Perceptual clustering for automatic hotspot detection from Ki‐67‐stained neuroendocrine tumour images

Hotspot detection plays a crucial role in grading of neuroendocrine tumours of the digestive system. Hotspots are often detected manually from Ki‐67‐stained images, a practice which is tedious, irreproducible and error prone. We report a new method to segment Ki‐67‐positive nuclei from Ki‐67‐stained slides of neuroendocrine tumours. The method combines minimal graph cuts along with the multistate difference of Gaussians to detect the individual cells from images of Ki‐67‐stained slides. It, then, automatically defines the composite function, which is used to determine hotspots in neuroendocrine tumour slide images. We combine modified particle swarm optimization with message passing clustering to mimic the thought process of the pathologist during hotspot detection in neuroendocrine tumour slide images. The proposed method was tested on 55 images of size 10 × 5 K and resulted in an accuracy of 94.60%. The developed methodology can also be part of the workflow for other diseases such as breast cancer and glioblastomas.

[1]  Dirk P. Kroese,et al.  Kernel density estimation via diffusion , 2010, 1011.2602.

[2]  F. Bosman,et al.  WHO Classification of Tumours of the Digestive System , 2010 .

[3]  G. Zack,et al.  Automatic measurement of sister chromatid exchange frequency. , 1977, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[4]  Dorin Comaniciu,et al.  The Variable Bandwidth Mean Shift and Data-Driven Scale Selection , 2001, ICCV.

[5]  Joel H. Saltz,et al.  Histopathological Image Analysis Using Model-Based Intermediate Representations and Color Texture: Follicular Lymphoma Grading , 2009, J. Signal Process. Syst..

[6]  Larry V McIntire,et al.  Automated Selection of DAB-labeled Tissue for Immunohistochemical Quantification , 2003, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[7]  Johannes Gerdes,et al.  The Ki‐67 protein: From the known and the unknown , 2000, Journal of cellular physiology.

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

[9]  Delbert Dueck,et al.  Clustering by Passing Messages Between Data Points , 2007, Science.

[10]  Chris A. Glasbey,et al.  An Analysis of Histogram-Based Thresholding Algorithms , 1993, CVGIP Graph. Model. Image Process..

[11]  Marina Meila,et al.  An Experimental Comparison of Several Clustering and Initialization Methods , 1998, UAI.

[12]  N. Otsu A threshold selection method from gray level histograms , 1979 .

[13]  M. Khalid Khan,et al.  Entropy based quantification of Ki-67 positive cell images and its evaluation by a reader study , 2013, Medical Imaging.

[14]  Philip Chan,et al.  Determining the number of clusters/segments in hierarchical clustering/segmentation algorithms , 2004, 16th IEEE International Conference on Tools with Artificial Intelligence.

[15]  Yizong Cheng,et al.  Mean Shift, Mode Seeking, and Clustering , 1995, IEEE Trans. Pattern Anal. Mach. Intell..

[16]  A. Ruifrok,et al.  Quantification of histochemical staining by color deconvolution. , 2001, Analytical and quantitative cytology and histology.

[17]  Larry D. Hostetler,et al.  The estimation of the gradient of a density function, with applications in pattern recognition , 1975, IEEE Trans. Inf. Theory.

[18]  C. Compton,et al.  The American Joint Committee on Cancer: the 7th Edition of the AJCC Cancer Staging Manual and the Future of TNM , 2010, Annals of Surgical Oncology.

[19]  M. Khalid Khan,et al.  A Modified Particle Swarm Optimization Applied in Image Registration , 2010, 2010 20th International Conference on Pattern Recognition.

[20]  Dorin Comaniciu,et al.  Mean Shift: A Robust Approach Toward Feature Space Analysis , 2002, IEEE Trans. Pattern Anal. Mach. Intell..

[21]  Marco Saerens,et al.  Clustering methods applied in the detection of Ki67 hot‐spots in whole tumor slide images: An efficient way to characterize heterogeneous tissue‐based biomarkers , 2012, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[22]  M. Khalid Khan,et al.  Hot spot detection for breast cancer in Ki-67 stained slides: image dependent filtering approach , 2014, Medical Imaging.

[23]  Metin N Gurcan,et al.  Detecting and characterizing cellular responses to Mycobacterium tuberculosis from histology slides , 2014, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[24]  M. Guerrero,et al.  Trends of Incidence and Survival of Gastrointestinal Neuroendocrine Tumors in the United States: A Seer Analysis , 2012, Journal of Cancer.

[25]  Hui Kong,et al.  Follicular lymphoma grading using cell-graphs and multi-scale feature analysis , 2012, Medical Imaging.

[26]  M. Khalid Khan,et al.  Fully Automatic Heart Beat Rate Determination in Digital Video Recordings of Rat Embryos , 2008, Trans. Mass Data Anal. Images Signals.

[27]  Rui Xu,et al.  Clustering Algorithms in Biomedical Research: A Review , 2010, IEEE Reviews in Biomedical Engineering.

[28]  Rui Xu,et al.  Survey of clustering algorithms , 2005, IEEE Transactions on Neural Networks.

[29]  M. Khalid Khan,et al.  An automated method for counting cytotoxic T-cells from CD8 stained images of renal biopsies , 2013, Medical Imaging.