A novel method for mapping the heterogeneity in blood supply to normal and malignant tissues in the mouse dorsal window chamber
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Intravital Microscopy of Tumor-associated Vasculature Using Advanced Dorsal Skinfold Window Chambers on Transgenic Fluorescent Mice
Published on: January 19, 2018
Kathrine S Øye1, Geeta Gulati, Bjørn A Graff
1Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research,The Norwegian Radium Hospital, Montebello, Oslo, Norway.
Insights
This study introduces a new imaging technique to analyze blood flow in tumors and normal tissues. The method accurately maps blood flow velocity and supply time across entire tumor vascular networks.
Area of Science:
- Physiology
- Biomedical Engineering
- Oncology
Background:
- Understanding tumor vascular dynamics is crucial for developing effective cancer therapies.
- Current methods for assessing tumor blood flow can be limited in resolution and scope.
Purpose of the Study:
- To develop and validate a novel first-pass imaging method for studying microvascular blood flow.
- To enable simultaneous mapping of blood flow velocity and blood supply time (BST) in entire tumor vascular networks.
Main Methods:
- Intravenous administration of a bolus dose of a fluorescence-labeled macromolecule.
- Detection of the fluorescence signal as the bolus traverses the vascular network in mouse dorsal window chamber preparations.
- High-sensitivity imaging allowing detection in individual microvessels of tumors and normal tissues.
Main Results:
- The method successfully measured blood flow velocity and direction in individual microvessels of normal and malignant tissues.
- Accurate determination of blood supply time (BST) for individual tumor vessel segments was achieved.
- Comprehensive maps of blood flow velocity and BST across the entire microvascular network of xenografted tumors were generated.
Conclusions:
- This novel imaging method provides a sensitive and comprehensive approach to study tumor vascular physiology.
- The technique allows for detailed analysis of blood flow dynamics, crucial for preclinical cancer research and therapeutic development.
Abstract:
A novel first-pass imaging method for studying blood flow in tumors and normal tissues in mouse dorsal window chamber preparations is reported in this study. A fluorescence-labeled macromolecule is administered i.v. as a bolus dose, and the signal generated by the bolus is detected as the bolus passes through the vascular network. The sensitivity of the method is sufficiently high that the bolus can be detected in any tumor or normal tissue microvessel. The method is particularly useful for measuring the velocity and direction of blood flow in individual vessel segments of normal and malignant tissues and the blood supply time (BST) of individual tumor vessel segments; i.e., the time required for arterial blood to flow from a supplying tumor artery to a downstream microvessel segment. Since all vessels within a window chamber preparation can be studied simultaneously in a single imaging sequence, a significant benefit of the method is that it can be used to produce maps of velocity of blood flow and BST of the entire microvascular network of xenografted tumors.

