New imaging technique for the early detection of

image: Researchers at SIT, Japan, are proposing a new method to detect the presence of abnormal red blood cells that can allow early diagnosis of the onset of blood damage caused by cardiovascular assistive devices.
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Credit: Dr Antony P. McNamee from GU, Australia

Red blood cells (RBCs) or erythrocytes are constantly exposed to “shear stress” as they move through the body. This stress is usually mild, and the red blood cells are flexible enough to adapt to changes in shape in response. However, mechanical devices such as artificial hearts and circulatory (blood flow) support systems can often put great strain on them, stretching and breaking red blood cells in the process. Unfortunately, this is a common occurrence and so far it remains inevitable.

Conventional methods of examining blood damage involve the use of red blood cells that are already damaged beyond repair. This raises a relevant question: is it possible to detect the onset of damage at an earlier stage and reverse it? It is evident that real-time monitoring of sheared red blood cells could help us better understand the process and aid in the development of markers to detect the appearance of blood lesions at a sublethal stage.

In their new study published in Scientific reports, a team of researchers from Japan and Australia, led by Associate Professor Nobuo Watanabe from Shibaura Institute of Technology, Japan and Associate Professor Michael J. Simmonds from Griffith University (GU), Australia, devised a new approach to detect the changes that red blood cells undergo in shear. Unlike previous studies which inspected red blood cells in a static state, this study examined the “membrane symmetry” of red blood cells stressed during “supraphysiological shear” to see how much it differed from normal. Dr Watanabe explains, “Conventional image analysis methods are ill-equipped to detect the subtle shape changes associated with the morphological alterations observed in supraphysiological flow. With our technique, it becomes possible to assess and detect these changes in shape and damage.

To achieve this feat, the team used a custom-made shear chamber mounted on a microscope equipped with a high-speed capture camera to visualize the onset of red blood cell destruction. They collected blood samples from two healthy male volunteers aged 20 to 30 and subjected them to a range of shear loads of 10 to 60 pascals (Pa) for 5 minutes. They then examined the number of red blood cells and detected abnormalities on the video footage, optimizing the imaging system to improve detection of asymmetry.

They noticed something remarkable: after prolonged exposure to a stress load of 60 Pa, the red blood cells became unstable, changed shape and even disintegrated into smaller fragments. “While hemoglobin release represents endpoint or “hemolytic stage” cell destruction, our data suggests that bulk fragmentation, a fatal transition for red blood cells, can still be observed in the “subhemolytic” condition of. 60 Pa. ” says Dr Watanabe, enthralled by the results.

The team then hypothesized that irregular shear stress, rather than regular shear stress, would cause the cell to stiffen at low shear exposures before its appearance changed. To confirm this, they applied an additional 1 Pa shear after the 60 Pa exposure, observing aggregates of red blood cells with swollen vesicle-like structures swirling in the flow. Interestingly, the “elongation index” (EI), assessing the deviation of the cell from its normal axes, showed only minimal changes after exposure.

The team believe the technique will allow a more detailed examination of the structure of circulating red blood cells, speeding up research into blood damage processes caused by cardiovascular medical equipment. “The technology can be implemented in future next-generation equipment for near real-time diagnosis of blood lesions in patients requiring mechanical circulatory support.Explains Dr Watanabe. Speaking of potential future applications, he adds, “Our proposed strategy focuses on the early appearance of functional markers, when blood damage may still be reversible.. The integration of these functional assessment markers in the deployment of cardiovascular medical devices could help guide the future clinical practice of artificial organs to improve blood compatibility. and improve patient outcomes.

Hopefully his visions aren’t too far from coming true.




About the Shibaura Institute of Technology (SIT), Japan

Shibaura Institute of Technology (SIT) is a private university with campuses in Tokyo and Saitama. Since the establishment of its predecessor, the Tokyo Graduate School of Industry and Commerce, in 1927, it has maintained “learning by doing” as a philosophy in the education of engineers. SIT was the only private science and engineering university selected for the Top Global University Project sponsored by the Ministry of Education, Culture, Sports, Science and Technology and will receive support from the ministry for 10 years as of the 2014 academic year. Its motto, “Nurturing Engineers who Learn from Society and Contribute to Society”, reflects its mission to foster scientists and engineers who can contribute to the sustainable growth of the world by exhibiting their most from 8,000 students to culturally diverse environments, where they learn to face, collaborate and build relationships with other students around the world.


About Associate Professor Nobuo Watanabe

Dr Nobuo Watanabe is currently working as an Associate Professor at the Biofluid Science and Engineering Laboratory at the Shibaura Institute of Technology, Saitama, Japan. His research interests include cardiovascular physiology, artificial organs, hemolysis and thrombosis, blood cell deformation, and the use of engineering methodologies to create new diagnostic and therapy technologies. He is a member of the Japanese Society of Medical and Biological Engineering, the Society of Life Support Engineering, the Japanese Society of Biorheology, and the European Society of Artificial Organs, among other notable academic organizations. He has received numerous research grants and participates in collaborative research projects all over the world.

Funding Information

This study was funded by the Japan Society for the Promotion of Science, under grants JP17K01370 and JP20K12609.

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