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Thrombus Imaging Using 3D Printed Middle Cerebral Artery Model and Preclinical Imaging Techniques: Application to
Andrea Vítečková Wünschová1, Adam Novobilský1, Jana Hložková2,3
1Department of Pharmacology and Toxicology, Veterinary Research Institute, Hudcova 296/70, 621 00 Brno, Czech Republic.
Insights
This study introduces a 3D printed artery model and novel barium sulfate contrast agent for advanced blood clot imaging. This approach enhances preclinical research for diagnosing and treating clot-related diseases like stroke.
Area of Science:
- Biomedical Engineering
- Medical Imaging
- Translational Research
Background:
- Blood clots cause significant societal burden, necessitating advanced diagnostic and therapeutic research.
- Preclinical models are crucial for developing new diagnostic and therapeutic strategies targeting blood clots.
Purpose of the Study:
- To develop and validate a 3D printed middle cerebral artery model for imaging blood clots under flow.
- To evaluate various contrast agents for clot detection using preclinical imaging modalities.
- To demonstrate a novel thrombus labeling method for in vitro and in vivo clot imaging.
Main Methods:
- Utilized a 3D printed middle cerebral artery model with blood flow.
- Employed fluorescent whole-body imaging, MRI, and microCT for clot visualization.
- Introduced barium sulfate (Micropaque®) for thrombus labeling in in vitro and in vivo models.
- Assessed thrombolytic efficacy of recombinant tissue plasminogen activator (rtPA) using the model.
Main Results:
- Demonstrated successful imaging of clots within the 3D model under flow conditions using multiple imaging techniques.
- Validated liposome-based, fibrin-targeted, and non-targeted contrast agents for clot detection.
- Showcased barium sulfate as an effective contrast agent for evaluating thrombolysis time-course.
- Presented proof-of-concept for in vivo clot imaging in a rat middle cerebral artery occlusion model.
Conclusions:
- The 3D printed artery model effectively supports preclinical imaging of clots under flow.
- Barium sulfate labeling offers a novel and effective method for in vitro and in vivo clot imaging and thrombolysis assessment.
- This approach facilitates comparable in vitro and in vivo experiments, potentially reducing animal usage in research.
Abstract:
Diseases with the highest burden for society such as stroke, myocardial infarction, pulmonary embolism, and others are due to blood clots. Preclinical and clinical techniques to study blood clots are important tools for translational research of new diagnostic and therapeutic modalities that target blood clots. In this study, we employed a three-dimensional (3D) printed middle cerebral artery model to image clots under flow conditions using preclinical imaging techniques including fluorescent whole-body imaging, magnetic resonance imaging (MRI), and computed X-ray microtomography (microCT). Both liposome-based, fibrin-targeted, and non-targeted contrast agents were proven to provide a sufficient signal for clot imaging within the model under flow conditions. The application of the model for clot targeting studies and thrombolytic studies using preclinical imaging techniques is shown here. For the first time, a novel method of thrombus labeling utilizing barium sulphate (Micropaque®) is presented here as an example of successfully employed contrast agents for in vitro experiments evaluating the time-course of thrombolysis and thus the efficacy of a thrombolytic drug, recombinant tissue plasminogen activator (rtPA). Finally, the proof-of-concept of in vivo clot imaging in a middle cerebral artery occlusion (MCAO) rat model using barium sulphate-labelled clots is presented, confirming the great potential of such an approach to make experiments comparable between in vitro and in vivo models, finally leading to a reduction in animals needed.

