1. Therapy-induced modulation of tumor vasculature and oxygenation in a murine glioblastoma model quantified by deep learning-based feature extraction.
- Author
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Bauer, Nadine, Beckmann, Daniel, Reinhardt, Dirk, Frost, Nicole, Bobe, Stefanie, Erapaneedi, Raghu, Risse, Benjamin, and Kiefer, Friedemann
- Subjects
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DEEP learning , *FEATURE extraction , *NEOVASCULARIZATION inhibitors , *BLOOD vessels , *OXYGEN in the blood , *GLIOBLASTOMA multiforme - Abstract
Glioblastoma presents characteristically with an exuberant, poorly functional vasculature that causes malperfusion, hypoxia and necrosis. Despite limited clinical efficacy, anti-angiogenesis resulting in vascular normalization remains a promising therapeutic approach. Yet, fundamental questions concerning anti-angiogenic therapy remain unanswered, partly due to the scale and resolution gap between microscopy and clinical imaging and a lack of quantitative data readouts. To what extend does treatment lead to vessel regression or vessel normalization and does it ameliorate or aggravate hypoxia? Clearly, a better understanding of the underlying mechanisms would greatly benefit the development of desperately needed improved treatment regimens. Here, using orthotopic transplantation of Gli36 cells, a widely used murine glioma model, we present a mesoscopic approach based on light sheet fluorescence microscopic imaging of wholemount stained tumors. Deep learning-based segmentation followed by automated feature extraction allowed quantitative analyses of the entire tumor vasculature and oxygenation statuses. Unexpectedly in this model, the response to both cytotoxic and anti-angiogenic therapy was dominated by vessel normalization with little evidence for vessel regression. Equally surprising, only cytotoxic therapy resulted in a significant alleviation of hypoxia. Taken together, we provide and evaluate a quantitative workflow that addresses some of the most urgent mechanistic questions in anti-angiogenic therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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