Tissue microarrays (TMAs) are a high-throughput technique that facilitates the survey of very large numbers of tumours, important both in clinical and research applications. However, the assessment of stained TMA sections is laborious and still needs to be carried manually, constituting a bottleneck in the pathologist?s work-flow. This process is also prone to perceptual errors and observer variability.Thus, there is strong motivation for the development of automated quantitative analysis of TMA image data. The analysis of breast TMA sections subjected to nuclear immunostaining begins with the classification of each spot as to the maintype of tissue that it contains, namely tumour, normal, stroma, or fat. Tumour and normal spots are then assigned a so-called quickscore composed of a pair or integer values, the first reflecting the proportion of epithelial nuclei that are stained, and the second reflecting the strength of staining of those nuclei. In this work, an approach was developed to analyse breast TMA spots subjectedto progesterone receptor immunohistochemistry. Spots were classified into their four main types through a method that combined a bag of features approachand classifiers based on either multi-layer perceptrons or latent Dirichlet allocation models. A classification accuracy of 74.6 % was achieved. Tumour and normal spots were scored via an approach that involved the computation of global features formalising the quickscore values used by pathologists, and the use of Gaussian processes for ordinal regression to predict actual quickscores based on global features. Mean absolute errors of 0.888 and 0.779 were achieved in the prediction of the first and second quickscore values, respectively. By setting thresholds on prediction confidence, it was possible to classify and score fractions of spots with substantially higher accuracies and lower mean absolute errors. Amethod for the segmentation of TMA spots into regions of different types was also investigated, to explore the generative nature of latent Dirichlet allocation models.
|Date of Award||2010|
|Sponsors||Breast Cancer Research Trust|
|Supervisor||Stephen McKenna (Supervisor) & Alastair Thompson (Supervisor)|
- Breast cancer
- Tissue microarrays
- Medical image analysis