Evgeny Gladilin

Universität Heidelberg, Heidelburg, Baden-Württemberg, Germany

Are you Evgeny Gladilin?

Claim your profile

Publications (46)18.1 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: Mechanical properties of the cell nucleus play an important role in maintaining the integrity of the genome and controlling the cellular force balance. Irregularities in these properties have been related to disruption of a variety of force-dependent processes in the cell, such as migration, division, growth or differentiation. Characterizing mechanical properties of the cell nucleus in situ and relating these parameters to cellular phenotypes remain challenging tasks, as conventional micromanipulation techniques do not allow direct probing of intracellular structures. Here, we present a framework based on light microscopic imaging and automated mechanical modeling that enables characterization of the compressibility of the nuclear interior in situ. Based entirely on optical methods, our approach does not require application of destructive or contacting techniques and it enables measurements of a significantly larger number of cells. Compressibility, in this paper represented by Poisson's ratio ν, is determined by fitting a numerical model to experimentally observed time series of microscopic images of fluorescent cell nuclei in which bleached patterns are introduced. In a proof-of-principle study, this framework was applied to estimate ν in wild type cells and cells lacking important structural proteins of the nuclear envelope (LMNA(-/-)). Based on measurements of a large number of cells, our study revealed distinctive changes in compressibility of the nuclear interior between these two cell types. Our method allows an automated, contact-free estimation of mechanical properties of intracellular structures. Combined with knockdown and overexpression screens, it paves the way towards a high-throughput measurement of intracellular mechanical properties in functional phenotyping screens.
    Journal of biomechanics 09/2011; 44(15):2642-8. · 2.66 Impact Factor
  • Biophysical Journal 01/2011; 100(3). · 3.67 Impact Factor
  • E Gladilin, M Schulz, C Kappel, R Eils
    [show abstract] [hide abstract]
    ABSTRACT: Mechanical properties of the chromatin-bearing nucleus in normal and pathological cells are of general interest for epigenetics and medicine. Conventional techniques for quantitative measurements of material properties of cellular matter are based on application of controlled forces onto the cellular or nuclear boundary and do not allow probing intracellular structures that are not directly accessible for physical contact inside the living cell. In this work, we present a novel approach for contactless determination of the nuclear compressibility (i.e. the Poisson's ratio ν) in living cells by means of image- and model-based analysis of drug-induced cell deformation. The Poisson's ratio of the HeLa cell nucleus is determined from time-series of 3D images as a parameter of constitutive model that minimizes the dissimilarity between the numerically predicted and experimentally observed images.
    Journal of Microscopy 12/2010; 240(3):216-26. · 1.63 Impact Factor
  • Evgeny Gladilin, Roland Eils
    [show abstract] [hide abstract]
    ABSTRACT: Determination of constitutive properties of cells is important for quantitative description of cellular mechanics. Existing approaches to mechanical cell manipulation are based on experimental techniques that do not allow unsupervised analysis of large number of cells and/or probing of intracellular structures that are not directly exposed to external loads. Alternatively, mechanical behavior of cellular matter can be studied in time-series of microscopic images. In this work, we present an image- and model-based framework for determination of constitutive properties of living cells. Our experimental studies demonstrate application of this approach for quantitative analysis of cellular mechanics on the basis of image data assessed by different experimental techniques, including microplate stretching, optical stretching and contactless cellular deformation induction using cytoskeleton-disrupting drugs.
    Proc SPIE 03/2010;
  • E. Gladilin, R. Eils
    [show abstract] [hide abstract]
    ABSTRACT: Determination of constitutive properties plays a key role in quantitative description of cellular mechanics. Existing methods of experimental cell mechanics have one of the following drawbacks: they do not allow unsupervised analysis of large number of cells and/or probing of intracellular structures that are not directly exposed to boundary forces. Alternatively, mechanical behavior of cellular matter can be studied in time-series of microscopic images that capture successive deformation of cellular matter. In this work, we present an image- and model-based framework for determination of constitutive properties of living cells and subcellular structures. Our experimental studies demonstrate application of this approach for quantitative analysis of cellular mechanics on the basis of image data assessed by different experimental techniques, including microplate and optical stretchers as well as fully contactless procedures based on optical monitoring of drug-induced cellular deformation.
    01/2010;
  • Evgeny Gladilin, Roland Eils
    [show abstract] [hide abstract]
    ABSTRACT: Unsupervised analysis of time-series of live-cell images is one of the important tools of quantitative biology. Due to permanent cell motility or displacements of subcellular structures, microscopic images exhibit intrinsic non-uniform motion. In this article, we present a novel approach for detection of non-uniform multi-body motion which is based on combination of the Fourier-phase correlation with iterative probing target and background image regions similar to the strategy known from saccadic eye movements. We derive theoretical expressions that yield plausible explanation why this strategy turns out to be advantageous for tracking particular image pattern. Our experiments with synthetic and live-cell images demonstrate that the proposed approach is capable of accurately detecting non-uniform motion in synthetic and live-cell images.
    Proc SPIE 02/2009;
  • Evgeny Gladilin, Alexander Ivanov
    [show abstract] [hide abstract]
    ABSTRACT: Cranio-maxillofacial (CMF) surgery operations are associated with rearrangement of facial hard and soft tissues, leading to dramatic changes in facial geometry. Often, correction of the aesthetical patient's appearance is the primary objective of the surgical intervention. Due to the complexity of the facial anatomy and the biomechanical behaviour of soft tissues, the result of the surgical impact cannot always be predicted on the basis of surgeon's intuition and experience alone. Computational modelling of soft tissue outcome using individual tomographic data and consistent numerical simulation of soft tissue mechanics can provide valuable information for surgeons during the planning stage. In this article, we present a general framework for computer-assisted planning of CMF surgery interventions that is based on the reconstruction of patient's anatomy from 3D computer tomography images and finite element analysis of soft tissue deformations. Examples from our clinical case studies that deal with the solution of direct and inverse surgical problems (i.e. soft tissue prediction, inverse implant shape design) demonstrate that the developed approach provides a useful tool for accurate prediction and optimisation of aesthetic surgery outcome.
    Computer Methods in Biomechanics and Biomedical Engineering 12/2008; 12(3):305-18. · 1.39 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Topological analysis of cells and subcellular structures on the basis of image data, is one of the major trends in modern quantitative biology. However, due to the dynamic nature of cell biology, the optical appearance of different cells or even time-series of the same cell is undergoing substantial variations in shape and texture, which makes a comparison of shapes and distances across different cells a nontrivial task. In the absence of canonical invariances, a natural approach to the normalization of cells consists of spherical mapping, enabling the analysis of targeted regions in terms of canonical spherical coordinates, that is, radial distances and angles. In this work, we present a physically-based approach to spherical mapping, which has been applied for topological analysis of multichannel confocal laser scanning microscopy images of human fibroblast nuclei. Our experimental results demonstrate that spherical mapping of entire nuclear domains can automatically be obtained by inverting affine and elastic transformations, performed on a spherical finite element template mesh.
    Journal of Microscopy 07/2008; 231(Pt 1):105-14. · 1.63 Impact Factor
  • Evgeny Gladilin, Roland Eils
    [show abstract] [hide abstract]
    ABSTRACT: Linear elastic model widely applied for simulation of soft tissue deformations in biomedical imaging applications is basically limited to the range of small deformations and rotations. Thus, computation of large deformations and rotations using linear elastic approximation and its derivatives is associated with substantial error. More realistic modeling of mechanical behavior of soft tissue requires handling of different types of nonlinearities. This paper presents a framework for more accurate modeling of deformable structures based on the St. Venant-Kirchhoff law with the nonlinear Green-Lagrange strain tensor and variable material constants, which considers both material and geometric nonlinearities. We derive the governing partial differential equation of nonlinear elasticity, which represents consistent extension of the Lame-Navier PDE of linear elasticity, and describe two alternative numerical schemes for solving this nonlinear PDE via the Newton's and fixed point method, respectively. The results of our comparative studies demonstrate the advantages of nonlinear elastic model for accurate computing of large deformations and rotations in comparison to the linear elastic approximation.
    Proc SPIE 04/2008;
  • [show abstract] [hide abstract]
    ABSTRACT: Mechanical forces play an important role in many microbiological phenomena such as embryogenesis, regeneration, cell proliferation and differentiation. Micromanipulation of cells in a controlled environment is a widely used approach for understanding cellular responses with respect to external mechanical forces. While modern micromanipulation and imaging techniques provide useful optical information about the change of overall cell contours under the impact of external loads, the intrinsic mechanisms of energy and signal propagation throughout the cell structure are usually not accessible by direct observation. This work deals with the computational modelling and simulation of intracellular strain state of uniaxially stretched cells captured in a series of images. A nonlinear elastic finite element method on tetrahedral grids was applied for numerical analysis of inhomogeneous stretching of a rat embryonic fibroblast 52 (REF 52) using a simplified two-component model of a eukaryotic cell consisting of a stiffer nucleus surrounded by a softer cytoplasm. The difference between simulated and experimentally observed cell contours is used as a feedback criterion for iterative estimation of canonical material parameters of the two-component model such as stiffness and compressibility. Analysis of comparative simulations with varying material parameters shows that (i) the ratio between the stiffness of cell nucleus and cytoplasm determines intracellular strain distribution and (ii) large deformations result in increased stiffness and decreased compressibility of the cell cytoplasm. The proposed model is able to reproduce the evolution of the cellular shape over a sequence of observed deformations and provides complementary information for a better understanding of mechanical cell response.
    Physical Biology 07/2007; 4(2):104-13. · 2.62 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Investigation of 3D chromatin structure in interphase cell nuclei is important for the understanding of genome function. For a reconstruction of the 3D architecture of the human genome, systematic fluorescent in situ hybridization in combination with 3D confocal laser scanning microscopy is applied. The position of two or three genomic loci plus the overall nuclear shape were simultaneously recorded, resulting in statistical series of pair and triple loci combinations probed along the human chromosome 1 q-arm. For interpretation of statistical distributions of geometrical features (e.g. distances, angles, etc.) resulting from finite point sampling experiments, a Monte-Carlo-based approach to numerical computation of geometrical probability density functions (PDFs) for arbitrarily-shaped confined spatial domains is developed. Simulated PDFs are used as bench marks for evaluation of experimental PDFs and quantitative analysis of dimension and shape of probed 3D chromatin regions. Preliminary results of our numerical simulations show that the proposed numerical model is capable to reproduce experimental observations, and support the assumption of confined random folding of 3D chromatin fiber in interphase cell nuclei.
    05/2007: pages 104-118;
  • [show abstract] [hide abstract]
    ABSTRACT: Investigation of 3D chromatin structure in interphase cell nuclei is important for the understanding of genome function. For a reconstruction of the 3D architecture of the human genome, systematic fluorescent in situ hybridization in combination with 3D confocal laser scanning microscopy is applied. The position of two or three genomic loci plus the overall nuclear shape were simultaneously recorded, resulting in statistical series of pair and triple loci combinations probed along the human chromosome 1 q-arm. For interpretation of statistical distributions of geometrical features (e.g. distances, angles, etc.) resulting from finite point sampling experiments, a Monte-Carlo-based approach to numerical computation of geometrical probability density functions (PDFs) for arbitrarily-shaped confined spatial domains is developed. Simulated PDFs are used as bench marks for evaluation of experimental PDFs and quantitative analysis of dimension and shape of probed 3D chromatin regions. Preliminary results of our numerical simulations show that the proposed numerical model is capable to reproduce experimental observations, and support the assumption of confined random folding of 3D chromatin fiber in interphase cell nuclei
    Computational Intelligence and Bioinformatics and Computational Biology, 2007. CIBCB '07. IEEE Symposium on; 05/2007
  • Evgeny Gladilin, Constantin Kappel, Roland Eils
    [show abstract] [hide abstract]
    ABSTRACT: High-throughput live-cell imaging is one of the important tools for the investigation of cellular structure and functions in modern experimental biology. Automatic processing of time series of microscopic images is hampered by a number of technical and natural factors such as permanent movements of cells in the optical field, alteration of optical cell appearance and high level of noise. Detection and compensation of global motion of groups of cells or relocation of a single cell within a dynamical multi-cell environment is the first indispensable step in the image analysis chain. This article presents an approach for detection of global image motion and single cell tracking in time series of confocal laser scanning microscopy images using an extended Fourier-phase correlation technique, which allows for analysis of non-uniform multi-body motion in partially-similar images. Our experimental results have shown that the developed approach is capable to perform cell tracking and registration in dynamical and noisy scenes, and provides a robust tool for fully-automatic registration of time-series of microscopic images.
    Proc SPIE 03/2007;
  • Source
    Evgeny Gladilin, Karl Rohr, Roland Eils
    [show abstract] [hide abstract]
    ABSTRACT: Non-physical techniques for elastic image registration such as difierent spline-based optimization methods are often applied in biomedi- cal applications for image normalization w.r.t. non-rigid transformations. Since mechanical properties of biological structures to be registered are usually unknown, a "ground truth" validation of the results of image registration is not possible. This article presents a framework for the val- idation of elastic image registration techniques by a direct comparison of displacement flelds vs analytical or numerical reference solutions of customizable boundary value problems. The proposed procedure enables an easy handling of material parameters, domain shapes and boundary conditions, and provides a ∞exible benchmark-tool for quantitative vali- dation of elastic image registration algorithms.
    Bildverarbeitung für die Medizin 2007, Algorithmen, Systeme, Anwendungen, Proceedings des Workshops vom 25.-27. März 2007 in München; 01/2007
  • Bioinformatics Research and Development, First International Conference, BIRD 2007, Berlin, Germany, March 12-14, 2007, Proceedings; 01/2007
  • Vladimir Pekar, Evgeny Gladilin, Karl Rohr
    [show abstract] [hide abstract]
    ABSTRACT: Deformable registration is an important application in medical image analysis and processing. We propose a physics-based parametric approach for deformable image registration, where non-rigid transformations are computed using an irregular grid of control points distributed within the image domain. The image is modelled as a three-dimensional (3D) homogeneous infinite elastic medium. It is assumed that a Gaussian-shaped force is applied at every control point, where the strengths, directions and influence areas of the forces as well as the positions of the control points are considered as free parameters whose optimization leads to maximization of the similarity measure between the images to be registered. For optimization, a computationally efficient Levenberg-Marquardt method is used. The proposed approach has certain advantages over traditional landmark-based methods or the registration methods based on regular grids, for example B-splines, since comparable results can be achieved by using less control points. Experimental results with 3D clinical images demonstrate that our method is capable of successfully coping with complex registration tasks.
    Physics in Medicine and Biology 02/2006; 51(2):361-77. · 2.70 Impact Factor
  • Source
    Evgeny Gladilin, Alexander Ivanov, Vitaly Roginsky
    [show abstract] [hide abstract]
    ABSTRACT: In dieser Arbeit beschreiben wir eine physikalisch basierte Methode zur Formoptimierung individueller Implantate in der craniofazialen Chirurgie, mit deren Hilfe eine ästhetische Korrektur des Weichgewebes erzielt werden kann. Im Unterschied zur Weichgewebevorhersage bei knochenumstellenden Operationen impliziert die Frage nach einer optimalen Implantatform ein inverses Problem der Strukturmechanik, bei dem die einer vorgegebenen Deformation zugrunde liegenden Randbedingungen bestimmt werden sollen. Wir präsentieren einen allgemeinen Finite-Elemente-basierten Ansatz zur numerischen Lösung inverser Randwertprobleme für das optimale Implantatdesign in der craniofazialen Chirurgie und Ergebnisse einer klinischen Studie zur implantatbasierten ästhetischen Korrektur einer bilateralen asymmetrischen Anophtalmie.
    Bildverarbeitung für die Medizin 2006, Algorithmen, Systeme, Anwendungen, Proceedings des Workshops vom 19. - 21. März 2006 in Hamburg; 01/2006
  • Source
    Evgeny Gladilin, Roland Eils, Karl Rohr
    [show abstract] [hide abstract]
    ABSTRACT: Die Auswertung zellulärer Mikroskopieaufnahmen ist erheblich erschwert durch eine große Variabilität in der optischen Erscheinung unterschiedlicher Zellen oder in Zeitreihen derselben Zelle. Bedingt durch die kontinuierliches Zellwachstum und Deformationen unter der Einwirkung äußerer Kräfte unterliegen sowohl die Textur als auch die Form zellulärer Strukturen erheblichen Schwankungen. Da es i.a. schwierig ist, eindeutige Strukturkorrespondenzen zwischen zwei unterschiedlichen Zellaufnahmen zu finden, bietet sich eine topologieerhaltende Abbildung der Zellaufnahmen auf eine geeignete Referenzgeometrie zur Formnormalisierung an. In dieser Arbeit präsentieren wir eine neue Methode zur elastischen Kugelabbildung drei-dimensionaler Objekte für die Formnormalisierung von konfokalen Lasermikroskopieaufnahmen humaner Fibroblastzellkerne. Der entwickelte Ansatz ermöglicht die topologische Analyse markierter Genbereiche im Zellkern mittels normalisierter radialer Abstände.
    Bildverarbeitung für die Medizin 2006, Algorithmen, Systeme, Anwendungen, Proceedings des Workshops vom 19. - 21. März 2006 in Hamburg; 01/2006
  • Source
    E Gladilin, V Pekar, K Rohr, H S Stiehl
    [show abstract] [hide abstract]
    ABSTRACT: The aim of medical image registration is to bring different images into the best possible spatial correspondence in order to obtain complementary information for clinical applications. When using physically-based techniques for image registration the transformation of images is typically obtained as the solution of partial differential equations of continuum mechanics. Because of the complexity of real boundary conditions, these equations can usually be solved with the help of numerical techniques only. One standard numerical method is the boundary element method (BEM) which allows to compute the solution exclusively through boundary integration. This paper investigates the applicability of BEM for registration of medical images and quantitatively assesses its advantages and disadvantages in comparison to the previously used finite element method (FEM). q 2006 Elsevier B.V. All rights reserved.
    Image Vision Comput. 01/2006; 24.
  • [show abstract] [hide abstract]
    ABSTRACT: Topological analysis of cells and subcellular structures on the basis of image data is one of the major trends in modern quantitative biology. However, due to the dynamic nature of cell biology, the optical appearance of different cells or even time series of the same cell is undergoing substantial variations in shape and texture which makes the analysis of image data a non-trivial task. In the absence of canonical invariances, a natural approach to the normalization of cell images consists in dimension reduction of the 3D problem by means of spherical mapping which enables the analysis of targeted regions in terms of radial distances. In this work, we present a finite element template-based approach for physically-base spherical mapping which has been applied for topological analysis of confocal laser scanning microscopy images of cell nuclei.
    Proc SPIE 01/2006; 6144:1557-1566.

Publication Stats

184 Citations
102 Downloads
1k Views
18.10 Total Impact Points

Institutions

  • 2006–2011
    • Universität Heidelberg
      Heidelburg, Baden-Württemberg, Germany
  • 2007–2008
    • German Cancer Research Center
      • Division of Theoretical Bioinformatics
      Heidelburg, Baden-Württemberg, Germany
  • 2001–2004
    • Zuse-Institut Berlin
      • Department of Visualization and Data Analysis
      Berlín, Berlin, Germany