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Sieni, Elisabetta (2011) Biomedical applications of electromagnetic fields: human exposure, hyperthermia and cellular stimulation. [Ph.D. thesis]

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Abstract (english)

Electromagnetic fields are present in some environments of everybody life. Some of the most common sources of electromagnetic field that everybody experiments are the sun radiation, the electric current that supplies household (lights, television set, refrigerator, etc) and antennas for telecommunications. In industrial environments the magnetic and electric fields are exploited to the metal treatments and fusion, some magnetic fields are generated by means of electric welding applications or devices that use high intensity electric currents. In residential environment the diffusion of the induction cooktop increases the possibility of domestic exposure to magnetic fields. Nevertheless, electromagnetic fields can also be used with medical purpose.
This thesis evaluates the effects due to the interaction between electromagnetic fields and biological tissues. It is to be noted that the interaction of the magnetic field with a conductor material produces induced currents density that circulating in the media might heat it by means of the Joule effect. The most important application of this phenomenon is the treatment and melting of metals that have a large electrical conductivity (in the order of the millions of S/m) and high relative magnetic permeability. Nevertheless, in spite of the tissues of the human body are bad electrical conductors (conductivity in the order of the unity or lower and a unitary relative magnetic permeability), the induced current density might cause muscle contraction. The intensity of these currents depends on the intensity of the magnetic field that generates them and the effect is perceived if overcomes a given threshold. In this case adverse effect, like nerve or muscle stimulation might be induced. Then, every equipment that uses a high intensity electric current produces a magnetic field that might generate an induced current in the biological tissues. Some standards regulate the maximum of the electromagnetic field at which every person can be exposed. Among equipments that generate high magnetic field this work analyzed arc and resistance welding equipments and induction cooktops. In order to evaluate human exposure to magnetic field below 100 kHz, the magnetic flux density and induced current density have been computed using the Finite Element Method. Some simplified models of the human body have been implemented. The computation results obtained in these simplified volumes by means of numerical methods have been compared with these ones obtained using models that describe accurately the tissues of the human body.
Electric and magnetic fields can be exploited in some medical applications. For instance, the magnetic and electric fields are used in malignant tumor therapies. For instance, examples are the thermal ablation or the tissues heating in localized areas (laser, radiofrequency antennas, thermoseed, etc). A technique of new application is the Magnetic Fluid Hyperthermia (MFH), which the original idea is of 1950, but the first prototype device is of the end ninety. This technique uses magnetic nanoparticles inserted in the treatment areas. Nanoparticles are heated by means of an external time-varying magnetic field of suitable frequency and intensity and act as an internal source of heat. In this case the aim is reached a temperature close to a therapeutic value (42-43°C for the mild hyperthermia or overcome 60 °C for the thermal ablation).
Electric fields can also be used in order to stimulate different areas of the brain. An initial study shows some simulation results obtained in both human and rat brains. Moreover, in this case an experimental set up for measurements in vivo in a rat’s head has been developed.
All the computations of thermal and electromagnetic fields have been solved using Finite Element Analysis. Some of the algorithms for the solution of coupled magnetic and thermal problems and the code for the optimization procedure have been implemented inside a commercial software tool. In particular, the optimization algorithm included in the Finite Element Analysis tool is an Evolution Strategy code.
In order to calculate magnetic field, magnetic flux density, induced current density and electric field for the solution of the Maxwell equations, different formulations have been used, whereas the thermal problem has been solved using the heat transfer equation, including the Pennes term that describes the effect of the blood perfusion.
Optimization codes have been used in order to design a Magnetic Fluid Hyperthermia device. At first, optimization the uniformity of the magnetic field has been optimized, under the hypothesis that magnetic nanoparticles are uniformly distributed in tissues. This step has allowed the generation of a first design of the magnetic field source. In a second step, the optimization code has been used to search the temperature uniformity in the treated areas; then, the coupling of a magnetic with a thermal problem has been developed. In this case, the transition from the magnetic problem to the thermal one has required the computation of the power density generated by means of magnetic nanoparticles, from the value of the intensity of the magnetic field, using an analytical relation that depend also on instantaneous temperature and physical characteristics and the concentration of magnetic nanoparticles.
The optimization of the temperature uniformity in the treated area, also in term of temperature rate, can be also seen from the point of view of the design of the magnetic field source that is the magnetic fluid design (dimensions and concentration of nanoparticles). Both these aspects have been investigated. Finally, the problem of the real distribution of nanoparticles in tumor tissues has been investigated in term of temperature disuniformity, due to the different nanoparticles concentration. An algorithm for the optimization of the points of injection of nanoparticles in situ has been developed, in order to limit the temperature disuniformity related to nanoparticles local concentration.
Some computations of the electric field have been performed in order to evaluate the feasibility to reach internal structures of the brain with electric fields, applying a voltage to suitable points of the external skull. The frequency of the applied voltage is 4 MHz, an unusual frequency for the instrumentation normally used to measure electric potentials in vivo in laboratory animals. The experimental part has been developed in order to compare the voltage computed with the Finite Element models with the voltage measured inside the brain tissue using glass micropipettes. It is to be noted that at 4 MHz the micropipette has a different impedance from the one it has in the normal use of instruments (below 1 kHz). A measurement set up has been designed in order to convert the signal measured by means of a micropipette and an oscilloscope, considering the real impedance of the micropipette. The potential at the micropipette point is derived by means of calibration curves evaluated through specific experiments. Measurements have been used to validate the Finite Element simulations of electric fields.
The main results of this thesis are models of living organisms implemented for biomedical applications in order to evaluate the effect of electromagnetic fields in biological tissues. Moreover, different formulations have been used to solve electromagnetic problems, and the solution of magnetic and thermal coupled problems has been proposed. Optimization algorithms have been used for the design of magnetic devices and treatment planning (e.g. position of the magnetic field source as a function of the patient and treatment area) or in the magneto fluid drug composition (size of nanoparticles and concentration).

Abstract (italian)

I campi elettromagnetici sono diffusi in molti ambienti industriali e residenziali. Alcune delle più comuni sorgenti di campo elettromagnetico sono le radiazioni solari, la corrente elettrica che alimenta gli elettrodomestici (luci, televisore, frigorifero, ecc.) e le antenne per le telecomunicazioni. Negli ambienti industriali i campi elettrici e magnetici sono utilizzati per la fusione e il trattamento dei metalli, in particolare alcuni dispositivi per la saldatura possono generare campi elettromagnetici di intensità elevata. In ambiente residenziale la diffusione del piano di cottura a induzione ha aumentato la possibilità di esposizione della popolazione a campi magnetici che potrebbero essere intensi. Inoltre i campi elettromagnetici possono essere utilizzati a scopo medico in alcune terapie.
Questa tesi analizza l'interazione tra campi elettromagnetici e tessuti biologici. È da notare che l'interazione del campo magnetico con un materiale conduttore produce correnti indotte che circolano nel materiale e producono calore per effetto Joule. L'applicazione più importante di questo fenomeno è il trattamento e la fusione dei metalli che hanno una elevata conducibilità elettrica (dell'ordine dei milioni di Sm-1) ed alta permeabilità magnetica relativa. Nonostante i tessuti del corpo umano siano cattivi conduttori elettrici (conducibilità dell'ordine l'unità o più bassa e una permeabilità magnetica relativa unitaria), la densità di corrente indotta può causare la contrazione muscolare. L'intensità di queste correnti indotte dipende dall'intensità del campo magnetico che le genera e il loro effetto è percepibile se superano la soglia di stimolazione dei nervi o dei muscoli. Quindi, ogni apparecchiatura che utilizza una corrente elettrica produce un campo magnetico che può generare correnti indotte nei tessuti biologici. Alcune norme regolano il massimo valore del campo elettromagnetico a cui ogni persona può essere esposta. Tra le apparecchiature che generano campi magnetici questo lavoro analizza le saldatrici ad arco e a resistenza e i piani di cottura a induzione. Al fine di valutare l'esposizione umana al campo magnetico sotto i 100 kHz, si valuta l’induzione magnetica e la corrente indotta in opportuni volumi che simulano il corpo umano mediante il metodo degli Elementi Finiti. La corrente indotta calcolata con i modelli semplificati del corpo umano è stata confrontata con quella calcolata utilizzando modelli che descrivono con precisione i tessuti del corpo umano.
Campi elettrici e magnetici possono inoltre essere utilizzati in alcune applicazioni mediche. Ad esempio, il campo magnetico ed elettrico possono trovare impiego nella terapia dei tumori. Esempi sono l'ablazione termica dei tessuti o il riscaldamento di zone localizzate (laser, antenne a radiofrequenza, thermoseed, ecc.). Una tecnica di nuova generazione è l’ipertermia magneto fluida, la cui idea originaria risale agli anni ‘50, ma il primo prototipo è della fine degli anni novanta. Questa tecnica utilizza nanoparticelle magnetiche inserite nelle aree da trattare. Le nanoparticelle sono riscaldate per mezzo di un campo magnetico tempo variante esterno di frequenza e di intensità adeguate e agiscono come una fonte interna di calore. In questo caso la temperatura raggiunta dai tessuti deve raggiungere la soglia terapeutica (42-43°C per l'ipertermia o superare i 60 °C per l'ablazione termica).
Il campo elettrico può essere utilizzato anche per stimolare diverse aree del cervello. Un primo studio mostra alcuni risultati di simulazione ottenuti sia in un cervello umano sia di ratto. Inoltre, per questo esempio è stato sviluppato un set up sperimentale per misure in vivo nei tessuti della testa di un ratto.
Il calcolo del campo termico ed elettromagnetico è stato risolto utilizzando il Metodo degli Elementi Finiti. Inoltre sono stati implementati alcuni algoritmi per la soluzione di problemi di accoppiamento magnetico e termico e un codice per la procedura di ottimizzazione. Il codice di ottimizzazione, di tipo Evolution Strategy, è stato implementato all'interno di un software commerciale per risolvere problemi elettromagnetici e termici mediante il metodo degli Elementi Finiti.
Per la soluzione delle equazioni di Maxwell per il calcolo del campo magnetico, l’induzione magnetica, la densità di corrente indotta e il campo elettrico sono state utilizzate diverse formulazioni, mentre il problema termico è stato risolto utilizzando l'equazione di trasferimento del calore, includendo il termine Pennes che descrive l'effetto della perfusione sanguigna.
I codici di ottimizzazione sono stati utilizzati principalmente per la progettazione di un dispositivo per l’ipertermia magneto fluida. Per un primo disegno della sorgente di campo magnetico si è ottimizzata l’uniformità del campo magnetico, sotto l'ipotesi che le nanoparticelle magnetiche fossero distribuite uniformemente nei tessuti. In seguito il codice di ottimizzazione è stato utilizzato per cercare l'uniformità della temperatura nelle zone da trattare, e quindi è si è risolto un problema magnetico-termico accoppiato. In questo caso il passaggio dal problema magnetico a quello termico ha richiesto il calcolo della densità di potenza generata dalle nanoparticelle magnetiche a partire dall'intensità del campo magnetico. In questo caso si è utilizzata una relazione analitica che valuta la potenza a partire dalla temperatura istantanea dei tessuti, le caratteristiche fisiche delle nanoparticelle magnetiche e l’intensità e la frequenza del campo magnetico.
L'ottimizzazione dell’uniformità della temperatura nella zona trattata, anche in termini di rateo di temperatura, può essere vista come progettazione sia della sorgente del campo magnetico sia del magnetofluido (dimensioni e concentrazione delle nanoparticelle) . Entrambi questi aspetti sono stati indagati. Infine è stato valutato l’effetto della reale distribuzione delle nanoparticelle nei tessuti tumorali sulla disuniformità di temperatura legata alla disuniformità della concentrazione delle nanoparticelle. In questo caso, per limitare la disuniformità di temperatura correlata alla concentrazione delle nanoparticelle, si è sviluppato un algoritmo per l'ottimizzazione dei punti di iniezione in situ delle nanoparticelle.
Infine è stata studiata la distribuzione del campo elettrico creato da una differenza di potenziale applicata alla scatola cranica per valutare la fattibilità di raggiungere le strutture interne del cervello. Il segnale di tensione utilizzato è a 4 MHz, una frequenza non usuale per la strumentazione normalmente utilizzata per misurare i potenziali elettrici in vivo su animali. Per confrontare la tensione calcolata con i codici numerici con quella misurata all'interno del tessuto cerebrale usando micropipette di vetro, è stato studiato un set up di misura. La micropipetta alla frequenza di 4 MHz ha impedenza differente rispetto quella che si ha nel normale uso dello strumento (frequenze inferiori a 1 kHz). Mediante l’esperimento progettato si sono ottenute delle curve di taratura per convertire il segnale misurato con la micropipetta e l’oscilloscopio. Tali curve tengono conto della reale impedenza della micropipetta. Queste misurazioni sono state utilizzate per validare le simulazioni numeriche del campo elettrico.
I principali risultati di questa tesi sono i modelli di organismi viventi implementati per valutare le interazione dei campi elettromagnetici con i tessuti biologici. In particolare, per risolvere i problemi elettromagnetici e di accoppiamento magnetico e termico sono state utilizzate diverse formulazioni. Inoltre, per la progettazione dei dispositivi magnetici, la pianificazione del trattamento (posizionamento della sorgente di campo magnetico in funzione paziente) e la composizione del magneto fluido (dimensioni e concentrazione delle nanoparticelle) sono stati utilizzati algoritmi di ottimizzazione.

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EPrint type:Ph.D. thesis
Tutor:Dughiero, Fabrizio
Ph.D. course:Ciclo 23 > Scuole per il 23simo ciclo > INGEGNERIA DELL'INFORMAZIONE > BIOINGEGNERIA
Data di deposito della tesi:UNSPECIFIED
Anno di Pubblicazione:31 January 2011
Key Words:Electromagnetic fields, human exposure, magnetic fluid hyperthermia
Settori scientifico-disciplinari MIUR:Area 09 - Ingegneria industriale e dell'informazione > ING-INF/06 Bioingegneria elettronica e informatica
Area 09 - Ingegneria industriale e dell'informazione > ING-IND/31 Elettrotecnica
Struttura di riferimento:Dipartimenti > Dipartimento di Ingegneria dell'Informazione
Codice ID:4040
Depositato il:21 Jul 2011 12:54
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