Cross-Modality Imaging of Murine Tumor Vasculature—a Feasibility Study

Molecular Imaging and Biology - Tập 23 Số 6 - Trang 874-893 - 2021
Lydia M. Zopf1, Patrick Heimel2, Stefan H. Geyer3, Anoop Kavirayani1, Susanne Reier1, Vanessa Fröhlich4, Alexander Stiglbauer-Tscholakoff4, Zhe Chen5, Lukas Nics5, Jelena Zinnanti1, Wolfgang Drexler5, Markus Mitterhauser5, Thomas H. Helbich4, Wolfgang J. Weninger3, Paul Slezak2, Anna C. Obenauf6, Katja Bühler7, Andreas Walter1
1Austrian BioImaging/CMI, Vienna BioCenter Core Facilities GmbH (VBCF), Vienna, Austria
2Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in the AUVA Trauma Research Center, Austrian BioImaging/CMI, Vienna, Austria
3Division of Anatomy, MIC, Medical University of Vienna, Austrian BioImaging/CMI, Vienna, Austria
4Department of Biomedical Imaging and Image-guided Therapy, Division of Molecular and Structural Preclinical Imaging, Medical University of Vienna, Vienna, Austria
5Medical University of Vienna, Vienna, Austria
6Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria
7VRVis Zentrum für Virtual Reality und Visualisierung Forschungs-GmbH, Austrian BioImaging/CMI, Vienna, Austria

Tóm tắt

Abstract

Tumor vasculature and angiogenesis play a crucial role in tumor progression. Their visualization is therefore of utmost importance to the community. In this proof-of-principle study, we have established a novel cross-modality imaging (CMI) pipeline to characterize exactly the same murine tumors across scales and penetration depths, using orthotopic models of melanoma cancer. This allowed the acquisition of a comprehensive set of vascular parameters for a single tumor. The workflow visualizes capillaries at different length scales, puts them into the context of the overall tumor vessel network and allows quantification and comparison of vessel densities and morphologies by different modalities. The workflow adds information about hypoxia and blood flow rates. The CMI approach includes well-established technologies such as magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT), and ultrasound (US), and modalities that are recent entrants into preclinical discovery such as optical coherence tomography (OCT) and high-resolution episcopic microscopy (HREM). This novel CMI platform establishes the feasibility of combining these technologies using an extensive image processing pipeline. Despite the challenges pertaining to the integration of microscopic and macroscopic data across spatial resolutions, we also established an open-source pipeline for the semi-automated co-registration of the diverse multiscale datasets, which enables truly correlative vascular imaging. Although focused on tumor vasculature, our CMI platform can be used to tackle a multitude of research questions in cancer biology.

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