Diss. (sammanfattning) Linköping : Linköpings universitet, 2008. / Härtill 5 uppsatser. Includes bibliographical references.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2008. / Härtill 5 uppsatser.

Microhemodynamics is the study of blood flow in small vessels, usually on the order of 50 to 100 µm. The in vitro study of blood flow in small channels is analogous to the in vivo study of the microcirculation. At this scale the Reynolds and Womersly numbers are significantly less than 1 and the viscous stress and pressure gradient are the main determinant of flow. Blood is a non-homogeneous, non-Newtonian fluid and this complex composition and behavior has a greater impact at the microscale. A key parameter is the shear stress at the wall, which is involved in many processes such as platelet activation, gas exchange, embryogenesis and angiogenesis. In order to measure the shear rate in these blood flows the velocity profile must be measured. The measured profile can be characterized by the maximum velocity, the flow rate, the shear rate at the wall, or a shape parameter reflecting the bluntness of the velocity profile. The technique of micro-particle image velocimetry (µPIV) was investigated to measure the velocity profiles of blood microflows. The material of the channel, the type of tracer particles, the camera used, and the choice in data processing were all validated to improve the overall accuracy of µPIV as a blood microflow measurement method. The knowledge gained through these experiments is of immediate interest to applications such as the design of lab-on-a-chip components for blood analysis, analysis of blood flow behavior, understanding the shear stress on blood in the microcirculation and blood substitute analysis. Polymer channels were fabricated from polydimethylsiloxane (PDMS) by soft lithography in a clean room. PDMS was chosen for ease of fabrication and biocompatibility. The contacting properties of saline, water, and blood with various polymer channel materials was measured. As PDMS is naturally hydrophilic, surface treatment options were explored. Oxygenated plasma treatment was found to be less beneficial for blood than for water. The choice of camera and tracer particles were validated. Generally, for in vivo studies, red blood cells (RBCs) are used as tracer particles for the µPIV method, while for in vitro studies, artificial fluorescent micro particles are added to the blood. It is demonstrated here that the use of RBCs as tracer particles creates a large depth of correlation (DOC), which can approach the size of vessel itself and decreases the accuracy of the method. Next, the accuracy of each method is compared directly. Pulsed images used in conjunction with fluorescing tracer particles are shown to give results closest to theoretical approximations. The effect of the various post-processing methods currently available were compared for accuracy and computation time. It was shown that changing the amount of overlap in the post-processing parameters affects the results by nearly 10%. Using the greatest amount of correlation window overlap with elongated windows aligned with the flow was shown to give the best results when coupled with a image pre-processing method previously published for microflows of water. Finally the developed method was applied to a relevant biomedical engineering problem: the evaluation of blood substitutes and blood viscosity modifiers. Alginate is a frequently used viscosity modifier which has many uses in industry, including biomedical applications. Here the effect of alginate on the blood rheology, i.e., the shape of the velocity profile and the maximum velocity of blood flow in microchannels, was investigated. Alginate was found to blunt the shape of the velocity profile while also decreasing the shear rate at the wall. Overall, the accuracy of µPIV measurements of blood flows has been improved by this thesis. The work presented here has extended the known methods and accuracy issues of blood flow measurements in µPIV, improved the understanding of the blood velocity profile behavior, and applied that knowledge and methods to interesting, relevant problems in biomedical and biofluids engineering.

Microhemodynamics is the study of blood flow in small vessels, usually on the order of 50 to 100 µm. The in vitro study of blood flow in small channels is analogous to the in vivo study of the microcirculation. At this scale the Reynolds and Womersly numbers are significantly less than 1 and the viscous stress and pressure gradient are the main determinant of flow. Blood is a non-homogeneous, non-Newtonian fluid and this complex composition and behavior has a greater impact at the microscale. A key parameter is the shear stress at the wall, which is involved in many processes such as platelet activation, gas exchange, embryogenesis and angiogenesis. In order to measure the shear rate in these blood flows the velocity profile must be measured. The measured profile can be characterized by the maximum velocity, the flow rate, the shear rate at the wall, or a shape parameter reflecting the bluntness of the velocity profile. The technique of micro-particle image velocimetry (µPIV) was investigated to measure the velocity profiles of blood microflows. The material of the channel, the type of tracer particles, the camera used, and the choice in data processing were all validated to improve the overall accuracy of µPIV as a blood microflow measurement method. The knowledge gained through these experiments is of immediate interest to applications such as the design of lab-on-a-chip components for blood analysis, analysis of blood flow behavior, understanding the shear stress on blood in the microcirculation and blood substitute analysis. Polymer channels were fabricated from polydimethylsiloxane (PDMS) by soft lithography in a clean room. PDMS was chosen for ease of fabrication and biocompatibility. The contacting properties of saline, water, and blood with various polymer channel materials was measured. As PDMS is naturally hydrophilic, surface treatment options were explored. Oxygenated plasma treatment was found to be less beneficial for blood than for water. The choice of camera and tracer particles were validated. Generally, for in vivo studies, red blood cells (RBCs) are used as tracer particles for the µPIV method, while for in vitro studies, artificial fluorescent micro particles are added to the blood. It is demonstrated here that the use of RBCs as tracer particles creates a large depth of correlation (DOC), which can approach the size of vessel itself and decreases the accuracy of the method. Next, the accuracy of each method is compared directly. Pulsed images used in conjunction with fluorescing tracer particles are shown to give results closest to theoretical approximations. The effect of the various post-processing methods currently available were compared for accuracy and computation time. It was shown that changing the amount of overlap in the post-processing parameters affects the results by nearly 10%. Using the greatest amount of correlation window overlap with elongated windows aligned with the flow was shown to give the best results when coupled with a image pre-processing method previously published for microflows of water. Finally the developed method was applied to a relevant biomedical engineering problem: the evaluation of blood substitutes and blood viscosity modifiers. Alginate is a frequently used viscosity modifier which has many uses in industry, including biomedical applications. Here the effect of alginate on the blood rheology, i.e., the shape of the velocity profile and the maximum velocity of blood flow in microchannels, was investigated. Alginate was found to blunt the shape of the velocity profile while also decreasing the shear rate at the wall. Overall, the accuracy of µPIV measurements of blood flows has been improved by this thesis. The work presented here has extended the known methods and accuracy issues of blood flow measurements in µPIV, improved the understanding of the blood velocity profile behavior, and applied that knowledge and methods to interesting, relevant problems in biomedical and biofluids engineering.

在這篇論文中，我們提出了在醫學模擬應用的血管或傷口上作相互作用的粒子血流變模型框架。通過平滑粒子流體動力學（SPH）制定的非牛頓流體，進行了血液流變學的模擬。通過建模血管壁結構虛擬粒子，流體 - 結構相互作用（FSI）是一個純粹的拉格朗日(Lagrange)顆粒模型進行建模的血管或血液的交互。我們的建議的方法基於純粹的非網格方法，可用於常見的動脈瘤和血管狹窄等病症的建立上。如需模擬開放性傷口在手術部位中發生較大的變形情況時，我們則採用質量 - 彈簧系統進行血顆粒的交互，此交互框架可應用到幾個開放性手術模擬，如骨科或胃鏡檢查為基礎的手術。無論是常見的醫療圖像：如CT血管造影（CTA）、磁共振血管造影（MRA）或基於網格的數據也可以 作為系統輸入的數據。血栓形成與溶解模型也被集成到這個流固耦合框架中。實驗結果證明採用我們建議的粒子互相作用框架在模擬血管中的凝血過程是可行的。受益於簡潔的拉格朗日粒子交互作用模擬，我們的系統可以保持在互動幀速率中。 / 首先，我們在這篇論文中建議把無網格流變模擬框架應用於血管手術的建模中。於非牛頓粘性流動的假設下，我們建立了血液結構的一般模型方程：以平滑粒子流體動力學實現多血粘度模型與低彈性血管壁模型。血流動力學和軟組織都可以於相同的拉格朗日粒子為基礎下模擬。在這個意義上說，通過延伸平滑粒子流體動力學的密度和動量求和不管顆粒的性質下，本論文提出了一個有效的流體 - 固體交互作用模型。該模型是特別有利於整合多種類型的介質（包括固體或液體）的。在這方面，我們進一步提出了一個與流體相關的血塊凝集溶解模型，可以適用於許多不同種類的醫學模擬：例如血栓栓塞。 / 其次，本論文亦提出了如何基於粒子的血液建模框架的前提下，擴展到大變形的軟組織互動。我們是以耦合雙向階段性質量 - 彈簧系統與固體顆粒，去代替無網格粒子固體的建模，用以維持真正人體組織的高保真度，此方法可以實現類似軟組織的皮膚或真皮的交互式模擬。而耦合血顆粒與平滑粒子方面，則由一個聰明的碰撞模塊處理，使得利用模擬皮膚表面之上，可以模擬出真實的表皮出血現象。該模型的動態計算進一步以物理學處理單元加速；而渲染的模型則是通過一個強大的圖形處理單元為基礎的立方體運行（marching cubes）的方法來實現。該模型已應用於全身血液管理培訓中。 / In this thesis, we propose particle-based rheological modeling frameworks for blood-vessel and blood-wound interaction in medical simulation applications. The effect of blood rheology has been simulated through a smoothed particle hydrodynamics (SPH) formulation of non-Newtonian flow. By modeling the vessel wall structure as virtual particles, a pure Lagrange particle formulation for fluid-structure interaction (FSI) is proposed for modeling the blood-vessel or blood-device interaction. Our proposed framework synthesizes common vascular complication sites such as stenosis and aneurysm based on purely mesh-less approach. For larger deformation situations happened in surgical sites such as open wound, we adopt a mass-spring system to interact with the blood particles; the blood-wound interaction framework can be applied to several open surgery simulations such as orthopedics or endoscopy-based interventions. Input of the data can be obtained from either common medical modalities like computed tomographic angiography (CTA), magnetic resonance angiography (MRA) or processing mesh-based data. A thrombus (clot) formation-dissolution model is also integrated into this fluid-solid interaction framework. Results have demonstrated the feasibility of employing our proposed particle framework in simulating blood-vessel interaction in the clotting process which is essential to vascular procedure simulations. Having benefited from the elegant formulation of Lagrangian particle interaction; the simulation can be maintained at interactive frame-rates. / In this thesis, first, a meshless rheological modeling framework for medical simulation of vascular procedures is proposed. Instead of assuming a Newtonian non-viscous flow, we have built our model based on the general constitutive equation of blood. The multi-regime of viscosity in blood model with a hypoelastic model of vessel wall has been realized under a SPH formulation. The hemodynamic and the soft tissue can all be simulated under the same Lagrangian particle-based formulation. In this sense, an efficient formulation of fluid-solid interaction is proposed through extending SPH summations of density and momentum regardless the nature of particles. This model is particularly beneficial to the integration of multiple types of media (including solids or fluids). With this regards, we further propose a flow related clot aggregation-dissolution model which can be applicable to many different kinds of medical simulation e.g. thrombo-embolization. / Second, the proposed particle-based blood modeling framework has been extended to interact with large deformation of soft tissue. Instead of modeling the solid as meshless particles, a bi-phasic mass-spring system is coupled with solid particles so that an interactive simulation of skin or dermis like soft tissue can be realized with high fidelity to real human tissue. To couple with the SPH formulation of blood particles, a smart collision handling module is exploited so that a realistic bleeding simulation on top of the skin surface can be created. The dynamic computation of this model is further accelerated by the physics processing unit; while the rendering of the model is realized through a robust graphics processing unit based marching cube approach. The proposed model has been applied to provide general blood management training. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Chui, Yim Pan. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 98-113). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese. / Abstract --- p.ii / Chapter 1 --- Introduction --- p.1 / Chapter 2 --- Related works on physically based fluid-structure models --- p.7 / Chapter 2.1 --- Eulerian grid-based methods --- p.8 / Chapter 2.2 --- Lagrangian grid-based methods --- p.9 / Chapter 2.3 --- Lagrangian meshfree methods --- p.11 / Chapter 2.4 --- Fluid-structure interaction (FSI) --- p.12 / Chapter 2.5 --- Endovascular simulation --- p.14 / Chapter 2.6 --- Overview of Our Model --- p.15 / Chapter 3 --- Meshless blood-clot interaction --- p.16 / Chapter 3.1 --- Basic equations of fluid dynamics --- p.17 / Chapter 3.2 --- SPH basics --- p.18 / Chapter 3.3 --- SPH Rheological hemodynamics of blood --- p.20 / Chapter 3.4 --- SPH modeling of the hypoelastic vessel --- p.26 / Chapter 3.5 --- Fluid-solid interaction model --- p.28 / Chapter 3.6 --- Flow-related clot aggregation-dissolution model --- p.33 / Chapter 3.7 --- Time integration --- p.36 / Chapter 3.8 --- Hardware-friendly formulation --- p.37 / Chapter 3.9 --- Results --- p.39 / Chapter 3.9.1 --- Classical Dam-break problem --- p.41 / Chapter 3.9.2 --- Poiseuille flow --- p.43 / Chapter 3.9.3 --- Couette flow --- p.45 / Chapter 3.9.4 --- Mechanical model with material strength --- p.47 / Chapter 3.9.5 --- Hemoelastic feedback system --- p.49 / Chapter 3.9.6 --- Clotting in a stenosed vessel --- p.52 / Chapter 3.9.7 --- Timing results --- p.53 / Chapter 4 --- Meshless modeling of thrombo-embolization --- p.55 / Chapter 4.1 --- Modeling framework for thrombus formation within blood vessel . --- p.60 / Chapter 4.2 --- Geometric Modeling and Flow Simulation --- p.61 / Chapter 4.2.1 --- Data processing on vascular data --- p.61 / Chapter 4.2.2 --- Blood-Vessel particle distribution --- p.62 / Chapter 4.2.3 --- Blood-structure Interaction --- p.65 / Chapter 4.3 --- Visualization and Thrombosis Simulation --- p.66 / Chapter 4.3.1 --- Flow Visualization --- p.66 / Chapter 4.3.2 --- Thromb-Embolization Simulation --- p.68 / Chapter 4.4 --- Conclusion and discussion --- p.72 / Chapter 5 --- Lagrangian modeling framework for bleeding simulation --- p.76 / Chapter 5.1 --- SPH-based bleeding model --- p.78 / Chapter 5.2 --- Biphasic Soft-tissue deformation --- p.79 / Chapter 5.3 --- Interaction between blood and soft tissue --- p.83 / Chapter 5.4 --- Integrated training for blood management --- p.87 / Chapter 6 --- Discussion and Conclusion --- p.93 / Bibliography --- p.98

Le premier objectif de cette thèse était d’améliorer l’utilisation et la compréhension des outils de mesure de la déformabilité du globule rouge (GR) dans la drépanocytose (Etudes 1 et 2). L’étude 1 a montré l’importance de la standardisation des mesures de déformabilité par ektacytométrie chez les enfants drépanocytaires. Au cours de l’étude 2, les propriétés des GR ont été modifiées et la variation des courbes de déformabilité érythrocytaire « classique » (index d’élongation en fonction de la contrainte de cisaillement en milieu isotonique) a été comparée aux résultats d’osmoscan (mesure de la déformabilité érythrocytaire en gradient osmolaire à contrainte de cisaillement fixe), méthode de référence pour étudier les anomalies de la membrane du GR. Ainsi, les variations de déformabilité érythrocytaire au-delà de 3 Pa sont affectées à la fois par la viscosité interne du GR et par des modifications de la surface cellulaire (rapport surface/volume) alors que les modifications de l’élasticité membranaire affectent la déformabilité érythrocytaire quelles que soient les forces de cisaillements utilisées (faibles, modérées ou hautes). Le deuxième objectif de cette thèse était d’apporter des éléments supplémentaires sur l’implication des facteurs génétiques, des paramètres hémorhéologiques et du niveau de stress oxydant sur la survenue des complications vaso-occlusives chez les patients atteints de syndrome drépanocytaire majeur (Etudes 3 à 6). La mise en commun des résultats d’hémorhéologie obtenus sur 165 patients de notre cohorte lyonnaise et 240 patients de la cohorte guadeloupéenne a permis de montrer que la rhéologie du GR chez les patients drépanocytaires était dépendante de l’âge. Ainsi, la viscosité sanguine augmente avec l’âge pour atteindre un plateau vers 30 ans alors que la déformabilité érythrocytaire diminue avec l’âge (Etude 3). Ces modifications participent vraisemblablement à l’apparition de complications chroniques chez l'adulte drépanocytaire. Les études 4 et 5 ont été réalisées sur la cohorte pédiatrique lyonnaise. Au cours de ces 2 études, nous avons étudié l’influence sur la rhéologie du sang et la survenue de crises vaso-occlusives (CVO) des facteurs génétiques (alpha-thalassémie, déficit en Glucose-6-Phosphate Déshydrogénase (G6PD) et haplotypes S) d’une part (Etude 4) et du niveau de stress oxydant et nitrosatif d’autre part (Etude 5). L’alpha-thalassémie augmente la déformabilité des GR et l’agrégation érythrocytaire. Ces 2 phénomènes pourraient participer à augmenter le risque de CVO. De plus, l’alpha-thalassémie, en diminuant l’hémolyse, diminuerait le niveau de stress oxydant, élément majeur impliqué dans la physiopathologie de la drépanocytose. Enfin, l’étude 6 a montré que la rhéologie sanguine des patients Sbêta+ était quasi-identique à celle des sujets sains AA mais que les patients les plus sévères pourraient avoir un déficit en monoxyde d’azote circulant. En conclusion, mon travail de thèse contribue à une meilleure compréhension de la physiopathologie de la drépanocytose / The first goal of this thesis (Study 1 and 2) was to improve the use and the comprehension of tools for red blood cell (RBC) deformability measurements in sickle cell disease (SCD). The first study showed the importance of standardization of RBC deformability measurements by ektacytometry in SCD children. In the study 2, the RBC proprieties was modified and the variation of « classic » RBC deformability curve (elongation index as a function of the shear stress in isotonic medium) was compared to osmoscan results (elongation index in hyperosmolar gradient and constant shear stress), the gold standard for RBC membrane defect studies. Thus, the modifications of RBC deformability curve above 3 Pa were affected by RBC internal viscosity and cellular surface modification (and thus surface/volume ratio) while membran elasticity modifications affected RBC deformability whatever the shear stress (low, moderate or high). The second goal of this thesis was to study the effects of genetic modifiers, hemorheological parameters and oxidative stress level on vaso-occlusive complications (VOC) in SCD (Study 3 to 6). Hemorheological parameters were measured on 165 patients from Lyon and 240 patients from Gwada and the results showed that blood viscosity increased until the age of 30 and RBC deformability decreased with age (Study 3). This modifications probably play role in the chronic complications of SCD adult patients. The studies 4 and 5 were conducted on SCD children. We studied the effects of genetic modifiers (alpha-thalassemia, glucose-6-phospho-deshydrogenase deficiency and S haplotypes ; study 3) and nitro-oxidative stress level (study 5). Alpha-thalassemia increase RBC deformability and RBC aggregation. This phenomenon could contribute to increase VOC. Moreover, alpha-thalassemia decreased hemolysis and thus oxidative stress, a major component of SCD physiopathology. Then the study 6 showed that Sbeta+ patient hemorheology was quite the same of AA ubjects but the more severe patients could have a defect in circulating nitric oxide. To conclude, my thesis contribute to a better understanding of SCD physiopathology

Mechanical stresses and flow dynamics alteration in a stented artery region are known to stimulate intimal thickening and increase the risk of restenosis, the closure of a revascularized artery. Particle imaging velocimetry (PIV) is an optical flow visualization technique that can be used to characterize the local flow dynamics around different stent structures. However, the usual cylindrical stent geometries present visualization difficulties when using an optical measurement technique such as the PIV technique. Using a flat configuration of a stent model presents advantages over the usual cylindrical model. A planar stent model makes data acquisition easier in planes cutting through the model due to its flat geometry that is compatible with the PIV planar flow investigation technique. Furthermore, with the planar stent configuration model velocity measurements and their associated flow features can be done without inducing refraction of the laser light sheet occurring with the cylindrical model's curvature. The refraction of light should be avoided since measurement errors and reflections are the resulting effects of this laser light plane deviation when passing through the curvature of a cylindrical stent model. / The spatial and temporal distribution of the Wall Shear Stress (WSS), which is believed to be of primary importance in the development of restenosis should be comparable between the flat and the cylindrical stent configuration models. The velocity and shear strain rate distributions will be compared between the flat and cylindrical stent configurations using computational fluid dynamics (CFD) simulations in order to analyse the feasibility of using a flat instead of a cylindrical version of the stent model for PIV experiments. It will be shown that for a physiological pulsatile flow the flat model yields results in shear strain rate spatial and temporal distribution that is comparable to the cylindrical model. A more PIV compatible, efficient and less refractive error prone validated flat model would be advantageous when several stent designs influence on the local hemodynamics around the strut geometries have to be studied quantitatively and optimized.

La drépanocytose est une hémoglobinopathie aux formes et aux sévérités cliniques très hétérogènes qui affectent de nombreux organes chez les patients touchés. Pour cette raison le terme de syndrome drépanocytaire majeur est généralement employé. Tous les syndromes drépanocytaires majeurs ont en commun une mutation ponctuelle du gène β-globine appelée mutation βs . Cette mutation βs conduit à la synthèse de la protéine d'hémoglobine S (HbS) caractérisée par sa capacité à polymériser dans sa forme désoxygénée. La polymérisation de l'HbS est l'élément déclencheur de la falciformation du globule rouge et conduit à de nombreuses altérations hématologiques et hémorhéologiques. Ces dernières sont à l'origine de troubles de l'hémodynamique, de l'oxygénation sanguine et de la perfusion tissulaire en oxygène. Il en résulte de nombreuses complications aigues (crise vaso-occlusive, accident vasculaire cérébral, syndrome thoracique aigu etc.) et/ou chroniques (glomérulopathie, ostéonécrose de la tête fémorale etc.) causés par un défaut d'oxygénation des tissus. / Sickle cell anemia is a hemoglobinopathy forms and severities very heterogeneous clinical affecting many organs in affected patients. For this reason the term major sickle cell syndrome is generally used. All major sickle cell syndromes have a common point mutation in the gene called β-globin mutation βs. This βs mutation leads to the synthesis of the protein hemoglobin S (HbS) is characterized by its ability to polymerize in its deoxygenated form. The polymerization of HbS is the trigger for the sickling of red blood cells and leads to many Hematological and hemorheological. These are at the origin of disorders hemodynamics, blood oxygenation and tissue perfusion with oxygen. This results in many acute complications (vaso-occlusive crisis, stroke, acute chest syndrome, etc..) And / or chronic (glomerulopathy, osteonecrosis of the femoral head etc.). Caused by a defect of tissue oxygenation.

La drépanocytose ou anémie falciforme est la maladie génétique la plus répandue dans le monde. Elle affecte plus particulièrement les populations des régions africaines sub-sahariennes, du sous-continent Indien et celles issues de ces populations. La Guadeloupe, archipel des Antilles françaises est une zone à forte prévalence drépanocytaire. La drépanocytose se caractérise par des anomalies de l’hémoglobine et du globule rouge qui mènent à des complications aigues et chroniques pouvant toucher tous les organes, dont les yeux. Récemment, plusieurs auteurs ont rapporté une prévalence importante de la maculopathie dans la drépanocytose mais la physiopathologie reste très mal comprise. Ainsi, nous avons réalisé deux études. La première, consistait à étudier la prévalence de la rétinopathie et de la maculopathie drépanocytaires et de tester l’association entre ces deux complications. De plus, nous avons recherché un éventuel lien avec différentes anomalies biologiques. Nous avons montré que la rétinopathie et la maculopathie étaient deux complications fréquentes mais indépendantes dans la drépanocytose. Les résultats de cette première étude ne supportent pas un lien éventuel entre les anomalies hématologiques, hémorhéocarlogiques ou le génotype et ces deux complications. Dans une deuxième étude nous avons essayé de mieux caractériser la maculopathie drépanocytaire en réalisant un électrorétinogramme multifocal (mfERG) et une tomographie en cohérence optique spectral domain (SD-OCT) chez des patients SS et SC sans signe clinique de maculopathie. Nous avons pu mettre en évidence des altérations maculaires électrophysiologiques chez les patients drépanocytaires paraissant exempt de toute maculopathie à l’examen clinique. Par ailleurs, nous avons retrouvé que la maculopathie drépanocytaire est aussi fréquente chez les SS que chez les SC.Notre travail confirme le caractère fréquent des complications rétiniennes drépanocytaires. Cependant, elles apparaissent comme complètement indépendantes l’une de l’autre et les mécanismes physiopathologiques sous-jacents restent mal compris / Sickle cell disease (SCD) also known as sickle cell anemia is the most common genetic affection in the world. Most of SCD cases occur in sub-Saharan Africa, india and among people of African and indian descent living in other parts of the world. SCD is common in Guadeloupe, French West indies. It results in an abnormal hemoglobin leading to rigid sickle like shape red blood cells responsible for a great number of acute and chronical systemic complications including ophthalmic affections. Recently, a wild prevalence of maculopathy has been reported by several authors but its pathophysiology remains unclear.We performed two studies. The aim of the first one was to investigate the prevalence of SCD retinopathy and maculopathy and to test the association between these two conditions. Moreover, we looked for a possible link with biological abnormalities. Our study confirmed that SCD maculopathy and retinopathy are common but they remain two independent affections. Nevertheless, we found no association with hematological parameters, blood rheology of genetic.In the second study, we described and compared spectral domain ocular coherence tomography (SD-OCT) and multifocal electroretinogram (mfERG) findings in patients with SCD without clinical sign of maculopathy, according to the hemoglobin genotype. We found electrophysiological macular dysfunction in SCD patients with no clinical maculopathy. Furthermore, maculopathy was as frequent in SCA than in SCC patients.Our work confirms that retinal affections are common in SCD. Nevertheless, retinopathy and maculopathy seem to be two independent complications and their pathophysiology remains misunderstood.

Extracorporeal Membrane Oxygenation (ECMO) is a life-saving therapy usedfor support in critical heart and/or lung failure. Patient’s blood is pumped viaan artificial lung for oxygenation outside of the body. The circuit is composedof a blood pump, cannulae for drainage and reinfusion, a membrane lung,tubing and connectors. Its use is associated with thromboembolic complicationsand hemolytic damage. Detailed numerical studies of two blood pumps anda lighthouse tip drainage cannula were undertaken to characterize the flowstructures in different scenarios and their link to platelet activation. The pumpsimulations were modelled according to manufacturer’s proclaimed use but alsoin off-design conditions with flow rates used in adult and neonatal patients.Lagrangian Particle Tracking (LPT) was used to simulate the injection ofparticles similar in size to platelets to compute platelet activation state (PAS).The results indicated that low flow rates impacted PAS similarly to high flowrates due to increased residence time leading to prolonged exposure to shearstress despite the fact that shear per se was lower at low flow rate. Regardingthe cannula, the results showed that a flow pattern similar to a jet in crossflowdeveloped at the side holes. A parameter study was conducted to quantifydrainage characteristics in terms of flow rate distribution across the holes wheninput variables of flow rate, modelled fluid, and hematocrit were altered. Thefindings showed, across all the cases, that the most proximal hole row drainedthe largest fraction of fluid. The effects due to the non-Newtonian nature ofblood were confined to regions far from the cannula holes and the flow structuresshowed very limited dependence on the hematocrit. A scaling law was found tobridge the global drainage performance of fluid between water and blood. / <p>QC 210906</p>