Prostate cancer (CaP) is evidenced by profound changes in the spatial distribution of cells. Spatial arrangement and architectural organization of nuclei, especially clustering of the cells, within CaP histopathology is known to be predictive of disease aggressiveness and potentially patient outcome. Quantitative histomorphometry is a relatively new field which attempt to develop and apply novel advanced computerized image analysis and feature extraction methods for the quantitative characterization of tumor morphology on digitized pathology slides. Recently, graph theory has been used to characterize the spatial arrangement of these cells by constructing a graph with cell/nuclei as the node. One disadvantage of several extant graph based algorithms (Voronoi, Delaunay, Minimum Spanning Tree) is that they do not allow for extraction of local spatial attributes from complex networks such as those that emerges from large histopathology images with potentially thousands of nuclei. In this paper, we define a cluster of cells as a node and construct a novel graph called Cell Cluster Graph (CCG) to characterize local spatial architecture. CCG is constructed by first identifying the cell clusters to use as nodes for the construction of the graph. Pairwise spatial relationship between nodes is translated into edges of the CCG, each of which are assigned certain probability, i.e. each edge between any pair of a nodes has a certain probability to exist. Spatial constraints are employed to deconstruct the entire graph into subgraphs and we then extract global and local graph based features from the CCG. We evaluated the ability of the CCG to predict 5 year biochemical failures in men with CaP and who had previously undergone radical prostatectomy. Extracted features from CCG constructed using nuclei as nodal centers on tissue microarray (TMA) images obtained from the surgical specimens of 80 patients allowed us to train a support vector machine classifier via a 3 fold randomized cross validation procedure which yielded a classification accuracy of 83:1±1:2%. By contrast the Voronoi, Delaunay, and Minimum spanning tree based graph classifiers yielded corresponding classification accuracies of 67:1±1:8% and 60:7±0:9% respectively.
KEYWORDS: Image segmentation, Performance modeling, Tumor growth modeling, Statistical modeling, Prostate, Data modeling, Visual process modeling, Principal component analysis, Breast, Breast cancer
Active contours and active shape models (ASM) have been widely employed in image segmentation. A major
limitation of active contours, however, is in their (a) inability to resolve boundaries of intersecting objects and
to (b) handle occlusion. Multiple overlapping objects are typically segmented out as a single object. On the
other hand, ASMs are limited by point correspondence issues since object landmarks need to be identified across
multiple objects for initial object alignment. ASMs are also are constrained in that they can usually only
segment a single object in an image. In this paper, we present a novel synergistic boundary and region-based
active contour model that incorporates shape priors in a level set formulation. We demonstrate an application
of these synergistic active contour models using multiple level sets to segment nuclear and glandular structures
on digitized histopathology images of breast and prostate biopsy specimens. Unlike previous related approaches,
our model is able to resolve object overlap and separate occluded boundaries of multiple objects simultaneously.
The energy functional of the active contour is comprised of three terms. The first term comprises the prior
shape term, modeled on the object of interest, thereby constraining the deformation achievable by the active
contour. The second term, a boundary based term detects object boundaries from image gradients. The third
term drives the shape prior and the contour towards the object boundary based on region statistics. The results
of qualitative and quantitative evaluation on 100 prostate and 14 breast cancer histology images for the task of
detecting and segmenting nuclei, lymphocytes, and glands reveals that the model easily outperforms two state of
the art segmentation schemes (Geodesic Active Contour (GAC) and Roussons shape based model) and resolves
up to 92% of overlapping/occluded lymphocytes and nuclei on prostate and breast cancer histology images.
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