L'élastographie ultrasonore dynamique vasculaire : une nouvelle modalité d'imagerie non-invasive pour la caractérisation mécanique de la thrombose veineuse

The venous thromboembolism such as the lower limb deep venous thrombosis (DVT) is a vascular pathology characterized by a blood clot formation that induces partial or total vessel lumen occlusion. Pulmonary embolism is a fatal complication of DVT where the clot detaches from the wall, circulates in the blood flow, and produces an obstruction of pulmonary arterial branches. The combination of clinical prediction rules (signs or symptoms) and blood tests (D-dimer testing) coupled to venous ultrasonography (i.e. compression ultrasonography, color Doppler) allows an accurate diagnosis of first DVT. Nevertheless, such clinical tools present poor results to detect recurrent thrombotic events. Then, in order to guide patients towards optimal therapy, the problem is no more to detect the presence of thrombus, but to evaluate its maturity and its age, which are correlated to their mechanical properties (e.g. elasticity, viscosity). The dynamic elastography (DE) has been recently proposed as a novel non-invasive imaging modality capable to characterize the quantitative mechanical properties of tissues. The DE is based on the analysis of acoustical parameters (i.e. velocity, attenuation, wave pattern) of low frequency (10-7000 Hz) shear waves propagating within the probed medium. Such shear waves generated by external vibration, or remotely using ultrasound beam focalisation (radiation force), were tracked using ultra-fast ultrasound or magnetic resonance imaging. A method based on DE and adapted to mechanical characterization of venous thrombosis may allow the quantification of diseases severity in order to improve the final diagnosis. This thesis presents the works related to the development and complete validation of a novel non-invasive elastography imaging method for the quantitative and reliable estimation of mechanical properties of venous thrombosis.  In order to fulfil the main objective, it is first necessary to improve knowledge about mechanical behaviours of blood clot (coagulated blood) subjected to a dynamic solicitation similar to DE. The shear storage (elastic behaviour, G’) and loss (viscous behavior, G’’) moduli of porcine blood clots are measured by DE during the blood coagulation kinetics (at 70 Hz) and after completely coagulation (between 50 Hz and 160 Hz). These results are the first dynamic behaviour measurements of blood clots in such wide frequency range.   The subsequent step consists in introducing an innovative reference instrument (« gold standard »), called RheoSpectris, dedicated to measure the hyper-frequency viscoelasticity (between 10 Hz and 1000 Hz) of materials and biomaterials. This tool is indispensable to validate new dynamic elastography techniques. A comparative study between RheoSpectris and classical rheometry is performed to validate the measurements on different materials (silicon, thermoplastic, biomaterials, gel). The excellent agreement between both technologies allows to conclude that RheoSpectris is a reliable instrument for mechanical measurements at high frequencies, which is not always possible with current tools. The theoretical basis of a novel elastographic imaging modality, labelled SWIRE (« shear wave induced resonance dynamic elastography ») is presented and validated on vascular phantoms. Such approach allows the characterization of mechanical properties of a confined inclusion (e.g. blood clot) from its resonance (displacement amplification) due to the propagation of judiciously oriented shear waves. SWIRE has also the advantage to amplify the vibration amplitude within the heterogeneity to help for its detection and segmentation.  Finally, the method DVT-SWIRE ((« Deep venous thrombosis – SWIRE ») is adapted to the quantitative elasticity estimation of venous thrombosis in the context of clinical use. DVT-SWIRE exploits the first resonance frequency measured within the thrombosis during the plane (vibration of rigid plate) or cylindrical (simulating supersonic radiation force generation) shear waves propagation. The technique is applied on DVT phantoms and the results are compared to those given by the RheoSpectris reference instrument. This method is also used successfully in an ex vivo study for the elasticity assessment of explanted porcine thrombosis surgically induced in vivo.

Keyphrases: coagulation sanguine, deep venous thrombosis, dynamic elastography, rheology, blood coagulation, viscoelastic measurement, hyper-frequency, biomaterials, ultrasound imaging, mechanical resonance