Due to the importance of nuclear structure in cancer diagnosis, several predictive models have been described for diagnosing a wide variety of cancers based on nuclear morphology. In many computer-aided diagnosis (CAD) systems, cancer detection tasks can be generally formulated as set classification problems, which can not be directly solved by classifying single instances. In this paper, we propose a novel set classification approach SetSVM to build a predictive model by considering any nuclei set as a whole without specific assumptions. SetSVM features highly discriminative power in cancer detection challenges in the sense that it not only optimizes the classifier decision boundary but also transfers discriminative information to set representation learning. During model training, these two processes are unified in the support vector machine (SVM) maximum separation margin problem. Experiment results show that SetSVM provides significant improvements compared with five commonly used approaches in cancer detection tasks utilizing 260 patients in total across three different cancer types, namely, thyroid cancer, liver cancer, and melanoma. In addition, we show that SetSVM enables visual interpretation of discriminative nuclear characteristics representing the nuclei set. These features make SetSVM a potentially practical tool in building accurate and interpretable CAD systems for cancer detection.

We propose a new mathematical and algorithmic framework for unsupervised image segmentation, which is a critical step in a wide variety of image processing applications. We have found that most existing segmentation methods are not successful on histopathology images, which prompted us to investigate segmentation of a broader class of images, namely those without clear edges between the regions to be segmented. We model these images as occlusions of random images, which we call textures, and show that local histograms are a useful tool for segmenting them. Based on our theoretical results, we describe a flexible segmentation framework that draws on existing work on nonnegative matrix factorization and image deconvolution. Results on synthetic texture mosaics and real histology images show the promise of the method.

We present a method for identifying colitis in colon biopsies as an extension of our framework for the automated identification of tissues in histology images. Histology is a critical tool in both clinical and research applications, yet even mundane histological analysis, such as the screening of colon biopsies, must be carried out by highly-trained pathologists at a high cost per hour, indicating a niche for potential automation. To this end, we build upon our previous work by extending the histopathology vocabulary (a set of features based on visual cues used by pathologists) with new features driven by the colitis application. We use the multiple-instance learning framework to allow our pixel-level classifier to learn from image-level training labels. The new system achieves accuracy comparable to state-of-the-art biological image classifiers with fewer and more intuitive features.

Nuclear morphology and structure as visualized from histopathology microscopy images can yield important diagnostic clues in some benign and malignant tissue lesions. Precise quantitative information about nuclear structure and morphology, however, is currently not available for many diagnostic challenges. This is due, in part, to the lack of methods to quantify these differences from image data. We describe a method to characterize and contrast the distribution of nuclear structure in different tissue classes (normal, benign, cancer, etc.). The approach is based on quantifying chromatin morphology in different groups of cells using the optimal transportation (Kantorovich-Wasserstein) metric in combination with the Fisher discriminant analysis and multidimensional scaling techniques. We show that the optimal transportation metric is able to measure relevant biological information as it enables automatic determination of the class (e.g., normal versus cancer) of a set of nuclei. We show that the classification accuracies obtained using this metric are, on average, as good or better than those obtained utilizing a set of previously described numerical features. We apply our methods to two diagnostic challenges for surgical pathology: one in the liver and one in the thyroid. Results automatically computed using this technique show potentially biologically relevant differences in nuclear structure in liver and thyroid cancers.