Flexible and Latent Structured Output Learning - Application to Histology

Malignant tumors that contain a high proportion of regions deprived of adequate oxygen supply (hypoxia) in areas supplied by a microvessel (i.e., a microcirculatory supply unit MCSU) have been shown to present resistance to common cancer treatments. Given the importance of the estimation of this proportion for improving the clinical prognosis of such treatments, a manual annotation has been proposed, which uses two image modalities of the same histological specimen and produces the number and proportion of MCSUs classified as normoxia (normal oxygenation level), chronic hypoxia (limited diffusion), and acute hypoxia (transient disruptions in perfusion), but this manual annotation requires an expertise that is generally not available in clinical settings. Therefore, in this paper, we propose a new methodology that automates this annotation. The major challenge is that the training set comprises weakly labeled samples that only contains the number of MCSU types per sample, which means that we do not have the underlying structure of MCSU locations and classifications. Hence, we formulate this problem as a latent structured output learning that minimizes a high order loss function based on the number of MCSU types, where the underlying MCSU structure is flexible in terms of number of nodes and connections. Using a database of 89 pairs of weakly annotated images (from eight tumors), we show that our methodology produces highly correlated number and proportion of MCSU types compared to the manual annotations.