abstract: Treatment of cerebral aneurysms using non-invasive methods has existed for decades. Since the advent of modern endovascular techniques, advancements to embolic materials have largely focused on improving platinum coil technology. However, the recent development of Onyx®, a liquid-delivery precipitating polymer system, has opened the door for a new class of embolic materials--liquid-fill systems. These liquid-fill materials have the potential to provide better treatment outcomes than platinum coils. Initial clinical use of Onyx has proven promising, but not without substantial drawbacks, such as co-delivery of angiotoxic compounds and an extremely technical delivery procedure. This work focuses on formulation, characterization and testing of a novel liquid-to-solid gelling polymer system, based on poly(propylene glycol) diacrylate (PPODA) and pentaerythritol tetrakis(3-mercaptopropionate) (QT). The PPODA-QT system bypasses difficulties associated with Onyx embolization, yet still maintains non-invasive liquid delivery--exhibiting the properties of an ideal embolic material for cerebral aneurysm embolization. To allow for material visibility during clinical delivery, an embolic material must be radio-opaque. The PPODA-QT system was formulated with commercially available contrast agents and the gelling kinetics were studied, as a complete understanding of the gelling process is vital for clinical use. These PPODA-QT formulations underwent in vitro characterization of material properties including cytotoxicity, swelling, and degradation behaviors. Formulation and characterization tests led to an optimized PPODA-QT formulation that was used in subsequent in vivo testing. PPODA-QT formulated with the liquid contrast agent ConrayTM was used in the first in vivo studies. These studies employed a swine aneurysm model to assess initial biocompatibility and test different delivery strategies of PPODA-QT. Results showed good biocompatibility and a suitable delivery strategy, providing justification for further in vivo testing. PPODA-QT was then used in a small scale pilot study to gauge long-term effectiveness of the material in a clinically-relevant aneurysm model. Results from the pilot study showed that PPODA-QT has the capability to provide successful, long-term treatment of model aneurysms as well as facilitate aneurysm healing. / Dissertation/Thesis / Ph.D. Bioengineering 2011

A través de la simulación numérica de la mecánica de aneurismas cerebrales, el profesor Dr. Ing. Álvaro Valencia del Departamento de Ingeniería Mecánica de la Universidad de Chile, en el marco del segundo año de desarrollo del proyecto Fondecyt 'FLOW DYNAMICS AND ARTERIAL WALL INTERACTION IN REALISTIC CEREBRAL ANEURYSM MODELS', está desarrollando una metodología de apoyo a las decisiones médicas, donde las simulaciones computacionales puedan brindar un grado mayor de certidumbre en el diagnóstico y evaluación de este tipo de patologías. Producto de este trabajo, se cuenta con una metodología consolidada para la reconstrucción de casos de aneurismas cerebrales reales y para la realización de simulaciones de mecánica de fluidos computacional (CFD) y con interacción fluido - estructura (FSI), para el estudio de aneurismas cerebrales sin tratamiento. Por otro lado, el efecto del tratamiento de un aneurisma, desde el punto de vista mecánico, es un punto aún no abordado. A grandes rasgos existen dos tipos de tratamientos de aneurismas: la cirugía convencional, y el tratamiento endovascular. Éste último busca modificar la circulación de sangre en el aneurisma para evitar su ruptura. En esta memoria de título se modeló y simuló un modelo de tratamiento endovascular tipo stent, que consiste en introducir una malla trenzada de metal flexible dentro de la arteria portadora del aneurisma, y se realizó una comparación de los resultados obtenidos de la simulación con el modelo de stent con los obtenidos previo al tratamiento, en el contexto de las simulaciones CFD. Se observó que el stent no tiene efectos importantes aguas arriba y aguas abajo del aneurisma, pero sí tiene efectos significativos en la zona del aneurisma. Los esfuerzos de corte en la pared del aneurisma disminuyen con la inserción del stent, llegando a disminuciones cercanas al 80% en el fondo del aneurisma. La velocidad de entrada al aneurisma también disminuye, lo cual provoca que el caudal de entrada siga la misma tendencia, obteniéndose reducciones del 38%. También se redujo la velocidad en el plano transversal paralelo al sentido del flujo en la arteria. Finalmente, debido a la utilización de un modelo de fluido no newtoniano, se notó un aumento de la viscosidad efectiva en el interior del aneurisma, en un plano transversal, paralelo al sentido del flujo sanguíneo en la arteria.

abstract: Cerebral aneurysms are pathological balloonings of blood vessels in the brain, commonly found in the arterial network at the base of the brain. Cerebral aneurysm rupture can lead to a dangerous medical condition, subarachnoid hemorrhage, that is associated with high rates of morbidity and mortality. Effective evaluation and management of cerebral aneurysms is therefore essential to public health. The goal of treating an aneurysm is to isolate the aneurysm from its surrounding circulation, thereby preventing further growth and rupture. Endovascular treatment for cerebral aneurysms has gained popularity over traditional surgical techniques due to its minimally invasive nature and shorter associated recovery time. The hemodynamic modifications that the treatment effects can promote thrombus formation within the aneurysm leading to eventual isolation. However, different treatment devices can effect very different hemodynamic outcomes in aneurysms with different geometries. Currently, cerebral aneurysm risk evaluation and treatment planning in clinical practice is largely based on geometric features of the aneurysm including the dome size, dome-to-neck ratio, and parent vessel geometry. Hemodynamics, on the other hand, although known to be deeply involved in cerebral aneurysm initiation and progression, are considered to a lesser degree. Previous work in the field of biofluid mechanics has demonstrated that geometry is a driving factor behind aneurysmal hemodynamics. The goal of this research is to develop a more combined geometric/hemodynamic basis for informing clinical decisions. Geometric main effects were analyzed to quantify contributions made by geometric factors that describe cerebral aneurysms (i.e., dome size, dome-to-neck ratio, and inflow angle) to clinically relevant hemodynamic responses (i.e., wall shear stress, root mean square velocity magnitude and cross-neck flow). Computational templates of idealized bifurcation and sidewall aneurysms were created to satisfy a two-level full factorial design, and examined using computational fluid dynamics. A subset of the computational bifurcation templates was also translated into physical models for experimental validation using particle image velocimetry. The effects of geometry on treatment were analyzed by virtually treating the aneurysm templates with endovascular devices. The statistical relationships between geometry, treatment, and flow that emerged have the potential to play a valuable role in clinical practice. / Dissertation/Thesis / Doctoral Dissertation Bioengineering 2016

Objectives: Clinical implementation of 3D ultrasound (3D-US) in vascular surgery is in its infancy. The aim of this thesis was to develop novel clinical applications for 3D-US in the diagnosis and management of abdominal aortic aneurysm (AAA). Methods: Four principle clinical applications were investigated. 1) Intraoperative imaging – The ability of 3D-US to detect and classify endoleaks was compared with digital subtraction angiography in patients undergoing EVAR. 2) Detection and classification of endoleaks following endovascular aneurysm repair (EVAR) – The abilityof 3D-US to accurately detect and classify endoleaks following EVAR was compared to CTA and the final multi-disciplinary team decision. 3) AAA volume measurement – measurements using magnetic and optically-tracked 3D-US were compared to CTA. 4) Biomechanical analysis – the challenges of using 3D-US to generate surface models for biomechanical simulation was explored by development of an interactive segmentation technique and comparison of paired CT and 3D-US datasets. Optimal results were used in finite element analysis (FEA) and computational fluid dynamic(CFD) simulations. Results: 3D-US out-performed uniplanar angiography for the detection of endoleaks during EVAR. This approach allowed contrast-free EVAR to be performed in patients with poor renal function. 3D contrast-enhanced ultrasound was superior to CTA for endoleak detection and classification when compared with the final decision of the multi-disciplinary team. Optimal results for AAA volume measurements were gained using an optically tracked 3D-US system in EVAR surveillance. However, there remained a significant mean difference of 13.6ml between CT and 3D-US. Complete technical success of generating geometries for use in biomechanical analysis using 3D-US was only 5%. When the optimal results were used, a comparable CFD analysis under the conditions of steady, laminar and Newtonian flow was achieved. Using basic modelling assumptions in FEA, peak von Mises and principle wall stress was found to be at the same anatomical location on both the CT and 3D-US models but the 3D-US model overestimated the wall stress values by 41% and 51% respectively. Conclusions: 3D-US could be clinically implemented for intra-operative imaging and EVAR surveillance in specific cases. 3D-US volume measurement is feasible but future work should aim to improve accuracy and inter-observer reliability. Although the results of biomechanical analysis using the optimal results was encouraging and provided a proof-of-principal, there are a number of technical developments required to make this approach feasible in a larger number of patients.

Introdução: Acretismo placentário é condição pouco frequente na qual há aderência anormal do tecido trofoblástico à parede uterina. É uma causa importante de hemorragia puerperal, associada a altas taxas de morbimortalidade maternofetal, grande necessidade de transfusão de hemoconcentrados. Os tratamentos propostos variam desde conduta conservadora até a histerectomia pós-parto, associada ou não a procedimentos endovasculares. Objetivo: O presente estudo visa descrever a técnica endovascular de balonamento temporário e embolização das artérias ilíacas internas durante o parto cesáreo, avaliar sua eficácia em reduzir o sangramento materno relacionado ao acretismo placentário, bem como relatar a segurança e o índice de complicações relacionadas ao tratamento endovascular. Materiais e métodos: Coorte retrospectiva de pacientes com diagnóstico pré-natal de acretismo placentário submetidas a tratamento endovascular de balonamento temporário e embolização das artérias ilíacas internas, seguido de histerectomia puerperal no nosso serviço, no período de janeiro de 2012 até novembro de 2016. Foram analisados dados relativos aos antecedentes gestacionais e cirúrgicos, achados de exames de imagem, achados histológicos, níveis de hemoglobina prévios, durante e após o parto, bem como volumes de hemoconcentrados administrados e taxa de complicações relacionadas ao procedimento endovascular. Resultados: Trinta e Siqueira FM 7 cinco pacientes foram submetidas ao manejo proposto durante o período estudado. Foi observado um volume médio de transfusão relacionado ao procedimento e perda sanguínea estimada de 540 ml e 1229 ml, respectivamente. Ocorreram complicações relacionadas ao procedimento endovascular em quatro pacientes, sendo um caso de necrose muscular glútea, um de lesão isquêmica cutânea superficial e dois casos de trombose arterial aguda de membros inferiores. Conclusão: O presente estudo demonstrou que o balonamento temporário e embolização das artérias ilíacas internas reduziu significativamente as necessidades transfusionais relacionadas ao parto nas pacientes com acretismo placentário, quando comparado com casos da literatura nos quais não foram realizadas intervenções endovasculares, com baixo índice de complicações relacionadas ao procedimento. / Introduction: Placenta accreta (PA) is the infrequent condition in which there is abnormal adherence of the trophoblastic tissue to the uterine wall. It\'s considered a major cause of puerperal bleeding, associated with high maternal morbimortality and need for blood products transfusion. Proposed treatments range from conservative to postpartum hysterectomy, combined or not to endovascular techniques. Objectives: to describe the detailed endovascular technique of temporary balloon occlusion followed by embolization of the internal iliac arteries (IIA) during cesarean section, evaluate the ability in reducing birth-related blood loss in patients with diagnosed PA and to assess safety and complications related to the endovascular procedure. Materials and methods: retrospective cohort of patients diagnosed with PA submitted to temporary balloting and embolization of the IAA followed by puerperal hysterectomy in our institution from January 2012 to November 2016. We recorded patient data such as gestational and surgical history, pre-natal radiological image findings, histopathological description, pre e postoperative hemoglobin levels and volume of blood products transfused in all patients. Follow up accounted for possible complications related to the procedure. Results: thirty-five patients were submitted to the approach during the study period. The median volume of packed red blood cells (RBC) and estimated blood loss were 540 ml and 1229 ml respectively. A total of 4 patients had complications attributed to the endovascular procedure - one case of Siqueira FM 9 deep glute tissue necrosis, one of superficial tissue necrosis and two cases of acute arterial thrombosis of the inferior limbs. Conclusion: the present study demonstrated that temporary ballooning and embolization of the IAA was able to significantly reduce birth-related blood loss and transfusion needs in patients with PA when compared to other literature series where no endovascular procedures were performed, with a low rate of procedure-related complications.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22037号 / 医博第4522号 / 新制||医||1038(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 髙橋 良輔, 教授 湊谷 謙司, 教授 井上 治久 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DGAM

Background: Mechanical thrombectomy is the gold standard for treating patients with certain acute ischemic stroke (AIS) due to large vessel occlusion (LVO). However, even with major advancements and increasing procedural volumes, acute endovascular therapy remains a high-risk procedure with a considerable 90-day mortality rate, affected by a variety of factors. Purpose: To investigate various clinical and procedural factors associated with 90-day mortality in patients undergoing mechanical thrombectomy for emergent treatment of AIS and determine which of these factors made unique contributions to post-thrombectomy prognosis. Methods: We examined a prospective registry of 323 patients treated with endovascular thrombectomy for AIS between 2016 and 2019 at a high-volume comprehensive stroke center in central Massachusetts. We developed two multivariable logistic regression models adjusting for the contributions of baseline characteristics and recanalization parameters, to identify potential predictors of mortality at 90 days. Results: Among 323 AIS patients treated with mechanical thrombectomy, the overall rate of successful recanalization was 86% and the overall post-procedure mortality rate was 29% by 90 days. After univariate analysis, a baseline multivariable model comprised of: history of stroke (OR 0.28, 95% CI 0.09 – 0.68), pre-stroke modified Rankin Scale (mRS 2: OR 3.75, 95% CI), severe admission National Institutes of Health Stroke Scale (NIHSS 21–42: OR 12.36, 95% CI 1.48 – 103.27), internal carotid artery (ICA) occlusion (OR 2.77, 95% CI 1.18 – 6.55), and posterior circulation occlusion (OR 2.69, 95% CI 1.06 – 6.83) was prognostic of 90-day mortality. A second multivariable model also found the procedural factors of: clot obtained after each pass (OR 0.49, 95% CI 0.24 – 1.00), successful recanalization (OR 0.21, 95% CI 0.06 – 0.8) and symptomatic intracranial hemorrhage (sICH; OR 17.89, 95% CI 5.22 – 61.29) to be identifiable predictors of post-thrombectomy mortality. Conclusion: Death within 90 days after thrombectomy was increased among patients with higher pre-stroke disability, higher stroke severity on admission, ICA or posterior occlusion, and those with sICH complication. A history of stroke, clot extraction after each device pass, and successful recanalization are associated with decreased 90-day mortality. These identifiable contributors may inform patient selection, prognosis evolution, and shared decision-making regarding emergent thrombectomy for treatment of AIS.

Traumatic arteriovenous fistulas of the neck are a relatively uncommon injury, whose ramifications can include immediate or delayed neurological insults, massive bleeding, or death. Angiography and embolization have been increasingly used to manage this complex injury pattern. In this particular case, the patient underwent management of bilateral communicating arteriovenous fistulae using a commercially available plug occlusion device. Epidemiology, with an emphasis on patient management and outcomes, is discussed.

Die Häufigkeit der endovaskulären Interventionen (EI) an den unteren Extremitäten zur Behandlung der peripheren arteriellen Verschlusskrankheit (pAVK) hat in den letzten Jahren zugenommen. Bei steigender Inzidenz der pAVK und bei gleichzeitiger Reduzierung der Rate mit operativen Interventionen (OI) profitieren die Patienten von der EI. Außerdem stieg die Anzahl der älteren Patienten, die aufgrund einer pAVK im Krankenhaus einer EI zugeführt wurden. Es zeigt sich eine Erweiterung der Indikationen für eine EI von den Claudicanten hin zu den Patienten mit den Stadien der kritischen Ischämie. Hierdurch werden gerade ältere und morbidere Patienten mit komplexeren endovaskulären Prozeduren konfrontiert. Insbesondere im Krankenhaus ergibt sich die Möglichkeit, den pAVK-Patienten, die bisher eine OI mit einer anästhesiologischen Begleitung erhielten, eine EI in SPA anzubieten. In der Regel werden EI in Lokalanästhesie durchgeführt. Die Anwendung der SPA bei EI ist interessant, da es möglicherweise neben der kompletten Schmerzausschaltung der unteren Extremitäten bei erhaltener Kommunikation zu Synergieeffekten durch die periphere Vasodilatation kommen kann. Als ein seltenes Verfahren zur Verbesserung der peripheren Durchblutung hat dies die CT-gesteuerte temporäre Sympathikolyse nach erfolgter EI gezeigt. Um prospektiv zu untersuchen, ob eine EI in SPA eine Verbesserung des Outcome und des Behandlungsablaufs mit sich bringt, ist zunächst wichtig zu zeigen, dass die Anwendung von SPA bei EI nicht gefährlich ist. Hierzu stehen Daten aus der Allgemein-, Viszeral- und Gefäßchirurgischen Abteilung des Klinikums Main-Spessart zur Verfügung. Im Zeitraum vom 15.12.2009 bis 22.01.2015 wurden bei 59 Patienten EI in SPA durchgeführt. Bei keinem der 59 Patienten kam es durch die Anwendung der SPA zu anästhesieabhängigen Komplikationen. Als zu erwartende Nebenwirkung trat der durch temporäre Sympathikolyse ausgelöste Blutdruckabfall bei allen Patienten auf. Im Mittel sank der Wert um 24,2 % des Ausgangswerts, bei 13 Patienten (22,0 %) wurde eine Korrektur des Blutdruckabfalls mit Akrinor® durchgeführt und gut beherrscht. Für die Stärke des Blutdruckabfalls konnte keine Signifikanz bei der ASA-Einteilung, der Geschlechterverteilung und dem Alter nachgewiesen werden, somit besteht für eine EI in SPA keine Kontraindikation für den älteren und kränkeren pAVK-Patienten. Die Ergebnisse dieser Dissertation zeigen, dass die Anwendung der SPA bei EI ein sicheres Verfahren ist. Die SPA kann, gerade bei zu erwartenden komplexen peripheren EI eine für den Patienten und Interventionisten angenehme und sichere Alternative zur Lokalanästhesie sein. Der personelle und materialbedingte Aufwand einer EI in SPA, im Vergleich mit einer EI in Lokalanästhesie, ist dabei deutlich erhöht und scheint übertrieben. Dass die EI in SPA Synergieeffekte mit sich bringt und deshalb sinnvoll ist, kann nur vermutet werden. Dieser Zusammenhang könnte im Rahmen einer prospektiven Studie, die beide Anästhesieverfahren für eine EI vergleicht, gezeigt werden. / The frequency of endovascular interventions (EI) on the lower extremities for the treatment of peripheral arterial occlusive disease (PAOD) has increased in recent years. With an increasing incidence of PAOD and a simultaneous reduction in the rate of surgical interventions (SI), older patients in particular benefit from EI. There is an expansion of the indications for EI from claudicants (patients with intermittent claudication) to patients with the stages of critical ischemia. As a result, older and more morbid patients in particular are confronted with more complex endovascular procedures. In hospitals in particular, there is the possibility of offering PAOD patients who have previously received an SI with anesthesiology accompaniment an EI in spinal anesthesia (SPA). Usually, EI are performed under local anesthesia. The use of SPA for EI is interesting because, in addition to the complete elimination of pain in the lower extremities, if communication with the patient is maintained, there may be synergy effects due to peripheral vasodilation. In order to investigate prospectively whether an EI in SPA leads to an improvement in the outcome and the treatment process, it is first important to show that the use of SPA in EI is not dangerous. Data from 59 patients were available. No anesthesia-related complications occurred in any of these 59 patients. As an expected side effect, the drop in blood pressure caused by temporary sympathicolysis occurred in all patients. On average, the value fell by 24.2% from the initial value; in 13 patients (22.0%), the drop in blood pressure was corrected with Akrinor® and was well controlled. For the severity of the drop in blood pressure, no significance could be demonstrated in the ASA classification, gender distribution and age, so there is no contraindication for EI in SPA for older and sicker PAOD patients. The results of this dissertation show that the use of SPA in EI is a safe procedure. The SPA can be a comfortable and safe alternative to local anesthesia for the patient and the interventionist, especially when complex peripheral EI is expected. The personnel and material-related expenditure of an EI in a SPA, compared to an EI in local anesthesia, is significantly higher and seems excessive. It can only be assumed that the EI in SPA brings synergy effects and therefore makes sense. This relationship could possibly be shown in a prospective study comparing both anesthetic methods for an EI.

No description available.