Multiscale topology characterizes dynamic tumor vascular networks

Author:

Stolz Bernadette J.1ORCID,Kaeppler Jakob2ORCID,Markelc Bostjan23ORCID,Braun Franziska4ORCID,Lipsmeier Florian5ORCID,Muschel Ruth J.2,Byrne Helen M.1ORCID,Harrington Heather A.16ORCID

Affiliation:

1. Mathematical Institute, University of Oxford, Oxford, UK.

2. Oxford Institute for Radiation Oncology, University of Oxford, Oxford, UK.

3. Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.

4. Data Science, pRED Informatics, Pharma Research & Early Development, Roche Innovation Center Munich, Munich, Germany.

5. Digital Biomarkers, pRED Informatics, Pharma Research & Early Development, Roche Innovation Center Basel, Basel, Switzerland.

6. Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.

Abstract

Advances in imaging techniques enable high-resolution three-dimensional (3D) visualization of vascular networks over time and reveal abnormal structural features such as twists and loops, and their quantification is an active area of research. Here, we showcase how topological data analysis, the mathematical field that studies the “shape” of data, can characterize the geometric, spatial, and temporal organization of vascular networks. We propose two topological lenses to study vasculature, which capture inherent multiscale features and vessel connectivity, and surpass the single-scale analysis of existing methods. We analyze images collected using intravital and ultramicroscopy modalities and quantify spatiotemporal variation of twists, loops, and avascular regions (voids) in 3D vascular networks. This topological approach validates and quantifies known qualitative trends such as dynamic changes in tortuosity and loops in response to antibodies that modulate vessel sprouting; furthermore, it quantifies the effect of radiotherapy on vessel architecture.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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