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Aneurysmal Arterial Mechanics: Into the Structure

Periodic Reporting for period 3 - AArteMIS (Aneurysmal Arterial Mechanics: Into the Structure)

Reporting period: 2018-04-01 to 2019-09-30

The rupture of an Aortic Aneurysm (AA), which is often lethal, is a biomechanical phenomenon that occurs when the wall stress state exceeds the local strength of the tissue. Current understanding of arterial rupture mechanisms is poor, as the physics taking place at the microscopic scale in collagenous structures remains an open area of research. Understanding, modelling, and quantifying the micro-mechanisms which drive the mechanical response of such tissue and locally trigger rupture represents the most challenging and promising pathway towards predictive diagnosis and personalized care of AA.
The PI's group was recently able to detect, in advance, at the macro-scale, rupture-prone areas in bulging arterial tissues. The next step is to characterize the details of the arterial microstructure in order to elucidate the mechanisms controlling the rupture response.
Through the achievements of AArteMIS, the local mechanical state of the fibrous microstructure of the tissue, especially close to its rupture state, will be quantitatively analyzed using multi-photon confocal microscopy and numerically reconstructed to establish quantitative micro-scale rupture criteria. AArteMIS will also address micro-macro modelling based on the collected data.
The entire project will be completed through collaboration with medical doctors and engineers, experts in all required fields for the success of AArteMIS.
AArteMIS is expected to open longed-for pathways for research in soft tissue mechanobiology which focuses on cell environment and to enable essential clinical applications for the quantitative assessment of AA rupture risk. It will significantly contribute to understanding fatal vascular events and improving cardiovascular treatments. It will provide a tremendous source of data and inspiration for subsequent applications and research by answering most fundamental questions on AA rupture behaviour.
The implementation of AArteMIS’ actions has been successful so far and led to understanding and solving many technical issues related to the very challenging experiments planned in AArteMIS. The main achievements of AArteMIS in this first reporting period concern the development of two in vitro experimental apparatus.
The first one consists of a bulging test bench to be used under a multiphoton microscope. Using fluorescence properties of the constituents, this type of microscope allows 3D imaging within the depth of the tissue, at the scale of micron-sized details. Hence the objective is to observe and analyze, very locally, the microstructure while it deforms and approaches rupture. The development of this original experiment requires solving several technical issues related to (i) testing and imaging soft biological tissues, (ii) controlling stability to avoid blurring in the images, (iii) controlling the mechanical test in synchronization with the images and (iv) obtaining high quality images for further analysis. Most of these challenges were iteratively addressed and solutions were proposed. Current work will focus on acquiring images for several specimens and analyzing them to better understand the micro-mechanisms involved.
The second experiment developed consists of a method to perform tension testing of arterial specimens in an X-ray micro-tomograph. This imaging technique allows imaging the internal structure of a material using X-ray absorption contrast like medical scanners. The advantage of this equipment is the scale of observation. It is tunable and makes it possible to visualize details having a size of a few microns while observing a large view of the sample at the same time. Hence this technique is highly complementary to the microscopy described above as it provides information on the progression of damage in the whole sample. So far, unique images of arterial specimens delaminating and rupturing were obtained which constitutes a step forward in understanding one possible mechanism of arterial rupture.
Dissemination of these advances is currently in progress with scientific papers being under preparation.
So far, the main progresses of AArteMIS lie in developing and adjusting high-complexity experiments. Preliminary results are very encouraging as they led to acquire never-seen microstructure images that will constitute a highly valuable input for the community. It is believed that they will shed light on arterial rupture and pave the way for further research and developments in this domain.
Possible societal implications are mid-term and long-term applications where the results can be incorporated in diagnosis tools to be used in a clinical setup to improve healthcare cardiovascular risk patients.