Stadelmann-Nessler, Christine

[["dc.bibliographiccitation.firstpage","6940"],["dc.bibliographiccitation.issue","27"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences of the United States of America"],["dc.bibliographiccitation.lastpage","6945"],["dc.bibliographiccitation.volume","115"],["dc.contributor.author","Töpperwien, Mareike"],["dc.contributor.author","Meer, Franziska van der"],["dc.contributor.author","Stadelmann-Nessler, Christine"],["dc.contributor.author","Salditt, Tim"],["dc.date.accessioned","2020-03-11T09:06:18Z"],["dc.date.available","2020-03-11T09:06:18Z"],["dc.date.issued","2018"],["dc.description.abstract","To quantitatively evaluate brain tissue and its corresponding function, knowledge of the 3D cellular distribution is essential. The gold standard to obtain this information is histology, a destructive and labor-intensive technique where the specimen is sliced and examined under a light microscope, providing 3D information at nonisotropic resolution. To overcome the limitations of conventional histology, we use phase-contrast X-ray tomography with optimized optics, reconstruction, and image analysis, both at a dedicated synchrotron radiation endstation, which we have equipped with X-ray waveguide optics for coherence and wavefront filtering, and at a compact laboratory source. As a proof-of-concept demonstration we probe the 3D cytoarchitecture in millimeter-sized punches of unstained human cerebellum embedded in paraffin and show that isotropic subcellular resolution can be reached at both setups throughout the specimen. To enable a quantitative analysis of the reconstructed data, we demonstrate automatic cell segmentation and localization of over 1 million neurons within the cerebellar cortex. This allows for the analysis of the spatial organization and correlation of cells in all dimensions by borrowing concepts from condensed-matter physics, indicating a strong short-range order and local clustering of the cells in the granular layer. By quantification of 3D neuronal \"packing,\" we can hence shed light on how the human cerebellum accommodates 80% of the total neurons in the brain in only 10% of its volume. In addition, we show that the distribution of neighboring neurons in the granular layer is anisotropic with respect to the Purkinje cell dendrites."],["dc.identifier.doi","10.1073/pnas.1801678115"],["dc.identifier.pmid","29915047"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/63291"],["dc.language.iso","en"],["dc.relation.eissn","1091-6490"],["dc.relation.issn","0027-8424"],["dc.relation.orgunit","Institut für Röntgenphysik"],["dc.relation.workinggroup","RG Salditt (Structure of Biomolecular Assemblies and X-Ray Physics)"],["dc.rights","CC BY-NC-ND 4.0"],["dc.subject.gro","x-ray imaging"],["dc.subject.gro","biomedical tomography"],["dc.title","Three-dimensional virtual histology of human cerebellum by X-ray phase-contrast tomography"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","24"],["dc.bibliographiccitation.issue","S2"],["dc.bibliographiccitation.journal","Microscopy and Microanalysis"],["dc.bibliographiccitation.lastpage","25"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Töpperwien, Mareike"],["dc.contributor.author","Eckermann, Marina"],["dc.contributor.author","Robisch, Anna Lena"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Salditt, Tim"],["dc.date.accessioned","2020-03-04T13:40:15Z"],["dc.date.available","2020-03-04T13:40:15Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1017/S1431927618012540"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/63109"],["dc.language.iso","en"],["dc.relation.issn","1431-9276"],["dc.relation.issn","1435-8115"],["dc.relation.orgunit","Institut für Röntgenphysik"],["dc.relation.workinggroup","RG Salditt (Structure of Biomolecular Assemblies and X-Ray Physics)"],["dc.subject.gro","x-ray imaging"],["dc.subject.gro","biomedical tomography"],["dc.title","3d Virtual Histology of Human Cerebellum by Propagation-Based X-Ray Phase-Contrast Tomography"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e2113835118"],["dc.bibliographiccitation.issue","48"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.volume","118"],["dc.contributor.author","Eckermann, Marina"],["dc.contributor.author","Schmitzer, Bernhard"],["dc.contributor.author","van der Meer, Franziska"],["dc.contributor.author","Franz, Jonas"],["dc.contributor.author","Hansen, Ove"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Salditt, Tim"],["dc.date.accessioned","2022-01-11T14:05:50Z"],["dc.date.available","2022-01-11T14:05:50Z"],["dc.date.issued","2021"],["dc.description.abstract","We have studied the three-dimensional (3D) cytoarchitecture of the human hippocampus in neuropathologically healthy and Alzheimer’s disease (AD) individuals, based on phase-contrast X-ray computed tomography of postmortem human tissue punch biopsies. In view of recent findings suggesting a nuclear origin of AD, we target in particular the nuclear structure of the dentate gyrus (DG) granule cells. Tissue samples of 20 individuals were scanned and evaluated using a highly automated approach of measurement and analysis, combining multiscale recordings, optimized phase retrieval, segmentation by machine learning, representation of structural properties in a feature space, and classification based on the theory of optimal transport. Accordingly, we find that the prototypical transformation between a structure representing healthy granule cells and the pathological state involves a decrease in the volume of granule cell nuclei, as well as an increase in the electron density and its spatial heterogeneity. The latter can be explained by a higher ratio of heterochromatin to euchromatin. Similarly, many other structural properties can be derived from the data, reflecting both the natural polydispersity of the hippocampal cytoarchitecture between different individuals in the physiological context and the structural effects associated with AD pathology."],["dc.identifier.doi","10.1073/pnas.2113835118"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/97758"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/369"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/53"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-507"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | B01: The role of inflammatory cytokine signaling for efficient remyelination in multiple sclerosis"],["dc.relation.eissn","1091-6490"],["dc.relation.issn","0027-8424"],["dc.relation.orgunit","Institut für Röntgenphysik"],["dc.relation.workinggroup","RG Salditt (Structure of Biomolecular Assemblies and X-Ray Physics)"],["dc.relation.workinggroup","RG Stadelmann-Nessler"],["dc.rights","CC BY-NC-ND 4.0"],["dc.subject.gro","biomedical tomography"],["dc.title","Three-dimensional virtual histology of the human hippocampus based on phase-contrast computed tomography"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","116523"],["dc.bibliographiccitation.journal","NeuroImage"],["dc.bibliographiccitation.volume","210"],["dc.contributor.author","Töpperwien, Mareike"],["dc.contributor.author","Meer, Franziska van der"],["dc.contributor.author","Stadelmann-Nessler, Christine"],["dc.contributor.author","Salditt, Tim"],["dc.date.accessioned","2020-03-04T13:20:09Z"],["dc.date.available","2020-03-04T13:20:09Z"],["dc.date.issued","2020"],["dc.description.abstract","Alzheimer's disease (AD) is a neurodegenerative disorder which is characterized by increasing dementia. It is accompanied by the development of extracellular β-amyloid plaques and neurofibrillary tangles in the gray matter of the brain. Histology is the gold standard for the visualization of this pathology, but also has intrinsic shortcomings. Fully three-dimensional analysis and quantitative metrics of alterations in the tissue structure require a complementary approach. In this work we use x-ray phase-contrast tomography to obtain three-dimensional reconstructions of human hippocampal tissue affected by AD. Due to intrinsic electron density differences, tissue components and structures such as the granule cells of the dentate gyrus, blood vessels, or mineralized plaques can be identified and segmented in large volumes. Based on correlative histology, protein (tau, β-amyloid) and elemental content (iron, calcium) can be attributed to certain morphological features occurring in the entire volume. In the vicinity of senile plaques, an accumulation of microglia in combination with a loss of neuronal cells can be observed."],["dc.identifier.doi","10.1016/j.neuroimage.2020.116523"],["dc.identifier.pmid","31935519"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/63101"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/26"],["dc.language.iso","en"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1095-9572"],["dc.relation.issn","1053-8119"],["dc.relation.orgunit","Institut für Röntgenphysik"],["dc.relation.workinggroup","RG Salditt (Structure of Biomolecular Assemblies and X-Ray Physics)"],["dc.relation.workinggroup","RG Stadelmann-Nessler"],["dc.rights","CC BY-NC-ND 4.0"],["dc.subject.gro","x-ray imaging"],["dc.subject.gro","biomedical tomography"],["dc.title","Correlative x-ray phase-contrast tomography and histology of human brain tissue affected by Alzheimer's disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","7582"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Biomedical Optics Express"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Eckermann, Marina"],["dc.contributor.author","van der Meer, Franziska"],["dc.contributor.author","Cloetens, Peter"],["dc.contributor.author","Ruhwedel, Torben"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Salditt, Tim"],["dc.date.accessioned","2022-01-11T14:06:10Z"],["dc.date.available","2022-01-11T14:06:10Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1364/BOE.434885"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/97842"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/362"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/142"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-507"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | A02: Bestimmung der Struktur synaptischer Organellen durch Röntgenbeugungs- und Bildgebungsverfahren"],["dc.relation.eissn","2156-7085"],["dc.relation.issn","2156-7085"],["dc.relation.orgunit","Institut für Röntgenphysik"],["dc.relation.workinggroup","RG Salditt (Structure of Biomolecular Assemblies and X-Ray Physics)"],["dc.relation.workinggroup","RG Möbius"],["dc.relation.workinggroup","RG Stadelmann-Nessler"],["dc.subject.gro","biomedical tomography"],["dc.title","Three-dimensional virtual histology of the cerebral cortex based on phase-contrast X-ray tomography"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","013501"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Medical Imaging"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Robisch, Anna Lena"],["dc.contributor.author","Eckermann, Marina"],["dc.contributor.author","Töpperwien, Mareike"],["dc.contributor.author","Meer, Franziska van der"],["dc.contributor.author","Stadelmann-Nessler, Christine"],["dc.contributor.author","Salditt, Tim"],["dc.date.accessioned","2020-03-04T13:21:36Z"],["dc.date.available","2020-03-04T13:21:36Z"],["dc.date.issued","2020"],["dc.description.abstract","X-ray cone-beam holotomography of unstained tissue from the human central nervous system reveals details down to subcellular length scales. This visualization of variations in the electron density of the sample is based on phase-contrast techniques using intensities formed by self-interference of the beam between object and detector. Phase retrieval inverts diffraction and overcomes the phase problem by constraints such as several measurements at different Fresnel numbers for a single projection. Therefore, the object-to-detector distance (defocus) can be varied. However, for cone-beam geometry, changing defocus changes magnification, which can be problematic in view of image processing and resolution. Alternatively, the photon energy can be altered (multi-E). Far from absorption edges, multi-E data yield the wavelength-independent electron density. We present the multi-E holotomography at the Göttingen Instrument for Nano-Imaging with X-Rays (GINIX) setup of the P10 beamline at Deutsches Elektronen-Synchrotron. The instrument is based on a combined optics of elliptical mirrors and an x-ray waveguide positioned in the focal plane for further coherence, spatial filtering, and high numerical aperture. Previous results showed the suitability of this instrument for nanoscale tomography of unstained brain tissue. We demonstrate that upon energy variation, the focal spot is stable enough for imaging. To this end, a double-crystal monochromator and automated alignment routines are required. Three tomograms of human brain tissue were recorded and jointly analyzed using phase retrieval based on the contrast transfer function formalism generalized to multiple photon energies. Variations of the electron density of the sample are successfully reconstructed."],["dc.identifier.doi","10.1117/1.JMI.7.1.013501"],["dc.identifier.pmid","32016134"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/63102"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/20"],["dc.language.iso","en"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.issn","2329-4302"],["dc.relation.orgunit","Institut für Röntgenphysik"],["dc.relation.workinggroup","RG Salditt (Structure of Biomolecular Assemblies and X-Ray Physics)"],["dc.relation.workinggroup","RG Stadelmann-Nessler"],["dc.subject.gro","x-ray imaging"],["dc.subject.gro","biomedical tomography"],["dc.title","Nanoscale x-ray holotomography of human brain tissue with phase retrieval based on multienergy recordings"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","01"],["dc.bibliographiccitation.journal","Journal of Medical Imaging"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Eckermann, Marina"],["dc.contributor.author","Töpperwien, Mareike"],["dc.contributor.author","Robisch, Anna Lena"],["dc.contributor.author","Meer, Franziska van der"],["dc.contributor.author","Stadelmann-Nessler, Christine"],["dc.contributor.author","Salditt, Tim"],["dc.date.accessioned","2020-03-03T08:42:36Z"],["dc.date.available","2020-03-03T08:42:36Z"],["dc.date.issued","2020"],["dc.description.abstract","Purpose: Recently, progress has been achieved in implementing phase-contrast tomography of soft biological tissues at laboratory sources. This opens up opportunities for three-dimensional (3-D) histology based on x-ray computed tomography (μ- and nanoCT) in the direct vicinity of hospitals and biomedical research institutions. Combining advanced x-ray generation and detection techniques with phase reconstruction algorithms, 3-D histology can be obtained even of unstained tissue of the central nervous system, as shown, for example, for biopsies and autopsies of human cerebellum. Depending on the setup, i.e., source, detector, and geometric parameters, laboratory-based tomography can be implemented at very different sizes and length scales. We investigate the extent to which 3-D histology of neuronal tissue can exploit the cone-beam geometry at high magnification M using a nanofocus transmission x-ray tube (nanotube) with a 300 nm minimal spot size (Excillum), combined with a single-photon counting camera. Tightly approaching the source spot with the biopsy punch, we achieve high M  ≈  101  −  102, high flux density, and exploit the superior efficiency of this detector technology. Approach: Different nanotube configurations such as spot size and flux, M, as well as exposure time, Fresnel number, and coherence are varied and selected in view of resolution, field of view, and/or phase-contrast requirements. Results: The data show that the information content for the cytoarchitecture is enhanced by the phase effect. Comparison of results to those obtained at a microfocus rotating-anode x-ray tomography setup with a high-resolution detector, i.e., in low-M geometry, reveals similar to slightly superior data quality for the nanotube setup. In addition to its compactness, reduced power consumption by a factor of 103, and shorter scan duration, the particular advantage of the nanotube setup also lies in its suitability for pixel detector technology, enabling an increased range of opportunities for applications in laboratory phase-contrast x-ray tomography. Conclusions: The phase retrieval scheme utilized mixes amplitude and phase contrast, with results being robust with respect to reconstruction parameters. Structural information content is comparable to slightly superior to previous results achieved with a microfocus rotating-anode setup but can be obtained in shorter scan time. Beyond advantages as compactness, lowered power consumption, and flexibility, the nanotube setup’s scalability in view of the progress in pixel detector technology is particularly beneficial. Further progress is thus likely to bring 3-D virtual histology to the performance in scan time and throughput required for clinical practice in neuropathology."],["dc.identifier.doi","10.1117/1.JMI.7.1.013502"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/63074"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/23"],["dc.language.iso","en"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.issn","2329-4302"],["dc.relation.orgunit","Institut für Röntgenphysik"],["dc.relation.workinggroup","RG Salditt (Structure of Biomolecular Assemblies and X-Ray Physics)"],["dc.relation.workinggroup","RG Stadelmann-Nessler"],["dc.subject.gro","x-ray imaging"],["dc.subject.gro","biomedical tomography"],["dc.title","Phase-contrast x-ray tomography of neuronal tissue at laboratory sources with submicron resolution"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]