Automatic Rigid Registration of Aortic Aneurysm Arterial System

An abdominal aortic aneurysm is defined as a local and abnormal dilation of the aortic wall that can lead to rupture and death without treatment. A useful tool for the patient's postoperative follow-up is segmentation registration to see the evolution of the aneurysm between two examinations. Here, we propose a method to automatically register the entire arterial system: the segmentation is divided in three parts (suprarenal, infrarenal zone, and iliac arteries) and each part is registered separately. We chose a rigid point set to point set registration through the iterative closest point algorithm. We also compute the displacement fields and derive a criterion to accept or reject the registration of the infrarenal zone and iliac arteries. Registration is successful in 96% of cases for the infrarenal zone, in 94% for the suprarenal zone and in 65% for the iliac arteries

Rôle de la voie Hedgehog dans la physiopathologie de l’ischémie critique de membre inférieur et le maintien de l’intégrité endothéliale

The prevalence of diabetes and critical limb ischemia (CLI) is steadily increasing. These pathologies remain incurable and often intertwined. Results suggest that Hedgehog (Hh) signaling is involved in maintaining microvessel integrity, and downregulation of Desert Hh (Dhh) is associated with cardiovascular risk factors, such as age, diabetes, and obesity.The main objective of this thesis was to explore the pathophysiological mechanisms leading to CLI with the hypothesis that endothelial Dhh is essential for the maintenance of vascular integrity.We have shown that endogenous Sonic Hh (Shh) does not promote post-ischemic angiogenesis and that the absence of Shh leads to aberrant ischemic tissue inflammation and increased transient angiogenesis. In humans, CLI was associated with dysfunctional capillaries rather than a decrease in capillary density, and Dhh was expressed in endothelial cells (EC). In mice, Dhh knockdown was associated with EC activation and capillary leakage secondary to the alteration of adherent junctions. Dhh's agonist significantly improved EC function without promoting angiogenesis, which subsequently improved muscle perfusion.Thus, restoration of EC function leads to a significant recovery of perfusion and muscle repair in the context of CLI. The Hh signaling pathway, and more particularly Dhh, appears to be a promising therapeutic target for preventing the endothelial dysfunction involved in ischemic vascular pathologies.La prévalence du diabète et de l’ischémie critique chronique (ICC) est en constante augmentation. Ces pathologies demeurent incurables et souvent intriquées. Des résultats suggèrent que la signalisation Hedgehog (Hh) participe au maintien de l'intégrité des microvaisseaux, et une régulation négative de Desert Hh (Dhh) est associée aux facteurs de risque cardiovasculaires, tels que l'âge, le diabète et l'obésité.L’objectif principal de cette thèse était d’explorer les mécanismes physiopathologiques conduisant à l’ICC avec pour hypothèse que la protéine Dhh dérivée de l'endothélium est essentielle au maintien de l'intégrité vasculaire.Nous avons démontré que Sonic Hh (Shh) endogène ne favorise pas l'angiogenèse post-ischémie et que l'absence de Shh conduit à une inflammation tissulaire ischémique aberrante et à une angiogenèse transitoire accrue. Chez l’homme, l'ICC était associée à des capillaires dysfonctionnels plutôt qu'à une diminution de la densité capillaire et Dhh était exprimé dans les cellules endothéliales (CE). Chez la souris, une carence en Dhh induisait une activation des CE et une fuite capillaire en raison d'une altération des jonctions adhérentes. L'agoniste de la signalisation Dhh améliorait significativement la fonction des CE sans favoriser l'angiogenèse, ce qui améliorait par la suite la perfusion musculaire.Ainsi, la restauration de la fonction des CE conduit à une récupération significative de la perfusion et de la réparation musculaire dans un contexte d’ICC de membre. La voie Hh, et plus particulièrement Dhh, semble être une cible thérapeutique prometteuse pour prévenir le dysfonctionnement endothélial impliqué dans les pathologies vasculaires ischémiques

Role of the Hedgehog signalling pathway in the physiopathology of critical limb ischemia and the maintenance of endothelial integrity

La prévalence du diabète et de l’ischémie critique chronique (ICC) est en constante augmentation. Ces pathologies demeurent incurables et souvent intriquées. Des résultats suggèrent que la signalisation Hedgehog (Hh) participe au maintien de l'intégrité des microvaisseaux, et une régulation négative de Desert Hh (Dhh) est associée aux facteurs de risque cardiovasculaires, tels que l'âge, le diabète et l'obésité.L’objectif principal de cette thèse était d’explorer les mécanismes physiopathologiques conduisant à l’ICC avec pour hypothèse que la protéine Dhh dérivée de l'endothélium est essentielle au maintien de l'intégrité vasculaire.Nous avons démontré que Sonic Hh (Shh) endogène ne favorise pas l'angiogenèse post-ischémie et que l'absence de Shh conduit à une inflammation tissulaire ischémique aberrante et à une angiogenèse transitoire accrue. Chez l’homme, l'ICC était associée à des capillaires dysfonctionnels plutôt qu'à une diminution de la densité capillaire et Dhh était exprimé dans les cellules endothéliales (CE). Chez la souris, une carence en Dhh induisait une activation des CE et une fuite capillaire en raison d'une altération des jonctions adhérentes. L'agoniste de la signalisation Dhh améliorait significativement la fonction des CE sans favoriser l'angiogenèse, ce qui améliorait par la suite la perfusion musculaire.Ainsi, la restauration de la fonction des CE conduit à une récupération significative de la perfusion et de la réparation musculaire dans un contexte d’ICC de membre. La voie Hh, et plus particulièrement Dhh, semble être une cible thérapeutique prometteuse pour prévenir le dysfonctionnement endothélial impliqué dans les pathologies vasculaires ischémiques.The prevalence of diabetes and critical limb ischemia (CLI) is steadily increasing. These pathologies remain incurable and often intertwined. Results suggest that Hedgehog (Hh) signaling is involved in maintaining microvessel integrity, and downregulation of Desert Hh (Dhh) is associated with cardiovascular risk factors, such as age, diabetes, and obesity.The main objective of this thesis was to explore the pathophysiological mechanisms leading to CLI with the hypothesis that endothelial Dhh is essential for the maintenance of vascular integrity.We have shown that endogenous Sonic Hh (Shh) does not promote post-ischemic angiogenesis and that the absence of Shh leads to aberrant ischemic tissue inflammation and increased transient angiogenesis. In humans, CLI was associated with dysfunctional capillaries rather than a decrease in capillary density, and Dhh was expressed in endothelial cells (EC). In mice, Dhh knockdown was associated with EC activation and capillary leakage secondary to the alteration of adherent junctions. Dhh's agonist significantly improved EC function without promoting angiogenesis, which subsequently improved muscle perfusion.Thus, restoration of EC function leads to a significant recovery of perfusion and muscle repair in the context of CLI. The Hh signaling pathway, and more particularly Dhh, appears to be a promising therapeutic target for preventing the endothelial dysfunction involved in ischemic vascular pathologies

Automatic Rigid Registration of Aortic Aneurysm Arterial System

An abdominal aortic aneurysm is defined as a local and abnormal dilation of the aortic wall that can lead to rupture and death without treatment. A useful tool for the patient's postoperative follow-up is segmentation registration to see the evolution of the aneurysm between two examinations. Here, we propose a method to automatically register the entire arterial system: the segmentation is divided in three parts (suprarenal, infrarenal zone, and iliac arteries) and each part is registered separately. We chose a rigid point set to point set registration through the iterative closest point algorithm. We also compute the displacement fields and derive a criterion to accept or reject the registration of the infrarenal zone and iliac arteries. Registration is successful in 96% of cases for the infrarenal zone, in 94% for the suprarenal zone and in 65% for the iliac arteries

Presse Med

Lower-limb peripheral arterial disease (PAD), is a common manifestation of systemic atherosclerosis, resulting from a partial or complete obstruction of at least one lower-limb arteries. PAD is a major endemic disease with an excess risk of major cardiovascular events and death. It also leads to disability, high rates of lower-limb adverse events and non-traumatic amputation. In patients with diabetes, PAD is particularly frequent and has a worse prognosis than in patients without diabetes. The risk factors of PAD are comparable to those for cardiovascular disease. The ankle-brachial index is usually recommended to screen PAD despite its limited performance in patients with diabetes, affected by the presence of peripheral neuropathy, medial arterial calcification, incompressible arteries and infection. Toe brachial index and toe pressure emerge as alternative screening tools. The management of PAD requires strict control of cardiovascular risk factors including diabetes, hypertension and dyslipidaemia, the use of antiplatelet agents and lifestyle management, to reduce cardiovascular adverse events, but few randomized controlled trials have evaluated the benefits of these treatments in PAD. Several advances have been achieved in endovascular and surgical revascularization procedures, with obvious improvement in PAD prognosis. Further studies are required to increase our understanding of the pathophysiology of PAD and to evaluate the interest of different therapeutic strategies in the occurrence and progression of PAD in patients with diabetes. Here, we present a narrative and contemporary review to synthesize the key epidemiology findings, screening and diagnosis methods, and major therapeutic advances regarding PAD in patients with diabetes

BCG Aortitis, a Rare Complication of BCG Therapy

Introduction: Intravesical Bacillus Calmette-Guerin (BCG) is an effective treatment for in situ bladder carcinomas; however, extravesical BCG infection may occur in remote organs in patients with underlying primary immunodeficiency and is a potentially serious complication in 3–5% of cases. It includes granulomatous pneumonia, hepatitis as well as specific dermatological, ophthalmic, and haematopoietic manifestations. Diagnosis is difficult and often based on high clinical suspicion as in many cases Mycobacterium bovis is not isolated. This report presents a rare case of BCGaortitis treated in a tertiary care centre. Report: A 74 year old man, with a history of bladder cancer treated with BCG therapy over a year ago, presented with malaise, abdominal pain, anorexia, and significant weight loss for several months associated with acute on chronic renal failure and a tender aneurysm. He was diagnosed with hepatic BCGitis and pararenal BCGaortitis. He was considered too high risk for open surgery after a multidisciplinary team meeting and was treated with a four vessel physician modified endograft (PMEG) and antituberculous therapy. At seven month follow up, he was clinically well and control computed tomography showed a patent endograft with complete exclusion of the aortic aneurysm. Discussion: Infectious BCG complications after intravesical BCG administration for in situ bladder carcinomas can lead to severe early and late complications. In the present case, the patient presented with both liver and aortic BCG infection. The lack of positive microbiological data should not discourage clinicians from considering BCG infection even if several months have passed since the last BCG instillation

Automatic branch detection of the arterial system from abdominal aortic segmentation

International audienceWe present a new method to automatically identify the different arteries present in an abdominal aortic segmentation. In this approach, the arterial system is first represented by a vascular tree, extracted from the segmentation and containing the topologic and geometric features (branch position, branch direction, branch length, branch diameter) of the arterial system. Then, the branches of the vascular tree are matched with the main arteries origi- nating from the aorta: celiac artery, superior mesenteric artery, renal arteries and common iliac arteries. This match is determined by maximizing a similarity measure between the dif- ferent branches and corresponding arteries. We evaluate this method on 239 segmentations obtained from 102 different patients. The results demonstrate the accuracy of the proposed method, capable of delivering an error of less than 2.5% for the identification of the celiac and superior mesenteric arteries, 8.4% for the renal arteries, and 2.1% for the common iliac arteries

Endogenous Sonic Hedgehog limits inflammation and angiogenesis in the ischaemic skeletal muscle of mice

Aims: Hedgehog (Hh) signalling has been shown to be re-activated in ischaemic tissues and participate in ischaemia-induced angiogenesis. Sonic Hedgehog (Shh) is upregulated by more than 80-fold in the ischaemic skeletal muscle, however its specific role in ischaemia-induced angiogenesis has not yet been fully investigated. The purpose of the present study was to investigate the role of endogenous Shh in ischaemia-induced angiogenesis. Methods and results: To this aim, we used inducible Shh knock-out (KO) mice and unexpectedly found that capillary density was significantly increased in re-generating muscle of Shh deficient mice 5 days after hind limb ischaemia was induced, demonstrating that endogenous Shh does not promote angiogenesis but more likely limits it. Myosin and MyoD expression were equivalent in Shh deficient mice and control mice, indicating that endogenous Shh is not required for ischaemia-induced myogenesis. Additionally, we observed a significant increase in macrophage infiltration in the ischaemic muscle of Shh deficient mice. Our data indicate that this was due to an increase in chemokine expression by myoblasts in the setting of impaired Hh signalling, using tissue specific Smoothened conditional KO mice. The increased macrophage infiltration in mice deficient for Hh signalling in myocytes was associated with increased VEGFA expression and a transiently increased angiogenesis, demonstrating that Shh limits inflammation and angiogenesis indirectly by signalling to myocytes. Conclusion: Although ectopic administration of Shh has previously been shown to promote ischaemia-induced angiogenesis, the present study reveals that endogenous Shh does not promote ischaemia-induced angiogenesis. On the contrary, the absence of Shh leads to aberrant ischaemic tissue inflammation and a transiently increased angiogenesis