京都大学 / 新制・課程博士 / 博士(医学) / 甲第24966号 / 医博第5020号 / 新制||医||1069(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 江木 盛時, 教授 浅野 雅秀, 教授 湊谷 謙司 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24789号 / 医博第4981号 / 新制||医||1066(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 江木 盛時, 教授 湊谷 謙司, 教授 花川 隆 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Diss. (sammanfattning) Linköping : Linköpings universitet, 2004. / Härtill 5 uppsatser.

The diploma thesis deals with the assessment of the prediction of brain aneurysm rupture based on its geometrical and material properties. In the first part of the thesis there is a~detailed research study of cardiovascular systems with a focus on the cerebral artery and aneurysm occurring on their bifurcates. The second part of the thesis is focused on the creation of two models of arterial cerebral bifurcation with the presence of aneurysm and on obtaining their geometry in unloaded state. Emphasis is placed on the most realistic constitutive model of the artery wall material based on real data from uniaxial tensile tests and on a suitably chosen blood pressure load. This blood pressure may be step-changed, for example, in bungee jumping. In the work, a calculation of the increase in blood pressure during the step-change is performed, which is subsequently used in calculations of tension in the wall of the cerebral aneurysm. In conclusion, the risk of rupture is evaluated in two model idealized brain aneurysms and a discussion of the credibility of the results is given.

Esta pesquisa analisa experimentalmente as diferenças de comportamento entre a versão clássica e a modificada da craniotomia subtemporal quanto à retração do lobo temporal. A retração é medida pelo ângulo de visão, através do microscópio, obtido ao mirar-se estruturas previamente estabelecidas. Estudou-se a correlação estatística entre a retração cerebral e os diâmetros transversos do crânio, a profundidade da fossa temporal e a altura da bifurcação medida em relação à tenda do cerebelo e à clinóide posterior. É considerada a relação entre estes achados e os aspectos pertinentes à opção entre as craniotomias pterional e subtemporal para o tratamento cirúrgico dos aneurismas da porção superior da artéria basilar. / This paper is an experimental analysis between the classic and the modified subtemporal procedures, regarding the cerebral retraction required to approach the interpeduncular cistern and the basilar artery bifurcation. The retraction is assumed to be proportional to the angle of sight, through the microscope, required to observe the basilar bifurcation and other structures. The statistical correlations between the degree of brain retraction and the transverse diameters of the skull, the vertical length of the temporal fossa and the position of the basilar bifurcation in relation to the posterior clinoid and the tentorium are analysed. Considerations are made regarding these findings and the many aspects involved in the options between the pterional and the subtemporal approaches in the surgical treatment of the basilar bifurcation aneurysms

Esta pesquisa analisa experimentalmente as diferenças de comportamento entre a versão clássica e a modificada da craniotomia subtemporal quanto à retração do lobo temporal. A retração é medida pelo ângulo de visão, através do microscópio, obtido ao mirar-se estruturas previamente estabelecidas. Estudou-se a correlação estatística entre a retração cerebral e os diâmetros transversos do crânio, a profundidade da fossa temporal e a altura da bifurcação medida em relação à tenda do cerebelo e à clinóide posterior. É considerada a relação entre estes achados e os aspectos pertinentes à opção entre as craniotomias pterional e subtemporal para o tratamento cirúrgico dos aneurismas da porção superior da artéria basilar. / This paper is an experimental analysis between the classic and the modified subtemporal procedures, regarding the cerebral retraction required to approach the interpeduncular cistern and the basilar artery bifurcation. The retraction is assumed to be proportional to the angle of sight, through the microscope, required to observe the basilar bifurcation and other structures. The statistical correlations between the degree of brain retraction and the transverse diameters of the skull, the vertical length of the temporal fossa and the position of the basilar bifurcation in relation to the posterior clinoid and the tentorium are analysed. Considerations are made regarding these findings and the many aspects involved in the options between the pterional and the subtemporal approaches in the surgical treatment of the basilar bifurcation aneurysms

Subarachnoid hemorrhage (SAH) is a disease with high risk of mortality and morbidity. Elderly patients have an even higher risk of poor outcome. The incidence of SAH increases with age and the elderly constitute a substantial and increasing proportion of the population. Thus, the management of elderly SAH patients is an imminent clinical challenge. Time trends in clinical management and outcome were investigated in 281 SAH patients aged ≥65 years admitted over an 18-year period. The volume of elderly patients, especially patients ≥70 years and patients in worse clinical condition increased over time. The proportion of patients with favorable outcome increased over time, without an increase in severely disabled patients. Technical results and clinical outcome of endovascular aneurysm treatment (EVT) was investigated in 62 elderly SAH patients. EVT can be performed in elderly SAH patients with high technical success, acceptable aneurysm occlusion degree, acceptable procedural complication rate, and fair outcome results. EVT was compared to neurosurgical clipping (NST) in 278 elderly SAH patients in the International Subarachnoid Aneurysm Trial. In good grade elderly SAH patients, EVT should probably be the favored treatment for internal carotid and posterior communicating artery aneurysms, while elderly patients with middle cerebral artery aneurysms appear to benefit from NST. Occurrence of secondary insults and their impact on clinical deterioration were studied in 99 patients with severe SAH. High intracranial pressure increased and high cerebral perfusion pressure decreased the risk of clinical deterioration. Elderly patients had less intracranial hypertension insults and more hypertensive, hypotensive and hypoxemic insults. Good outcome was achieved in 24% of elderly patients with severe SAH, and the proportion of severe disability was similar to that of younger patients. Patient age was not a significant predictor for vasospasm in 413 SAH patients when admission and treatment variables were adjusted for with multiple logistic regression.

Στην παρούσα Διπλωματική Εργασία μελετάται η ανάπτυξη ενός μοντέλου προσομοίωσης αλληλεπίδρασης ρευστού-στερεού για τον προσδιορισμό ρευστοδυναμικών παραμέτρων (Wall Shear Stress, Von Mises Stress κ.α.) μέσω των οποίων θα μπορεί μελλοντικά να προβλεφθεί η ρήξη ή όχι ενός ενδοκρανιακού ανευρύσματος. Αρχικά γίνεται μια σύντομη παρουσίαση του ιατρικού προβήματος ώστε να γίνει κατανοητή η σπουδαιότητα της ανάπτυξης του υπολογιστικού μοντέλου με σκοπό τον υπολογισμό παραμέτρων οι οποίες μπορούν να φανούν χρήσιμες. Κατά τη διάρκεια ανάπτυξης του μοντέλου αξιοποιήθηκαν πραγματικά δεδομένα απεικονιστικών διατάξεων ασθενών του Αττικού Πανεπιστημιακού Γενικού Νοσο- κομείου. Εν συνεχεία, η επεξεργασία των εικόνων αυτών διεξήχθει στο λογισμικό ανοιχτού κώδικα VMTK (Vascular Modeling Toolkit) από όπου προήλθε και η τρισδιάστα- τη ανακατασκευη τους. Στο επόμενο στάδιο, οι γεωμετρίες που προέκυψαν από την επεξεργασία εικόνας εισήχθησαν στο λογισμικό εμπορικού κώδικα ANSYS όπου και αναπτύχθηκε το υπολογιστικό μοντέλο το οποίο περιείχε και την αλληλεπίδραση ρευστού και στερεού (FSI). Αξίζει να αναφερθεί το γεγονός ότι το μοντέλο που αναπτύχθηκε περιείχε κινούμενα στοιχεία πλέγματος (Moving Mesh), τα οποία συμβάλλουν στον ακριβέστερο υπολογισμό και αποτύπωση παραμέτρων που υπολογίστηκαν στη συνέχεια. Τέλος αναφέρονται κάποιοι μελλοντικοί στόχοι και προοπτικές μέσω των αποτελεσ- μάτων που προέκυψαν από την ανάλυση του μοντέλου. / In the present M.Sc thesis we are studying the development of a numerical model that simulates fluid-solid interaction for determining fluid dynamics parameters (Wall Shear Stress, Von Mises Stress etc) through which through which could be predicted the rupture or not of an intracranial aneurysm. First, a brief presentation of the medical problem is being made, to understand the importance of developing the computational model in order to calculate parameters which can be useful. During the development of the model, real imaging data from CT scans taken from patients of Attikon General University Hospital were exploited. Thereafter, the processing of these images was performed in the open-source software VMTK (Vascular Modeling Toolkit) from where came the three-dimensional reconstruction. In the next step, the geometries obtained from the image processing have been introduced in the commercial software ANSYS where the computational model that contains the interaction of fluid and solid has been developed (FSI). It is worth mentioning that the model developed, contained moving mesh elements, which contribute to more accurate calculation and mapping of parameters which were calculated after. Finally, some future objectives and prospects are being referred, through the results obtained from the analysis of the model.

Background: Impaired homocysteine metabolism is associated with a number of vasculopathies including extracranial aneurysms. We analyzed the possible association of nine genetic variants of homocysteine metabolism with the occurrence of intracranial aneurysms. Methods: Caucasian patients (n = 255) treated at two German hospitals for intracranial aneurysms and local controls (n = 348) were genotyped for the following polymorphisms: methionine synthase (MTR) c.2756A→G, methylenetetrahydrofolate reductase (MTHFR) c.677C→T, MTHFR c.1298A→C, cystathionine β-synthase (CBS) c.844_855ins68, CBS c.833T→C, dihydrofolate reductase (DHFR) c.594 + 59del19bp, glutathione S-transferase Ω-1 (GSTO1) c.428C→A, reduced folate carrier 1 (RFC1) c.80G→A and transcobalamin 2 (Tc2) c.776C→G. Results: The G-allele of the missense polymorphism Tc2 c.777C→G was found to be underrepresented in patients, suggesting that this variant may protect from the formation of cerebral aneurysms [odds ratio per two risk alleles (OR) 0.48; 95% confidence interval (CI) 0.30–0.77; p = 0.002]. We obtained borderline results for the G-allele of RFC1 c.80G→A (OR 1.64; 95% CI 1.01–2.65; p = 0.051) and the insertion allele of DHFR c.594 + 59del19bp (OR 1.61; 95% CI 1.00–2.60; p = 0.059), which were found to be overrepresented in patients. Conclusion: Polymorphisms of homocysteine metabolism are possible risk factors for the formation of intracranial aneurysms. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Background: There is growing evidence that genetic variants have an impact on the pathogenesis of intracranial aneurysm (IA). Recently, the genetic locus around the elastin gene (7q11) has been identified as linked to IA in a Japanese population. Our aim was to confirm these results in Caucasian populations. Methods: We conducted a case-control study in 120 Caucasian patients with IA and 172 controls to investigate 8 single nucleotide polymorphisms (SNPs) and various haplotypes within the elastin gene, which were frequently found and associated with the phenotype in the Japanese populations. Real-time PCR and melting curve analysis were used for the detection of genotypes. Results: Allele frequencies and genotypes were equally distributed between Caucasian cases and controls. We failed to identify haplotypes that are associated with the phenotype in our population, which is in contrast to the Japanese study. However, allele frequencies in control populations differ between Caucasians and Japanese. Conclusions: We found no association between SNPs and haplotypes of the elastin gene and the occurrence of IA in our Caucasian populations. However, our data provide strong evidence for racial/ethnic differences in the association of SNP and specific haplotypes of the elastin gene with the phenotype. There might be other genetic variants of the elastin gene associated with IA in Caucasians. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.