Orientador: Evandro Pinto da Luz de Oliveira / Tese (doutorado) - Universidade Estadual de Campinas. Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-15T07:57:17Z (GMT). No. of bitstreams: 1 ChaddadNeto_FeresEduardoAparecido_D.pdf: 73496991 bytes, checksum: 1ed841dc2b8fa51a8c132cb82f523160 (MD5) Previous issue date: 2010 / Resumo: A craniotomia pterional é o acesso cirúrgico mais utilizado na prática neurocirúrgica atual. É utilizada para abordar a maior parte dos aneurismas da circulação anterior e lesões tumorais envolvendo a região supra-selar e parte das estruturas da fossa anterior e média. No entanto, se caracteriza como sendo um acesso limitado para as lesões que envolvem a maior parte do lobo temporal, o assoalho da fossa média do crânio e o complexo da artéria basilar. Para tanto, foram desenvolvidas as craniotomias pré-temporal e orbitozigomática. No entanto a literatura é ainda relativamente carente quanto ao estudo do posicionamento exato da cabeça para a melhor abordagem de cada patologia, em particular. Esse trabalho tem por objetivo estudar o melhor posicionamento da cabeça para a realização das craniotomias mencionadas, visando a melhor exposição de cada lesão em particular / Abstract: The pterional approach is the most applied neurosurgical access in the customized practice nowadays. It is used for approaching most of the anterior circulation aneurysms and tumors involving the anterior and the middle cranial space. However, it is considered a limited approach to some pathologies involving the temporal lobe, the middle cranial space floor and the basilar artery complex region. As a result, the orbitozygomatic and the pretemporal craniotomies developed since it was necessary to enlarge such access to the temporal area. However, there is not a systematic evaluation of head positioning study about the best approach to each specific pathology. This study aims to demonstrate the best way to position the head according to each specific pathology, in order to offer a better surgical visualization by using the most appropriated craniotomy / Doutorado / Neurologia / Doutor em Ciências Médicas

Cerebral aneurysm formation, growth, and rupture are active areas of investigation in the medical community. To model and test the mechanical processes involved, small aneurysm (< 5 mm) segmentations need to be performed quickly and reliably for large patient populations. In the absence of robust automatic segmentation methods, the Vascular Modeling Toolkit (VMTK) provides scripts for the complex tasks involved in computer-assisted segmentation. Though these tools give researchers a great amount of flexibility, they also make reproduction of results between investigators difficult and unreliable. We introduce a VMTK pipeline protocol that minimizes the user interaction for vessel and aneurysm segmentation and a training method for new users. This protocol allows for decision tree handling for CTA and MRA images. Furthermore, we investigate the variation between two expert users and two novice users for six patients using shape index measures developed by Ma et al. and Raghavan et al.

This thesis focuses on special arterial fluid mechanics techniques developed for patient-specific computer modeling of blood flow in cerebral arteries with aneurysm and stent. These techniques are used in conjunction with the core computational technique, which is the space–time version of the variational multiscale (VMS) method and is called “DST/SST-VMST.” The special techniques include using NURBS for the spatial representation of the surface over which the stent mesh is built, mesh generation techniques for both the finite- and zero-thickness representations of the stent, techniques for generating refined layers of mesh near the arterial and stent surfaces, and models for representing double stent. We compute the unsteady flow patterns in the aneurysm and investigate how those patterns are influenced by the presence of single and double stents. We also compare the flow patterns obtained with the finite- and zero-thickness representations of the stent.

Motivated by the need to design minimally-invasive treatments for wide-necked cerebral aneurysms, we used computational modeling to assess aneurysm hemodynamics, examined in vitro cellular responses arising from mechanical and chemical stresses, and designed novel materials that cooperatively adhere to the endothelium. We first hypothesized that because aneurysm geometry plays an important role in hemodynamics, changes in flow patterns may affect the shear stress experienced on the aneurysm wall. We defined flow regimes based on aneurysm hemodynamic and geometric parameters, which may correlate with aneurysm rupture. Because of the direct contact between endothelial cells (ECs) and blood flow, we then evaluated how changes in hemodynamics and inflammatory cytokines affect the expression of cell adhesion molecules (CAMs) and matrix remodeling factors on ECs. We subsequently designed biomaterials that complement the dynamic EC surface and have the ability to conform to any geometry through in situ crosslinking. Antibody-conjugated hydrogels facilitated synergistic EC adhesion using cooperativity as an adhesion strategy. We optimized the presentation of antibodies to inflammatory CAMs on polyvinyl alcohol (PVA) and alginate hydrogels to achieve strong adhesion to inflamed ECs. We synthesized photocrosslinkable, aminated PVA hydrogels and determined the effect of substrate stiffness on cell adhesion. We also evaluated the effects of antibody presentation on cell adhesion strength and dynamics using alginate hydrogels. Taken together, the results of this work may be used to design hydrogels for vascular remodeling applications under shear stress, including embolic agents for cerebral aneurysms. / Engineering and Applied Sciences

An estimated 85% of haemorrhagic strokes are secondary to the rupture of an intracranial aneurysm (IA), a localised, blood-filled dilation of the artery wall. The clinically observed rupture of occluded IAs has led to hypothesise that the presence of thrombus may restrict the transport of nutrients, most notably oxygen, to the aneurysmal wall, thus heightening the risk of rupture through the deleterious effects of hypoxia on cellular functionality. The limited research into O2 transport within IAs demonstrate the need for further exploration into the possible detrimental hypoxic conditions as a result of intrasaccular haemodynamics and thrombusformation in untreated, treated and evolving IAs, with the ultimate goal of further understanding disease evolution and developing prognostic decision support models for clinical intervention. Preliminary computational fluid dynamic simulations conducted on a 2Daxisymmetric model of a thrombosed artery highlighted the relative importance of wall-side versus the fluid-side mass transport of oxygen. A sensitivity analysis demonstrated that variations in thrombus thickness, and arterial wall cellular respiration rates have the greatest influence on the oxygen distribution to the portion of wall in direct contact with the thrombus. The results of the coupled flow-mass transport computational fluid dynamic simulations within patient-specific IA show that a reduction in intrasaccular flow as a consequence of stent deployment affects the rate at which oxygenated blood reaches the entirety of the dome. Nonetheless, the distribution ofO2 to the aneurysmal wall itself does not differ from the observed oxygen distribution across the wall when the same IA is left untreated. Conversely, the low velocity recirculations observed in an IA presenting with a very high aspect ratio (i.e a narrow neck and high sack height) limited the transport of oxygen to such an extent as to completely deprive the delivery of oxygen to the fundus. The presence of thrombus within the IA dome results in a dramatic reduction in oxygen delivery to the wall, the extent of which is dependent on the local thrombus thickness. Finally, a novel fluid-solid-growth-mass transport (FSGT) mathematical model is conceived to explore the biochemical role of thrombus on the evolution of an IA. The shear-regulate propagation of a thrombus layer during membrane expansion leads to the gradual decrease in oxygen tension within the wall. Moreover, as a consequence of coupling this oxygen deficiency to fibroblast functionality, the collagen fibre mass density was shown to increase at an insufficient rate to compensate for the transfer in load from the degrading elastinous consitituents to the collagenous constituents, thus resulting in the increased stretch of collagen fibres in order to maintain mechanical equilibrium. Moreover this over-expansion results in the gradual unstable evolution of the IA. The observed obstruction to oxygen delivery as a result of intrasaccular haemodynamics and thrombosis compounds the need for further development of more comprehensive chemo-mechano-biological models of IAs so as to better ascertain the level of rupture risk posed by a hypoxic environment. Refinement to the models proposed within this work would prove invaluable to creating a fully integrated multi-physics, multi-scale in silico framework in aid to patient diagnostics and individual treatment planning of IAs.

<p>  </p> <p>Three key challenges in developing advanced image-based computational models of cerebral aneurysms are: (i) disentangling the effect of biomechanics and confounding clinical risk factors on aneurysmal progression, (ii) accounting for arterial wall mechanics, and (iii) incorporating the effect of surrounding tissue support on vessel motion and deformation. This thesis addresses these knowledge gaps by developing fluid-structure interaction (FSI) models of subject-specific geometries of cerebral aneurysms to elucidate the effect of coupled hemodynamics and biomechanics. A consistent methodology for obtaining physiologically realistic computational FSI models from standard-of-care imaging data is developed. In this process, a novel technique to estimate heterogeneous arterial wall thickness in the absence of subject-specific arterial wall imaging data is proposed. To address a limitation in the mesh generation workflow of the state-of-the-art cardiovascular flow modeling tool SimVascular, generation of meshes with boundary-layer mesh refinement near the blood-vessel wall interface is proposed for computational geometries with nonuniform wall thickness. Computational murine models of thoracic aortic aneurysms were developed using the proposed methodology. These models were used to inform external tissue support boundary conditions for human cerebral aneurysm subjects via a scaling analysis. Then, the methodology was applied to subjects with multiple unruptured cerebral aneurysms. A comparative computational FSI analysis of aneurysmal biomechanics was performed for each subject-specific pair of computational models for the stable and growing aneurysms, which act as self-controls for confounding clinical risk factors. A higher percentage of area exposed to low shear and high median-peak-systolic arterial wall deformation, each by factors of 1.5 to 2, was observed in growing aneurysms, compared to stable ones. Furthermore, a novel metric – the oscillatory stress index (OStI) – was defined and proposed to indicate locations of oscillating arterial wall stresses. Growing aneurysms demonstrated significant areas with a combination of low wall shear and low OStI, which were hypothesized to be associated with regions of collagen degradation and remodeling. On the other hand, such regions were either absent (or were a small percentage of the total aneurysmal area) in the stable cases. This thesis, therefore, provides a groundwork for future studies, with larger patient cohorts, which will evaluate the role of these biomechanical parameters in cerebral aneurysm growth.</p>

This thesis is focused on stress in brain aneurysms. It consists of three parts. First part is aimed for gaining information about the topic from scientific resources. Next part consists of analyses of geometry of cerebral aneurysms on the computed wall stress. Analyses are performed on four basic geometrical models and results are being discussed. The risky areas in each investigated shape have been identified as well as the comparisons of stress between those shapes have been performed and the most dangerous shape among investigated shapes has been determined. Third part investigates the influence of surrounding tissue on the brain aneurysm. Conclusion of this thesis is that brain gray tissue has positive yet negligible effect on the computed wall stress.

Cette thèse est basée sur ma contribution à différents projets liés à la recherche clinique sur les anévrismes intracrâniens, le traitement endovasculaire, la compréhension des patients et la participation aux essais cliniques. Ce travail a donné lieu à quatre publications à ce jour. Pour cette thèse, je fournis d'abord quelques informations sur les anévrismes cérébraux et la façon dont ils sont gérés. Deuxièmement, je passerai brièvement en revue les principes de l'éthique médicale et de la recherche. J'aborde ensuite l'essai de soins ‘Comprehensive Aneurysm Management (CAM)’, car une partie du travail effectué pour ma thèse consistait à rendre compte des taux de recrutement dans CAM. J'ai également contribué à un article sur la démarcation recherche-soins, et pourquoi elle doit être révisée, ainsi qu'à un éditorial qui affirme que la recherche clinique doit être conçue dans le meilleur intérêt des patients. Enfin, j'ai apporté des contributions originales en concevant une enquête et en interrogeant des patients neurovasculaires avant qu'ils ne soient vus par un médecin dans le cadre d'un suivi. Les résultats de cette étude ont montré que les patients ont une meilleure compréhension de l'incertitude clinique et de l'existence d'options alternatives de prise en charge lorsqu'ils ont participé à des essais de soins. / This thesis is based on my contribution to different projects related to clinical research on intracranial aneurysms, endovascular treatment, patient understanding and participation in clinical trials. This work has led to four publications thus far. For this thesis, I first provide some background on cerebral aneurysms and how they are managed. Second, I briefly review medical and research ethics principles. I then discuss the Comprehensive Aneurysm Management (CAM) care trial because a portion of the work done for my thesis was to report on the recruitment rates in CAM. I also contributed to a paper on the research-care demarcation and why it must be revised, as well as to an editorial claiming that clinical research should be designed in patients' best interests. Finally, I made original contributions by designing a survey and interviewing neurovascular patients prior to being seen by a physician in follow-up. The results of that study showed that patients have a better understanding of clinical uncertainty and the existence of alternative management options when participating in care trials.