1. Detection of Prostate Cancer from Whole-Mount Histology Images Using Markov Random Fields James P. Monaco 1, John E. Tomaszewski 2, Michael D. Feldman 2, Mehdi Moradi 3, Parvin Mousavi 3, Alexander Boag 3, Chris Davidson 3, Purang Abolmaesumi 3, Anant Madabhushi 1 1 Rutgers University, USA 2 University of Pennsylvania, USA 3 Queen’s University, Canada Laboratory for Computational Imaging and Bioinformatics, lcib.rutgers.edu

2. Prostate Cancer (CaP) Protocol PSA/Rectal exam TRUS Biopsy Pathologist Diagnosis Prostatectomy Pathologist Diagnosis Post-surgical Treatment 0 lcib.rutgers.edu

3. Aid doctors with time consuming task – Digitized data about 60,000x40,000 at 0.5 micron Can help supply “ground truth” for other modalities Quantifiable features facilitate data mining Computer Aided Detection of CaP in Whole-Mount Histology lcib.rutgers.edu

4. Novel Contributions First CAD system for detecting CaP in whole- mount histological images – Tailored to operate at low-resolution (10 micron) Novel nonparametric method for modeling Markov Random Fields lcib.rutgers.edu

5. Low-Resolution CaP Detection Glands are the prominent visible structures Cancerous glands: 1) small, 2) surrounded by cancerous glands lcib.rutgers.edu

6. Overview of Cap Detection Algorithm Gland Segmentation Gland Classification Markov Random Field Iteration Boundary Aggregation lcib.rutgers.edu

7. Segmentation S.A. Hojjatoleslami and J. Kittler, “Region growing: a new approach,” IEEE Trans. on Image Processing, vol. 7, no. 7, pp. 1079–1084, July 1998. lcib.rutgers.edu

8. Classification: Glandular Area Malignant Histogram Benign Histogram Remove legend Remove legend lcib.rutgers.edu

9. Markov Random Field Basics Goal: Inject knowledge that malignant glands are near malignant glands Establish a graph connecting the glands Let {a 1, a 2,…, a N } be the gland areas Let {l 1, l 2,…, l N } be the gland labels with l i  {m,b} lcib.rutgers.edu

10. Markov Random Field Models Prevalent parametric model (Ising) – Generic model used for its simplicity Novel nonparametric model – Generated directly from image statistics lcib.rutgers.edu

11. Experiments Experiment 1 Evaluate CAD gland classification performance Experiment 2 Compare parametric (Ising) and nonparametric models Dataset four H&E stained whole-mount histological sections at 10 micron lcib.rutgers.edu

12. Experiment 1: CAD Performance Area-based with MRF lcib.rutgers.edu

13. Experiment 2: Compare Ising and Nonparametric Model Ising Nonparametric Gland Segmentation Gland Classification Nonparametric MRF Ising MRF lcib.rutgers.edu

14. Concluding Remarks First CAD system for detecting CaP in whole- mount histological images – Sensitivity of 0.8670 and specificity of 0.9524 – Requires 4-5 minutes on a 2100×3200 image using standard desktop PC Introduced a novel nonparametric model for Markov Random Fields – Better performance than Ising model – Easily extended to other biological applications lcib.rutgers.edu

15. Acknowledgements Wallace H. Coulter Foundation New Jersey Commission on Cancer Research National Cancer Institute Society for Imaging and Informatics on Medicine Life Science Commercialization Award lcib.rutgers.edu

16. The End lcib.rutgers.edu

17. Gibbs Formulations Generic Ising Model Nonparametric Formulation

18. MRF Basics: Markov Properties Let G={S,E} define a graph on N glands Let y = {y 1, y 2,…, y N } be the gland areas Let x = {x 1, x 2,…, x N } be the gland labels with x i  {m,b} Use maximum a posteriori estimation to obtain x Simplify with Markov Property: p(x s |x -s )=p(x s |x r :r  s ) Markov Property implies p(x) is a Gibbs distribution

19. Among men in the US prostate cancer (Cap) is second most common cancer and the second leading cause of cancer-related death. Histological analysis provides the definite test for CaP. Analysis of whole mount histological sections (WMHSs) – Staging and grading of CaP – Ground truth for other modalities Prostate Cancer

20. MRF Results

21. Glands to Regions

22. Segmentation: Region Growing Current Boundary (CB) Internal Boundary (IB) Current Region (CR) boundary_measure = mean(IB)-mean(CB) Iteration1 2 34514 45 132126178

23. Neighborhood Structure of the Glands

24. Quantitative Results Review of algorithm – Segmentation – Classification using area (requires a probability threshold) – MRF Iteration Initial conditions affect MRF results ROC curve over varying thresholds Gland Classification Performance

25. Qualitative Results

26. Experiment 1: Gland Classification Evaluate the ability to discriminate malignant from benign glands. A gland whose centroid lies within the blue truth is considered cancerous, otherwise it is benign. Training/test data consists of four slices using a leave- one-out training