Fuhai Li, Ph.D. BBP-TMHRI, Feb D Tumor Stem Cell Niche Image Analysis NCI-ICBP CMCD U54 Progress Report

Tumor Stem Cell Niche J Rosen, BCM

From 2D to 3D From center grant proposal DAPIGFP DextranSuperimposed.44 μm X.44 μm X 1 μm

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

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

Blood Vessel and Nuclei Segmentation

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

3D Blood Vessel Image

Maximum Intensity Projection (MIP)

Validation of Available Segmentation Software

NeuronStudio

V3D

FARSIGHT

Multi-scale Filtering and Optimal Linking Based Approach

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

Binary Image of MIP (Original)

Multiscale Vessel Enhancement Filtering

Removal of Debris

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

Binary 3D View

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

Nuclei Segmentation Technical Challenges: Uneven Intensity and Cell Clustering

3D View

FARSIGHT 3D Analysis

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

2D Image Analysis

TT Proposed 3D Analysis

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

Ongoing Work 1.Blood vessel smoothing & broken points linking 2.Nuclei ellipsoid fitting, Image quantification & dividing cell identification 3.Process large volumes of image data to derive information for tumor modeling 4.Graphic user interface (GUI) tools for image analysis, visualization & tumor simulation

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

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