Unsupervised learning for vascular heterogeneity assessment of glioblastoma based on magnetic resonance imaging: The Hemodynamic Tissue Signature

This thesis focuses on the research and development of the Hemodynamic Tissue Signature (HTS) method: an unsupervised machine learning approach to describe the vascular heterogeneity of glioblastomas by means of perfusion MRI analysis. The HTS builds on the concept of habitats. An habitat is defined as a sub-region of the lesion with a particular MRI profile describing a specific physiological behavior. The HTS method delineates four habitats within the glioblastoma: the High Angiogenic Tumor (HAT) habitat, as the most perfused region of the enhancing tumor; the Low Angiogenic Tumor (LAT) habitat, as the region of the enhancing tumor with a lower angiogenic profile; the potentially Infiltrated Peripheral Edema (IPE) habitat, as the non-enhancing region adjacent to the tumor with elevated perfusion indexes; and the Vasogenic Peripheral Edema (VPE) habitat, as the remaining edema of the lesion with the lowest perfusion profile. The results of this thesis have been published in ten scientific contributions, including top-ranked journals and conferences in the areas of Medical Informatics, Statistics and Probability, Radiology & Nuclear Medicine, Machine Learning and Data Mining and Biomedical Engineering. An industrial patent registered in Spain (ES201431289A), Europe (EP3190542A1) and EEUU (US20170287133A1) was also issued, summarizing the efforts of the thesis to generate tangible assets besides the academic revenue obtained from research publications. Finally, the methods, technologies and original ideas conceived in this thesis led to the foundation of ONCOANALYTICS CDX, a company framed into the business model of companion diagnostics for pharmaceutical compounds, thought as a vehicle to facilitate the industrialization of the ONCOhabitats technology.