Morphological analysis of the thoracic aorta in case of TBAD without treatment.

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1 Master project: Hemodynamic pattern of type B aortic dissection progression and remodelling of the false lumen after endovascular treatment: imaging informed numerical simulations Aortic dissection is a life-threatening pathology and one of the most frequent acute aortic conditions. The incidence is about 3/100,000 inhabitant per year [1] and increased by 50% in man and 30% in woman in the last two decades due to the population aging [2]. Aortic dissection is defined by the presence of an entry tear with a longitudinal division of the media, mostly antegrade, and creating two lumens: false lumen (FL) and true lumen (TL). TL FL Severity of such pathology is related to the risk of rupture and ischemic complications, during the acute phase, and to aneurysmal dilatation and rupture in the chronic phase. Thus, 20% of patients died before reaching the hospital, 30% intra or postoperatively and further 20% in the 10 following years [2]. These rates vary according to the entry tear (ET) location, which can be in the ascending aorta (type A dissection) or descending aorta (type B dissection: TBAD). For complicated TBAD, endovascular treatment is now considered as the first line therapy. The aims of the interventional treatment of aortic dissection are: (1) occlusion of the ET; (2) exclusion of the FL from systemic circulation or promotion of FL thrombosis or both. Clinical success of endovascular procedure is assessed by the quality of FL remodelling commonly defined as TL expansion and reduction or complete regression of the FL.

2 However, the main issue of this technique remains the need for re-intervention (mean rate 18%, range 0 to 60%) and 40% of these secondary procedures are performed to treat aneurysmal dilation distal to stent-graft [3]. Nowadays indications of treatment tend to expand to involve not only complicated dissections but also uncomplicated dissections with high risks of aneurysmal degeneration. The subacute phase (15 to 92 days after symptoms onset) is the optimal period to treat those patients due to the higher rate of favourable remodelling. Clinical studies have unfortunately failed to identify patients at high risk of FL aneurysmal expansion and late complications who would benefit from endovascular techniques. In total endovascular technique is currently the best treatment option for type B aortic dissection, however two main questions remains unresolved: (1) the optimal indication, (2) the optimal technique (length of aorta covered, type of stent-graft). The currently available imaging techniques failed to answer these questions. Indeed numerous morphological parameters have been advocated as linked to progressive aortic dilatation, but no clear recommendation is validated. Computational biomechanics has been used to investigate complex cardiovascular pathologies. Numerical simulations can indeed be helpful to improve the treatment indication and outcomes of stent-graft for aortic dissection. Given the interaction between hemodynamics and FL expansion, there is an increasing interest to look to wall shear stress and fluid dynamics indices in the FL as potential predictive factors of aneurysmal expansion and late complications. As fluid indices are difficult to acquire and analyse in vivo, numerical simulation informed by magnetic resonance imaging (MRI) could provide interesting fluid indices. Studies on the FL

3 hemodynamics before treatment are limited. New MRI technics of 4D phase contrast flows have been used without further quantification [4], [5]. This project aims to identify fluid factors influencing the aortic dissection progression and its remodelling of the FL after treatment. The research includes clinical and numerical study enabling creation of a realistic model of the dissection pre and post treatment. It is divided into two steps: Morphological analysis of the thoracic aorta in case of TBAD without treatment. Retrospective multicentre (CHU Nord, CHU Timone) study including 50 patients with native TBAD and 50 patients with residual t TBADs. While morphometrical analysis [6] [8] were limited, we developed a CT scan morphometrical analysis which includes: diameters and area of lumens in the aorta (*4), total and lumens volumes, intimal flap thickness, aortic tortuosity, EP location, angle between FL and TL centre lines. Such results will be used to identify extreme morphologies for aortic dissection model creation using a Arbritrary Lagrangian Eulerian method [9]. Hemodynamic analysis of the thoracic aorta in TBAD with endoprostheses: Prospective multi-centric study including 20 patients with severe TBAD selected for treatment with endoprosthesis: patients will underwent MRI flow protocol including 2D and 4D-PC flows. MRI analysis will be used for analysis the FL and TL flows as well as flap motion during cardiac cycle. The fluid indices are of two types: (1) detection of the coherent structure for thrombosis analysis [10] (2) analysis of the fluid particles paths [11]. Those indices will be validated on an experimental phantom of aortic dissection and iterative comparison will be used to improve the model. This project will be performed thanks to a close collaboration between the CRMBM (UMR 7339, CNRS/Aix-Marseille Université) and the LBA (UMRT24 IFSTTAR, Aix Marseille Université) Candidate should be a last year master (or equivalence from engineering school in biomechanics mechanics or fluid mechanics and could have previous experience in biomedical and numerical fields.

4 Project tutors: 1. Mourad BOUFI Service de chirurgie vasculaire- CHU Nord, Marseille 2. Morgane EVIN 3. Michel BEHR Host Laboratory: Faculté de Médecine secteur Nord ; Marseille Training scheme will take place at the Laboratoire de Biomécanique Appliquée- UMR T24- IFSTTAR

5 [1] W. D. Clouse et al., Acute aortic dissection: population-based incidence compared with degenerative aortic aneurysm rupture, Mayo Clin. Proc., vol. 79, no. 2, pp , Feb [2] C. Olsson, S. Thelin, E. Ståhle, A. Ekbom, and F. Granath, Thoracic aortic aneurysm and dissection: increasing prevalence and improved outcomes reported in a nationwide population-based study of more than 14,000 cases from 1987 to 2002, Circulation, vol. 114, no. 24, pp , Dec [3] Boufi M, Patterson B, Grima Joe, and et al., Systematic review of reintervention after thoracic endovascular repair for chronic type B dissection, Ann. Thorac surg, no. In press, [4] R. E. Clough, M. Waltham, D. Giese, P. R. Taylor, and T. Schaeffter, A new imaging method for assessment of aortic dissection using four-dimensional phase contrast magnetic resonance imaging, J. Vasc. Surg., vol. 55, no. 4, pp , Apr [5] D. Dillon-Murphy, A. Noorani, D. Nordsletten, and C. A. Figueroa, Multi-modality image-based computational analysis of haemodynamics in aortic dissection, Biomech. Model. Mechanobiol., vol. 15, no. 4, pp , Aug [6] B. J. Manning et al., Endovascular Treatment for Chronic Type B Dissection: Limitations of Short Stent-Grafts Revealed at Midterm Follow-up, J. Endovasc. Ther., vol. 16, no. 5, pp , Oct [7] S. T. Scali et al., Efficacy of thoracic endovascular stent repair for chronic type B aortic dissection with aneurysmal degeneration, J. Vasc. Surg., vol. 58, no. 1, p e1, Jul [8] M. Lee et al., Outcomes of endovascular management for complicated chronic type B aortic dissection: effect of the extent of stent graft coverage and anatomic properties of aortic dissection, J. Vasc. Interv. Radiol. JVIR, vol. 24, no. 10, pp , Oct [9] W. Wei, M. Behr, and C. J. F. Kahn, The Aorta Heart System Finite Element Modelling with Fluid Structure Interaction Methods and Validation against Blood Hydrodynamics, in IRCOBI Conference Proceedings, [10] M. Evin et al., Left atrium MRI 4D-flow in atrial fibrillation: association with LA function, Conputing and Cardiology, RD Young Investigator Award. [11] M. Evin, F. Callaghan, K. Broadhouse, and S. M. Grieve, Aortic Valve Replacement by 4D-PC Flow., CANZ Congress August 2016.