Journal Article
. 2013 Jul; 4:11.
doi: 10.4103/2153-3539.112696.

A gamma-gaussian mixture model for detection of mitotic cells in breast cancer histopathology images

Adnan Mujahid Khan 1 Hesham Eldaly  Nasir M Rajpoot  
Affiliations
  • PMID: 23858386
  •     4 References
  •     11 citations

Abstract

Unlabelled: In this paper, we propose a statistical approach for mitosis detection in breast cancer histological images. The proposed algorithm models the pixel intensities in mitotic and non-mitotic regions by a Gamma-Gaussian mixture model (GGMM) and employs a context aware post-processing (CAPP) in order to reduce false positives. Experimental results demonstrate the ability of this simple, yet effective method to detect mitotic cells (MCs) in standard H & E breast cancer histology images.

Context: Counting of MCs in breast cancer histopathology images is one of three components (the other two being tubule formation, nuclear pleomorphism) required for developing computer assisted grading of breast cancer tissue slides. This is very challenging since the biological variability of the MCs makes their detection extremely difficult. In addition, if standard H & E is used (which stains chromatin rich structures, such as nucleus, apoptotic, and MCs dark blue) and it becomes extremely difficult to detect the latter given the fact that former two are densely localized in the tissue sections.

Aims: In this paper, a robust MCs detection technique is developed and tested on 35 breast histopathology images, belonging to five different tissue slides.

Settings And Design: Our approach mimics a pathologists' approach to MCs detections. The idea is (1) to isolate tumor areas from non-tumor areas (lymphoid/inflammatory/apoptotic cells), (2) search for MCs in the reduced space by statistically modeling the pixel intensities from mitotic and non-mitotic regions, and finally (3) evaluate the context of each potential MC in terms of its texture.

Materials And Methods: Our experimental dataset consisted of 35 digitized images of breast cancer biopsy slides with paraffin embedded sections stained with H and E and scanned at × 40 using an Aperio scanscope slide scanner.

Statistical Analysis Used: We propose GGMM for detecting MCs in breast histology images. Image intensities are modeled as random variables sampled from one of the two distributions; Gamma and Gaussian. Intensities from MCs are modeled by a gamma distribution and those from non-mitotic regions are modeled by a gaussian distribution. The choice of Gamma-Gaussian distribution is mainly due to the observation that the characteristics of the distribution match well with the data it models. The experimental results show that the proposed system achieves a high sensitivity of 0.82 with positive predictive value (PPV) of 0.29. Employing CAPP on these results produce 241% increase in PPV at the cost of less than 15% decrease in sensitivity.

Conclusions: In this paper, we presented a GGMM for detection of MCs in breast cancer histopathological images. In addition, we introduced CAPP as a tool to increase the PPV with a minimal loss in sensitivity. We evaluated the performance of the proposed detection algorithm in terms of sensitivity and PPV over a set of 35 breast histology images selected from five different tissue slides and showed that a reasonably high value of sensitivity can be retained while increasing the PPV. Our future work will aim at increasing the PPV further by modeling the spatial appearance of regions surrounding mitotic events.

Keywords: Breast cancer grading; histopathology image analysis; mitotic cell detection; statistical modeling of mitotic cells.

Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up.
C W Elston, I O Ellis.
Histopathology, 1991 Nov 01; 19(5). PMID: 1757079
Highly Cited.
Automated mitosis detection of stem cell populations in phase-contrast microscopy images.
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Vincent Roullier, Olivier Lézoray, Vinh-Thong Ta, Abderrahim Elmoataz.
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HyMaP: A hybrid magnitude-phase approach to unsupervised segmentation of tumor areas in breast cancer histology images.
Adnan M Khan, Hesham El-Daly, Emma Simmons, Nasir M Rajpoot.
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Workflow for high-content, individual cell quantification of fluorescent markers from universal microscope data, supported by open source software.
Simon R Stockwell, Sibylle Mittnacht.
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Mapping spatial heterogeneity in the tumor microenvironment: a new era for digital pathology.
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Ziba Gandomkar, Patrick C Brennan, Claudia Mello-Thoms.
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