Projet de recherche doctoral numero :8081

Description

Date depot: 18 mars 2021
Titre: A Joint Discriminative-Generative Approach for Tumor Angiogenesis Assessment in Computational Pathology
Directeur de thèse: Daniel RACOCEANU (ICM)
Domaine scientifique: Sciences et technologies de l'information et de la communication
Thématique CNRS : Non defini

Resumé: Angiogenesis is the process through which new blood vessels are formed from pre-existing ones. During angiogenesis, tumour cells secrete growth factors that activate the proliferation and migra- tion of endothelial cells and stimulate over production of the vascular endothelial growth factor (VEGF). The fundamental role of vascular supply in tumour growth and anti-cancer therapies makes the evaluation of angiogenesis crucial in assessing the effect of anti-angiogenic therapies as a promising anti-cancer therapy.In this study, we establish a quantitative and qualitative panel to evaluate tumour blood vessels structures on non-invasive fluorescence images and histopathological slide across the full tumour to identify architectural features and quantitative measurements that are often associated with prediction of therapeutic response.We develop a Markov Random Field (MFRs) and Watershed framework to segment blood vessel structures and tumour micro-enviroment components to assess quantitatively the effect of the anti-angiogenic drug Pazopanib on the tumour vasculature and the tumour micro-enviroment interaction.The anti-angiogenesis agent Pazopanib was showing a direct effect on tumour network vasculature via the endothelial cells crossing the whole tumour. Our results show a specific relationship between apoptotic neovascularization and nucleus density in murine tumor treated by Pazopanib.Then, qualitative evaluation of tumour blood vessels structures is performed in whole slide images, known to be very heterogeneous. We develop a discriminative-generative neural network model based on both learning driven model convolutional neural network (CNN), and rule-based knowledge model Marked Point Process (MPP) to segment blood vessels in very heterogeneous images using very few annotated data comparing to the state of the art. We detail the intuition and the design behind the discriminative-generative model, and we analyze its similarity with Generative Adversarial Network (GAN). Finally, we evaluate the performance of the proposed model on histopathology slide and synthetic data. The limits of this promising framework as its perspectives are shown.

Doctorant.e: Laifa Oumeima