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Book: Advancing the Characterization of Neuronal Cyto-Architecture by X-ray Phase-Contrast Tomography

Eckermann, Marina

(Göttingen Series in X-ray Physics ; 27)

2022

Abstract: To bring physiology and pathology of the human brain into better micro-anatomical and histological context, studies with different methodologies are required. Established techniques such as electron microscopy or histology show limitations in view of ... ...

Series title	Göttingen Series in X-ray Physics ; 27
Abstract	To bring physiology and pathology of the human brain into better micro-anatomical and histological context, studies with different methodologies are required. Established techniques such as electron microscopy or histology show limitations in view of invasiveness, labor-intense and artifact-prone sample preparation, as well as an adequate ratio between resolution and volume throughput. For this reason, X-ray phase-contrast tomography (PC-CT) has been proposed as a three-dimensional non-destru...
Keywords	non-destructive imaging technique ; scalability ; X-ray phase-contrast tomography (PC-CT)
Language	English
Size	273 p.
Publisher	Universitätsverlag Göttingen
Document type	Book
Note	PDA Manuell_15
Format	170 x 240
ISBN	9783863955281 ; 3863955285
Database	PDA

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Article ; Online: 3d Virtual Histology Reveals Pathological Alterations of Cerebellar Granule Cells in Multiple Sclerosis.

Frost, Jakob / Schmitzer, Bernhard / Töpperwien, Mareike / Eckermann, Marina / Franz, Jonas / Stadelmann, Christine / Salditt, Tim

Neuroscience

2023 Volume 520, Page(s) 18–38

Abstract: We investigate structural properties of neurons in the granular layer of human cerebellum with respect to their involvement in multiple sclerosis (MS). To this end we analyze data recorded by X-ray phase contrast tomography from tissue samples collected ... ...

Abstract	We investigate structural properties of neurons in the granular layer of human cerebellum with respect to their involvement in multiple sclerosis (MS). To this end we analyze data recorded by X-ray phase contrast tomography from tissue samples collected post mortem from a MS and a healthy control group. Using automated segmentation and histogram analysis based on optimal transport theory (OT) we find that the distributions representing nuclear structure in the granular layer move to a more compact nuclear state, i.e. smaller, denser and more heterogeneous nuclei in MS. We have previously made a similar observation for neurons of the dentate gyrus in Alzheimer's disease, suggesting that more compact structure of neuronal nuclei which we attributed to increased levels of heterochromatin, may possibly represent a more general phenomenon of cellular senescence associated with neurodegeneration.
MeSH term(s)	Humans ; Multiple Sclerosis/diagnostic imaging ; Multiple Sclerosis/pathology ; Neurons/physiology ; Cerebellum ; Cellular Senescence ; Alzheimer Disease/pathology
Language	English
Publishing date	2023-04-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	196739-3
ISSN	1873-7544 ; 0306-4522
ISSN (online)	1873-7544
ISSN	0306-4522
DOI	10.1016/j.neuroscience.2023.04.002
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Article: Elemental quantification and analysis of structural abnormalities in neurons from Parkinson's-diseased brains by X-ray fluorescence microscopy and diffraction.

Joppe, Karina / Nicolas, Jan-David / Grünewald, Tilman A / Eckermann, Marina / Salditt, Tim / Lingor, Paul

Biomedical optics express

2020 Volume 11, Issue 7, Page(s) 3423–3443

Abstract: In this work we use scanning X-ray microscopy to study the structure and elemental composition of neuromelanin-positive neurons in substantia nigra tissue of Parkinson patients (PD) and controls. A total of 53 neurons were analyzed with X-ray ... ...

Abstract	In this work we use scanning X-ray microscopy to study the structure and elemental composition of neuromelanin-positive neurons in substantia nigra tissue of Parkinson patients (PD) and controls. A total of 53 neurons were analyzed with X-ray fluorescence (XRF) and diffraction using sub-µm-focused synchrotron radiation. A statistical evaluation identified copper as the most group-discriminating element and indicated that interindividual and intraindividual variations are of great relevance in tissue measurements of diseased patients and prevent from automated group clustering. XRF analyses of two Lewy bodies (LBs) highlight a heterogeneity in elemental distributions in these LBs, whereas an innovative X-ray diffraction-based method approach was used to reveal β-sheet-rich crystalline structures in LBs. Overall, sub-µm-focus X-ray microscopy highlighted the elemental heterogeneity in PD pathology.
Language	English
Publishing date	2020-06-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2572216-5
ISSN	2156-7085
ISSN	2156-7085
DOI	10.1364/BOE.389408
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Article: Phase-contrast x-ray tomography of neuronal tissue at laboratory sources with submicron resolution.

Eckermann, Marina / Töpperwien, Mareike / Robisch, Anna-Lena / van der Meer, Franziska / Stadelmann, Christine / Salditt, Tim

Journal of medical imaging (Bellingham, Wash.)

2020 Volume 7, Issue 1, Page(s) 13502

Abstract: Purpose: ...

Abstract	Purpose:
Language	English
Publishing date	2020-02-20
Publishing country	United States
Document type	Journal Article
ISSN	2329-4302
ISSN	2329-4302
DOI	10.1117/1.JMI.7.1.013502
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Article: Three-dimensional virtual histology of the cerebral cortex based on phase-contrast X-ray tomography.

Eckermann, Marina / van der Meer, Franziska / Cloetens, Peter / Ruhwedel, Torben / Möbius, Wiebke / Stadelmann, Christine / Salditt, Tim

Biomedical optics express

2021 Volume 12, Issue 12, Page(s) 7582–7598

Abstract: In this work, we optimize the setups and experimental parameters of X-ray phase-contrast computed-tomography for the three-dimensional imaging of the cyto- and myeloarchitecture of cerebral cortex, including both human and murine tissue. We present ... ...

Abstract	In this work, we optimize the setups and experimental parameters of X-ray phase-contrast computed-tomography for the three-dimensional imaging of the cyto- and myeloarchitecture of cerebral cortex, including both human and murine tissue. We present examples for different optical configurations using state-of-the art synchrotron instruments for holographic tomography, as well as compact laboratory setups for phase-contrast tomography in the direct contrast (edge-enhancement) regime. Apart from unstained and paraffin-embedded tissue, we tested hydrated tissue, as well as heavy metal stained and resin-embedded tissue using two different protocols. Further, we show that the image quality achieved allows to assess the neuropathology of multiple sclerosis in a biopsy sample collected during surgery.
Language	English
Publishing date	2021-11-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2572216-5
ISSN	2156-7085
ISSN	2156-7085
DOI	10.1364/BOE.434885
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Article ; Online: Three-dimensional virtual histology of the human hippocampus based on phase-contrast computed tomography.

Eckermann, Marina / Schmitzer, Bernhard / van der Meer, Franziska / Franz, Jonas / Hansen, Ove / Stadelmann, Christine / Salditt, Tim

Proceedings of the National Academy of Sciences of the United States of America

2021 Volume 118, Issue 48

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 ... ...

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.
MeSH term(s)	Brain Mapping/methods ; Cell Nucleus/metabolism ; Contrast Media ; Dentate Gyrus/diagnostic imaging ; Euchromatin/chemistry ; Gray Matter/diagnostic imaging ; Heterochromatin/chemistry ; Hippocampus/diagnostic imaging ; Humans ; Imaging, Three-Dimensional/methods ; Machine Learning ; Normal Distribution ; Pattern Recognition, Automated ; Principal Component Analysis ; Reproducibility of Results ; Tomography, X-Ray Computed/methods ; White Matter/diagnostic imaging
Chemical Substances	Contrast Media ; Euchromatin ; Heterochromatin
Language	English
Publishing date	2021-11-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2113835118
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Article ; Online: X-ray multiscale 3D neuroimaging to quantify cellular aging and neurodegeneration postmortem in a model of Alzheimer's disease.

Barbone, Giacomo E / Bravin, Alberto / Mittone, Alberto / Pacureanu, Alexandra / Mascio, Giada / Di Pietro, Paola / Kraiger, Markus J / Eckermann, Marina / Romano, Mariele / Hrabě de Angelis, Martin / Cloetens, Peter / Bruno, Valeria / Battaglia, Giuseppe / Coan, Paola

European journal of nuclear medicine and molecular imaging

2022 Volume 49, Issue 13, Page(s) 4338–4357

Abstract: Purpose: Modern neuroimaging lacks the tools necessary for whole-brain, anatomically dense neuronal damage screening. An ideal approach would include unbiased histopathologic identification of aging and neurodegenerative disease.: Methods: We report ... ...

Abstract	Purpose: Modern neuroimaging lacks the tools necessary for whole-brain, anatomically dense neuronal damage screening. An ideal approach would include unbiased histopathologic identification of aging and neurodegenerative disease. Methods: We report the postmortem application of multiscale X-ray phase-contrast computed tomography (X-PCI-CT) for the label-free and dissection-free organ-level to intracellular-level 3D visualization of distinct single neurons and glia. In deep neuronal populations in the brain of aged wild-type and of 3xTgAD mice (a triply-transgenic model of Alzheimer's disease), we quantified intracellular hyperdensity, a manifestation of aging or neurodegeneration. Results: In 3xTgAD mice, the observed hyperdensity was identified as amyloid-β and hyper-phosphorylated tau protein deposits with calcium and iron involvement, by correlating the X-PCI-CT data to immunohistochemistry, X-ray fluorescence microscopy, high-field MRI, and TEM. As a proof-of-concept, X-PCI-CT was used to analyze hippocampal and cortical brain regions of 3xTgAD mice treated with LY379268, selective agonist of group II metabotropic glutamate receptors (mGlu2/3 receptors). Chronic pharmacologic activation of mGlu2/3 receptors significantly reduced the hyperdensity particle load in the ventral cortical regions of 3xTgAD mice, suggesting a neuroprotective effect with locoregional efficacy. Conclusions: This multiscale micro-to-nano 3D imaging method based on X-PCI-CT enabled identification and quantification of cellular and sub-cellular aging and neurodegeneration in deep neuronal and glial cell populations in a transgenic model of Alzheimer's disease. This approach quantified the localized and intracellular neuroprotective effects of pharmacological activation of mGlu2/3 receptors.
MeSH term(s)	Animals ; Mice ; Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/pathology ; Calcium ; Cellular Senescence ; Iron ; Mice, Transgenic ; Neurodegenerative Diseases ; Neuroimaging ; Neuroprotective Agents/pharmacology ; Receptors, Metabotropic Glutamate/agonists ; Receptors, Metabotropic Glutamate/metabolism ; tau Proteins/metabolism ; X-Rays
Chemical Substances	Calcium (SY7Q814VUP) ; Iron (E1UOL152H7) ; Neuroprotective Agents ; Receptors, Metabotropic Glutamate ; tau Proteins
Language	English
Publishing date	2022-07-19
Publishing country	Germany
Document type	Journal Article
ZDB-ID	8236-3
ISSN	1619-7089 ; 0340-6997 ; 1619-7070
ISSN (online)	1619-7089
ISSN	0340-6997 ; 1619-7070
DOI	10.1007/s00259-022-05896-5
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Article: Nanoscale x-ray holotomography of human brain tissue with phase retrieval based on multienergy recordings.

Robisch, Anna-Lena / Eckermann, Marina / Töpperwien, Mareike / van der Meer, Franziska / Stadelmann, Christine / Salditt, Tim

Journal of medical imaging (Bellingham, Wash.)

2020 Volume 7, Issue 1, Page(s) 13501

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 ...

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.
Language	English
Publishing date	2020-01-22
Publishing country	United States
Document type	Journal Article
ISSN	2329-4302
ISSN	2329-4302
DOI	10.1117/1.JMI.7.1.013501
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Article ; Online: 3d phase-contrast nanotomography of unstained human skin biopsies may identify morphological differences in the dermis and epidermis between subjects.

Eckermann, Marina / Peruzzi, Niccolò / Frohn, Jasper / Bech, Martin / Englund, Elisabet / Veress, Béla / Salditt, Tim / Dahlin, Lars B / Ohlsson, Bodil

Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI)

2020 Volume 27, Issue 3, Page(s) 316–323

Abstract: Background: Enteric neuropathy is described in most patients with gastrointestinal dysmotility and may be found together with reduced intraepidermal nerve fiber density (IENFD). The aim of this pilot study was to assess whether three-dimensional (3d) ... ...

Abstract	Background: Enteric neuropathy is described in most patients with gastrointestinal dysmotility and may be found together with reduced intraepidermal nerve fiber density (IENFD). The aim of this pilot study was to assess whether three-dimensional (3d) imaging of skin biopsies could be used to examine various tissue components in patients with gastrointestinal dysmotility. Material and methods: Four dysmotility patients of different etiology and two healthy volunteers were included. From each subject, two 3-mm punch skin biopsies were stained with antibodies against protein gene product 9.5 or evaluated as a whole with two X-ray phase-contrast computed tomography (CT) setups, a laboratory µCT setup and a dedicated synchrotron radiation nanoCT end-station. Results: Two patients had reduced IENFD, and two normal IENFD, compared with controls. µCT and X-ray phase-contrast holographic nanotomography scanned whole tissue specimens, with optional high-resolution scans revealing delicate structures, without differentiation of various fibers and cells. Irregular architecture of dermal fibers was observed in the patient with Ehlers-Danlos syndrome and the patient with idiopathic dysmotility showed an abundance of mesenchymal ground substance. Conclusions: 3d phase-contrast tomographic imaging may be useful to illustrate traits of connective tissue dysfunction in various organs and to demonstrate whether disorganized dermal fibers could explain organ dysfunction.
MeSH term(s)	Biopsy ; Dermis ; Epidermis ; Humans ; Nerve Fibers ; Pilot Projects ; Skin/diagnostic imaging
Language	English
Publishing date	2020-10-06
Publishing country	England
Document type	Journal Article
ZDB-ID	1229160-2
ISSN	1600-0846 ; 0909-752X ; 1397-1344
ISSN (online)	1600-0846
ISSN	0909-752X ; 1397-1344
DOI	10.1111/srt.12974
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Book ; Online ; Thesis: Sicherheit der Plasmapherese bei Patienten mit Kollagenose

Eckermann, Marina [Verfasser] / Heemann, Uwe [Akademischer Betreuer] / Heemann, Uwe [Gutachter] / Stock, Konrad [Gutachter]

2019

Author's details	Marina Eckermann ; Gutachter: Uwe Heemann, Konrad Stock ; Betreuer: Uwe Heemann
Keywords	Medizin, Gesundheit ; Medicine, Health
Subject code	sg610
Language	German
Publisher	Universitätsbibliothek der TU München
Publishing place	München
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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