Johns Hopkins Medicine researchers have developed and tested a new imaging approach that they believe will accelerate imaging-based research in the laboratory by allowing researchers to capture images of blood vessels at different spatial scales. Tested in mouse tissue, the method, dubbed “VascuViz,” includes a blend of fast-setting polymers to fill blood vessels and make them visible in multiple imaging techniques. The approach allows researchers to visualize the structure of a tissue’s vasculature, which, in conjunction with detailed mathematical models or complementary images of other tissue elements, can clarify the complex role of blood flow in health and disease, say the researchers. Combined images of blood vessels should not only improve the study of the biology of diseases that involve blood flow abnormalities, such as cancer and stroke, but also advance our understanding of tissue structures and functions in whole body, they say.
The report was published on February 10, 2022 in Natural methods.
“Usually, if you want to collect data about the blood vessels of a given tissue and combine it with all of its surrounding context, like the structure and types of cells growing in it, you have to relabel the tissue multiple times, acquire several images and put together the complementary information,” says Arvind Pathak, Ph.D., professor of radiology, biomedical and electrical engineering and member of Sidney Kimmel Comprehensive Cancer at Johns Hopkins University School of Medicine. “It can be a process costly and time-consuming that risks destroying the architecture of the tissue, preventing our ability to use the combined information in novel ways.”
Researchers use many different imaging methods, such as MRI, CT scans and microscopy to study the role of blood vessels in the laboratory. These images are useful for understanding the dynamics of how tissue develops disease or responds to treatment. However, integrating the available data into these images has remained a challenge because the agents used to make a blood vessel visible by one imaging method may render it invisible on other tools. This limits the amount of data researchers can collect from a single sample.
VascuViz overcomes this problem by making the structure of the largest arteries to the smallest microvasculature visible to a variety of imaging tools, allowing researchers to develop a multi-layered understanding of blood vessels and associated tissue components with less time. and effort.
The development of VascuViz is particularly useful for creating computerized visualizations of the functioning of complex biological systems such as the circulatory system, and is a feature of the burgeoning field of “image-based” vascular systems biology.
“Now, rather than using an approximation, we can more accurately estimate features such as blood flow in real blood vessels and combine them with complementary information, such as cell density,” says Akanksha Bhargava, Ph.D. ., postdoctoral fellow at the Pathak Lab. in the Department of Radiology and Radiologic Sciences at Johns Hopkins University School of Medicine. To do this, VascuViz-based measurements are fed into computer simulations of blood flow, such as the cancer models studied by Bhargava.
To create VascuViz, Bhargava tested several combinations of existing imaging agents and their suitability for different imaging methods. After several iterations, she discovered that a CT contrast agent named BriteVu and a fluorescence-labeled MRI contrast agent called Galbumin-Rhodamine could be combined to create a compound that makes macro and microvasculature simultaneously visible during imaging. by MRI, CT and optical imaging techniques. without interference.
With the compound working in test tubes, the researchers then tested it in a variety of mouse tissues, perfusing it through breast cancer models’ vasculature, leg muscles, brain and kidney tissue. . The resulting tissue images acquired with MRI, CT and light microscopy were then combined to create stunning 3D visualizations of the vasculature and associated components including these disease models and organ systems.
Due to VascuViz’s affordability and commercially available components, Pathak and his team hope it will be globally adopted by scientists to help shed new light on different diseases involving the vascular system.
Reference: “VascuViz: A Multimodality and Multiscale Imaging and Visualization Pipeline for Vascular Systems Biology” by Akanksha Bhargava, Benjamin Monteagudo, Priyanka Kushwaha, Janaka Senarathna, Yunke Ren, Ryan C. Riddle, Manisha Aggarwal, and Arvind P. Pathak, February 10, 2022 , Natural methods.
Other researchers involved in this study include Benjamin Monteagudo, Priyanka Kushwaha, Janaka Senarathna, Yunke Ren, Ryan Riddle and Manisha Aggarwal from Johns Hopkins University School of Medicine.
This work was supported by National Cancer Institute (51R01CA196701-05, 1R01CA237597-01A1), National Institute of Dental & Craniofacial Research (5R01DE027957-02) and NIH Instrumentation grant (S10OD012287) and Sidney Kimmel Comprehensive Cancer Center, Quantitative Science Pilot Project Grant.