TexValveMonitoring - Multimodal longitudinal imaging of biohybrid heart valves

• Applicants: Professor Dr. Stefan Jockenhövel; Professor Dr. Fabian Kiessling
• Subject Area: Medical Physics, Biomedical Technology
• Term: since 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 403039938

Tissue-engineered cardiovascular implants have many advantages over conventionally used synthetic solutions. For example, they can adapt to individual conditions and, in the case of pediatric applications, even grow with the child. However, the high adaptability carries the risk of faulty remodeling and thus loss of function. Diagnostic procedures that capture essential features of the remodeling process are, therefore, essential for the clinical translation. In the first term of PAK961, we were able to develop an imaging concept that allows us to comprehensively characterize tissue-engineered vascular grafts (TEVGs). Here, non-degradable components of the textile scaffold could be visualized by 19F MRI, and the degradation of degradable components after labeling with iron oxide nanoparticles (SPION) could be assessed and quantified by 1H MRI. Furthermore, we were able to detect the synthesis of new extracellular matrix using molecular MRI probes, and molecular ultrasound imaging provided us with important information about the endothelial activation state.In the second phase of the project, we plan to transfer the imaging concept to tissue-engineered heart valves. For this, essential adaptations are necessary: On one hand, the stability of the textile scaffold needs to be adapted to the higher mechanical stress. For this purpose, the novel "elastin-like recombinamers" (ELR) will be tested. Furthermore, we need to gain a deeper understanding of the synthesis of extracellular matrix by the cells. Here, it is interesting to note that under in vitro conditions, we only observed deposition of collagen, but not elastin. Insufficient αvβ3 integrin-mediated interactions between endothelial cells and myofibroblasts could be a cause here. To observe these processes by imaging, a bioreactor must be constructed that is MRI compatible, allows the controlled beating of tissue-engineered heart valves inside the MRI, and provides access for ultrasound studies without contaminating or destroying the valves. Furthermore, imaging techniques must be adapted to the moving heart valves. This is particularly challenging for MRI because the leaflets are thin, and flow-related artifacts are expected. To address these demands, the MR fingerprinting technique will be used together with motion gating. Furthermore, the combination of MRI and Magnetic Particle Imaging (MPI) will be investigated whether it is a reasonable option for the fast and sensitive detection of SPION-labeled fibers.Thus, we will develop and provide important monitoring methods for the entire consortium that can be applied to characterize tissue-engineered heart valves during bioreactor maturation and after in vivo implantation.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Christian Apel