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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - BIO-CAPTURE (Biomechanical Characterization of Carotid Plaque Rupture)

Teaser

Summary

This project tackled an urgent health problem, arterial atherosclerosis, a major cause of cardiovascular events. Current clinical decisions for surgical intervention are made without assessing the plaque vulnerability as no reliable means for vulnerability assessment exists today. Biomechanics can help to develop useful risk assessment tools; yet, the fundamental knowledge on atherosclerotic plaque biomechanics are to great extent missing. The project aimed at biomechanical characterization of atherosclerotic arteries. This was done by combining experimental work, high-end plaque imaging and computational modelling. The project provided biomechanical characterization, more specifically material properties of atherosclerotic arteries, their structural organization and potential mechanisms for material failure.

Work performed

Human arteries with atherosclerotic plaques were collected post-mortem, in compliance with Medical Ethics Approval Committee (METC) obtained from the host institute. The arteries were tested with a custom-built ex-vivo inflation test rig, designed and manufactured by the research team. The mechanical test rig enabled inflating the arteries, mimicking the physiological loading conditions and environment, and obtaining local deformation of the atherosclerotic arterial structure in high detail. The imaging for the local deformation measurements were acquired in high spatial resolution with a high frequency ultrasound system (Vevo 2100, Visualsonics Inc.), equipped with a mechanical drive. The raw ultrasound data was acquired during the inflation testing, which was later utilized for plaque deformation quantification. This manner, unique data set of mechanical testing and deformation of atherosclerotic arteries were obtained in an ex-vivo setting, mimicking physiological mechanical loading and biological environment the arteries are in (Figure 1).

Subsequently an algorithm in MATLAB environment was developed to acquire local deformation in atherosclerotic arteries from the raw ultrasound data. The developed algorithm was successfully applied to the data collected during the inflation tests. With this approach, local tissue deformation information during the intraluminal pressurization in atherosclerotic arteries was obtained (Figure 2). Plaque specific, heterogeneous material properties, essential for accurate biomechanical investigation of atherosclerotic arteries were obtained in the next phase of the project. Structural information of the arteries was acquired with high resolution MRI technique, also developed by the research team. The MR images enabled characterization of the mechanically important plaque structures, which were to be implemented in the biomechanical models. Plaque-specific FE models were created from high detail plaque geometries. The reconstructed plaque geometries registered to the ultrasound images. Using inverse FE technique, the material properties of atherosclerotic arteries were obtained (Figure 3).

With this project, the research team identified heterogenous biomechanical characteristics of atherosclerotic arteries, for the first time in such detail and under conditions mimicking physiological conditions. The intermediate and final results of the project was presented to large audiences with diverse backgrounds (biomechanical scientists, biomedical engineers, cardiovascular clinicians) in various scientific meetings such as 1.) Congress of the European Society of Biomechanics 2019, Vienna, Austria; 2.) Summer Biomechanics, Bioengineering and Biotransport Conference (SB3C) 2019, Pittsburgh, USA; 3.) Vulnerable Patient Meeting 2019, Stresa, Italy; 4.) International Conference on Computational and Mathematical Biomedical Engineering 2019, Sendai City, Japan; 5.) Biomechanics in Vascular Biology and Cardiovascular Disease 2019, London, England; 6.) 7th Dutch Bio-Medical Engineering Conference 2019, Egmond aan Zee, NL; 7.) World Congress of Biomechanics 2018, Dublin, Ireland. In total I have given 14 talks and 18 abstracts published. During the course of the project, three articles were published in the following peer reviewed, international journals: 1.) Journal of Biomechanics; 2.) Interface Focus; 3.) Journal of Structural Biology

Final results

With this project, the research team identified heterogenous biomechanical characteristics of atherosclerotic arteries, for the first time in such high detail and under conditions mimicking physiological conditions. The very near-future impact of the results will be clearly in the cardiovascular biomechanics field, especially in-silico analysis research field. The long-term impact of the project outcomes will be in a much broader spectrum in the atherosclerosis research, with the final impact on developing new strategies for treatment decision making for atherosclerosis-related interventions.

At the personal (career) level, the project impacted the PI by helping him gain new scientific skills in medical imaging, publishing in high-impact, peer-reviewed, international journals, providing significant exposure to wide variety of audiences by attending multiple scientific conferences, symposia and meetings, and starting new national and international interinstitutional collaborations. The successful performance of the PI in this project surely positively impacted his acceptance as an assistant professor at the host institution in July, 2019.