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Pathologists routinely classify breast tumors according to recurring patternsof nuclear grades, cytoplasmic coloration, and large-scale morphologicalformations (i.e. streams of spindle cells, adenoid islands, etc.). The factthat there are large-scale morphological formations suggest that tumor cellsstill possess the genetic programming to arrange themselves in orderlypatterns. However, small regions of order or subtle patterns of order areinvisible to the human eye. The ability to detect subtle regions of order andcorrelate them with clinical outcome and resistance to treatment can enhancediagnostic efficacy. By measuring the acute angle that results when the lineextending from the longest length within a nucleus intersects with thecorresponding line of an adjacent nucleus, the degree of alignment between twoadjacent nuclei can be measured. Through a series of systematictransformations, subtle regions of order and disorder within a tumor image canbe quantified and visualized in the form of a heat map. This numericaltransformation of spatial relationships between nuclei within tumors allows forthe detection of subtly ordered regions.

Quantifying Subtle Regions of Order and Disorder in Tumor Architecture by Calculating the Nearest-Neighbor Angular Profile