Publications

What is a Publication?
6 Publications visible to you, out of a total of 6

Abstract (Expand)

MOTIVATION: Over the last decades, image processing and analysis have become one of the key technologies in systems biology and medicine. The quantification of anatomical structures and dynamic processes in living systems is essential for understanding the complex underlying mechanisms and allows, i.e. the construction of spatio-temporal models that illuminate the interplay between architecture and function. Recently, deep learning significantly improved the performance of traditional image analysis in cases where imaging techniques provide large amounts of data. However, if only a few images are available or qualified annotations are expensive to produce, the applicability of deep learning is still limited. RESULTS: We present a novel approach that combines machine learning-based interactive image segmentation using supervoxels with a clustering method for the automated identification of similarly colored images in large image sets which enables a guided reuse of interactively trained classifiers. Our approach solves the problem of deteriorated segmentation and quantification accuracy when reusing trained classifiers which is due to significant color variability prevalent and often unavoidable in biological and medical images. This increase in efficiency improves the suitability of interactive segmentation for larger image sets, enabling efficient quantification or the rapid generation of training data for deep learning with minimal effort. The presented methods are applicable for almost any image type and represent a useful tool for image analysis tasks in general. AVAILABILITY AND IMPLEMENTATION: The presented methods are implemented in our image processing software TiQuant which is freely available at tiquant.hoehme.com. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Authors: A. Friebel, T. Johann, D. Drasdo, S. Hoehme

Date Published: 30th Sep 2022

Publication Type: Journal

Abstract (Expand)

Mouse models of non-alcoholic fatty liver disease (NAFLD) are required to define therapeutic targets, but detailed time-resolved studies to establish a sequence of events are lacking. Here, we fed malee, we fed male C57Bl/6N mice a Western or standard diet over 48 weeks. Multiscale time-resolved characterization was performed using RNA-seq, histopathology, immunohistochemistry, intravital imaging, and blood chemistry; the results were compared to human disease. Acetaminophen toxicity and ammonia metabolism were additionally analyzed as functional readouts. We identified a sequence of eight key events: formation of lipid droplets; inflammatory foci; lipogranulomas; zonal reorganization; cell death and replacement proliferation; ductular reaction; fibrogenesis; and hepatocellular cancer. Functional changes included resistance to acetaminophen and altered nitrogen metabolism. The transcriptomic landscape was characterized by two large clusters of monotonously increasing or decreasing genes, and a smaller number of ‘rest-and-jump genes’ that initially remained unaltered but became differentially expressed only at week 12 or later. Approximately 30% of the genes altered in human NAFLD are also altered in the present mouse model and an increasing overlap with genes altered in human HCC occurred at weeks 30–48. In conclusion, the observed sequence of events recapitulates many features of human disease and offers a basis for the identification of therapeutic targets.

Authors: Ahmed Ghallab, Maiju Myllys, Adrian Friebel, Julia Duda, Karolina Edlund, Emina Halilbasic, Mihael Vucur, Zaynab Hobloss, Lisa Brackhagen, Brigitte Begher-Tibbe, Reham Hassan, Michael Burke, Erhan Genc, Lynn Johann Frohwein, Ute Hofmann, Christian H. Holland, Daniela González, Magdalena Keller, Abdel-latif Seddek, Tahany Abbas, Elsayed S. I. Mohammed, Andreas Teufel, Timo Itzel, Sarah Metzler, Rosemarie Marchan, Cristina Cadenas, Carsten Watzl, Michael A. Nitsche, Franziska Kappenberg, Tom Luedde, Thomas Longerich, Jörg Rahnenführer, Stefan Hoehme, Michael Trauner, Jan G. Hengstler

Date Published: 1st Oct 2021

Publication Type: Journal

Abstract (Expand)

Small‐molecule flux in tissue‐microdomains is essential for organ function, but knowledge of this process is scant due to the lack of suitable methods. We developed two independent techniques that allow the quantification of advection (flow) and diffusion in individual bile canaliculi and in interlobular bile ducts of intact livers in living mice, namely Fluorescence Loss After Photoactivation (FLAP) and Intravital Arbitrary Region Image Correlation Spectroscopy (IVARICS). The results challenge the prevailing ‘mechano‐osmotic’ theory of canalicular bile flow. After active transport across hepatocyte membranes bile acids are transported in the canaliculi primarily by diffusion. Only in the interlobular ducts, diffusion is augmented by regulatable advection. Photoactivation of fluorescein bis‐(5‐carboxymethoxy‐2‐nitrobenzyl)‐ether (CMNB‐caged fluorescein) in entire lobules demonstrated the establishment of diffusive gradients in the bile canalicular network and the sink function of interlobular ducts. In contrast to the bile canalicular network, vectorial transport was detected and quantified in the mesh of interlobular bile ducts. In conclusion, the liver consists of a diffusion dominated canalicular domain, where hepatocytes secrete small molecules and generate a concentration gradient and a flow‐augmented ductular domain, where regulated water influx creates unidirectional advection that augments the diffusive flux.

Authors: Nachiket Vartak, Georgia Guenther, Florian Joly, Amruta Damle‐Vartak, Gudrun Wibbelt, Jörns Fickel, Simone Jörs, Brigitte Begher‐Tibbe, Adrian Friebel, Kasimir Wansing, Ahmed Ghallab, Marie Rosselin, Noemie Boissier, Irene Vignon‐Clementel, Christian Hedberg, Fabian Geisler, Heribert Hofer, Peter Jansen, Stefan Hoehme, Dirk Drasdo, Jan G. Hengstler

Date Published: 19th Jun 2020

Publication Type: Journal

Abstract

Not specified

Authors: Adrian Friebel, Tim Johann, Dirk Drasdo, Stefan Hoehme

Date Published: 18th May 2020

Publication Type: Misc

Abstract (Expand)

Small-molecule flux in tissue-microdomains is essential for organ function, but knowledge of this process is scant due to the lack of suitable methods applicable to live animals. We developed a methodology based on dynamic and correlative imaging for quantitative intravital flux analysis. Application to the liver, challenged the prevailing ‘mechano-osmotic’ theory of canalicular bile flow. After active transport across hepatocyte membranes bile salts are transported in the canaliculi primarily by diffusion. Only in the interlobular ducts, diffusion is augmented by regulatable advection. We corroborate these observations with in silico simulations and pan-species comparisons of lobule size. This study demonstrates a flux mechanism, where the energy invested in transmembrane transport entropically dissipates in a sub-micron scale vessel network.

Authors: Nachiket Vartak, Georgia Guenther, Florian Joly, Amruta Damle-Vartak, Gudrun Wibbelt, Jörns Fickel, Simone Jörs, Brigitte Begher-Tibbe, Adrian Friebel, Kasimir Wansing, Ahmed Ghallab, Marie Rosselin, Noemie Boissier, Irene Vignon-Clementel, Christian Hedberg, Fabian Geisler, Heribert Hofer, Peter Jansen, Stefan Hoehme, Dirk Drasdo, Jan G. Hengstler

Date Published: 26th Sep 2019

Publication Type: Journal

Abstract (Expand)

The intricate (micro)vascular architecture of the liver has not yet been fully unravelled. Although current models are often idealized simplifications of the complex anatomical reality, correct morphological information is instrumental for scientific and clinical purposes. Previously, both vascular corrosion casting (VCC) and immunohistochemistry (IHC) have been separately used to study the hepatic vasculature. Nevertheless, these techniques still face a number of challenges such as dual casting in VCC and limited imaging depths for IHC. We have optimized both techniques and combined their complementary strengths to develop a framework for multilevel reconstruction of the hepatic circulation in the rat. The VCC and micro-CT scanning protocol was improved by enabling dual casting, optimizing the contrast agent concentration, and adjusting the viscosity of the resin (PU4ii). IHC was improved with an optimized clearing technique (CUBIC) that extended the imaging depth for confocal microscopy more than five-fold. Using in-house developed software (DeLiver), the vascular network - in both VCC and IHC datasets - was automatically segmented and/or morphologically analysed. Our methodological framework allows 3D reconstruction and quantification of the hepatic circulation, ranging from the major blood vessels down to the intertwined and interconnected sinusoids. We believe that the presented framework will have value beyond studies of the liver, and will facilitate a better understanding of various parenchymal organs in general, in physiological and pathological circumstances.

Authors: Geert Peeters, Charlotte Debbaut, Wim Laleman, Adrian Friebel, Diethard Monbaliu, Ingrid Vander Elst, Jan R Detrez, Tim Vandecasteele, Tim Johann, Thomas De Schryver, Luc Van Hoorebeke, Kasper Favere, Jonas Verbeke, Dirk Drasdo, Stefan Hoehme, Patrick Segers, Pieter Cornillie, Winnok H De Vos

Date Published: 28th Dec 2016

Publication Type: Not specified

Powered by
(v.1.15.2)
Copyright © 2008 - 2024 The University of Manchester and HITS gGmbH