A new imaging method has been designed and tested by scientists from Johns Hopkins Medicine. According to them, this newly developed approach will expedite imaging-based study in the laboratory by enabling investigators to capture images of blood vessels at various spatial scales.
A visual demonstration of the result of the VascuViz imaging pipeline. Video Credit: Johns Hopkins Medicine.
The method, called dubbed “VascuViz,” has been tested in mouse tissues and consists of a quick-setting polymer mixture to fill blood vessels and make them visible in numerous imaging techniques.
According to the scientists, the method allows them to envision the structure of a tissue’s vasculature, which jointly with elaborate mathematical models or complementary images of other tissue elements could simplify the complicated role of blood flow in health and disease.
The integrated images of the blood vessels must not only improve the study of the biology of diseases that includes abnormalities in blood flow, like stroke and cancer, but also develop the understanding of the structures and functions of tissues across the body.
The study has been reported in the Nature Methods journal on February 10th, 2022.
Usually, if you want to gather data on blood vessels in a given tissue and combine it with all of its surrounding context like the structure and the types of cells growing there, you have to re-label the tissue several times, acquire multiple images and piece together the complementary information.”
Arvind Pathak, PhD, Professor, Radiology, Biomedical and Electrical Engineering, Johns Hopkins University
He is also a member of the Sidney Kimmel Comprehensive Cancer in Johns Hopkins University School of Medicine.
Pathak added, “This can be an expensive and time-consuming process that risks destroying the tissue’s architecture, precluding our ability to use the combined information in novel ways.”
Scientists make use of many different imaging techniques, like CT, MRI, and microscopy to study the role of blood vessels in the laboratory. Such images are beneficial for comprehending the dynamics of how tissues tend to develop disease or react to treatment.
But, integrating the data available in such images has stayed a challenge since agents employed to make a blood vessel visible to one imaging technique can make it invisible on other methods. This restricts the amount of data scientists could collect from a single sample.
VascuViz overcomes this issue by making the structure of the biggest arteries to the smallest microvasculature visible to a range of imaging tools. This enables scientists to design a multilayered understanding of blood vessels and their associated tissue components with less effort and time.
Especially, the development of VascuViz is beneficial in making computerized visualizations of how complicated biological systems like the circulatory system work, and it is known as a hallmark of the growing field of “image-based” vascular systems biology.
Now, rather than using an approximation, we can more precisely estimate features like blood flow in actual blood vessels and combine it with complementary information, such as cell density.”
Akanksha Bhargava, PhD, Postdoctoral Fellow, Pathak Lab, Department of Radiology and Radiological Science, School of Medicine, Johns Hopkins University
To perform this, VascuViz-based measurements are fed into computer simulations of blood flow, like the cancer models Bhargava studies.
To make VascuViz, Bhargava tested various combinations of present imaging agents and their suitability for various imaging methods.
As soon as multiple iterations are over, she discovered that a CT contrast agent called BriteVu and a fluorescently labeled MRI contrast agent known as Galbumin-Rhodamine can be integrated to make a compound that creates the macro- and microvasculature visible at the same time while imaging with CT, MRI, and optical imaging methods without interference.
Having the compound working in test tubes, the scientists further tested it in a range of mouse tissues, perfusing it via the vascular system of breast cancer models, the brain, leg muscles, and kidney tissues.
The consequent images of the tissues obtained with CT, MRI, and optical microscopy were further integrated to make stunning 3D visualizations of the vasculature and linked components comprising these organ systems and disease models.
As a result of the VascuViz’s low-cost and commercially available components, Pathak and his team hope it is adopted worldwide by researchers to help shed new light on various diseases involving vasculature.
The other scientists involved in this study include Benjamin Monteagudo, Priyanka Kushwaha, Janaka Senarathna, Yunke Ren, Ryan Riddle, and Manisha Aggarwal of the Johns Hopkins University School of Medicine.
Bhargava, A., et al. (2022) VascuViz: a multimodality and multiscale imaging and visualization pipeline for vascular systems biology. Nature Methods. doi.org/10.1038/s41592-021-01363-5.