Contrast-enhanced micro-CT for 3D X-ray based histology to assess the influence of antiangiogenic drugs on tumor vascularization and necrosis

Details

Supervisors

Kerckhofs, Greet

Faculty

Ecole polytechnique de Louvain

Degree label

Master [120] : ingénieur civil biomédical, à finalité spécialisée

Abstract

Cancer treatment faces numerous challenges, prompting ongoing research to explore new strategies. One such strategy involves targeted therapies, particularly the use of antiangiogenic drugs. The aim of this type of drug is to inhibit the formation of new blood vessels, which are crucial for tumor growth and metastasis. This thesis focuses on a specific antiangiogenic drug which is pazopanib, a tyrosine kinase inhibitor, to evaluate its efficacy in treating tumors. For this purpose, this research focuses on a specific category of tumors, soft tissue sarcoma, and more specifically on two dedifferentiated liposarcomas. These liposarcomas tumors, harvested from patients, were transplanted into immunodeficient mice. Visualisation of tumor blood vessels was achieved by staining tumors with Hf-POM and conducting ex-vivo computed tomography scans. Moreover, histopathological evaluation using H\&E and CD31 stains was also performed. The general aim of this thesis is to assess the complementarity and added value of contrast-enhanced microfocus X-ray computed tomography (CECT) compared to classical 2D histology for ex-vivo tumor visualization. Classical 2D histology, while the reference method for examining tumors, offers limited visualization of blood vessels due to its 2D representation. Moreover, this technique relies on the subjective analysis of pathologists and the specific sections selected, which can lead to slice-dependent conclusions given to heterogeneous nature of tumors. The first objective is to compare tumor visualization using classical 2D histology and CECT to identify blood vessels, necrosis, and adipocytes. Despite the advantages of CECT, issues with the uniform distribution of the contrast agent persist, as twelve tumors showed areas without contrast agent. Secondly, improved visualization of tumor vasculature is studied by exploring and refining blood vessels segmentation in CECT images. Although the methods tested were satisfactory, challenges remain in accurately segmenting complex blood vessel structures, ensuring connectivity, eliminating hemorrhagic zones, and detecting small, centrally located blood vessels. Finally, the effectiveness of ex-vivo CECT in measuring impact of pazopanib on liposarcomas is investigated. No significant differences were found between control and pazopanib tumors in terms of volume, blood vessels density, and average blood vessels thickness. However, control tumors had larger blood vessels at the edges, while pazopanib tumors had smaller, more centrally located blood vessels.