Thursday, 22 March 2018

Olivier DEBEIR

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tel.:++32.2.650.22.93 fax:++32.2.650.22.98

ULB - LISA CP165/57

50, Av. F.Roosevelt

1050 Bruxelles



Professor for the following course:

  • BIME-H-407 Introduction to medical imaging and to optical microscopy


  • PROJ-H-416 Medical imaging project
  • PROJ-H-500 Ethique et questions actuelles d'ingénierie médicale


  • Deep convolutional networks and machine learning
    • Thermal image superresolution
    • People detection in video images
    • Microscopy image analysis
    • Automatic document analysis
  • Augmented reality applied to neuropathic pain treatment

Other research topics

Open source

Contributor to skimage

Pyrankfilter is a python module that implements rank filters on 2D images (numpy array)

IVCtrack is a python framework that implements cell tracking algorithm based on mean-shift kernels as described in:

The tracking algorithm is also implemented in the iTrack4U software which is provided by Fabrice P. Cordelières here.



T. Roumeguere, F. Legrand, E. El Rassy, M. Idrissi Kaitouni, S. Albisinni, A. Rousseau, M. Vanhaeverbeek, S. Rorive, C. Decaestecker, O. Debeir, K. Zouaoui Boudjeltia, F. Aoun,
A prospective clinical study of the implications of IL-8 in the diagnosis, aggressiveness and prognosis of prostate cancer.
Future science OA, Vol. 4, 2, pp. FSO266, 2018
Bibtex : info:hdl:2013/266399
Note : Language of publication: en
Abstract : We evaluated the relationship between IL-8 and prostate cancer (PCa) with emphasis on diagnosis, aggressiveness and prognosis.

Y. Van Eycke, J. Allard, I. Salmon, O. Debeir, C. Decaestecker,
Image processing in digital pathology: an opportunity to solve inter-batch variability of immunohistochemical staining
Scientific Reports, Vol. 7, 2017
Bibtex : info:hdl:2013/246463
Note : SCOPUS: ar.j
Abstract : Immunohistochemistry (IHC) is a widely used technique in pathology to evidence protein expression in tissue samples. However, this staining technique is known for presenting inter-batch variations. Whole slide imaging in digital pathology offers a possibility to overcome this problem by means of image normalisation techniques. In the present paper we propose a methodology to objectively evaluate the need of image normalisation and to identify the best way to perform it. This methodology uses tissue microarray (TMA) materials and statistical analyses to evidence the possible variations occurring at colour and intensity levels as well as to evaluate the efficiency of image normalisation methods in correcting them. We applied our methodology to test different methods of image normalisation based on blind colour deconvolution that we adapted for IHC staining. These tests were carried out for different IHC experiments on different tissue types and targeting different proteins with different subcellular localisations. Our methodology enabled us to establish and to validate inter-batch normalization transforms which correct the non-relevant IHC staining variations. The normalised image series were then processed to extract coherent quantitative features characterising the IHC staining patterns.

Matthias Dorfer, Tom Kazmar, Matej Smid, Sanchit Sing, Julia Kneiss, Simone Keller, Olivier Debeir, Birgit Luber, Julian Mattes,
Associating approximate paths and temporal sequences of noisy detections: Application to the recovery of spatio-temporal cancer cell trajectories
Medical Image Analysis, Vol. 27, pp. 72--83, Jan 2016
Bibtex : dorfer2016

P. Masuzzo, L. Martens, . 2014 Cell Migration Workshop Participants, C. Ampe, K. Anderson, J. Barry, O. De Wever, O. Debeir, C. Decaestecker, H. Dolznig, P. Friedl, C. Gaggioli, B. Geiger, I. Goldberg, E. Horn, R. Horwitz, Z. Kam, S. Le Dévédec, D. Vignjevic, J. Moore, J. Olivo-Marin, E. Sahai, S. Sansone, V. Sanz-Moreno, S. Str{\"o}mblad, J. Swedlow, J. Textor, M. Van Troys, R. Zantl,
An open data ecosystem for cell migration research.
Trends in cell biology, Vol. 25, 2, pp. 55-58, 2015
Bibtex : info:hdl:2013/197899
Note : SCOPUS: no.j
Abstract : Cell migration research has recently become both a high content and a high throughput field thanks to technological, computational, and methodological advances. Simultaneously, however, urgent bioinformatics needs regarding data management, standardization, and dissemination have emerged. To address these concerns, we propose to establish an open data ecosystem for cell migration research.

X. Moles Lopez, E. D'Andrea, P. Barbot, A. Bridoux, S. Rorive, I. Salmon, O. Debeir, C. Decaestecker,
An Automated Blur Detection Method for Histological Whole Slide Imaging
PloS one, Vol. 8, 12, 2013
Bibtex : info:hdl:2013/152899
Note : SCOPUS: ar.j
Abstract : Whole slide scanners are novel devices that enable high-resolution imaging of an entire histological slide. Furthermore, the imaging is achieved in only a few minutes, which enables image rendering of large-scale studies involving multiple immunohistochemistry biomarkers. Although whole slide imaging has improved considerably, locally poor focusing causes blurred regions of the image. These artifacts may strongly affect the quality of subsequent analyses, making a slide review process mandatory. This tedious and time-consuming task requires the scanner operator to carefully assess the virtual slide and to manually select new focus points. We propose a statistical learning method that provides early image quality feedback and automatically identifies regions of the image that require additional focus points.

D. Tondeleir, A. Lambrechts, M. Mueller, V. Jonckheere, T. Doll, D. Vandamme, K. Bakkali, D. Waterschoot, M. Lemaistre, O. Debeir, C. Decaestecker, B. Hinz, A. Staes, E. Timmerman, N. Colaert, K. Gevaert, J. Vanderkerckove, C. Ampe,
Cells lacking β-actin are genetically reprogrammed and maintain conditional migratory capacity
Molecular & cellular proteomics, Vol. 11, 8, pp. 255-71, 2012
Bibtex : info:hdl:2013/113768
Note : SCOPUS: ar.j
Abstract : Vertebrate nonmuscle cells express two actin isoforms: cytoplasmic β- and γ-actin. Because of the presence and localized translation of β-actin at the leading edge, this isoform is generally accepted to specifically generate protrusive forces for cell migration. Recent evidence also implicates β-actin in gene regulation. Cell migration without β-actin has remained unstudied until recently and it is unclear whether other actin isoforms can compensate for this cytoplasmic function and/or for its nuclear role. Primary mouse embryonic fibroblasts lacking β-actin display compensatory expression of other actin isoforms. Consistent with this preservation of polymerization capacity, β-actin knockout cells have unchanged lamellipodial protrusion rates despite a severe migration defect. To solve this paradox we applied quantitative proteomics revealing a broad genetic reprogramming of β-actin knockout cells. This also explains why reintroducing β-actin in knockout cells does not restore the affected cell migration. Pathway analysis suggested increased Rho-ROCK signaling, consistent with observed phenotypic changes. We therefore developed and tested a model explaining the phenotypes in β-actin knockout cells based on increased Rho-ROCK signaling and increased TGFβ production resulting in increased adhesion and contractility in the knockout cells. Inhibiting ROCK or myosin restores migration of β-actin knockout cells indicating that other actins compensate for β-actin in this process. Consequently, isoactins act redundantly in providing propulsive forces for cell migration, but β-actin has a unique nuclear function, regulating expression on transcriptional and post-translational levels, thereby preventing myogenic differentiation. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.

X. Moles Lopez, O. Debeir, C. Maris, S. Rorive, I. Roland, M. Saerens, I. Salmon, C. Decaestecker,
Clustering methods applied in the detection of Ki67 hot-spots in whole tumor slide images: An efficient way to characterize heterogeneous tissue-based biomarkers.
Cytometry. Part A, Vol. 81, 9, pp. 765-775, 2012
Bibtex : info:hdl:2013/127791
Note : Journal Article
Abstract : Whole-slide scanners allow the digitization of an entire histological slide at very high resolution. This new acquisition technique opens a wide range of possibilities for addressing challenging image analysis problems, including the identification of tissue-based biomarkers. In this study, we use whole-slide scanner technology for imaging the proliferating activity patterns in tumor slides based on Ki67 immunohistochemistry. Faced with large images, pathologists require tools that can help them identify tumor regions that exhibit high proliferating activity, called "hot-spots" (HSs). Pathologists need tools that can quantitatively characterize these HS patterns. To respond to this clinical need, the present study investigates various clustering methods with the aim of identifying Ki67 HSs in whole tumor slide images. This task requires a method capable of identifying an unknown number of clusters, which may be highly variable in terms of shape, size, and density. We developed a hybrid clustering method, referred to as Seedlink. Compared to manual HS selections by three pathologists, we show that Seedlink provides an efficient way of detecting Ki67 HSs and improves the agreement among pathologists when identifying HSs. © 2012 International Society for Advancement of Cytometry.

I. Adanja, V. Megalizzi, O. Debeir, C. Decaestecker,
A New Method to Address Unmet Needs for Extracting Individual Cell Migration Features from a Large Number of Cells Embedded in 3D Volumes
PloS one, Vol. 6, 7, 2011
Bibtex : info:hdl:2013/94206
Note : SCOPUS: ar.j
Abstract : Background: In vitro cell observation has been widely used by biologists and pharmacologists for screening molecule-induced effects on cancer cells. Computer-assisted time-lapse microscopy enables automated live cell imaging in vitro, enabling cell behavior characterization through image analysis, in particular regarding cell migration. In this context, 3D cell assays in transparent matrix gels have been developed to provide more realistic in vitro 3D environments for monitoring cell migration (fundamentally different from cell motility behavior observed in 2D), which is related to the spread of cancer and metastases. Methodology/Principal Findings: In this paper we propose an improved automated tracking method that is designed to robustly and individually follow a large number of unlabeled cells observed under phase-contrast microscopy in 3D gels. The method automatically detects and tracks individual cells across a sequence of acquired volumes, using a template matching filtering method that in turn allows for robust detection and mean-shift tracking. The robustness of the method results from detecting and managing the cases where two cell (mean-shift) trackers converge to the same point. The resulting trajectories quantify cell migration through statistical analysis of 3D trajectory descriptors. We manually validated the method and observed efficient cell detection and a low tracking error rate (6\%). We also applied the method in a real biological experiment where the pro-migratory effects of hyaluronic acid (HA) were analyzed on brain cancer cells. Using collagen gels with increased HA proportions, we were able to evidence a dose-response effect on cell migration abilities. Conclusions/Significance: The developed method enables biomedical researchers to automatically and robustly quantify the pro- or anti-migratory effects of different experimental conditions on unlabeled cell cultures in a 3D environment. © 2011 Adanja et al.

I. Adanja, O. Debeir, V. Megalizzi, R. Kiss, N. Warzée, C. Decaestecker,
Automated tracking of unmarked cells migrating in three-dimensional matrices applied to anti-cancer drug screening.
Experimental cell research, Vol. 316, 2, pp. 181-193, 2010
Bibtex : info:hdl:2013/52535
Note : Journal Article
Abstract : In oncology, combating the spread of tumor cells is a clinical need which currently remains unsatisfied. Identifying anti-migratory compounds usually requires in vitro screening of a large number of molecules. Efficient and realistic (i.e., preferably 3D) in vitro tests are thus required in order to quantify the anti-migratory effects of anti-cancer drugs. To remain compatible with high-throughput screening, we focus on assays where unlabeled cells are migrating in 3D transparent gels and are observed under time-lapse 3D phase-contrast microscopy. In this context, we present a method for automatically tracking cells that combines a template matching preprocessing step with a mean-shift process. The preprocessing step consists in performing a correlation of a cell template with each observed volume in order to provide a phase-contrast artifact-free volume where the cells appear as correlation peaks surrounded by smooth gradients. This transformation enables the cells to be efficiently tracked by a mean-shift process. Robustness and efficiency of this approach are qualitatively and quantitatively shown in various experiments. Finally, we successfully applied our method to the quantitative characterization of the anti-migratory impact of cytochalasin-D on cancer cells. In conclusion, our method can efficiently be used for drug screening aiming to evidence drug-induced effects on cell migration in 3D transparent environments, such as matrix gels.

N. Wauthoz, P. Deleuze, J. Hecq, I. Roland, S. Saussez, I. Adanja, O. Debeir, C. Decaestecker, V. Mathieu, R. Kiss, K. Amighi,
In vivo assessment of temozolomide local delivery for lung cancer inhalation therapy.
European journal of pharmaceutical sciences, Vol. 39, pp. 402-411, 2010
Bibtex : info:hdl:2013/51846
Abstract : The aim of this study was to compare the efficacy of local drug delivery by inhalation to intravenous delivery in a B16F10 melanoma metastatic lung model. Temozolomide was formulated as a suspension, which was elaborated and evaluated in terms of particle size, shape and agglomeration. An endotracheal administration device was used to aerosolise the suspension. This mode of delivery was evaluated at different temozolomide concentrations and was optimized for the uniformity of delivered dose, the droplet size distribution and the distribution of droplets in vivo. Of the particles in the stabilised suspension, 79\% were compatible with the human respirable size range, and this formulation retained 100\% in vitro anticancer activity as compared to temozolomide alone in three distinct cancer cell lines. The pulmonary delivery device provided good reproducibility in terms of both the dose delivered and the droplet size distribution. Most of the lung tissues that were exposed to aerosol droplets contained the particles, as revealed by fluorescent microscopy techniques. The global in vivo antitumour activity of the inhaled temozolomide provided a median survival period similar to that for intravenous temozolomide delivery, and three out of 27 mice (11\%) survived with almost complete eradication of the lung tumours. The present study thus shows that inhalation of a simple liquid formulation is well tolerated and active against a very biologically aggressive mouse melanoma pulmonary pseudo-metastatic model. This inhalation delivery could be used to deliver other types of anticancer drugs.

C. Decaestecker, X. Moles Lopez, N. D'Haene, I. Roland, S. Guendouz, C. Duponchelle, A. Berton, O. Debeir, I. Salmon,
Requirements for the valid quantification of immunostains on tissue microarray materials using image analysis.
Proteomics, Vol. 9, 19, pp. 4478-4494, 2009
Bibtex : info:hdl:2013/52938
Note : Journal Article
Abstract : Antibody-based proteomics applied to tissue microarray (TMA) technology provides a very efficient means of visualizing and locating antigen expression in large collections of normal and pathological tissue samples. To characterize antigen expression on TMAs, the use of image analysis methods avoids the effects of human subjectivity evidenced in manual microscopical analysis. Thus, these methods have the potential to significantly enhance both precision and reproducibility. Although some commercial systems include tools for the quantitative evaluation of immunohistochemistry-stained images, there exists no clear agreement on best practices to allow for correct and reproducible quantification results. Our study focuses on practical aspects regarding (i) image acquisition (ii) segmentation of staining and counterstaining areas and (iii) extraction of quantitative features. We illustrate our findings using a commercial system to quantify different immunohistochemistry markers targeting proteins with different expression patterns (cytoplasmic, nuclear or membranous) in colon cancer or brain tumor TMAs. Our investigations led us to identify several steps that we consider essential for standardizing computer-assisted immunostaining quantification experiments. In addition, we propose a data normalization process based on reference materials to be able to compare measurements between studies involving different TMAs. In conclusion, we recommend certain critical prerequisites that commercial or in-house systems should satisfy in order to permit valid immunostaining quantification.

V. Megalizzi, C. Decaestecker, O. Debeir, S. Spiegl-Kreinecker, W. Berger, F. Lefranc, R. Kast, R. Kiss,
Screening of anti-glioma effects induced by sigma-1 receptor ligands: potential new use for old anti-psychiatric medicines.
European journal of cancer, Vol. 45, 16, pp. 2893-2905, 2009
Bibtex : info:hdl:2013/51188
Note : Journal Article
Abstract : The prognosis of glioblastoma (GBM) remains poor. Diffuse invasion of distant brain tissue by migrating cells from the primary tumour mass has already occurred at time of diagnosis. Anti-cancer effects of a selective sigma-1 agonist, 4-(N-benzylpiperidin-4-yl)-4-iodobenzamide (4-IBP), in glioblastoma were shown previously, leading to the present work where the effects on glioblastoma cells of 17 agonists or antagonists of sigma-1 receptors were studied, including currently marketed drugs fluvoxamine, dextromethorphan, donepezil, memantine and haloperidol. We first showed that established GBM cell lines, primary cultures and surgical specimens express sigma-1 receptors. In vitro analyses then focused on anti-proliferation and anti-migratory effects on human glioblastoma cell lines using quantitative videomicroscopy analyses. These cell monitoring assays revealed specific impacts on the mitotic cell process. Using an aggressive glioma model orthotopically grafted into the brains of immunocompromised mice, we showed that combining donepezil and temozolomide gave additive benefit in terms of long survivors as compared to temozolomide or donepezil alone. Clinical study is planned if further rodent dose-ranging studies of donepezil with temozolomide continue to show evidence of benefit in this model.

S. Leyman, M. Sidani, L. Ritsma, D. Waterschoot, R. Eddy, D. Dewitte, O. Debeir, C. Decaestecker, J. Vandekerckhove, J. van Rheenen, C. Ampe, J. Condeelis, M. Van Troys,
Unbalancing the phosphatidylinositol-4,5-bisphosphate-cofilin interaction impairs cell steering.
Molecular biology of the cell, Vol. 20, 21, pp. 4509-4523, 2009
Bibtex : info:hdl:2013/52937
Note : Journal Article
Abstract : Cofilin is a key player in actin dynamics during cell migration. Its activity is regulated by (de)phosphorylation, pH, and binding to phosphatidylinositol-4,5-bisphosphate [PI(4,5)P(2)]. Here, we here use a human cofilin-1 (D122K) mutant with increased binding affinity for PI(4,5)P(2) and slower release from the plasma membrane to study the role of the PI(4,5)P(2)-cofilin interaction in migrating cells. In fibroblasts in a background of endogenous cofilin, D122K cofilin expression negatively affects cell turning frequency. In carcinoma cells with down-regulated endogenous cofilin, D122K cofilin neither rescues the drastic morphological defects nor restores the effects in cell turning capacity, unlike what has been reported for wild-type cofilin. In cofilin knockdown cells, D122K cofilin expression promotes outgrowth of an existing lamellipod in response to epidermal growth factor (EGF) but does not result in initiation of new lamellipodia. This indicates that, next to phospho- and pH regulation, the normal release kinetics of cofilin from PI(4,5)P(2) is crucial as a local activation switch for lamellipodia initiation and as a signal for migrating cells to change direction in response to external stimuli. Our results demonstrate that the PI(4,5)P(2) regulatory mechanism, that is governed by EGF-dependent phospholipase C activation, is a determinant for the spatial and temporal control of cofilin activation required for lamellipodia initiation.

M. Le Mercier, F. Lefranc, T. Mijatovic, O. Debeir, B. Haibe-Kains, G. Bontempi, C. Decaestecker, R. Kiss, V. Mathieu,
Evidence of galectin-1 involvement in glioma chemoresistance.
Toxicology and applied pharmacology, Vol. 229, 2, pp. 172-183, 2008
Bibtex : info:hdl:2013/51198
Note : Journal Article
Abstract : Glioblastomas (GBMs) are resistant to apoptosis but less so to autophagy; a fact that may at least partly explain the therapeutic benefits of the pro-autophagic drug temozolomide in the treatment of GBM patients. Galectin-1 (Gal1) whose expression is stimulated by hypoxia is a potent modulator of GBM cell migration and a pro-angiogenic molecule. Hypoxia is also known to confer cancer cells with resistance to chemotherapy and radiotherapy and to modulate the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. The present study investigates whether decreasing Gal1 expression (by means of a siRNA approach) in human Hs683 GBM cells increases their sensitivity to pro-autophagic or pro-apoptotic drugs. The data reveal that temozolomide, the standard treatment for glioma patients, increases Gal1 expression in Hs683 cells both in vitro and in vivo. However, reducing Gal1 expression in these cells by siRNA increases the anti-tumor effects of various chemotherapeutic agents, in particular temozolomide both in vitro and in vivo. This decrease in Gal1 expression in Hs683 cells does not induce apoptotic or autophagic features, but is found to modulate p53 transcriptional activity and decrease p53-targeted gene expression including DDIT3/GADD153/CHOP, DUSP5 ATF3 and GADD45A. The decrease in Gal1 expression also impairs the expression levels of seven other genes implicated in chemoresistance: ORP150, HERP, GRP78/Bip, TRA1, BNIP3L, GADD45B and CYR61, some of which are located in the ER and whose expression is also known to be modified by hypoxia. This novel facet of Gal1 involvement in glioblastoma biology may be amenable to therapeutic manipulation.

S. Rorive, A. Berton, N. D'Haene, C. Takacs, O. Debeir, C. Decaestecker, I. Salmon,
Matrix metalloproteinase-9 interplays with the IGFBP2-IGFII complex to promote cell growth and motility in astrocytomas.
GLIA, Vol. 56, 15, pp. 1679-1690, 2008
Bibtex : info:hdl:2013/52950
Note : Journal Article
Abstract : Insulin-like growth factor II (IGFII) acts as a potent mitogen for several tumor types and has been reported to positively influence astrocytoma cell growth and motility. In the central nervous system, IGFII bioavailability is mainly modulated by insulin-like growth factor binding protein 2 (IGFBP2), which sequestrates IGFII and therefore prevents its interaction with the type-1 IGF receptor (IGF-IR). Proteolysis of IGFBP2 is the predominant mechanism recognized to reduce the binding affinity of IGFBP2 for IGFII, thus favoring dissociation of IGFII from the IGFBP2-IGFII complex. It is known that certain proteases involved in astrocytoma malignancy, such as matrix metalloproteinase-7 (MMP-7), plasmin, and cathepsin D, are able to proteolyze IGFBP2 in vitro. The present study aims to investigate whether other proteases expressed by astrocytomas, specifically MMP-2, MMP-9, and membrane-type 1 matrix metalloprotease (MT1-MMP), are able to proteolyze the IGFBP2-IGFII complex. Our results show the following: (i) MMP-9 proteolyzes the IGFBP2-IGFII complex in vitro, while MMP-2 and MT1-MMP do not; (ii) this MMP-9-induced IGFBP2-IGFII complex proteolysis releases free IGFII, which contributes to enhance the motility and the growth of LN229 astrocytoma cells. Furthermore, this study also highlights that the formation of the IGFBP2-IGFII complex inhibits IGFBP2's cell motility promoting effect by reducing the pool of free IGFBP2. In conclusion, MMP-9-induced IGFBP2 proteolysis may be regarded as an important post-translational event involved in astrocytoma aggressiveness. These new findings support drug targeting of MMP-9 as an interesting approach in the treatment of astrocytoma.

O. Debeir, V. Megalizzi, N. Warzée, R. Kiss, C. Decaestecker,
Videomicroscopic extraction of specific information on cell proliferation and migration in vitro.
Experimental cell research, Vol. 314, 16, pp. 2985-2998, 2008
Bibtex : info:hdl:2013/52065
Note : Journal Article
Abstract : In vitro cell imaging is a useful exploratory tool for cell behavior monitoring with a wide range of applications in cell biology and pharmacology. Combined with appropriate image analysis techniques, this approach has been shown to provide useful information on the detection and dynamic analysis of cell events. In this context, numerous efforts have been focused on cell migration analysis. In contrast, the cell division process has been the subject of fewer investigations. The present work focuses on this latter aspect and shows that, in complement to cell migration data, interesting information related to cell division can be extracted from phase-contrast time-lapse image series, in particular cell division duration, which is not provided by standard cell assays using endpoint analyses. We illustrate our approach by analyzing the effects induced by two sigma-1 receptor ligands (haloperidol and 4-IBP) on the behavior of two glioma cell lines using two in vitro cell models, i.e., the low-density individual cell model and the high-density scratch wound model. This illustration also shows that the data provided by our approach are suggestive as to the mechanism of action of compounds, and are thus capable of informing the appropriate selection of further time-consuming and more expensive biological evaluations required to elucidate a mechanism.

V. Megalizzi, V. Mathieu, T. Mijatovic, P. Gailly, O. Debeir, N. De Nève, M. Van Damme, G. Bontempi, B. Haibe-Kains, C. Decaestecker, Y. Kondo, R. Kiss, F. Lefranc,
4-IBP, a sigma1 receptor agonist, decreases the migration of human cancer cells, including glioblastoma cells, in vitro and sensitizes them in vitro and in vivo to cytotoxic insults of proapoptotic and proautophagic drugs.
Neoplasia (New York, N.Y.), Vol. 9, 5, pp. 358-369, 2007
Bibtex : info:hdl:2013/51212
Note : Journal Article
Abstract : Although the molecular function of sigma receptors has not been fully defined and the natural ligand(s) is still not known, there is increasing evidence that these receptors and their ligands might play a significant role in cancer biology. 4-(N-benzylpiperidin-4-yl)-4-iodobenzamide (4-IBP), a selective sigma1 agonist, has been used to investigate whether this compound is able to modify: 1) in vitro the migration and proliferation of human cancer cells; 2) in vitro the sensitivity of human glioblastoma cells to cytotoxic drugs; and 3) in vivo in orthotopic glioblastoma and non-small cell lung carcinoma (NSCLC) models the survival of mice co-administered cytotoxic agents. 4-IBP has revealed weak antiproliferative effects on human U373-MG glioblastoma and C32 melanoma cells but induced marked concentration-dependent decreases in the growth of human A549 NSCLC and PC3 prostate cancer cells. The compound was also significantly antimigratory in all four cancer cell lines. This may result, at least in U373-MG cells, from modifications to the actin cytoskeleton. 4-IBP modified the sensitivity of U373-MG cells in vitro to proapoptotic lomustin and proautophagic temozolomide, and markedly decreased the expression of two proteins involved in drug resistance: glucosylceramide synthase and Rho guanine nucleotide dissociation inhibitor. In vivo, 4-IBP increased the antitumor effects of temozolomide and irinotecan in immunodeficient mice that were orthotopically grafted with invasive cancer cells.

C. Decaestecker, O. Debeir, P. Van Ham, R. Kiss,
Can anti-migratory drugs be screened in vitro? A review of 2D and 3D assays for the quantitative analysis of cell migration.
Medicinal research reviews, Vol. 27, 2, pp. 149-176, 2007
Bibtex : info:hdl:2013/51824
Note : Journal Article
Abstract : The aim of the present review is to detail and analyze the pros and cons of in vitro tests available to quantify the anti-migratory effects of anti-cancer drugs for their eventual use in combating the dispersal of tumor cells, a clinical need which currently remains unsatisfied. We therefore briefly sum up why anti-migratory drugs constitute a promising approach in oncology while at the same time emphasizing that migrating cancer cells are resistant to apoptosis. To analyze the pros and cons of the various in vitro tests under review we also briefly sum up the molecular and cellular stages of cancer cell migration, an approach that enables us to argue both that no single in vitro test is sufficient to characterize the anti-migratory potential of a drug and that standardization is needed for the efficient quantitative analysis of cell locomotion in a 3D environment. Before concluding our review we devote the final two parts (i) to the description of new prototypes which, in the near future, could enter the screening process with a view to identifying novel anti-migratory compounds, and (ii) to the anti-migratory compounds currently developed against cancer, with particular emphasis on how these compounds were selected before entering the clinical trial phase.

C. Hayot, O. Debeir, P. Van Ham, M. Van Damme, R. Kiss, C. Decaestecker,
Characterization of the activities of actin-affecting drugs on tumor cell migration.
Toxicology and applied pharmacology, Vol. 211, 1, pp. 30-40, 2006
Bibtex : info:hdl:2013/52107
Note : Comparative Study
Abstract : Metastases kill 90\% of cancer patients. It is thus a major challenge in cancer therapy to inhibit the spreading of tumor cells from primary tumor sites to those particular organs where metastases are likely to occur. Whereas the actin cytoskeleton is a key component involved in cell migration, agents targeting actin dynamics have been relatively poorly investigated. Consequently, valuable in vitro pharmacological tools are needed to selectively identify this type of agent. In response to the absence of any standardized process, the present work aims to develop a multi-assay strategy for screening actin-affecting drugs with anti-migratory potentials. To validate our approach, we used two cancer cell lines (MCF7 and A549) and three actin-affecting drugs (cytochalasin D, latrunculin A, and jasplakinolide). We quantified the effects of these drugs on the kinetics of actin polymerization in tubes (by means of spectrofluorimetry) and on the dynamics of actin cytoskeletons within whole cells (by means of fluorescence microscopy). Using quantitative videomicroscopy, we investigated the actual effects of the drugs on cell motility. Finally, the combined drug effects on cell motility and cell growth were evaluated by means of a scratch-wound assay. While our results showed concordant drug-induced effects on actin polymerization occurring in vitro in test tubes and within whole cells, the whole cell assay appeared more sensitive than the tube assay. The inhibition of actin polymerization induced by cytochalasin D was paralleled by a decrease in cell motility for both cell types. In the case of jasplakinolide, which induces actin polymerization, while it significantly enhanced the locomotion of the A549 cells, it significantly inhibited that of the MCF-7 ones. All these effects were confirmed by means of the scratch-wound assay except of the jasplakinolide-induced effects on MCF-7 cell motility. These later seemed compensated by an additional effect occurring during wound recolonization (possibly acting on the cell growth features). In conclusion, the use of multi-assays with different levels of sophistication and biological relevance is recommended in the screening of new actin-affecting drugs with potentially anti-migratory effects.

F. Dubois, C. Yourassowsky, O. Monnom, J. Legros, O. Debeir, P. Van Ham, R. Kiss, C. Decaestecker,
Digital holographic microscopy for the three-dimensional dynamic analysis of in vitro cancer cell migration.
Journal of biomedical optics, Vol. 11, 5, pp. 054032, 2006
Bibtex : info:hdl:2013/52096
Note : Evaluation Studies
Abstract : Cancer cell motility and invasion are critical targets for anticancer therapeutics. Whereas in vitro models could be designed for rapid screening with a view to investigate these targets, careful consideration must be given to the construction of appropriate model systems. Most investigations focus on two-dimensional (2-D) assays despite the fact that increasing evidence suggests that migration across rigid and planar substrates fails to recapitulate in vivo behavior. In contrast, few systems enable three-dimensional (3-D) cell migration to be quantitatively analyzed. We previously developed a digital holographic microscope (DHM) working in transmission with a partially spatial coherence source. This configuration avoids the noise artifacts of laser illumination and makes possible the direct recording of information on the 3-D structure of samples consisting of multiple objects embedded in scattering media, such as cell cultures in matrix gels. The software driving our DHM system is equipped with a time-lapse ability that enables the 3-D trajectories of living cells to be reconstituted and quantitatively analyzed.

S. Rorive, C. Maris, O. Debeir, F. Sandras, M. Vidaud, I. Bièche, I. Salmon, C. Decaestecker,
Exploring the distinctive biological characteristics of pilocytic and low-grade diffuse astrocytomas using microarray gene expression profiles.
Journal of neuropathology and experimental neurology, Vol. 65, 8, pp. 794-807, 2006
Bibtex : info:hdl:2013/52951
Note : Journal Article
Abstract : Although World Health Organization (WHO) grade I pilocytic astrocytomas and grade II diffuse astrocytomas have been classified for decades as different clinicopathologic entities, few, if any, data are available on the biologic features explaining these differences. Although more than 50 microarray-related studies have been carried out to characterize the molecular profiles of astrocytic tumors, we have identified only 11 that provide sound data on low-grade astrocytomas. We have incorporated these data into a comparative analysis for the purpose of identifying the most relevant molecular markers characterizing grade I pilocytic and grade II diffuse astrocytomas. Our analysis has identified various interesting genes that are differentially expressed in either grade I or grade II astrocytomas when compared with normal tissue and/or high-grade (WHO grade III and IV) astrocytomas. A large majority of these genes encode adhesion, extracellular matrix, and invasion-related proteins. Interestingly, a group of 6 genes (TIMP4, C1NH, CHAD, THBS4, IGFBP2, and TLE2) constitute an expression profile characteristic of grade I astrocytomas as compared with all other categories of tissue (normal brain, grade II, and high-grade astrocytomas). The end products (proteins) of these genes act as antimigratory compounds, a fact that could explain why pilocytic astrocytomas behave as compact (well-circumscribed) tumors as opposed to all the other astrocytic tumor types that diffusely invade the brain parenchyma. Having validated these molecular markers by means of real-time reverse transcriptase-polymerase chain reaction, an integrated model was proposed illustrating how and why pilocytic astrocytomas constitute a distinct biologic and pathologic entity when compared with diffuse astrocytomas.

S. Servotte, I. Camby, O. Debeir, C. Deroanne, C. Lambert, C. Lapière, R. Kiss, B. Nusgens, C. Decaestecker,
The in vitro influences of neurotensin on the motility characteristics of human U373 glioblastoma cells.
Neuropathology and applied neurobiology, Vol. 32, 6, pp. 575-584, 2006
Bibtex : info:hdl:2013/52097
Note : In Vitro
Abstract : Astrocytic tumours are associated with dismal prognoses due to their pronounced ability to diffusely invade the brain parenchyma. Various neuropeptides, including gastrin, are able to modulate tumour astrocyte migration. While neurotensin has been shown to influence the proliferation of glioma cells and the migratory ability of a large set of other cell types, its role in glioma cell migration has never been investigated. Neurotensin-induced modifications to the motility features of human U373 glioblastoma cells therefore constitute the topic of the present study. We evidenced that three subtypes of neurotensin receptors (NTR1, NTR2 and NTR3) are expressed in U373 glioblastoma cells, at least as far as their mRNAs are concerned. Treating U373 tumour cells with 10 nM neurotensin markedly modified the morphological patterns of these cells and also profoundly altered the organization of their actin cytoskeletons. Pull-down assays revealed that neurotensin induced the activation in U373 cells of both Rac1 and Cdc42 but not RhoA. Scratch wound assays evidenced that neurotensin (0.1 and 10 nM) very significantly inhibited wound colonization by U373 cells cultured in the absence of serum. In addition, quantitative phase-contrast videomicroscopy analyses showed that neurotensin decreases the motility levels of U373 glioblastoma cells when these cells are cultured on plastic. In sharp contrast, neurotensin stimulates the motility of U373 cells when they are cultured on laminin, which is a pro-adhesive extracellular matrix component ubiquitously secreted by glioma cells. Our data thus strongly suggest that, in addition to gastrin, neurotensin is a neuropeptide capable of modulating tumour astrocyte migration into the brain parenchyma.

O. Debeir, P. Van Ham, R. Kiss, C. Decaestecker,
Tracking of migrating cells under phase-contrast video microscopy with combined mean-shift processes.
IEEE transactions on medical imaging, Vol. 24, 6, pp. 697-711, 2005
Bibtex : info:hdl:2013/52108
Note : Evaluation Studies
Abstract : In this paper, we propose a combination of mean-shift-based tracking processes to establish migrating cell trajectories through in vitro phase-contrast video microscopy. After a recapitulation on how the mean-shift algorithm permits efficient object tracking we describe the proposed extension and apply it to the in vitro cell tracking problem. In this application, the cells are unmarked (i.e., no fluorescent probe is used) and are observed under classical phase-contrast microscopy. By introducing an adaptive combination of several kernels, we address several problems such as variations in size and shape of the tracked objects (e.g., those occurring in the case of cell membrane extensions), the presence of incomplete (or noncontrasted) object boundaries, partially overlapping objects and object splitting (in the case of cell divisions or mitoses). Comparing the tracking results automatically obtained to those generated manually by a human expert, we tested the stability of the different algorithm parameters and their effects on the tracking results. We also show how the method is resistant to a decrease in image resolution and accidental defocusing (which may occur during long experiments, e.g., dozens of hours). Finally, we applied our methodology on cancer cell tracking and showed that cytochalasin-D significantly inhibits cell motility.

O. Debeir, I. Camby, R. Kiss, P. Van Ham, C. Decaestecker,
A model-based approach for automated in vitro cell tracking and chemotaxis analyses
Cytometry. Part A, Vol. 60, 1, pp. 29-40, 2004
Bibtex : info:hdl:2013/52124
Note : Journal Article
Abstract : BACKGROUND: Chemotaxis may be studied in two main ways: 1) counting cells passing through an insert (e.g., using Boyden chambers), and 2) directly observing cell cultures (e.g., using Dunn chambers), both in response to stationary concentration gradients. This article promotes the use of Dunn chambers and in vitro cell-tracking, achieved by video microscopy coupled with automatic image analysis software, in order to extract quantitative and qualitative measurements characterizing the response of cells to a diffusible chemical agent. METHODS: Previously, we set up a videomicroscopy system coupled with image analysis software that was able to compute cell trajectories from in vitro cell cultures. In the present study, we are introducing a new software increasing the application field of this system to chemotaxis studies. This software is based on an adapted version of the active contour methodology, enabling each cell to be efficiently tracked for hours and resulting in detailed descriptions of individual cell trajectories. The major advantages of this method come from an improved robustness with respect to variability in cell morphologies between different cell lines and dynamical changes in cell shape during cell migration. Moreover, the software includes a very small number of parameters which do not require overly sensitive tuning. Finally, the running time of the software is very short, allowing improved possibilities in acquisition frequency and, consequently, improved descriptions of complex cell trajectories, i.e. trajectories including cell division and cell crossing. RESULTS: We validated this software on several artificial and real cell culture experiments in Dunn chambers also including comparisons with manual (human-controlled) analyses. CONCLUSIONS: We developed new software and data analysis tools for automated cell tracking which enable cell chemotaxis to be efficiently analyzed.

F. Lefranc, T. Mijatovic, V. Mathieu, S. Rorive, C. Decaestecker, O. Debeir, J. Brotchi, P. Van Ham, I. Salmon, R. Kiss,
Characterization of gastrin-induced proangiogenic effects in vivo in orthotopic U373 experimental human glioblastomas and in vitro in human umbilical vein endothelial cells.
Clinical cancer research, Vol. 10, 24, pp. 8250-8265, 2004
Bibtex : info:hdl:2013/51225
Note : In Vitro
Abstract : PURPOSE: This study aims to investigate the role of gastrin-17 (G17) on angiogenesis features in gliomas both in vitro and in vivo. EXPERIMENTAL DESIGN: The influences of G17 and G17 receptor antagonists were characterized in vitro in terms of angiogenesis on human umbilical vein endothelial cell (HUVEC) tubulogenesis processes on Matrigel and in vivo with respect to U373 orthotopic glioma xenografts. The influence of phosphatidylinositol 3'-kinase, protein kinase C, and nuclear factor-kappaB inhibitors was characterized in vitro on G17-mediated HUVEC tubulogenesis. G17-mediated release of interleukin (IL)-8 from HUVECs and G17-induced modifications in nuclear factor-kappaB DNA binding activity were characterized by means of specific enzyme-linked immunosorbent assays. The influence of G17 on E- and P-selectin expression was determined by means of computer-assisted microscopy, whereas the influence of E- and P-selectin on HUVEC migration was approached by means of antisense oligonucleotides. The chemotactic influence of G17 and IL-8 on HUVEC migration was characterized by means of computer-assisted videomicroscopy with Dunn chambers. RESULTS: Messenger RNAs for cholecystokinin (CCK)A, CCKB, and CCKC receptors were present in HUVECs and microvessels dissected from a human glioblastoma. Whereas G17 significantly increased the levels of angiogenesis in vivo in the U373 experimental glioma model and in vitro in the HUVECs, the CCKB receptor antagonist L365,260 significantly counteracted the G17-mediated proangiogenic effects. G17 chemoattracted HUVECs, whereas IL-8 failed to do so. IL-8 receptor alpha (CXCR1) and IL-8 receptor beta (CXCR2) mRNAs were not detected in these endothelial cells. Gastrin significantly (but only transiently) decreased the level of expression of E-selectin, but not P-selectin, whereas IL-8 increased the expression of E-selectin. Specific antisense oligonucleotides against E- and P-selectin significantly decreased HUVEC tubulogenesis processes in vitro on Matrigel. CONCLUSIONS: The present study shows that gastrin has marked proangiogenic effects in vivo on experimental gliomas and in vitro on HUVECs. This effect depends in part on the level of E-selectin activation, but not on IL-8 expression/release by HUVECs.

P. Latinne, O. Debeir, C. Decaestecker,
Combining Different Methods and Numbers of Weak Decision Trees
Pattern Analysis and Applications, Vol. 5, 2, pp. 201-209, 2002
Bibtex : info:hdl:2013/52956
Note : Language of publication: en

P. Latinne, O. Debeir, C. Decaestecker,
Limiting the number of trees in random forests
Lecture notes in computer science, Vol. 2096, pp. 178-187, 2001
Bibtex : info:hdl:2013/229196
Note : SCOPUS: cp.k
Abstract : The aim of this paper is to propose a simple procedure that a priori determines a minimum number of classifiers to combine in order to obtain a prediction accuracy level similar to the one obtained with the combination of larger ensembles. The procedure is based on the McNe- mar non-parametric test of significance. Knowing a priori the minimum size of the classifier ensemble giving the best prediction accuracy, constitutes a gain for time and memory costs especially for huge data bases and real-time applications. Here we applied this procedure to four multiple classifier systems with C4.5 decision tree (Breiman's Bagging, Ho's Random subspaces, their combination we labeled ‘Bagfs', and Breiman's Random forests) and five large benchmark data bases. It is worth noticing that the proposed procedure may easily be extended to other base learning algorithms than a decision tree as well. The experimental results showed that it is possible to limit significantly the number of trees. We also showed that the minimum number of trees required for obtaining the best prediction accuracy may vary from one classifier combination method to another.

P. Latinne, O. Debeir, C. Decaestecker,
Different ways of weakening decision trees and their impact on classification accuracy of DT combination
Lecture notes in computer science, Vol. 1857 LNCS, pp. 200-209, 2000
Bibtex : info:hdl:2013/192154
Note : SCOPUS: cp.k
Abstract : Recent classifier combination frameworks have proposed several ways of weakening a learning set and have shown that these weakening methods improve prediction accuracy. In the present paper we focus on learning set sampling (Breiman's bagging) and random feature subset selections (Bay's Multiple Feature Subsets). We present a combination scheme labeled 'Bagfs', in which new learning sets are generated on the basis of both bootstrap replicates and selected feature subsets. The performances of the three methods (Bagging, MFS and Bagfs) are assessed by means of a decision-tree inducer (C4.5) and a majority voting rule. In addition, we also study whether the way in which weak classifiers are created has a significant influence on the performance of their combination. To answer this question, we undertook the strict application of the Cochran Q test. This test enabled us to compare the three weakening methods together on a given database, and to conclude whether or not these methods differ significantly. We also used the McNemar test to compare algorithms pair by pair. The first results, obtained on 14 conventional databases, show that on average, Bagfs exhibits the best agreement between prediction and supervision. The Cochran Q test indicated that the weak classifiers so created significantly influenced combination performance in the case of at least 4 of the 14 databases analyzed. © Springer-Verlag Berlin Heidelberg 2000.

O. Debeir, C. Decaestecker, J. Pasteels, I. Salmon, R. Kiss, P. Van Ham,
Computer-assisted analysis of epiluminescence microscopy images of pigmented skin lesions.
Cytometry, Vol. 37, 4, pp. 255-266, 1999
Bibtex : info:hdl:2013/52957
Note : Journal Article
Abstract : BACKGROUND: Epiluminescence microscopy (ELM) is a noninvasive clinical tool recently developed for the diagnosis of pigmented skin lesions (PSLs), with the aim of improving melanoma screening strategies. However, the complexity of the ELM grading protocol means that considerable expertise is required for differential diagnosis. In this paper we propose a computer-based tool able to screen ELM images of PSLs in order to aid clinicians in the detection of lesion patterns useful for differential diagnosis. METHODS: The method proposed is based on the supervised classification of pixels of digitized ELM images, and leads to the construction of classes of pixels used for image segmentation. This process has two major phases, i.e., a learning phase, where several hundred pixels are used in order to train and validate a classification model, and an application step, which consists of a massive classification of billions of pixels (i.e., the full image) by means of the rules obtained in the first phase. RESULTS: Our results show that the proposed method is suitable for lesion-from-background extraction, for complete image segmentation into several typical diagnostic patterns, and for artifact rejection. Hence, our prototype has the potential to assist in distinguishing lesion patterns which are associated with diagnostic information such as diffuse pigmentation, dark globules (black dots and brown globules), and the gray-blue veil. CONCLUSIONS: The system proposed in this paper can be considered as a tool to assist in PSL diagnosis.


Y. Van Eycke, J. Allard, M. Derock, I. Salmon, O. Debeir, C. Decaestecker,
Image normalization for quantitative immunohistochemistry in digital pathology
2016 IEEE 13th International Symposium on Biomedical Imaging (ISBI), pp. 795 - 798, Prague, Czech Republic, 2016
Bibtex : info:hdl:2013/233019
Note : SCOPUS: cp.p
Abstract : We propose to adapt to immunohistochemistry (IHC) some methods proposed to normalize images from histological slices stained with hematoxylin-eosin (H&E). Our final aim is to provide a coherent quantitative characterization of IHC biomarkers across different IHC batches with possible staining variations. In contrast to H&E, IHC staining strongly varies with the tissue analyzed and the protein targeted, making image normalization challenging. To solve this problem, we added in each IHC batch a slice from a reference tissue microarray (TMA) and then digitalized it to establish an inter-batch normalization transform. A comparison of two methods adapted to the specificity of IHC-stained slides evidences some normalization requirements to make valid IHC biomarker quantification across different staining batches.

Y. Van Eycke, O. Debeir, L. Verset, P. Demetter, I. Salmon, C. Decaestecker,
Automated Tissue Microarray Image Processing in Digital Pathology.
Proceedings of the Fifth joint WIC/IEEE SP Symposium on Information Theory and Signal Processing in the Benelux, Brussels, Belgium, 2015
Bibtex : info:hdl:2013/199489
Note : Language of publication: en

Y. Van Eycke, O. Debeir, L. Verset, P. Demetter, I. Salmon, C. Decaestecker,
High-Throughput Analysis of Tissue-Based Biomarkers in Digital Pathology
EMBC'15 Proceedings (IEEE Engineering in Medicine and Biology Society), pp. 7732 - 7735, Milan, 2015
Bibtex : info:hdl:2013/205314
Note : Language of publication: en

X. Moles Lopez, O. Debeir, C. Maris, I. Roland, I. Salmon, C. Decaestecker,
Ki-67 hot-spots detection on glioblastoma tissue sections
Proc. of the 2010 IEEE International Symposium on Biomedical Imaging: From Nano to Macro (ISBI 2010), pp. pp 149-152, Rotterdam, 2010
Bibtex : info:hdl:2013/70188
Note : Language of publication: en

N. Warzée, M. Groenen, J. Rosoux, O. Debeir, R. Ercek, C. Reichling,
Numérisation 3D de la grotte d'El Castillo (Puente Viesgo)
Actes du colloque Virtual Retrospect 2007, pp. 221-229, 2009
Bibtex : info:hdl:2013/71566
Note : Consultable à l'adresse suivante :

O. Debeir, I. Adanja, N. Warzée, P. Van Ham, C. Decaestecker,
Phase contrast image segmentation by weak watershed transform assembly
Proceedings of 5th IEEE International Symposium on Biomedical Imaging : From Nano to Macro (ISBI), pp. 724-727, ISBI)(Paris, France, 2008
Bibtex : info:hdl:2013/53020
Note : Language of publication: en

M. Le Mercier, F. Lefranc, T. Mijatovic, O. Debeir, B. Haibe-Kains, G. Bontempi, C. Decaestecker, R. Kiss, V. Mathieu,
Galectin-1 regulates p53 and is implicated in glioma cell resistance to cytotoxic drugs
Conference: Belgium Society for Cell and Developmental Biology Autumn Meeting(Louvain-la-Neuve), 2007
Bibtex : info:hdl:2013/158306
Note : Language of publication: en
Abstract : Purpose: Glioblastomas (GBMs) are resistant to apoptosis but less so to autophagy, a fact that may at least partly explain the therapeutic benefits of the pro-autophagic drug temozolomide in the treatment of GBM patients. Galectin-1 (Gal1) is a potent modulator of GBM cell migration and a pro-angiogenic molecule whose expression is stimulated by hypoxia. The present study investigates whether decreasing galectin-1 expression in human Hs683 GBM cells increases their sensitivity to pro-autophagic or pro-apoptotic drugs.Experimental design: A siRNA approach was used to decrease Gal1 expression in Hs683 GBM cells. The effects of temozolomide and of pro-apoptotic drugs in this model in vitro and in vivo were studied. Additionally genome-wide microarray analysis was employed to identify chemoresistance-related genes.Results: Temozolomide treatment increased Gal1 expression in Hs683 cells both in vitro and in vivo. Reducing Gal1 expression in these cells increased the anti-tumor effects of chemotherapeutical agents, in particular temozolomide both in vitro and in vivo. Decreasing Gal1 expression in Hs683 cells did not induce apoptotic or autophagic features, but decreased p53 transcriptional activity along with p53-targeted gene expression including DDIT3/GADD153/CHOP, DUSP5, ATF3 and GADD45A. The reduction in Gal1 expression also paralleled decreases in the expression levels of seven other genes implicated in chemoresistance: ORP150, HERP, Grp78/Bip, TRA1, BNIP3L, GADD45B and CYR61.Conclusions: This novel facet of Gal1 involvement in the chemoresistance of GBM cells may be amenable to therapeutic manipulation.

O. Debeir, R. Van Ginckel, I. Adanja, F. Darro, R. Kiss, C. Decaestecker,
High throughput characterization of anticancer compounds by means of cellular imaging and automatic image analysis.
Conference: (April 14-18: Los Angeles - USA), 2007
Bibtex : info:hdl:2013/71810
Note : Présentation orale (abstract 4965)

O. Debeir, I. Adanja, R. Kiss, C. Decaestecker,
Automatic in vitro cell division characterization by automatic image sequence analysis
Conference: Annual Symposium of the IEEE/EMBS Benelux Chapter(I: 7-8 December 2006: Brussels), 2006
Bibtex : info:hdl:2013/158307
Note : Language of publication: en
Abstract : In vitro cell observation has been widely used by biologists for years and covers a wide range of applications: cancer and cell proliferation, cell migration or chemotactism, embryology, drug testing. Nowadays the use of computer assisted-microscopy (or time-laps microscopy) allows the handling of considerably large amount of image data, which is acquired during experiments possibly lasting from several hours to several days. If cell cultures are observed for long periods of time (2-4 days), it becomes possible to detect less frequent cell events, such as cell division or cell death. We describe in this work a semi-automatic approach of studying the cell division event itself - starting from the cell exhibiting a round shaped form to the final daughter cells separation.

O. Debeir, R. Kiss, C. Decaestecker,
Cell division characterization by automatic cell tracking and cell lineage reconstruction
Conference: Belgium Society for Cell and Developmental Biology Autumn Meeting 2006(2006: Ghent), 2006
Bibtex : info:hdl:2013/158308
Note : Language of publication: en
Abstract : In vitro cell observation is widely used by biologists since years. Nowadays the use of computer assisted-microscopy (or time-laps microscopy) allows the management of huge amounts of image data generated during experiments of various durations. Periods of time from several hours to 1 day are generally sufficient to analyze cell trajectories in cell migration and chemotaxis studies. If cell cultures are observed during longer periods of time (3-4 days), it is possible to detect less frequent cell events, such as cell division or cell death. A wide range of applications can be covered by theses time-laps microscopy approaches, including embryology studies and anti-cancer drug testing.We showed in previous works that unmarked cells observed in vitro under classical phase-contrast microscopy during several days can be efficiently and automatically tracked, and their individual trajectories reconstituted and characterized by various measurements. We are now extending this technique for cell division detection using backward cell tracking (from the last to the 1st frame of the image sequence) and cell trajectory recombinations. In the present study, we describe a semi-automatic extension which is able to reconstruct tree structures characterizing cell lineages. The use of backward cell tracking enables easy cell division detection (by identifying cell trajectory merging), except in some cases when the tracking procedure fails. We thus added a “light” interactive step in order to select the actual cell division events among all the automatically detected ones; the operator has only to accept or to reject each proposed event.In order to characterize the action of specific drugs on cell motility and also on cell behavior during and just after cell division, specific features characterizing cell division events are extracted (in addition to those concerning cell movements). We illustrated our methodology on different examples including drug actions on cytokinesis, i.e. the cell separation event occurring at the end of cell division.

O. Debeir, D. Milojevic, T. Leloup, P. Van Ham, R. Kiss, C. Decaestecker,
Mitotic Tree Construction by Computer In Vitro Cell Tracking : a Tool for Proliferation and Motility Features Extraction
Proc. of the EUROCON 2005, pp. 951-954, Belgrade, Serbia, 2005
Bibtex : info:hdl:2013/53176
Note : Language of publication: en

S. Servotte, I. Camby, O. Debeir, C. Deroanne, C. Lapière, R. Kiss, B. Nusgens, C. Decaestecker,
Neurotensin activates rac1 and cdc42, but not rhoa, in human U373 glioblastoma cells, and modifies their migratory patterns
Conference: Cell migration in cancer and immunity: Joint BSCDB-BIS meeting(27-28 May 2005: Brussels), 2005
Bibtex : info:hdl:2013/158309
Note : Language of publication: en
Abstract : Astrocytic tumors are associated with dismal prognoses due to their pronounced ability to diffusely invade the brain parenchyma (Lefranc et al., J Clin Oncol 2005). Various neuropeptides display a large number of functions in the central and peripheral nervous system. Gastrin has already been shown to affect both cell proliferation and migration (Camby et al., J Natl Cancer Inst 1996; DeHauwer et al., J Neurobiol 1998; Lefranc et al., Lab Invest 2002) in human experimental gliomas. While we already suggested a role for neurotensin in glioma cell proliferation (Camby et al., Neuropeptide 1996), its action on glioma cell migration has never been investigated. Therefore, the present study aims at analyzing the neurotensin-induced alterations of the migratory patterns of human U373 glioblastoma cells. Most of the neuropeptides displaying physiological roles in the brain act through their binding to specific G-protein-coupled-receptors (GPCRs) on the surface of their target cells. Once a neuropeptide binds to its GPCR(s), it can induce profound changes in the organization of the actin cytoskeleton which is a major actor in the cell migration process (Rozengurt and Walsch, Annu Rev Physiol 2001). Three subtypes of neurotensin receptors have been cloned. While NT-R1 and NT-R2 belong to the GPCR family, NT-R3 is a new type of neuropeptide receptor which is a 95 kDa protein (identical to gp95/sortilin) with a single transmembrane domain. RT-PCR analyses evidenced that U373 tumor cells express mRNAs for NT-R1, -R2 and -R3. Treating U373 cells with 10 nM neurotensin markedly modified their morphological patterns as well as the organization of their actin cytoskeleton. The family of the Rho-GTPase proteins plays a pivotal role in regulating the actin cytoskeleton organization. While RhoA regulates the assembly of contractile actin-myosin filaments, Rac1 and Cdc42 regulate actin polymerization to form peripheral lamellipodial and filopodial protrusions respectively. Pull-down assays revealed that neurotensin induced a dose-dependent activation in U373 cells of both Rac1 and Cdc42, and, to a lesser extent, RhoA. By using a scratch wound assay, we observed that 0.1 and 10 nM neurotensin very significantly decreased the ability of U373 glioblastoma cells to migrate and colonize the wound (in the absence of fetal calf serum). Computer-assisted phase-contrast microscope analyses showed that neurotensin decreases the motility levels of U373 glioblastoma cells cultured on uncoated flasks (plastic). In sharp contrast, neurotensin stimulates the motility of U373 cells cultured on laminin (a pro-adhesive extracellular matrix component ubiquitously secreted by glioma cells, known for stimulating their migration in vitro and upregulated in high-grade astrocytic tumors). In conclusion, our data strongly suggest that neurotensin, in addition to gastrin, is a neuropeptide able to modulate tumor astrocyte migration into the brain parenchyma.

P. Latinne, O. Debeir, C. Decaestecker,
Limiting the Number of Trees in Random Forests
Multiple Classifier Systems: Proceedings of the Second International Workshop, pp. 178-187, 2001
Bibtex : info:hdl:2013/53183
Note : Language of publication: en

P. Latinne, O. Debeir, C. Decaestecker,
Different Ways of Weakening Decision Trees and Their Impact on Classification Accuracy of DT Combination
Multiple Classifier Systems: Proceedings of the First International Workshop, pp. 200-209, 2000
Bibtex : info:hdl:2013/53188
Note : Language of publication: en

P. Latinne, O. Debeir, C. Decaestecker,
Mixing Bagging and Multiple Feature Subsets to Improve Classification Accuracy of Decision Tree Combination
BENELEARN 2000, Tenth Belgian-Dutch Conference on Machine Learning, Tilburg University, Netherland, 2000
Bibtex : info:hdl:2013/53190
Note : Language of publication: en

Books chapters

Moles Lopez, Xavier, Debeir, Olivier, Salmon, Isabelle, Decaestecker, Christine,
Whole slide imaging and analysis for biomarker evaluation in digital pathology
A. Méndez-Vilas (Ed.), Microscopy: advances in scientific research and education, Vol. 2, pp. 776-787, 2014
Bibtex : info:hdl:2013/175598
Note : Language of publication: na

O. Debeir, I. Adanja, R. Kiss, C. Decaestecker,
Models of cancer cell migration and cellular imaging and analysis
Anja Lambrechts, Christophe Ampe (Eds). The Motile Actin System in Health and Disease, pp. 123-156, 2008
Bibtex : info:hdl:2013/99600
Note : Language of publication: en


Debeir O. - Segmentation supervisée d'image
Ph.D. Thesis, Université Libre de Bruxelles , 50, av. F.D.Roosevelt 1050 Bruxelles, Belgique, apr 2002
Author : Debeir O.
Title : Segmentation supervisée d'image
In : Ph.D. Thesis, Université Libre de Bruxelles -
Address : 50, av. F.D.Roosevelt 1050 Bruxelles, Belgique
Date : apr 2002


Debeir O. - DEA : Segmentation d'images par classification supervisée de régions
DEA, Université Libre de Bruxelles , 50, av. F.D.Roosevelt 1050 Bruxelles, Belgique,2001
Author : Debeir O.
Title : DEA : Segmentation d'images par classification supervisée de régions
In : DEA, Université Libre de Bruxelles -
Address : 50, av. F.D.Roosevelt 1050 Bruxelles, Belgique
Date : 2001


Project and stage

Analyse de signaux électromyographiques par reconnaisance de pattern en kinésithérapie (MFE Biomédicale 5)
Etudiants : Nadège TEBBACHE
Promoteurs : Antoine NONCLERCQ, Olivier DEBEIR

Application de la Méthode des Particules Filter à la Segmentation (MFE Biomédicale 5)
Etudiants : Karim GHADDAR
Promoteurs : Olivier DEBEIR

Is there any need for a comprehensive patient-specific soft-tissues envelope in a knee model ? A validated numerical tool for answering this question (Rapport d'avancement des recherches)
Etudiants : Silvia PIANIGIANI
Promoteurs : Bernardo INNOCENTI, Jos VANDER SLOTEN, Stéphane GODET, Olivier DEBEIR

Développement d'un programme de segmentation multi-paramétrique de la prostate sur des images de résonance magnétique selon PI-RADS (MFE Biomédicale 5)
Etudiants : Stephan HAHN
Promoteurs : Olivier DEBEIR

Développement d'une méthode de segmentation et d'analyse granulométrique sur des images de cellules obtenues par microscopie à fluorescence (MFE Biomed 5)
Etudiants : Alaa HAGE
Promoteurs : Olivier DEBEIR

Extraction automatisée de l'angle de pennation du muscle gastrocnémien par analyse d'images (MFE Info 5)
Etudiants : Yves-Rémi VAN EYCKE
Promoteurs : Olivier DEBEIR

Moteur de rendu de nuages de points (MFE Informatique 5)
Etudiants : Gautier DEVUYST
Promoteurs : Olivier DEBEIR

Création d’un outil de segmentation semi-automatique d'image (Projet Biomed 4)
Etudiants : Karim GHADDAR
Promoteurs : Xavier MOLES LOPEZ , Olivier DEBEIR

Interface pour l'extraction automatique de mesures par compartiment cellulaire à partir d'images de cellules acquises par microscope à fluorescence (Projet Biomed 4)
Etudiants : Florence GIESEN
Promoteurs : Olivier DEBEIR, Christine DECAESTECKER

Mesure de la variation de position de la jonction entre le muscle et le tendon (Projet Biomed 4)
Etudiants : Thanh VâN PHAN
Promoteurs : Olivier DEBEIR,Nadine WARZEE

Modélisation spatio-temporelle de la forme de la cellule in vitro par contraste de phase (Projet Biomed 4)
Etudiants : Lynda BERROUANE
Promoteurs : Olivier DEBEIR, Christine DECAESTECKER

3D Biomechanical Model of the Carpo-Metacarpal Joint of the Thumb (MFE Biomed 5)
Etudiants : Tran Phuong TOAN
Promoteurs : Pierre MATHYS, Olivier DEBEIR, Joris LEIJNSE

Conception et réalisation d'un système de mesure de distance pour l'aide à l'asservissement d'un instrument chirurgical sur un organe battant (MFE Biomed 5)
Etudiants : Barbara DEMOUTIER
Promoteurs : Olivier DEBEIR

Implémentation d'une méthode de reconstruction 3D d'objet utilisant la projection de lumière structurée et les NURBS (Projet Biomed 4)
Etudiants : Benjamin DE LEENER
Promoteurs : Benjamin MERTENS, Olivier DEBEIR

Segmentation d'image de lames histologiques par méthode "edge-less" (Projet Biomed 4)
Etudiants : Alaa HAGE
Promoteurs : Olivier DEBEIR

Automated tracking of unmarked cells migrating in three-dimensional matrices (Thèse)
Etudiants : Ivan ADANJA
Promoteurs : Christine DECAESTECKER, Olivier DEBEIR

Acquisition et reconstruction 3D à travers une fibre optique pour des applications endoscopiques (MFE Biomed 5)
Etudiants : Vincent HEYMANS
Promoteurs : Olivier DEBEIR

Identification de vaisseaux sanguins au sein de coupes histologiques par apprentissage et analyse d'images (MFE Biomed 5)
Etudiants : Frédéric MOREL
Promoteurs : Christine DECAESTECKER, Olivier DEBEIR

Improvement of Image Segmentation Based on Statistical Shape and Intensity Models (MFE Biomed 5)
Etudiants : Maximilien RENARD
Promoteurs : Olivier DEBEIR

Mesures de paramètres morphologiques de neurones à partir d'images obtenues par microscopie confocale (MFE Biomed 5)
Etudiants : Adrien FOUCART
Promoteurs : Olivier DEBEIR, David GALL

Analyse morphologique de cellules dans une séquence (Projet Informatique 4)
Etudiants : Geoffroy LOUMAYE
Promoteurs : Olivier DEBEIR

Calibration d'un système d'acquisition 3D (Projet Informatique 4)
Etudiants : Taheri Abdeslam BAKKALI
Promoteurs : Olivier DEBEIR

Détection de mitoses au sein d'une séquence acquise par microscopie à contraste de phase (Projet EM 4)
Etudiants : Aibek VAN DEN ACKERVEKEN
Promoteurs : Patrick HENDRIC, Olivier DEBEIR

Quantification de la fluorescence de cellules marquées à l'aide d'un procédé d'immunofluorescence (Projet Biomed 4)
Etudiants : Gwennaëlle MARIN
Promoteurs : Olivier DEBEIR, Xavier MOLES LOPEZ

Réalisation d'un scanner tomographique (Projet Biomed 2)
Promoteurs : Olivier DEBEIR, Laurent LONYS

Segmentation de noyaux soumis à un procédé d'immunofluorescence (Projet Biomed 4)
Etudiants : Barbara DEMOUTIER
Promoteurs : Olivier DEBEIR

Développement d'un logiciel de traitement d'images pour l'analyse quantitative de tâches hyperpigmentées sur un visage éclairé par de la lumière blanche (MFE Biomed 5)
Etudiants : Juliette ROSTAING
Promoteurs : Olivier DEBEIR, Dr HEENEN, Dr VEREECKEN

Conception et réalisation d'un robot d'aide aux personnes âgées dans la gestion ou le tri de leurs médicaments (Projet biomed 2)
Promoteurs : Quentin LURKIN, Olivier DEBEIR

Evaluation automatique de la surface recolonisée par des cellules cultivées in vitro lors d'une expérience de wound healing (Projet Biomed 4)
Etudiants : Juliette ROSTAING
Promoteurs : Olivier DEBEIR

Evaluation de l'éloignement d'outils en endoscopie flexible interventionnelle (Projet Biomed 4)
Etudiants : Vincent HEYMANS, Benjamin HORSMANS
Promoteurs : Olivier DEBEIR

Recalage de coupes sériées acquises par microscopie optique (Projet Biomed 4)
Etudiants : Fabian MARTINO, Frédéric MOREL
Promoteurs : Olivier DEBEIR

Développement d'une plate-forme d'analyse d'image dédiée à la biologie cellulaire. (Stage 2)
Etudiants : Mohamed ELHOUDERI
Promoteurs : Olivier DEBEIR

Développement d'une plate-forme d'analyse d'images sous Python. (Stage)
Etudiants : Louis BREMAND
Promoteurs : Olivier DEBEIR, Ivan ADANJA, Christine DECAESTECKER, Nadine WARZEE

Bathyscaphe (Projet BA 1)
Etudiants : Laurent PIELTAIN (Chef d'équipe de 6 étudiants)
Promoteurs : Olivier DEBEIR

Conception d'un automate manipulateur de boîtes à essais (Projet 2)
Etudiants : Patrick AHORUKOMEYE, Alexandre BALON-PERIN, Cécile CAILLOL, Anthony COYETTE, Alexandre DOMB, Cédric DUMOULIN, Stephan HAHN
Promoteurs : Olivier DEBEIR

Conception d'une table multi-touch (Projet 3)
Etudiants : Sothy CHAU, Willy-Dawid KHOV, Allan ROBERT
Promoteurs : Olivier DEBEIR

Le grand plongeon (Projet 1)
Etudiants : Xavier DUFOUR, Cyril MORTREU, Valerio CORDA, Marc SAINANEE, Maxime FONTEYNE, Nicolas HOLLANDER, Stevnen De Lobel
Promoteurs : Olivier DEBEIR

Mise en place d'une base de données de "Tissue Micro Array" (Projet Info 4)
Etudiants : Abdellah STITOU
Promoteurs : Xavier MOLEZ LOPEZ, Olivier DEBEIR

Réalisation d'un écran tactile multi-touch basé sur un module laser plan retro-éclairé et l'analyse d'image (Projet Info 3)
Etudiants : Sothy CHAU , Willy David KHOV , Allan ROBERT
Promoteurs : Olivier DEBEIR, Laurent ENGELS

Réalisation d'un lutrin virtuel interactif (Projet Info 4)
Etudiants : Anne-Sophie FEYAERTS
Promoteurs : Olivier DEBEIR, Frédéric DE GROEF

Robot manipulateur de boites de Petri (Projet BA 2)
Etudiants : Aurélie COLLIER , Bruno ROCHA , Ludovic LAFFINEUR , Alexandre DESCY, Thomas GEURY , Sébastien DASNOY-SUMELL
Promoteurs : Olivier DEBEIR, Laurent LONYS

Robot pipeteur (Projet BA 2)
Etudiants : Anthony COYETTE , Cécile CAILLOL , Patrick AHORUKOMEYE , Stephan HAHN , Alexandre BALON-PERIN , Cédric DUMOULIN , Alexandre DOMB
Promoteurs : Olivier DEBEIR

Réalisation d'un robot manipulateur de boîtes de Petri (Rapport 2)
Etudiants : Aurélie COLLIER, Sébastien DASNOY-SUMELL, Alexandre DESCY, Thomas GEURY, Ludovic LAFFINEUR, Bruno ROCHA
Promoteurs : Olivier DEBEIR, Laurent LONYS

Elaboration de descripteurs dynamiques de changement de forme d'objet 2D et leur application aux objets biologiques (MFE Biomed 5)
Etudiants : Aboubacar DIOP
Promoteurs : Olivier DEBEIR , Christine DECAESTECKER

Réalisation d'une table multi-touch (Projet 3)
Etudiants : Thibault DELEU, Anne-sophie FEYAERTS, Andreï NOVIKOV-DANEL
Promoteurs : Olivier DEBEIR

Système de navigation de séquences d’images 3D et recherche de plan focal (Projet Biomed 3)
Etudiants : Yassine KABBAJ
Promoteurs : Olivier DEBEIR, Ivan ADANJA

Analyse de la qualité d'image d'une empreinte digitale (MFE Informatique 5)
Etudiants : Yoppy Americo SATRIANTO
Promoteurs : Thierry LELOUP, Olivier DEBEIR, Nadine WARZEE

Elaboration de protocoles pour une quantification standardisée de marqueurs immunohistochimiques par analyse d’images digitales (MFE Biomed 5)
Etudiants : Younes JOURANI
Promoteurs : Olivier DEBEIR , Isabelle SALMON , Christine DECAESTECKER

Modèle 3D à partir d'acquisitions microscopiques sériées (Projet Télécommunications 5)
Etudiants : Alexandre VANDENBUSSCHE
Promoteurs : Olivier DEBEIR

Segmentation d'image par marche aléatoire (Projet 4)
Etudiants : Benjamin POULAIN
Promoteurs : Olivier DEBEIR

Optimisation d'une tourelle laser déterminant la position d'un robot (Projet Informatique 3)
Etudiants : Frédérick DEGROOF, Xavier SAND, Abdellah STITOU
Promoteurs : Olivier DEBEIR