An image generator platform to improve cell tracking algorithms: Simulation of objects of various morphologies, kinetics and clustering

Several major advances in Cell and Molecular Biology have been made possible by recent advances in live-cell microscopy imaging. To support these efforts, automated image analysis methods such as cell segmentation and tracking during a time-series analysis are needed. To this aim, one important step is the validation of such image processing methods. Ideally, the “ground truth” should be known, which is possible only by manually labelling images or in artificially produced images. To simulate artificial images, we have developed a platform for simulating biologically inspired objects, which generates bodies with various morphologies and kinetics and, that can aggregate to form clusters. Using this platform, we tested and compared four tracking algorithms: Simple Nearest-Neighbour (NN), NN with Morphology and two DBSCAN-based methods. We show that Simple NN works well for small object velocities, while the others perform better on higher velocities and when clustering occurs. Our new platform for generating new benchmark images to test image analysis algorithms is openly available at (http://griduni.uninova.pt/Clustergen/ClusterGen_vl.0.zip).

[1]  Hans-Peter Kriegel,et al.  A Density-Based Algorithm for Discovering Clusters in Large Spatial Databases with Noise , 1996, KDD.

[2]  Huiyu Zhou,et al.  Object tracking using SIFT features and mean shift , 2009, Comput. Vis. Image Underst..

[3]  M. West,et al.  Image segmentation and dynamic lineage analysis in single‐cell fluorescence microscopy , 2009, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[4]  Carlo Tomasi,et al.  Good features to track , 1994, 1994 Proceedings of IEEE Conference on Computer Vision and Pattern Recognition.

[5]  David Svoboda,et al.  On Simulating 3D Fluorescent Microscope Images , 2007, CAIP.

[6]  Olli Yli-Harja,et al.  Software for quantification of labeled bacteria from digital microscope images by automated image analysis. , 2005, BioTechniques.

[7]  Pekka Ruusuvuori,et al.  Computational Framework for Simulating Fluorescence Microscope Images With Cell Populations , 2007, IEEE Transactions on Medical Imaging.

[8]  K. Kruse 7.13 Bacterial Organization in Space and Time , 2012 .

[9]  Michal Kozubek,et al.  Generation of digital phantoms of cell nuclei and simulation of image formation in 3D image cytometry , 2009, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[10]  David Suter,et al.  Object tracking in image sequences using point features , 2005, Pattern Recognit..

[11]  Sim Heng Ong,et al.  Learning cell geometry models for cell image simulation: An unbiased approach , 2010, 2010 IEEE International Conference on Image Processing.

[12]  Robert F. Murphy,et al.  Nuclear segmentation in microscope cell images: A hand-segmented dataset and comparison of algorithms , 2009, 2009 IEEE International Symposium on Biomedical Imaging: From Nano to Macro.

[13]  Claire M. Brown,et al.  Live-cell microscopy – tips and tools , 2009, Journal of Cell Science.

[14]  Mohammad Bagher Menhaj,et al.  Multiple Target Tracking for Mobile Robots Using the JPDAF Algorithm , 2009, Tools and Applications with Artificial Intelligence.

[15]  Robert F Murphy,et al.  CellOrganizer: Image-derived models of subcellular organization and protein distribution. , 2012, Methods in cell biology.

[16]  Michal Daszykowski,et al.  Revised DBSCAN algorithm to cluster data with dense adjacent clusters , 2013 .

[17]  James M. Joyce Kullback-Leibler Divergence , 2011, International Encyclopedia of Statistical Science.

[18]  Christoph F. Mecklenbräuker,et al.  A Novel Automatic Cluster Tracking Algorithm , 2006, 2006 IEEE 17th International Symposium on Personal, Indoor and Mobile Radio Communications.

[19]  H. K. Abhyankar,et al.  Image Registration Techniques: An overview , 2009 .

[20]  Brian J. McGill,et al.  Null Versus Neutral Models: What's The Difference? , 2006 .

[21]  Pekka Ruusuvuori,et al.  Synthetic Images of High-Throughput Microscopy for Validation of Image Analysis Methods , 2008, Proceedings of the IEEE.

[22]  Timm Schroeder,et al.  Probing cellular processes by long-term live imaging – historic problems and current solutions , 2013, Journal of Cell Science.

[23]  E. Meijering Cell Segmentation : 50 Years Down the Road , 2012 .

[24]  O. Sliusarenko,et al.  High‐throughput, subpixel precision analysis of bacterial morphogenesis and intracellular spatio‐temporal dynamics , 2011, Molecular microbiology.

[25]  David Svoboda,et al.  TRAgen: A Tool for Generation of Synthetic Time-Lapse Image Sequences of Living Cells , 2015, ICIAP.

[26]  Leonardo Martins,et al.  ‘miSimBa’ — A simulator of synthetic time-lapsed microscopy images of bacterial cells , 2015, 2015 IEEE 4th Portuguese Meeting on Bioengineering (ENBENG).

[27]  T. Misteli Beyond the Sequence: Cellular Organization of Genome Function , 2011 .

[28]  Carlo Tomasi,et al.  Efficient Visual Object Tracking with Online Nearest Neighbor Classifier , 2010, ACCV.

[29]  Noël Bonnet,et al.  Some trends in microscope image processing. , 2004, Micron.

[30]  Satwik Rajaram,et al.  SimuCell: a flexible framework for creating synthetic microscopy images , 2012, Nature Methods.

[31]  Eric Mjolsness,et al.  Measuring single-cell gene expression dynamics in bacteria using fluorescence time-lapse microscopy , 2011, Nature Protocols.

[32]  Pekka Ruusuvuori,et al.  Benchmark set of synthetic images for validating cell image analysis algorithms , 2008, 2008 16th European Signal Processing Conference.

[33]  Myong-Hee Sung,et al.  Live cell imaging and systems biology , 2011, Wiley interdisciplinary reviews. Systems biology and medicine.

[34]  José Manuel Fonseca,et al.  CellAging: a tool to study segregation and partitioning in division in cell lineages of Escherichia coli , 2013, Bioinform..

[35]  N. Gordon,et al.  Novel approach to nonlinear/non-Gaussian Bayesian state estimation , 1993 .

[36]  Gaudenz Danuser,et al.  Computer Vision in Cell Biology , 2011, Cell.

[37]  Ting Zhao,et al.  Automated learning of generative models for subcellular location: Building blocks for systems biology , 2007, Cytometry. Part A : the journal of the International Society for Analytical Cytology.