title: Automated detection of regions of interest for tissue microarray experiments: an image texture analysis.
abstract: BACKGROUND
  Recent research with tissue microarrays led to a rapid progress toward quantifying the expressions of large sets of biomarkers in normal and diseased tissue. However, standard procedures for sampling tissue for molecular profiling have not yet been established.
  
  
  METHODS
  This study presents a high throughput analysis of texture heterogeneity on breast tissue images for the purpose of identifying regions of interest in the tissue for molecular profiling via tissue microarray technology. Image texture of breast histology slides was described in terms of three parameters: the percentage of area occupied in an image block by chromatin (B), percentage occupied by stroma-like regions (P), and a statistical heterogeneity index H commonly used in image analysis. Texture parameters were defined and computed for each of the thousands of image blocks in our dataset using both the gray scale and color segmentation. The image blocks were then classified into three categories using the texture feature parameters in a novel statistical learning algorithm. These categories are as follows: image blocks specific to normal breast tissue, blocks specific to cancerous tissue, and those image blocks that are non-specific to normal and disease states.
  
  
  RESULTS
  Gray scale and color segmentation techniques led to identification of same regions in histology slides as cancer-specific. Moreover the image blocks identified as cancer-specific belonged to those cell crowded regions in whole section image slides that were marked by two pathologists as regions of interest for further histological studies.
  
  
  CONCLUSIONS
  These results indicate the high efficiency of our automated method for identifying pathologic regions of interest on histology slides. Automation of critical region identification will help minimize the inter-rater variability among different raters (pathologists) as hundreds of tumors that are used to develop an array have typically been evaluated (graded) by different pathologists. The region of interest information gathered from the whole section images will guide the excision of tissue for constructing tissue microarrays and for high throughput profiling of global gene expression.
authors.affiliation: Center for Integrated Bioinformatics, School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania 19104-2875, USA. bilge@drexel.edu <bilge@drexel.edu>
authors.forename: Bilge
authors.initials: B
authors.lastname: Karaçali
authors.forename: Aydin
authors.initials: A
authors.lastname: Tözeren
mesh_terms: D000465:Algorithms; D001185:Artificial Intelligence; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D003936:Diagnosis, Computer-Assisted / Q000379:methods; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D009363:Neoplasm Proteins / Q000378:metabolism*; D010363:Pattern Recognition, Automated / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D046888:Tissue Array Analysis / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins