Suivi par élastographie ultrasonore après réparation endovasculaire d’anévrisme aorto-iliaque : étude de faisabilité in vivo

Cardiovascular diseases are the leading cause of death worldwide. Abdominal aortic aneurysms (AAAs) are part of these horrible diseases. An aneurysm is a dilatation of an artery that can lead to death. A rupture of an AAA can lead to death nearly 80% of the time. One way to treat AAAs is the insertion of a stent-graft (SG) in the aorta in order to reduce the pressure on the wall, commonly known as endovascular repair (EVAR). Endoleak, defined as persistent blood flow within the aneurysm sac and outside the SG, is the main complication of EVAR. This phenomenon increases the risk of rupture and can develop at any time after EVAR. A life-long surveillance follow-up with computed tomography (CT-scan) is required to detect endoleak, increasing the cost of EVAR, exposing patient to ionizing radiation and nephrotoxic contrast agent.  Aneurysm growth without evidence of endoleak on CT-scan is called endotension. After SG delivery, the blood is trapped between the SG and aneurysm wall. If there is no residual flow (endoleak), the blood will coagulate to form fresh thrombus that will progressively organize to become a fibrous thrombus leading to aneurysm shrinkage. There is little data in the literature to study the timing of this process and the relationship between thrombus organization and aneurysm shrinkage. The gold-standard of post-EVAR surveillance, the CT-scan, cannot detect the presence of fresh thrombus. There is a clear need to invest in a safe and cost effective technique for post-EVAR surveillance. A recent method, dynamic elastography, measures the elasticity of tissues in real time. The principle of this technique is based on the generation of shear waves and studies their propagations for the determination of elastic properties (stiffness) of tissues. This thesis aims the application of dynamic elastography for the detection of endoleak and to characterize mechanical properties of AAAs tissues after EVAR. This project reveals the potential of elastography to reduce costs, exposure to ionizing radiation and nephrotoxic contrast agents in CT-scan follow-up of AAAs post-EVAR. Dynamic elastography using the shear wave imaging (SWI) is promising and can complement the Doppler ultrasound (DUS), which is already used in post-EVAR follow-up. SWI has the potential to get information from thrombus organization and to detect endoleak. The first objective of this thesis was to test the SWI on AAAs in canines models for the detection of endoleak and the characterization of thrombus. SGs were implanted in 18 dogs after surgical creation of type I endoleaks (4 AAAs), type II endoleaks (13 AAAs) and no endoleaks (1 AAA). DUS and SWI were engaged before (baseline) and 7, 30, 90 and 180 days (sacrifice) after SG implantation. Digital subtraction angiography, CT-scan and macroscopic tissue sections were analyzed at sacrifice. Endoleak and thrombus areas were identified and segmented. Elasticity (Young's) moduli were measured in different regions of interest (endoleaks, fresh and organized thrombi) after registration of pathological findings. Rigidity values of the regions of interest were significantly different (P < 0.001). SWI was able to detect endoleaks where CT-scan (1) and DUS (3) failed. The second objective of this project was to characterize the evolution of the thrombus in time, also as the endotension after endoleak embolization in canines models. EVAR was done with creation of type I endoleak in 18 aneurysms created in nine dogs (common iliacs arteries). Two embolization gels (Chitosan (Chi) or Chitosan-Sodium-Tetradecyl-Sulfate (Chi-STS)) were injected in the sac to seal the endoleak and promote healing. SWI and DUS were performed at baseline (implantation, 1 week, 1 month, 3 months) whereas angiography and CT-scan were performed at sacrifice to evaluate the presence and type of the endoleak. Macroscopic and histopathological analyses were processed to identify and segment five different regions of interest (ROIs) (endoleak, fresh or organized thrombus, Chi or Chi-STS). Elasticity values of endoleak and fresh thrombus areas were significantly lower than organized thrombus, Chi and Chi-STS areas (P < 0.001). Elasticity values of fresh thrombus at 1 week and at 3 months indicated that SWI can evaluate thrombus maturation. It can also characterize embolization agents degradation. SWI was able to detect endoleak where DUS failed (2) and distinguish fresh thrombi which cannot be detected on CT-scan.  Finally, the last step of the doctoral project was to apply the SWI in a clinical phase with humans with an AAA for the detection of endoleak and characterizing elasticity of tissues. 25 patients were selected to participate in the study. Comparison of SWI, CT-scan and DUS images was conducted. Rigidity values by SWI of regions of interest (endoleak, thrombus) were identified and segmented. These were significantly different (P < 0.001). SWI detected 5 endoleaks on 6 (sensitivity of 83.3%) and had 6 false positives (specificity of 76%). SWI detected endoleaks where CT-scan (2) and DUS (2) failed. No statistical difference was found in elasticity between thrombus with an AAA with endoleak and thrombus with an AAA without endoleak. Also, no correlation was found between AAA diameter or its variation over time and thrombus elasticity. SWI has the potential to detect endoleaks and characterize thrombus. The approach could be combined with DUS surveillance of AAAs after EVAR, which is currently widely practiced to reduce the cost of AAA follow-up and exposure to ionizing radiation and contrast agents.

Keyphrases: Thrombus, Dynamic elastography, Abdominal aortic aneurysm, Endovascular repair, Endoleak, Computed tomography, Ultrasound imaging, Embolization agent, Histology, Angiography