Liver radioembolization: Computational particle–hemodynamics studies in a patient-specific hepatic artery under literature-based cancer scenarios.
Liver radioembolization is a promising treatment for combating primary and metastatic liver tumors. It consists of administering radioactive microspheres via an intraarterially placed microcatheter with the aim of lodging these microspheres, which are driven by the arterial bloodstream, in the tumor...
| Main Authors: | , |
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| Format: | info:eu-repo/semantics/doctoralThesis |
| Language: | eng |
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Servicio de Publicaciones. Universidad de Navarra
2022
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10171/63327 |
| _version_ | 1793400422878150656 |
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| author | Aramburu-Montenegro, J. (Jorge) Antón-Remírez, R. (Raúl) |
| author_facet | Aramburu-Montenegro, J. (Jorge) Antón-Remírez, R. (Raúl) |
| author_sort | Aramburu-Montenegro, J. (Jorge) |
| collection | DSpace |
| description | Liver radioembolization is a promising treatment for combating primary and metastatic liver tumors. It consists of administering radioactive microspheres via an intraarterially placed microcatheter with the aim of lodging these microspheres, which are driven by the arterial bloodstream, in the tumoral bed. The position of the microcatheter and the microsphere injection velocity are decided during a pretreatment assessment, by which the treatment is mimicked via the infusion of macroaggregated albumin microparticles.
It is assumed that the pretreatment microcatheter placement and microsphere injection velocity are reproduced during the treatment. Even though it is a safe and effective treatment, some complications (e.g., radiation-induced hepatitis or pneumonitis, gastrointestinal ulcers, etc.) may arise due to nontarget radiation, which can occur due to differences between pretreatment and treatment injection conditions related to microcatheter placement, the injection itself, and the patient’s bloodstream.
In terms of microcatheter placement, there are a number of parameters that can vary from pretreatment to treatment. Of those, the ones that are of special interest in this thesis are the longitudinal and radial position of the microcatheter tip, the microcatheter’s distal direction, the expandable-tip presence (for antireflux catheters only), and the tip orientation (for angled-tip microcatheters only). As for the injection itself, of the parameters that can be modified, this thesis is most concerned with two of them: the quantity and size of the microagent, and the particle injection velocity. With regard to the bloodstream, the arterial blood flow conditions might vary, e.g., due to microsphere-caused embolization of arterioles, leading to a reflux of microspheres. Any alteration in these parameters may be responsible for nontarget radiation and therefore radiation-induced complications.
In order to reduce these radiation-induced complications, it has been suggested that the pretreatment injection conditions be matched as closely as possible during treatment. An alternative solution is to modify the design of microcatheters. For instance, it has been reported that using an antireflux catheter has eliminated particle reflux.
The aim of this thesis is to analyze the influence of the abovementioned parameters on microsphere distribution via computational fluid–particle dynamics simulations. The thesis is divided into four major studies, each of which follows the same numerical strategy (i.e., the liver radioembolization is simulated in a patient-specific hepatic artery model under literature-based liver cancer scenarios). The first study analyzes the pretreatment as an actual treatment surrogate, the second analyzes the influence of an antireflux catheter, the third investigates the influence of the microcatheter distal direction and the injection point and velocity, and the last one explores the influence of an angled-tip microcatheter. Furthermore, prior to conducting these four studies, a methodology was developed to define realistic boundary conditions for numerical simulations in hepatic arteries.
For the study on the pretreatment, results suggest that microcatheter placement is of paramount importance, both in terms of its location in the artery (near a bifurcation or not) and in the longitudinal shifting in microcatheter tip locations between pretreatment and actual treatment. Moreover, the higher the cancer burden, the better the tumor targeting because of the enhanced particle transport power. For the study on antireflux catheter influence, the main conclusion that can be drawn is that injecting from a sufficiently long and tortuous artery branch may ensure a downstream particle distribution that matches flow split, almost regardless of catheter type due to the likely adequate conditions for microsphere redistribution in the bloodstream. With regard to the third study, despite the importance of microcatheter tip position, microcatheter direction and injection velocity seem also to play an important role in particle distribution; results show that unintentional modifications to microcatheter tip and direction and injection velocity during tumor targeting may influence procedure outcome. The final study involving the angled-tip microcatheter shows that the higher the injection velocity the more spread out the particle distribution across cross-sectional areas of artery lumen. Moreover, when only focusing on tip orientation, it is not possible to accurately predict which branch of the bifurcation will take the particles because the complex geometry of hepatic arteries makes the bloodstream take the form of helical and chaotic streamlines. This means that the particle pathlines are not initially intuitive, even though the particle distribution will be similar to flow split. |
| format | info:eu-repo/semantics/doctoralThesis |
| id | oai:dadun.unav.edu:10171-63327 |
| institution | Universidad de Navarra |
| language | eng |
| publishDate | 2022 |
| publisher | Servicio de Publicaciones. Universidad de Navarra |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-633272022-03-31T01:04:10Z Liver radioembolization: Computational particle–hemodynamics studies in a patient-specific hepatic artery under literature-based cancer scenarios. Aramburu-Montenegro, J. (Jorge) Antón-Remírez, R. (Raúl) Radioembolization. Hepatic artery. Liver cancer. Computational fluid–particle dynamics. Hemodynamics. Microcatheter. Antireflux catheter. Angled-tip microcatheter. Microsphere distribution. Liver radioembolization is a promising treatment for combating primary and metastatic liver tumors. It consists of administering radioactive microspheres via an intraarterially placed microcatheter with the aim of lodging these microspheres, which are driven by the arterial bloodstream, in the tumoral bed. The position of the microcatheter and the microsphere injection velocity are decided during a pretreatment assessment, by which the treatment is mimicked via the infusion of macroaggregated albumin microparticles. It is assumed that the pretreatment microcatheter placement and microsphere injection velocity are reproduced during the treatment. Even though it is a safe and effective treatment, some complications (e.g., radiation-induced hepatitis or pneumonitis, gastrointestinal ulcers, etc.) may arise due to nontarget radiation, which can occur due to differences between pretreatment and treatment injection conditions related to microcatheter placement, the injection itself, and the patient’s bloodstream. In terms of microcatheter placement, there are a number of parameters that can vary from pretreatment to treatment. Of those, the ones that are of special interest in this thesis are the longitudinal and radial position of the microcatheter tip, the microcatheter’s distal direction, the expandable-tip presence (for antireflux catheters only), and the tip orientation (for angled-tip microcatheters only). As for the injection itself, of the parameters that can be modified, this thesis is most concerned with two of them: the quantity and size of the microagent, and the particle injection velocity. With regard to the bloodstream, the arterial blood flow conditions might vary, e.g., due to microsphere-caused embolization of arterioles, leading to a reflux of microspheres. Any alteration in these parameters may be responsible for nontarget radiation and therefore radiation-induced complications. In order to reduce these radiation-induced complications, it has been suggested that the pretreatment injection conditions be matched as closely as possible during treatment. An alternative solution is to modify the design of microcatheters. For instance, it has been reported that using an antireflux catheter has eliminated particle reflux. The aim of this thesis is to analyze the influence of the abovementioned parameters on microsphere distribution via computational fluid–particle dynamics simulations. The thesis is divided into four major studies, each of which follows the same numerical strategy (i.e., the liver radioembolization is simulated in a patient-specific hepatic artery model under literature-based liver cancer scenarios). The first study analyzes the pretreatment as an actual treatment surrogate, the second analyzes the influence of an antireflux catheter, the third investigates the influence of the microcatheter distal direction and the injection point and velocity, and the last one explores the influence of an angled-tip microcatheter. Furthermore, prior to conducting these four studies, a methodology was developed to define realistic boundary conditions for numerical simulations in hepatic arteries. For the study on the pretreatment, results suggest that microcatheter placement is of paramount importance, both in terms of its location in the artery (near a bifurcation or not) and in the longitudinal shifting in microcatheter tip locations between pretreatment and actual treatment. Moreover, the higher the cancer burden, the better the tumor targeting because of the enhanced particle transport power. For the study on antireflux catheter influence, the main conclusion that can be drawn is that injecting from a sufficiently long and tortuous artery branch may ensure a downstream particle distribution that matches flow split, almost regardless of catheter type due to the likely adequate conditions for microsphere redistribution in the bloodstream. With regard to the third study, despite the importance of microcatheter tip position, microcatheter direction and injection velocity seem also to play an important role in particle distribution; results show that unintentional modifications to microcatheter tip and direction and injection velocity during tumor targeting may influence procedure outcome. The final study involving the angled-tip microcatheter shows that the higher the injection velocity the more spread out the particle distribution across cross-sectional areas of artery lumen. Moreover, when only focusing on tip orientation, it is not possible to accurately predict which branch of the bifurcation will take the particles because the complex geometry of hepatic arteries makes the bloodstream take the form of helical and chaotic streamlines. This means that the particle pathlines are not initially intuitive, even though the particle distribution will be similar to flow split. La radioembolización hepática es un tratamiento para combatir tumores hepáticos primarios y metástasis hepáticas. Consiste en administrar microesferas radiactivas mediante un microcatéter situado en la arteria hepática, de modo que esas microesferas, que son llevadas por la corriente sanguínea, se depositan en la malla tumoral. La posición del microcatéter y la velocidad de inyección de las partículas se deciden durante el pretratamiento, mediante el cual se emula el tratamiento por medio de la infusión de micropartículas de macroagregados de albúmina. Se supone que tanto la posición del microcatéter como la velocidad de inyección se repiten durante el tratamiento. Aunque sea un tratamiento seguro y efectivo, pueden aparecer complicaciones (hepatitis, neumonitis, úlceras gastrointestinales, etc.) por la irradiación de zonas que no debían irradiarse. Esta irradiación no deseada puede deberse a diferencias entre las condiciones de la inyección del pretratamiento y las del tratamiento. Esas condiciones son: el posicionamiento del microcatéter, la inyección y el flujo sanguíneo. En lo que respecta al posicionamiento del microcatéter, los parámetros que pueden variar del pretratamiento al tratamiento, entre otros, son: las posiciones longitudinal y radial de la punta del microcatéter, el direccionamiento distal del microcatéter, la presencia de una punta expandible (para el caso del catéter antirreflujo) y la orientación de la punta del microcatéter (sólo para los microcatéteres con la punta a 45º). En cuanto a la inyección, los parámetros que pueden ser alterados son: el tamaño y la cantidad del microagente inyectado, y la velocidad de inyección de las partículas, entre otros. En cuanto al flujo sanguíneo, éste puede variar, por ejemplo, debido a la embolización de las arteriolas, lo que puede conllevar el reflujo de partículas. La variación de los citados parámetros puede ocasionar irradiación no deseada, lo que conlleva complicaciones debidas a dicha irradiación. Para reducir estas complicaciones, por un lado se ha recomendado ajustar, durante el tratamiento, la posición del microcatéter y la velocidad de inyección definidas durante el pretratamiento. Por otro lado, se han propuesto diferentes diseños de microcatéteres. Por ejemplo, el reflujo de partículas se ha eliminado gracias al catéter antirreflujo. El objetivo de esta tesis es analizar la influencia de los parámetros citados en la distribución de microesferas mediante simulaciones numéricas del flujo de sangre con transporte de partículas. La tesis se divide en cuatro estudios que siguen la misma estrategia de simulación; es decir, la radioembolización es simulada en un modelo de arteria hepática específica de paciente bajo unos escenarios de cáncer basados en la literatura. El primer estudio analiza las diferencias que pueden darse entre el pretratamiento y el tratamiento. El segundo, estudia la influencia del catéter antirreflujo. El tercero, la influencia de la dirección distal del microcatéter, del punto de inyección y de la velocidad de inyección; y el cuarto, la influencia del microcatéter acabado con la punta a 45º. Además, antes de llevar a cabo estos cuatro estudios se tuvo que desarrollar una metodología para definir condiciones de contorno realistas aplicables a simulaciones numéricas en arterias hepáticas. En lo que respecta al estudio sobre el pretratamiento, los resultados muestran que la posición del microcatéter es muy importante, tanto en su posición en la arteria (cerca o lejos de una bifurcación) como en pequeños movimientos longitudinales de la punta del microcatéter entre el pretratamiento y el tratamiento. Además, cuanto mayor es el volumen de cáncer, tanto mayor es la capacidad de llegar a los tumores porque aumenta la capacidad de transportar las partículas. En cuanto al estudio sobre el catéter antirreflujo, la conclusión principal es que inyectar en una arteria lo suficientemente larga y tortuosa posibilita el alineamiento de las partículas con el flujo; de modo que, sea cual sea el catéter empleado para la inyección, la distribución de partículas tiende a parecerse a la distribución del flujo de sangre. Con respecto al tercer estudio, se concluye que a pesar de la importancia de la posición de la punta del microcatéter, también son importantes tanto la dirección distal del microcatéter como la velocidad de inyección de las partículas. Así, variaciones involuntarias de cualquiera de los tres parámetros puede conllevar resultados no deseados en el tratamiento. Por último, el cuarto estudio muestra que cuanto mayor es la velocidad de inyección de las partículas, más esparcidas viajan las partículas en el lumen de la arteria. Además, fijándose únicamente en la orientación de la punta del microcatéter no es posible predecir la rama de la bifurcación que van a tomar las partículas porque la complejidad de la geometría de las arterias hepáticas hace que el flujo sanguíneo tome estructuras hemodinámicas helicoidales y caóticas, por lo que la trayectoria de las partículas no es intuitiva, aunque la distribución de las partículas será similar a la del flujo de sangre. 2022-03-30T12:19:48Z 2022-03-30T12:19:48Z 2016-12 2016-12-22 info:eu-repo/semantics/doctoralThesis https://hdl.handle.net/10171/63327 eng info:eu-repo/semantics/openAccess application/pdf Servicio de Publicaciones. Universidad de Navarra |
| spellingShingle | Radioembolization. Hepatic artery. Liver cancer. Computational fluid–particle dynamics. Hemodynamics. Microcatheter. Antireflux catheter. Angled-tip microcatheter. Microsphere distribution. Aramburu-Montenegro, J. (Jorge) Antón-Remírez, R. (Raúl) Liver radioembolization: Computational particle–hemodynamics studies in a patient-specific hepatic artery under literature-based cancer scenarios. |
| title | Liver radioembolization: Computational particle–hemodynamics studies in a patient-specific hepatic artery under literature-based cancer scenarios. |
| title_full | Liver radioembolization: Computational particle–hemodynamics studies in a patient-specific hepatic artery under literature-based cancer scenarios. |
| title_fullStr | Liver radioembolization: Computational particle–hemodynamics studies in a patient-specific hepatic artery under literature-based cancer scenarios. |
| title_full_unstemmed | Liver radioembolization: Computational particle–hemodynamics studies in a patient-specific hepatic artery under literature-based cancer scenarios. |
| title_short | Liver radioembolization: Computational particle–hemodynamics studies in a patient-specific hepatic artery under literature-based cancer scenarios. |
| title_sort | liver radioembolization: computational particle–hemodynamics studies in a patient-specific hepatic artery under literature-based cancer scenarios. |
| topic | Radioembolization. Hepatic artery. Liver cancer. Computational fluid–particle dynamics. Hemodynamics. Microcatheter. Antireflux catheter. Angled-tip microcatheter. Microsphere distribution. |
| url | https://hdl.handle.net/10171/63327 |
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