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Fuhai Li, Ph.D. BBP-TMHRI, Feb 7 2011

3D Tumor Stem Cell Niche Image Analysis. NCI-ICBP CMCD U54 Progress Report. Fuhai Li, Ph.D. BBP-TMHRI, Feb 7 2011. http://www.methodisthealth.com/icbp. Tumor Stem Cell Niche. J Rosen, BCM. From 2D to 3D. DAPI. GFP. From center grant proposal. Dextran. Superimposed.

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Fuhai Li, Ph.D. BBP-TMHRI, Feb 7 2011

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  1. 3D Tumor Stem Cell Niche Image Analysis NCI-ICBP CMCD U54 Progress Report Fuhai Li, Ph.D. BBP-TMHRI, Feb 7 2011 http://www.methodisthealth.com/icbp

  2. Tumor Stem Cell Niche J Rosen, BCM

  3. From 2D to 3D DAPI GFP From center grant proposal Dextran Superimposed .44 μm X .44 μm X 1 μm

  4. Specific Aim • Digitize 3D images of tumor stem cell niche & provide quantitative data for • Tumor modeling • Blood vessel tracing • Nuclei segmentation

  5. What information is expected? • Anything we can see, image, and imagine! E.g., • Spatial distributions (in normal and tumor, before and after treatment) of blood vessels, stem cells, stroma, etc. • Cell morphology, proliferation and death From John, Tegy, Mei Zhang, Michael T. Lewis

  6. Blood Vessel and Nuclei Segmentation

  7. Blood Vessel Segmentation (Tracing) Technical Challenges: Noise Signal Broken Points and Vessel Crossing

  8. 3D Blood Vessel Image

  9. Maximum Intensity Projection (MIP)

  10. Validation of Available Segmentation Software http://research.mssm.edu/cnic/tools-ns.html

  11. NeuronStudio http://research.mssm.edu/cnic/tools-ns.html

  12. V3D http://penglab.janelia.org/proj/v3d/V3D/About_V3D.html

  13. FARSIGHT http://www.farsight-toolkit.org/wiki/Main_Page

  14. Multi-scale Filtering and Optimal Linking Based Approach

  15. Multiscale Vessel Enhancement Filtering Multiscale means image filtering with Gaussian filters (with different sigmas) The eigenvalues of Hessian matrix tell us where are the vessels Hessian Matrix A. Frangi, et. al, MICCAI, 1998

  16. Binary Image of MIP (Original)

  17. Multiscale Vessel Enhancement Filtering

  18. Removal of Debris

  19. Skeleton Extraction T.C. Lee, et. al, GVGIP, 1994

  20. Binary 3D View

  21. Optimal Linking by Integer Programming (ongoing) smoothness term Fitness term Cost function: Solving: subject to: can only be linked to at most to once!

  22. Nuclei Segmentation Technical Challenges: Uneven Intensity and Cell Clustering

  23. 3D View

  24. FARSIGHT 3D Analysis

  25. Flowchart of Nuclei Segmentation Z-Series 2D Images Adaptive Thresholding Distance Transform (Shape Info.) LoG Filtering (Intensity Info.) Seed Image (Non-Maximum Suppression) Level Set Segmentation

  26. 2D Image Analysis

  27. TT Proposed 3D Analysis

  28. Refine & Define Nuclei by Ellipsoid Fitting digital 3D tumor stem cell niche nucleus = {o, a, b, c, α, β} Low Z resolution

  29. Ongoing Work • Blood vessel smoothing & broken points linking • Nuclei ellipsoid fitting, Image quantification & dividing cell identification • Process large volumes of image data to derive information for tumor modeling • Graphic user interface (GUI) tools for image analysis, visualization & tumor simulation

  30. TT Normal Breast Tissue From Dr. Michael T. Lewis (John David Acquired)

  31. Acknowledgements BCM: Michael Lewis Mei Zhang Mary Dickinson John Landua Tegy Vadakkan Wei Wei BBP-TMHRI: Stephen Wong Xiaofeng Xia Hong Zhao Derek Cridebring NIH NCI-ICBP U54 Grant Support

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