Cellular 3D-reconstruction and analysis in the human cerebral cortex using automatic serial sections

Communications Biology

Published On 2021/9/2

Techniques involving three-dimensional (3D) tissue structure reconstruction and analysis provide a better understanding of changes in molecules and function. We have developed AutoCUTS-LM, an automated system that allows the latest advances in 3D tissue reconstruction and cellular analysis developments using light microscopy on various tissues, including archived tissue. The workflow in this paper involved advanced tissue sampling methods of the human cerebral cortex, an automated serial section collection system, digital tissue library, cell detection using convolution neural network, 3D cell reconstruction, and advanced analysis. Our results demonstrated the detailed structure of pyramidal cells (number, volume, diameter, sphericity and orientation) and their 3D spatial organization are arranged in a columnar structure. The pipeline of these combined techniques provides a detailed analysis of tissues …

Journal

Communications Biology

Published On

2021/9/2

Volume

4

Issue

1

Page

1030

Authors

Jesper Møller

Jesper Møller

Aalborg Universitet

Position

Professor in Statistics

H-Index(all)

46

H-Index(since 2020)

23

I-10 Index(all)

0

I-10 Index(since 2020)

0

Citation(all)

0

Citation(since 2020)

0

Cited By

0

Research Interests

Mathematical Statistics

Probability Theory

University Profile Page

Jon Sporring

Jon Sporring

Københavns Universitet

Position

H-Index(all)

21

H-Index(since 2020)

11

I-10 Index(all)

0

I-10 Index(since 2020)

0

Citation(all)

0

Citation(since 2020)

0

Cited By

0

Research Interests

(Medical) Image Processing

Computer Graphics

Information Theory

University Profile Page

Other Articles from authors

Jon Sporring

Jon Sporring

Københavns Universitet

Communications Biology

A semi-automatic method for extracting mitochondrial cristae characteristics from 3D focused ion beam scanning electron microscopy data

Mitochondria are the main suppliers of energy for cells and their bioenergetic function is regulated by mitochondrial dynamics: the constant changes in mitochondria size, shape, and cristae morphology to secure cell homeostasis. Although changes in mitochondrial function are implicated in a wide range of diseases, our understanding is challenged by a lack of reliable ways to extract spatial features from the cristae, the detailed visualization of which requires electron microscopy (EM). Here, we present a semi-automatic method for the segmentation, 3D reconstruction, and shape analysis of mitochondria, cristae, and intracristal spaces based on 2D EM images of the murine hippocampus. We show that our method provides a more accurate characterization of mitochondrial ultrastructure in 3D than common 2D approaches and propose an operational index of mitochondria’s internal organization. With an improved …

Jon Sporring

Jon Sporring

Københavns Universitet

Parametric volumetric registration

Volumetric registration (VR) is one of the most studied problems in the medical image analysis field. This chapter begins by highlighting common medical image analysis problems that require VR (e.g., within-subject longitudinal registration, fusion of imaging modalities during image-guided surgery, or groupwise normalization for fMRI analysis) and describing the basic elements of the VR pipeline, such as spatial transformations, dissimilarity metrics and regularization terms. The latter part of the chapter focuses on registration approaches that parameterize spatial transformations using a limited set of coefficients, including rigid/affine transformations and B-Spline transformations. The chapter closes with a discussion of real-world considerations for implementing parametric VR.

Jon Sporring

Jon Sporring

Københavns Universitet

Multiscale and multiresolution analysis

In this chapter, we describe the Gaussian scale-space in the spatial and intensity parameters, and we discuss the scale-selection algorithms for blob and edge detections.Image resolution is to some extent an artifact of the camera used, and with no prior knowledge, we seldomly can predict the size of objects in pixels in images. Thus, we must design algorithms that can adapt to a range of sizes. One such algorithm is to seek objects of fixed size and use this algorithm on a range of downsampled images. This is, however, not the most elegant method for this purpose, since the result depends on the initial offset of the origin of the camera grid and not the scened depicted. The Gaussian scale-space is a better structure in which to express multi-size or multi-scale algorithms. In the Gaussian scale-space, downsampling is replaced with convolution with a Gaussian kernel of width proportional to the downsampling factor …

Jesper Møller

Jesper Møller

Aalborg Universitet

arXiv preprint arXiv:2404.09525

Coupling results and Markovian structures for number representations of continuous random variables

A general setting for nested subdivisions of a bounded real set into intervals defining the digits of a random variable with a probability density function is considered. Under the weak condition that is almost everywhere lower semi-continuous, a coupling between and a non-negative integer-valued random variable is established so that have an interpretation as the ``sufficient digits'', since the distribution of conditioned on does not depend on . Adding a condition about a Markovian structure of the lengths of the intervals in the nested subdivisions, becomes a Markov chain of a certain order . If then are IID with a known distribution. When and the Markov chain is uniformly geometric ergodic, a coupling is established between and a random time so that the chain after time is stationary and follows a simple known distribution. The results are related to several examples of number representations generated by a dynamical system, including base- expansions, generalized L\"uroth series, -expansions, and continued fraction representations. The importance of the results and some suggestions and open problems for future research are discussed.

Jesper Møller

Jesper Møller

Aalborg Universitet

arXiv preprint arXiv:2404.08387

The asymptotic distribution of the scaled remainder for pseudo golden ratio expansions of a continuous random variable

Let be the base- expansion of a continuous random variable on the unit interval where is the positive solution to for an integer (i.e., is a generalization of the golden mean for which ). We study the asymptotic distribution and convergence rate of the scaled remainder when tends to infinity.

Jesper Møller

Jesper Møller

Aalborg Universitet

Methodology and Computing in Applied Probability

How many digits are needed?

Let be the digits in the base-q expansion of a random variable X defined on [0, 1) where is an integer. For , we study the probability distribution of the (scaled) remainder : If X has an absolutely continuous CDF then converges in the total variation metric to the Lebesgue measure on the unit interval. Under weak smoothness conditions we establish first a coupling between X and a non-negative integer valued random variable N so that follows and is independent of , and second exponentially fast convergence of and its PDF . We discuss how many digits are needed and show examples of our results.

Jon Sporring

Jon Sporring

Københavns Universitet

Nature Biotechnology

Young glial progenitor cells competitively replace aged and diseased human glia in the adult chimeric mouse brain

Competition among adult brain cells has not been extensively researched. To investigate whether healthy glia can outcompete diseased human glia in the adult forebrain, we engrafted wild-type (WT) human glial progenitor cells (hGPCs) produced from human embryonic stem cells into the striata of adult mice that had been neonatally chimerized with mutant Huntingtin (mHTT)-expressing hGPCs. The WT hGPCs outcompeted and ultimately eliminated their human Huntington’s disease (HD) counterparts, repopulating the host striata with healthy glia. Single-cell RNA sequencing revealed that WT hGPCs acquired a YAP1/MYC/E2F-defined dominant competitor phenotype upon interaction with the host HD glia. WT hGPCs also outcompeted older resident isogenic WT cells that had been transplanted neonatally, suggesting that competitive success depended primarily on the relative ages of competing populations …

Jon Sporring

Jon Sporring

Københavns Universitet

Proceedings of the National Academy of Sciences

Astrocytic engagement of the corticostriatal synaptic cleft is disrupted in a mouse model of Huntington’s disease

Astroglial dysfunction contributes to the pathogenesis of Huntington’s disease (HD), and glial replacement can ameliorate the disease course. To establish the topographic relationship of diseased astrocytes to medium spiny neuron (MSN) synapses in HD, we used 2-photon imaging to map the relationship of turboRFP-tagged striatal astrocytes and rabies-traced, EGFP-tagged coupled neuronal pairs in R6/2 HD and wild-type (WT) mice. The tagged, prospectively identified corticostriatal synapses were then studied by correlated light electron microscopy followed by serial block-face scanning EM, allowing nanometer-scale assessment of synaptic structure in 3D. By this means, we compared the astrocytic engagement of single striatal synapses in HD and WT brains. R6/2 HD astrocytes exhibited constricted domains, with significantly less coverage of mature dendritic spines than WT astrocytes, despite enhanced …

Jon Sporring

Jon Sporring

Københavns Universitet

Ultrastructure of mitochondria in 3D from volume electron microscopy

Ultrastructure of mitochondria in 3D from volume electron microscopy — Aarhus University Skip to main navigation Skip to search Skip to main content Aarhus University Home Aarhus University Logo Help & FAQ English Dansk Home Profiles Research units Projects Research output Prizes Activities Courses Press/Media Search by expertise, name or affiliation Ultrastructure of mitochondria in 3D from volume electron microscopy Chenhao Wang, Leif Østergaard, Stine Hasselholt, Jon Sporring Department of Clinical Medicine - Center of Functionally Integrative Neuroscience Research output: Contribution to conference › Conference abstract for conference › Research › peer-review Overview Original language English Publication date 12 Jun 2023 Publication status Published - 12 Jun 2023 Event Euromit: International meeting on mitochondrial pathology - Bologna, Italy Duration: 11 Jun 2023 → 15 Jun 2023 https://…

Jon Sporring

Jon Sporring

Københavns Universitet

arXiv preprint arXiv:2309.03908

Iron Oxide Nanoparticles as a Contrast Agent for Synchrotron Imaging of Sperm

Fast phase-contrast imaging offered by modern synchrotron facilities opens the possibility of imaging dynamic processes of biological material such as cells. Cells are mainly composed of carbon and hydrogen, which have low X-ray attenuation, making cell studies with X-ray tomography challenging. At specific low energies, cells provide contrast, but cryo-conditions are required to protect the sample from radiation damage. Thus, non-toxic labelling methods are needed to prepare living cells for X-ray tomography at higher energies. We propose using iron oxide nanoparticles due to their proven compatibility in other biomedical applications. We show how to synthesize and attach iron oxide nanoparticles and demonstrate that cell-penetrating peptides facilitate iron oxide nanoparticle uptake into sperm cells. We show results from the TOMCAT Nanoscope (Swiss Light Source), showing that iron oxide nanoparticles allow the heads and midpiece of fixed sperm samples to be reconstructed from X-ray projections taken at 10 keV.

Jesper Møller

Jesper Møller

Aalborg Universitet

arXiv preprint arXiv:2312.09652

The asymptotic distribution of the remainder in a certain base- expansion

Let be the base- expansion of a continuous random variable on the unit interval where is the golden ratio. We study the asymptotic distribution and convergence rate of the scaled remainder when tends to infinity.

2023/12/15

Article Details
Jesper Møller

Jesper Møller

Aalborg Universitet

Proceedings of the London Mathematical Society

Realizability and tameness of fusion systems

A saturated fusion system over a finite p$p$‐group S$S$ is a category whose objects are the subgroups of S$S$ and whose morphisms are injective homomorphisms between the subgroups satisfying certain axioms. A fusion system over S$S$ is realized by a finite group G$G$ if S$S$ is a Sylow p$p$‐subgroup of G$G$ and morphisms in the category are those induced by conjugation in G$G$. One recurrent question in this subject is to find criteria as to whether a given saturated fusion system is realizable or not. One main result in this paper is that a saturated fusion system is realizable if all of its components (in the sense of Aschbacher) are realizable. Another result is that all realizable fusion systems are tame: a finer condition on realizable fusion systems that involves describing automorphisms of a fusion system in terms of those of some group that realizes it. Stated in this way, these results depend on the …

Jon Sporring

Jon Sporring

Københavns Universitet

Journal of Mathematical Imaging and Vision

Morphology on categorical distributions

Mathematical morphology (MM) is an indispensable tool for post-processing. Several extensions of MM to categorical images, such as multi-class segmentations, have been proposed. However, none provide satisfactory definitions for morphology on probabilistic representations of categorical images. The categorical distribution is a natural choice for representing uncertainty about categorical images. Extending MM to categorical distributions is problematic because categories are inherently unordered. Without ranking categories, we cannot use the standard framework based on supremum and infimum. Ranking categories is impractical and problematic. Instead, we consider the probabilistic representation and operations that emphasize a single category. In this work, we review and compare previous approaches. We propose two approaches for morphology on categorical distributions: operating on Dirichlet …

Jesper Møller

Jesper Møller

Aalborg Universitet

ACM Transactions on Spatial Algorithms and Systems

Stochastic Routing with Arrival Windows

Arriving at a destination within a specific time window is important in many transportation settings. For example, trucks may be penalized for early or late arrivals at compact terminals, and early and late arrivals at general practitioners, dentists, and so on, are also discouraged, in part due to COVID. We propose foundations for routing with arrival-window constraints. In a setting where the travel time of a road segment is modeled by a probability distribution, we define two problems where the aim is to find a route from a source to a destination that optimizes or yields a high probability of arriving within a time window while departing as late as possible. In this setting, a core challenge is to enable comparison between paths that may potentially be part of a result path with the goal of determining whether a path is uninteresting and can be disregarded given the existence of another path. We show that existing solutions …

2023/11/21

Article Details
Jesper Møller

Jesper Møller

Aalborg Universitet

Spatial Statistics

Fitting the grain orientation distribution of a polycrystalline material conditioned on a Laguerre tessellation

The description of distributions related to grain microstructure helps physicists to understand the processes in materials and their properties. This paper presents a general statistical methodology for the analysis of crystallographic orientations of grains in a 3D Laguerre tessellation dataset which represents the microstructure of a polycrystalline material. We introduce complex stochastic models which may substitute expensive laboratory experiments: conditional on the Laguerre tessellation, we suggest interaction models for the distribution of cubic crystal lattice orientations, where the interaction is between pairs of orientations for neighbouring grains in the tessellation. We discuss parameter estimation and model comparison methods based on maximum pseudolikelihood as well as graphical procedures for model checking using simulations. Our methodology is applied for analysing a dataset representing a nickel …

Jesper Møller

Jesper Møller

Aalborg Universitet

Methodology and Computing in Applied Probability

Singular distribution functions for random variables with stationary digits

Let F be the cumulative distribution function (CDF) of the base-q expansion , where is an integer and is a stationary stochastic process with state space . In a previous paper we characterized the absolutely continuous and the discrete components of F. In this paper we study special cases of models, including stationary Markov chains of any order and stationary renewal point processes, where we establish a law of pure types: F is then either a uniform or a singular CDF on [0, 1]. Moreover, we study mixtures of such models. In most cases expressions and plots of F are given.

Jon Sporring

Jon Sporring

Københavns Universitet

bioRxiv

A Practical Approach to Estimating the Effect of Synchrotron Radiation on Sperm Motility and Viability

Studying the dynamics of sperm tail beating in 3D is important for understanding decreasing fertility trends related to motility. Synchrotron X-ray tomography (SXRT) shows promising results for imaging live biological samples in 3D and time, making it a candidate for imaging sperm tail beating patterns. However, the dose of ionizing radiation (IR) that the cells would receive during image acquisition is of concern as this is likely to affect essential cellular functions. The effect of IR on motility at the dose rates encountered in a synchrotron has never been assessed. Here, results are presented of analyzing the movement and viability of sperm cells exposed at varying durations at the TOMCAT beamline (Swiss Light Source (SLS)) which has the field of view and spatial resolution needed to reconstruct sperm cells coupled with sub-second exposure times. The results indicate that motility is affected long before viability and that sperm cell dynamics are affected very quickly by the beam.

Jon Sporring

Jon Sporring

Københavns Universitet

3D mitochondrial ultrastructure using volume electron microscopy

3D mitochondrial ultrastructure using volume electron microscopy — Aarhus University Skip to main navigation Skip to search Skip to main content Aarhus University Home Aarhus University Logo Help & FAQ English Dansk Home Profiles Research units Projects Research output Prizes Activities Courses Press/Media Search by expertise, name or affiliation 3D mitochondrial ultrastructure using volume electron microscopy Chenhao Wang, Leif Østergaard, Stine Hasselholt, Jon Sporring Department of Clinical Medicine - Center of Functionally Integrative Neuroscience Research output: Contribution to conference › Conference abstract for conference › Research › peer-review Overview Original language English Publication date 31 Oct 2023 Publication status Published - 31 Oct 2023 Event 6th Annual Research Meeting at the Department of Clinical Medicine - Aarhus Universitetshospital, Aarhus N, Denmark Duration: …

2023/10/31

Article Details
Jon Sporring

Jon Sporring

Københavns Universitet

Frontiers in Computer Science

An algebra for local histograms

In this article, we consider local overlapping histograms of functions between discrete domains and codomains. We develop a simple algebra for local histograms. Based on a separation of overlapping domains into non-overlapping domains, we 1) show how these can be used to enumerate the size of the set of possible histograms given the local histogram domains, and 2) enumerate the number of functions, which share a specific choice of a set of local histograms. Finally, we present a decoding algorithm, which given a set of overlapping histograms, and calculate the set of functions, which share these histograms.

2022/11/17

Article Details
Jon Sporring

Jon Sporring

Københavns Universitet

Structural and functional changes in a genetic model of amyotrophic lateral sclerosis

Structural and functional changes in a genetic model of amyotrophic lateral sclerosis — Aarhus University Skip to main navigation Skip to search Skip to main content Aarhus University Home Aarhus University Logo Help & FAQ English Dansk Home Profiles Research units Projects Research output Prizes Activities Courses Press/Media Search by expertise, name or affiliation Structural and functional changes in a genetic model of amyotrophic lateral sclerosis Stine Hasselholt, Hans JT Stephensen, Daan Janssen, Anne Hasselholt, Anaëlle Dubois, Ute Hahn, Yaqing Wang, Jon Sporring, Zhiheng Xu, Jens Randel Nyengaard Department of Clinical Medicine - Core Centre for Molecular Morphology, Section for Stereology and Microscopy Department of Ecoscience - Catchment Science and Environmental Management Department of Mathematics Research output: Contribution to conference › Conference abstract for …

2022/11/15

Article Details

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Communications Biology

Infant diarrheal disease in rhesus macaques impedes microbiome maturation and is linked to uncultured Campylobacter species

Diarrheal diseases remain one of the leading causes of death for children under 5 globally, disproportionately impacting those living in low- and middle-income countries (LMIC). Campylobacter spp., a zoonotic pathogen, is one of the leading causes of food-borne infection in humans. Yet to be cultured Campylobacter spp. contribute to the total burden in diarrheal disease in children living in LMIC thus hampering interventions. We performed microbiome profiling and metagenomic genome assembly on samples collected from over 100 infant rhesus macaques longitudinally and during cases of clinical diarrhea within the first year of life. Acute diarrhea was associated with long-lasting taxonomic and functional shifts of the infant gut microbiome indicative of microbiome immaturity. We constructed 36 Campylobacter metagenomic assembled genomes (MAGs), many of which fell within 4 yet to be cultured species …

Akinobu Watanabe

Akinobu Watanabe

New York Institute of Technology

Communications Biology

Avialan-like brain morphology in Sinovenator (Troodontidae, Theropoda)

Many modifications to the skull and brain anatomy occurred along the lineage encompassing non-avialan theropod dinosaurs and modern birds. Anatomical changes to the endocranium include an enlarged endocranial cavity, relatively larger optic lobes that imply elevated visual acuity, and proportionately smaller olfactory bulbs that suggest reduced olfactory capacity. Here, we use micro-computed tomographic (μCT) imaging to reconstruct the endocranium and its neuroanatomical features from an exceptionally well-preserved skull of Sinovenator changii (Troodontidae, Theropoda). While its overall morphology resembles the typical endocranium of other troodontids, Sinovenator also exhibits unique endocranial features that are similar to other paravian taxa and non-maniraptoran theropods. Landmark-based geometric morphometric analysis on endocranial shape of non-avialan and avialan dinosaurs points to …

Elizabeth Illingworth

Elizabeth Illingworth

Università degli Studi di Salerno

Communications Biology

Endothelial gene regulatory elements associated with cardiopharyngeal lineage differentiation

Endothelial cells (EC) differentiate from multiple sources, including the cardiopharyngeal mesoderm, which gives rise also to cardiac and branchiomeric muscles. The enhancers activated during endothelial differentiation within the cardiopharyngeal mesoderm are not completely known. Here, we use a cardiogenic mesoderm differentiation model that activates an endothelial transcription program to identify endothelial regulatory elements activated in early cardiogenic mesoderm. Integrating chromatin remodeling and gene expression data with available single-cell RNA-seq data from mouse embryos, we identify 101 putative regulatory elements of EC genes. We then apply a machine-learning strategy, trained on validated enhancers, to predict enhancers. Using this computational assay, we determine that 50% of these sequences are likely enhancers, some of which are already reported. We also identify a smaller …

Shinji Takenaka / 竹中 慎治

Shinji Takenaka / 竹中 慎治

Kobe University

Communications Biology

High-resolution structure and biochemical properties of the LH1–RC photocomplex from the model purple sulfur bacterium, Allochromatium vinosum

The mesophilic purple sulfur phototrophic bacterium Allochromatium (Alc.) vinosum (bacterial family Chromatiaceae) has been a favored model for studies of bacterial photosynthesis and sulfur metabolism, and its core light-harvesting (LH1) complex has been a focus of numerous studies of photosynthetic light reactions. However, despite intense efforts, no high-resolution structure and thorough biochemical analysis of the Alc. vinosum LH1 complex have been reported. Here we present cryo-EM structures of the Alc. vinosum LH1 complex associated with reaction center (RC) at 2.24 Å resolution. The overall structure of the Alc. vinosum LH1 resembles that of its moderately thermophilic relative Alc. tepidum in that it contains multiple pigment-binding α- and β-polypeptides. Unexpectedly, however, six Ca ions were identified in the Alc. vinosum LH1 bound to certain α1/β1- or α1/β3-polypeptides through a different Ca …

Daniel Segrè

Daniel Segrè

Boston University

Communications Biology

Multi-Attribute Subset Selection enables prediction of representative phenotypes across microbial populations

The interpretation of complex biological datasets requires the identification of representative variables that describe the data without critical information loss. This is particularly important in the analysis of large phenotypic datasets (phenomics). Here we introduce Multi-Attribute Subset Selection (MASS), an algorithm which separates a matrix of phenotypes (e.g., yield across microbial species and environmental conditions) into predictor and response sets of conditions. Using mixed integer linear programming, MASS expresses the response conditions as a linear combination of the predictor conditions, while simultaneously searching for the optimally descriptive set of predictors. We apply the algorithm to three microbial datasets and identify environmental conditions that predict phenotypes under other conditions, providing biologically interpretable axes for strain discrimination. MASS could be used to reduce the …