Heating of head tissues during TTFields therapy: a computational study

Detalhes bibliográficos
Autor(a) principal: Gentilal, Nichal
Data de Publicação: 2018
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Texto Completo: http://hdl.handle.net/10451/35668
Resumo: Tese de mestrado integrado em Engenharia Biomédica e Biofísica (Radiações em Diagnóstico e Terapia) Universidade de Lisboa, Faculdade de Ciências, 2018
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spelling Heating of head tissues during TTFields therapy: a computational studyDano térmicoEfeitodeJouleGlioblastomaModelo realista da cabeçaTumour Treating FieldsTeses de mestrado - 2018Departamento de FísicaTese de mestrado integrado em Engenharia Biomédica e Biofísica (Radiações em Diagnóstico e Terapia) Universidade de Lisboa, Faculdade de Ciências, 2018Glioblastoma Multiforme(GBM) is one of the deadliest brain diseases that is characterized by a rapid progression and a short survival time. The expected life time is only 15 months with optimal treatment and the current standard of care includes one technique that was first reported 15 years ago, named Tumour Treating Fields(TTFields).This non-invasive approach relies on injecting an alternate current in electrodes placed on the scalp with an optimal frequency of 200 kHz to produce an electric field with a minimal therapeutic intensity of 1V/cm at the tumour site. A field with these properties was shown in in-vitro studies to have an anti-mitotic effect capable of reducing the growth rate of the tumoural cells. This led to the creation of what is now a Food and Drug Administration (FDA) approved device named Optune®. These fields are applied injecting an alternating current with 900 mA amplitude per array in two perpendicular directions alternately (Left-Right and Anterior-Posterior), with a switching time of one second. Additionally, clinical trials showed that a daily usage of at least 18 hours can significantly enhance treatment outcomes. Apart from skin dermatitis underneath the regions where the electrodes are placed, there are no other major changes reported in the literature that can be considered as side-effects of this technique. However, it is a known fact that biological tissues heating occurs due to the Joule effect. This problem is addressed by shutting down the fields in both directions when a transducer reaches 41ºC which consequently leads to GBM not being treated at all. The aim of this project is to study this on/off process and evaluate the thermal damage to the healthy tissues while, at the same time, suggesting ways to improve how Optune® works. To accomplish these goals, a realistic head model already built by our research group based on Magnetic Resonance Imaging (MRI) data,was used. This model consists of six different biological tissues (scalp, skull, Cerebro Spinal Fluid(CSF), grey matter, white matter and eyeballs), the transducers arrays that mimic Optune® and a virtual lesion that intends to represent a GBM. The computational studies were done using COMSOL Multiphysics after performing validation tests to ensure the reliability of its results. This software uses the finite element method to calculate the electric potential and the temperature within each tissue as a function of space and time. The results obtained show that due to the thermal constraints and under normal conditions, Optune® is only being used to treat the tumour around one-third of the time(6hours).However, we show that it is possible to increase this time if the room temperature is lowered,if the injected current is controlled at the transducer level instead of at the array level and if just the array that has the electrode that reaches 41ºC is shut down instead of both arrays. Additionally, considering a hypothetical situation where Optune® works with half the injected current in each transducer but with both configurations applied simultaneously instead of alternately, we concluded that the device is more time on and might be a good alternative to enhance treatment outcomes. All the simulations surpassed the thresholds defined by the international agencies for the Specific Absorption Rate (SAR) values for a MRI diagnostic, which was expected considering that the time that the electric fields are applied should be maximized to treat this disease. Additionally, thermal damage evaluated using the Cumulative number of Equivalent Minutes at 43ºC (CEM 43ºC) showed that only minor and acute changes are expected at the skin level, while the thresholds for the skull, CSF and the eyeballs were not reached for one treatment day. For the brain, some changes such as increased Blood-Brain Barrier (BBB) permeability, a variation of the cerebral blood flow and an alteration of the Gamma-AminoButyric Acid(GABA),glycine and glutamate concentrations may occur. The conclusions here drawn consider that the metrics chosen can be used in TTFields without any major change to the thresholds from which they were developed for. Although this might not be completely true,the main points here achieved should be seen as a principle of proof that Joule heating inTTFields can be harmful and lead to some changes,especially in the brain, that may lower the quality of life of GBM patients. One important question that remains to be answered is if these results proved to be true, can the benefits of this technique really compensate the side-effects considering the low survival rate? To increase the validaty of these results this data should be compared with what is seen in clinical trials. We hope that these conclusions can be helpful to improve this technique and to increase the awareness of the thermal damage during TTFields therapy.Miranda, Pedro Cavaleiro, 1959-Repositório da Universidade de LisboaGentilal, Nichal2019-10-28T01:30:42Z201820182018-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10451/35668TID:202184714enginfo:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-03-17T13:59:27Zoai:repositorio.ulisboa.pt:10451/35668Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T03:00:04.924313Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Heating of head tissues during TTFields therapy: a computational study
title Heating of head tissues during TTFields therapy: a computational study
spellingShingle Heating of head tissues during TTFields therapy: a computational study
Gentilal, Nichal
Dano térmico
EfeitodeJoule
Glioblastoma
Modelo realista da cabeça
Tumour Treating Fields
Teses de mestrado - 2018
Departamento de Física
title_short Heating of head tissues during TTFields therapy: a computational study
title_full Heating of head tissues during TTFields therapy: a computational study
title_fullStr Heating of head tissues during TTFields therapy: a computational study
title_full_unstemmed Heating of head tissues during TTFields therapy: a computational study
title_sort Heating of head tissues during TTFields therapy: a computational study
author Gentilal, Nichal
author_facet Gentilal, Nichal
author_role author
dc.contributor.none.fl_str_mv Miranda, Pedro Cavaleiro, 1959-
Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Gentilal, Nichal
dc.subject.por.fl_str_mv Dano térmico
EfeitodeJoule
Glioblastoma
Modelo realista da cabeça
Tumour Treating Fields
Teses de mestrado - 2018
Departamento de Física
topic Dano térmico
EfeitodeJoule
Glioblastoma
Modelo realista da cabeça
Tumour Treating Fields
Teses de mestrado - 2018
Departamento de Física
description Tese de mestrado integrado em Engenharia Biomédica e Biofísica (Radiações em Diagnóstico e Terapia) Universidade de Lisboa, Faculdade de Ciências, 2018
publishDate 2018
dc.date.none.fl_str_mv 2018
2018
2018-01-01T00:00:00Z
2019-10-28T01:30:42Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/35668
TID:202184714
url http://hdl.handle.net/10451/35668
identifier_str_mv TID:202184714
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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