaxation mechanisms in the human substantia nigra: Towards quantifying iron load in dopaminergic neurons

Pathological iron accumulation in the human brain is a biomarker for neurodegeneration. Several diagnostically promising MR- based methods for in vivo iron quantification were proposed, based on the empirical relationship between R 2 * and iron concentration. However, these do not account for different chemical forms and cellular distribution of iron. We combined post mortem MRI, advanced quantitative histology and biophysical modeling to develop a generative theory linking obtained iron concentrations to quantitative MR parameters. The impact of nanoscale molecular interaction of water with iron and of iron-rich dopaminergic neurons was quantified in substantia nigra

Finding the best clearing approach: Towards 3D wide-scale multimodal imaging of aged human brain tissue

The accessibility of new wide-scale multimodal imaging techniques led to numerous clearing techniques emerging over the last decade. However, clearing mesoscopic-sized blocks of aged human brain tissue remains an extremely challenging task. Homogenizing refractive indices and reducing light absorption and scattering are the foundation of tissue clearing. Due to its dense and highly myelinated nature, especially in white matter, the human brain poses particular challenges to clearing techniques. Here, we present a comparative study of seven tissue clearing approaches and their impact on aged human brain tissue blocks (> 5 mm). The goal was to identify the most practical and efficient method in regards to macroscopic transparency, brief clearing time, compatibility with immunohistochemical processing and wide-scale multimodal microscopic imaging. We successfully cleared 26 × 26 × 5 mm3-sized human brain samples with two hydrophilic and two hydrophobic clearing techniques. Optical properties as well as light and antibody penetration depths highly vary between these methods. In addition to finding the best clearing approach, we compared three microscopic imaging setups (the Zeiss Laser Scanning Microscope (LSM) 880 , the Miltenyi Biotec Ultramicroscope ll (UM ll) and the 3i Marianas LightSheet microscope) regarding optimal imaging of large-scale tissue samples. We demonstrate that combining the CLARITY technique (Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging compatible Tissue hYdrogel) with the Zeiss LSM 880 and combining the iDISCO technique (immunolabeling-enabled three-dimensional imaging of solvent-cleared organs) with the Miltenyi Biotec UM ll are the most practical and efficient approaches to sufficiently clear aged human brain tissue and generate 3D microscopic images. Our results point out challenges that arise from seven clearing and three imaging techniques applied to non-standardized tissue samples such as aged human brain tissue

Phonon and Elastic Instabilities in MoC and MoN

We present several results related to the instability of MoC and MoN in the B1 (sodium chloride) structure. These compounds were proposed as potential superconductors with moderately high transition temperatures. We show that the elastic instability in B1-structure MoN, demonstrated several years ago, persists at elevated pressures, thus offering little hope of stabilizing this material without chemical doping. For MoC, another material for which stoichiometric fabrication in the B1-structure has not proven possible, we find that all of the cubic elastic constants are positive, indicating elastic stability. Instead, we find X-point phonon instabilities in MoC (and in MoN as well), further illustrating the rich behavior of carbo-nitride materials. We also present additional electronic structure results for several transition metal (Zr, Nb and Mo) carbo-nitride systems and discuss systematic trends in the properties of these materials. Deviations from strict electron counting dependencies are apparent.Comment: 5 pages and 4 trailing figures. Submitted to PR

Cell specific quantitative iron mapping on brain slices by immuno-μPIXE in healthy elderly and Parkinson’s disease

Iron is essential for neurons and glial cells, playing key roles in neurotransmitter synthesis, energy production and myelination. In contrast, high concentrations of free iron can be detrimental and contribute to neurodegeneration, through promotion of oxidative stress. Particularly in Parkinson’s disease (PD) changes in iron concentrations in the substantia nigra (SN) was suggested to play a key role in degeneration of dopaminergic neurons in nigrosome 1. However, the cellular iron pathways and the mechanisms of the pathogenic role of iron in PD are not well understood, mainly due to the lack of quantitative analytical techniques for iron quantification with subcellular resolution. Here, we quantified cellular iron concentrations and subcellular iron distribution in dopaminergic neurons and different types of glial cells in the SN both in brains of PD patients and in non-neurodegenerative control brains (Co). To this end, we combined spatially resolved quantitative element mapping using micro particle induced X-ray emission (μPIXE) with nickel-enhanced immunocytochemical detection of cell type-specific antigens allowing to allocate element-related signals to specific cell types. Distinct patterns of iron accumulation were observed across different cell populations. In the control (Co) SNc, oligodendroglial and astroglial cells hold the highest cellular iron concentration whereas in PD, the iron concentration was increased in most cell types in the substantia nigra except for astroglial cells and ferritin-positive oligodendroglial cells. While iron levels in astroglial cells remain unchanged, ferritin in oligodendroglial cells seems to be depleted by almost half in PD. The highest cellular iron levels in neurons were located in the cytoplasm, which might increase the source of non-chelated Fe3+, implicating a critical increase in the labile iron pool. Indeed, neuromelanin is characterised by a significantly higher loading of iron including most probable the occupancy of low-affinity iron binding sites. Quantitative trace element analysis is essential to characterise iron in oxidative processes in PD. The quantification of iron provides deeper insights into changes of cellular iron levels in PD and may contribute to the research in iron-chelating disease-modifying drugs

Cell specific quantitative iron mapping on brain slices by immuno-µPIXE in healthy elderly and Parkinson’s disease

Iron is essential for neurons and glial cells, playing key roles in neurotransmitter synthesis, energy production and myelination. In contrast, high concentrations of free iron can be detrimental and contribute to neurodegeneration, through promotion of oxidative stress. Particularly in Parkinson's disease (PD) changes in iron concentrations in the substantia nigra (SN) was suggested to play a key role in degeneration of dopaminergic neurons in nigrosome 1. However, the cellular iron pathways and the mechanisms of the pathogenic role of iron in PD are not well understood, mainly due to the lack of quantitative analytical techniques for iron quantification with subcellular resolution. Here, we quantified cellular iron concentrations and subcellular iron distributions in dopaminergic neurons and different types of glial cells in the SN both in brains of PD patients and in non-neurodegenerative control brains (Co). To this end, we combined spatially resolved quantitative element mapping using micro particle induced X-ray emission (mu PIXE) with nickel-enhanced immunocytochemical detection of cell type-specific antigens allowing to allocate element-related signals to specific cell types. Distinct patterns of iron accumulation were observed across different cell populations. In the control (Co) SNc, oligodendroglial and astroglial cells hold the highest cellular iron concentration whereas in PD, the iron concentration was increased in most cell types in the substantia nigra except for astroglial cells and ferritin-positive oligodendroglial cells. While iron levels in astroglial cells remain unchanged, ferritin in oligodendroglial cells seems to be depleted by almost half in PD. The highest cellular iron levels in neurons were located in the cytoplasm, which might increase the source of non-chelated Fe3+, implicating a critical increase in the labile iron pool. Indeed, neuromelanin is characterised by a significantly higher loading of iron including most probable the occupancy of low-affinity iron binding sites. Quantitative trace element analysis is essential to characterise iron in oxidative processes in PD. The quantification of iron provides deeper insights into changes of cellular iron levels in PD and may contribute to the research in iron-chelating disease-modifying drugs