Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Three-dimensional virtual histology of the human hippocampus based on phase-contrast computed tomography.

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.

SUBMITTER: Eckermann M

PROVIDER: S-EPMC8640721 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Three-dimensional virtual histology of human cerebellum by X-ray phase-contrast tomography.

Project description: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.

| S-EPMC6142271 | biostudies-literature

Three-dimensional virtual histology enabled through cytoplasm-specific X-ray stain for microscopic and nanoscopic computed tomography.

Project description:Many histological methods require staining of the cytoplasm, which provides instrumental details for diagnosis. One major limitation is the production of 2D images obtained by destructive preparation of 3D tissue samples. X-ray absorption micro- and nanocomputed tomography (microCT and nanoCT) allows for a nondestructive investigation of a 3D tissue sample, and thus aids to determine regions of interest for further histological examinations. However, application of microCT and nanoCT to biological samples (e.g., biopsies) is limited by the missing contrast within soft tissue, which is important to visualize morphological details. We describe an eosin-based preparation overcoming the challenges of contrast enhancement and selectivity for certain tissues. The eosin-based staining protocol is suitable for whole-organ staining, which then enables high-resolution microCT imaging of whole organs and nanoCT imaging of smaller tissue pieces retrieved from the original sample. Our results demonstrate suitability of the eosin-based staining method for diagnostic screening of 3D tissue samples without impeding further diagnostics through histological methods.

| S-EPMC5877988 | biostudies-literature

3D virtual histology of human pancreatic tissue by multiscale phase-contrast X-ray tomography.

Project description:A multiscale three-dimensional (3D) virtual histology approach is presented, based on two configurations of propagation phase-contrast X-ray tomography, which have been implemented in close proximity at the GINIX endstation at the beamline P10/PETRA III (DESY, Hamburg, Germany). This enables the 3D reconstruction of characteristic morphological features of human pancreatic normal and tumor tissue, as obtained from cancer surgery, first in the form of a large-scale overview by parallel-beam illumination, followed by a zoom into a region-of-interest based on zoom tomography using a Kirkpatrick-Baez mirror with additional waveguide optics. To this end 1 mm punch biopsies of the tissue were taken. In the parallel tomography, a volumetric throughput on the order of 0.01 mm3 s-1 was achieved, while maintaining the ability to segment isolated cells. With a continuous rotation during the scan, a total acquisition time of less than 2 min was required for a full tomographic scan. Using the combination of both setups, islets of Langerhans, a three-dimensional cluster of cells in the endocrine part of the pancreas, could be located. Cells in such an islet were segmented and visualized in 3D. Further, morphological alterations of tumorous tissue of the pancreas were characterized. To this end, the anisotropy parameter Ω, based on intensity gradients, was used in order to quantify the presence of collagen fibers within the entire biopsy specimen. This proof-of-concept experiment of the multiscale approach on human pancreatic tissue paves the way for future 3D virtual pathology.

| S-EPMC7642968 | biostudies-literature

X-ray Micro-Computed Tomography for Nondestructive Three-Dimensional (3D) X-ray Histology.

Project description:Historically, micro-computed tomography (μCT) has been considered unsuitable for histologic analysis of unstained formalin-fixed, paraffin-embedded soft tissue biopsy specimens because of a lack of image contrast between the tissue and the paraffin. However, we recently demonstrated that μCT can successfully resolve microstructural detail in routinely prepared tissue specimens. Herein, we illustrate how μCT imaging of standard formalin-fixed, paraffin-embedded biopsy specimens can be seamlessly integrated into conventional histology workflows, enabling nondestructive three-dimensional (3D) X-ray histology, the use and benefits of which we showcase for the exemplar of human lung biopsy specimens. This technology advancement was achieved through manufacturing a first-of-kind μCT scanner for X-ray histology and developing optimized imaging protocols, which do not require any additional sample preparation. 3D X-ray histology allows for nondestructive 3D imaging of tissue microstructure, resolving structural connectivity and heterogeneity of complex tissue networks, such as the vascular network or the respiratory tract. We also demonstrate that 3D X-ray histology can yield consistent and reproducible image quality, enabling quantitative assessment of a tissue's 3D microstructures, which is inaccessible to conventional two-dimensional histology. Being nondestructive, the technique does not interfere with histology workflows, permitting subsequent tissue characterization by means of conventional light microscopy-based histology, immunohistochemistry, and immunofluorescence. 3D X-ray histology can be readily applied to a plethora of archival materials, yielding unprecedented opportunities in diagnosis and research of disease.

| S-EPMC6680277 | biostudies-literature

Three-dimensional characterization of tissue-engineered constructs by contrast-enhanced nanofocus computed tomography.

Project description:To successfully implement tissue-engineered (TE) constructs as part of a clinical therapy, it is necessary to develop quality control tools that will ensure accurate and consistent TE construct release specifications. Hence, advanced methods to monitor TE construct properties need to be further developed. In this study, we showed proof of concept for contrast-enhanced nanofocus computed tomography (CE-nano-CT) as a whole-construct imaging technique with a noninvasive potential that enables three-dimensional (3D) visualization and quantification of in vitro engineered extracellular matrix (ECM) in TE constructs. In particular, we performed a 3D qualitative and quantitative structural and spatial assessment of the in vitro engineered ECM, formed during static and perfusion bioreactor cell culture in 3D TE scaffolds, using two contrast agents, namely, Hexabrix® and phosphotungstic acid (PTA). To evaluate the potential of CE-nano-CT, a comparison was made to standardly used techniques such as Live/Dead viability/cytotoxicity, Picrosirius Red staining, and to net dry weight measurements of the TE constructs. When using Hexabrix as the contrast agent, the ECM volume fitted linearly with the net dry ECM weight independent from the flow rate used, thus suggesting that it stains most of the ECM. When using PTA as the contrast agent, comparing to net weight measurements showed that PTA only stains a part of the ECM. This was attributed to the binding specificity of this contrast agent. In addition, the PTA-stained CE-nano-CT data showed pronounced distinction between flow conditions when compared to Hexabrix, indicating culture-specific structural ECM differences. This novel type of information can contribute to optimize bioreactor culture conditions and potentially critical quality characteristics of TE constructs such as ECM quantity and homogeneity, facilitating the gradual transformation of TE constructs in well-characterized TE products.

| S-EPMC3936499 | biostudies-literature

Visualizing polymeric bioresorbable scaffolds with three-dimensional image reconstruction using contrast-enhanced micro-computed tomography.

Project description:There are no previous studies showing how to visualize polymeric bioresorbable scaffolds (BRSs) by micro-computed tomography (mCT). There are no previous studies showing how to visualize polymeric bioresorbable scaffolds (BRSs) by micro-computed tomography (mCT). This study aimed to explore the feasibility of detecting polymeric BRS with 3-dimensional reconstruction of BRS images by contrast-enhanced mCT and to determine the optimal imaging settings. BRSs, made of poly-L-lactic acid (PLLA), were implanted in coronary bifurcation models. Five treatments were conducted to examine an optimal condition for imaging BRSs: Baseline treatment, samples were filled with normal saline and scanned with mCT immediately; Treatment-1, -2, -3 and -4, samples were filled with contrast medium and scanned with mCT immediately and 1, 2 and 3 h thereafter, corresponding to soaking time of contrast medium of 0, 1, 2 and 3 h. Compared to Baseline, mCT scanning completely discriminate the scaffold struts from the vascular lumen immediately after filling the samples with contrast agent but not from the vascular wall until the contrast agent soaking time was more than 2 h (Treatment-3 and -4). By setting 10-15 HU as a cut-point of CT values, the scaffold strut detectable rate at Baseline and Teatment-1, -2, -3 and -4 were 1.23 ± 0.31%, 1.65 ± 0.26%, 58.14 ± 12.84%, 97.97 ± 1.43% and 98.90 ± 0.38%, respectively (Treatment-3 vs. Treatment-2, p < 0.01); meanwhile, the success rate of 3D BRS reconstruction with high quality images at Baseline and Teatment-1, -2, -3 and -4 were 1.23%, 1.65%, 58.14%, 97.97% and 98.90%, respectively (Treatment-3 vs. Treatment-2, p < 0.01). In conclusions, reconstruction of 3D BRS images is technically feasible by contrast-enhanced mCT and soaking time of contrast agent for more than 2 h is necessary for complete separation of scaffold struts from the surrounding structures in the phantom samples.

| S-EPMC5383680 | biostudies-literature

Multiscale three-dimensional imaging of intact human organs down to the cellular scale using hierarchical phase-contrast tomography.

Project description:Human organs are complex, three-dimensional and multiscale systems. Spatially mapping the human body down through its hierarchy, from entire organs to their individual functional units and specialised cells, is a major obstacle to fully understanding health and disease. To meet this challenge, we developed hierarchical phase-contrast tomography (HiP-CT), an X-ray phase propagation technique utilising the European Synchrotron Radiation Facility's Extremely Brilliant Source: the world's first high-energy 4 th generation X-ray source. HiP-CT enabled three-dimensional and non-destructive imaging at near-micron resolution in soft tissues at one hundred thousand times the voxel size whilst maintaining the organ's structure. We applied HiP-CT to image five intact human parenchymal organs: brain, lung, heart, kidney and spleen. These were hierarchically assessed with HiP-CT, providing a structural overview of the whole organ alongside detail of the organ's individual functional units and cells. The potential applications of HiP-CT were demonstrated through quantification and morphometry of glomeruli in an intact human kidney, and identification of regional changes to the architecture of the air-tissue interface and alveolar morphology in the lung of a deceased COVID-19 patient. Overall, we show that HiP-CT is a powerful tool which can provide a comprehensive picture of structural information for whole intact human organs, encompassing precise details on functional units and their constituent cells to better understand human health and disease.

| S-EPMC7872374 | biostudies-literature

Cellular-resolution 3D virtual histology of human coronary arteries using x-ray phase tomography.

Project description:High-spatial-resolution histology of coronary artery autopsy samples play an important role for understanding heart disease such as myocardial infarction. Unfortunately, classical histology is often destructive, has thick slicing, requires extensive sample preparation, and is time-consuming. X-ray micro-CT provides fast nondestructive 3D imaging but absorption contrast is often insufficient, especially for observing soft-tissue features with high resolution. Here we show that propagation-based x-ray phase-contrast tomography has the resolution and contrast to image clinically relevant soft-tissue features in intact coronary artery autopsy samples with cellular resolution. We observe microscopic lipid-rich plaques, individual adipose cells, ensembles of few foam cells, and the thin fibrous cap. The method relies on a small-spot laboratory x-ray microfocus source, and provides high-spatial resolution in all three dimensions, fast data acquisition, minimum sample distortion and requires no sample preparation.

| S-EPMC6054690 | biostudies-other

Three-dimensional mouse brain cytoarchitecture revealed by laboratory-based x-ray phase-contrast tomography.

Project description:Studies of brain cytoarchitecture in mammals are routinely performed by serial sectioning of the specimen and staining of the sections. The procedure is labor-intensive and the 3D architecture can only be determined after aligning individual 2D sections, leading to a reconstructed volume with non-isotropic resolution. Propagation-based x-ray phase-contrast tomography offers a unique potential for high-resolution 3D imaging of intact biological specimen due to the high penetration depth and potential resolution. We here show that even compact laboratory CT at an optimized liquid-metal jet microfocus source combined with suitable phase-retrieval algorithms and a novel tissue preparation can provide cellular and subcellular resolution in millimeter sized samples of mouse brain. We removed water and lipids from entire mouse brains and measured the remaining dry tissue matrix in air, lowering absorption but increasing phase contrast. We present single-cell resolution images of mouse brain cytoarchitecture and show that axons can be revealed in myelinated fiber bundles. In contrast to optical 3D techniques our approach does neither require staining of cells nor tissue clearing, procedures that are increasingly difficult to apply with increasing sample and brain sizes. The approach thus opens a novel route for high-resolution high-throughput studies of brain architecture in mammals.

| S-EPMC5327439 | biostudies-literature

Three-dimensional visualization of the microvasculature of bile duct ligation-induced liver fibrosis in rats by x-ray phase-contrast imaging computed tomography.

Project description:X-ray phase-contrast imaging (PCI) can substantially enhance contrast, and is particularly useful in differentiating biological soft tissues with small density differences. Combined with computed tomography (CT), PCI-CT enables the acquisition of accurate microstructures inside biological samples. In this study, liver microvasculature was visualized without contrast agents in vitro with PCI-CT using liver fibrosis samples induced by bile duct ligation (BDL) in rats. The histological section examination confirmed the correspondence of CT images with the microvascular morphology of the samples. By means of the PCI-CT and three-dimensional (3D) visualization technique, 3D microvascular structures in samples from different stages of liver fibrosis were clearly revealed. Different types of blood vessels, including portal veins and hepatic veins, in addition to ductular proliferation and bile ducts, could be distinguished with good sensitivity, excellent specificity and excellent accuracy. The study showed that PCI-CT could assess the morphological changes in liver microvasculature that result from fibrosis and allow characterization of the anatomical and pathological features of the microvasculature. With further development of PCI-CT technique, it may become a novel noninvasive imaging technique for the auxiliary analysis of liver fibrosis.

| S-EPMC4515745 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data