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Biomedical applications of electromagnetic fields: human exposure, hyperthermia and cellular stimulation Titolo: Biomedical applications of electro Elisabetta Sieni hyperthermia and cellular stimulat Elisabetta Sieni Anno: 2011 Anno: 2011 Supervisore: Prof Fabrizio Dughiero Ph.D. candidate: Elisabetta Sieni Supervisore: Prof. Fabrizio Dughiero Year: 2011 Supervisor: Prof Fabrizio Dughiero Supervisor: Prof. Fabrizio Dughiero Ph.D. School Director: Prof. Matteo Bertocco ABSTRACT ABSTRACT Electromagnetic fields are spread in the environment because a lot of the modern devices are Electromagnetic fields are spread in the environment because a lot of the modern devices are supplied by means of an electric current and others equipments use electromagnetic waves It supplied by means of an electric current and others equipments use electromagnetic waves. It is well known that electromagnetic fields can interact with metal structures, then with is well known that electromagnetic fields can interact with metal structures, then with electrical conductor material, inducing a temperature increasing by means of Joule effect or energy deposition. Since electromagnetic fields can interact with electrical conductors, they might induce also the same effects on the human body structures. In fact, with the same mechanisms the electromagnetic fields can induce current density or heat in the human body . These interactions can be studied in order to prevent adverse effects, but also to use them in medical h h bd h b d f h d f treatments. For instance, the human body tissue heating can be used for the reduction of d th th i ht h th ti ff t h i th some cancer mass and, then, they might have a therapeutic effect, whereas in some case they might induce muscles contractions or nerve stimulation might induce muscles contractions or nerve stimulation. Finite Element Analysis has been used to solve electromagnetic and thermal problems in Finite Element Analysis has been used to solve electromagnetic and thermal problems in structure with electric and thermal characteristics like the human body tissue whereas structure with electric and thermal characteristics like the human body tissue, whereas optimizations techniques have been used to design a medical device optimizations techniques have been used to design a medical device. Example on the electromagnetic field exposure, Magnetic Fluid Hyperthermia (MFH) cancer Example on the electromagnetic field exposure, Magnetic Fluid Hyperthermia (MFH) cancer treatments and electric field distribution in the brain when a voltage difference is applied to the skull bone have been presented and solved by means of the above mentioned techniques. A. Electromagnetic fields in medical applications: MFH as tumor therapy The MFH provides the heating of cancer lesions up to a temperature that can damage tumor tissues. In this therapy the nanoparticles (NPs), injected in the human tissues, are heated by means of a time‐varying magnetic field which should be as much as possible uniform in the treatment area. I h d i f h i fi ld h i fi ld if i fi d h In the design of the magnetic field source the magnetic field uniformity at first and the lti t t if it th t i t t bj ti f ti Th i resulting temperature uniformity are the most important objective functions. Then, in addition the temperature rate in a predefined time interval that allows a temperature rise addition, the temperature rate in a predefined time interval that allows a temperature rise up to the therapeutic value (e g 42°C in mild hyperthermia or 60°C in the thermal ablation) up to the therapeutic value (e.g. 42 C in mild hyperthermia or 60 C in the thermal ablation) is be another plausible objective function is be another plausible objective function. t Thermal and magnetic uniformity solutions stop Start Variable values A. Thermal 1,8E‐02 2,0E‐02 UM_M Thermal inhomogeneity Variable values optimization 1,4E‐02 1,6E‐02 UM_ T M optimum Thermal 1,0E‐02 1,2E‐02 UM T optimum New variable values Set magnetic problem post‐process 6,0E‐03 8,0E‐03 Magnetic computation Thermal computation 2,0E‐03 4,0E‐03 Magnetic computation Thermal computation 0,0E+00 0,0E+00 2,0E‐02 4,0E‐02 6,0E‐02 8,0E‐02 Set thermal problem Magnetic UT Thermal Magnetic Magnetic field H Computation of the NP power density Magnetic post‐process Thermal uniformity Magnetic uniformity i Magnetic inhomogeneity B Magnetic Main coil Magnetic inhomogeneity B. Magnetic optimization coil stop Controlled region Controlled region (Tumor) (Tumor) (Tumor) (Tumor) Fl h f h i dh l ld i i i Correcting Flow chart for the magnetic and thermal coupled optimization and results optimization (Evolution Stratyegy algorithms) coil C il iti f th t ti i ti t t i and results optimization (Evolution Stratyegy algorithms) Search the thermal and magnetic field uniformity Coils position for the two optimization strategies. Both the magnetic fluid drug and the magnetic field source must be opportunely designed Both the magnetic fluid drug and the magnetic field source must be opportunely designed using optimization techniques in order to shape the magnetic field source and for the choice using optimization techniques in order to shape the magnetic field source and for the choice of the magnetic fluid parameters. 0,08 of the magnetic fluid parameters. 0,07 conc_ 0,1% M lti l Designi of the magnetic fluid (NP size and 0,06 K/s] conc_ 0,2% conc 0 3% Multiple solutions!! Designi of the magnetic fluid (NP size and concentration): 0,05 rate [ conc_ 0,3% conc_ 0,5% solutions!! ! Design of the temperature rate‐ Multiple solutions 0 03 0,04 rature conc_ 1% Ill-posed t T t t T − Δ + Ω Δ ) ( ) ( ) ( 1 1 0 02 0,03 emper 0 015 [K/s] synthesis problem t t T t t T T m m T Δ Δ + = Ω Δ ) ( ) ( ) ( 1 1 0,01 0,02 te 0.015 [K/s] problem t Δ Optimization 0,00 | * ) ( | ) , ( T T D F T Δ − Ω Δ ≡ φ function 0 10 20 30 40 50 l d [ ] nanoparticle diameter [nm] Developed designs by evolution strategy S • Eeffect of the algorithms: • • position of NPs •electromagnetic source based on magnetic • S injections. and thermal field uniformity; the solution of a • S Not uniform NPs coupled electromagnetic and thermal problem • 2 Not uniform NPs distribution . • heating source focusing some aspects of a h • • therapeutic treatment; NP ij ti it f i th th l d • • • NPs injection sites focusing the thermal and the therapy design problems • the therapy design problems. magnetic fields: human exposure, tion B Human exposure to magnetic fields B. Human exposure to magnetic fields Human models have been used in order to compute the induced current density in the Human models have been used in order to compute the induced current density in the human body tissues generated by means of a magnetic field at frequency under 100 kHz human body tissues generated by means of a magnetic field at frequency under 100 kHz. Some examples of evaluation of the magnetic field effects rising from welding equipments are Some examples of evaluation of the magnetic field effects rising from welding equipments are reported. reported. 18 mA/m 2 27 mA/m 2 H bd dl 18 mA/m 2 27 mA/m Human body model built from real CT built from real CT data segmenting data segmenting each slice in order each slice in order to distinguish the to distinguish the different organs different organs and discretized by tetrahedral elements for Finite Element Analysis. Induced current density in huma body model due to resistance welding equipment The numerical computation of induced current density is important in cases where the magnetic flux density overcomes prescribed limits. Since in some practical cases the current that supplies the device can be so high that the magnetic flux density overcomes li i h id d d i b l d i d d id if i limits, the induced current density must be evaluated in order to decide if equipment ti fi fi ld li it td b t d d satisfies field limits suggested by standards. C Electromagnetic fields in medical applications: electric field applications C. Electromagnetic fields in medical applications: electric field applications Electric field can be used to stimulate brain cells In this example an evaluation of the Electric field can be used to stimulate brain cells. In this example an evaluation of the possibility to reach the internal structure of the brain with an electric field enough intense to possibility to reach the internal structure of the brain with an electric field enough intense to allow the cell stimulation is proposed The electric field can be applied by means of two or allow the cell stimulation is proposed. The electric field can be applied by means of two or more electrodes on the surface of the head. P1 more electrodes on the surface of the head. P0 P0 P1 P0 P1 P0 P1 Si C Si B Electric field model and some P2 Electric field for different electrode Sim A Sim C Sim B Electric field model and some computation results P1 Electric field for different electrode voltage computation results Vn 0V Vn 0V osso osso osso l f ld h h df d ff f Electric field in human head for different position of the electrodes the electrodes Numerical analysis on real models of the head has been conducted in order to evaluate the effect on different positions of the electrodes on the skull in order to induce an electric field in the brain structures. It is to be noted that electrical characteristics of the tissues are a function of the frequency, and then a time‐varying electric field have a different behavior 35 30 25 20 m] 15 E [V/m 10 5 SimA simB Si C E0 0 SimC E0 0,00 0,05 0,10 0,15 0,20 Electric field in human head x [m] Electric field in human head Some papers •F Dughiero M Forzan E Sieni Numerical FEM models for the evaluation of EM fields exposure near welding machines Proc COMPUMAG 2009 •F . Dughiero, M. Forzan, E. Sieni Numerical FEM models for the evaluation of EM fields exposure near welding machines, Proc. COMPUMAG 2009 •E. Sieni, F. Dughiero, M. Forzan Evaluation of the exposure to magnetic field generated by welding equipment with reference to induced current density, Cedrat News, 2010 M B ll M Chi i F D hi E Si i d L Zilb ti N i l di ti f t d d i h dl b id ti ki li P It ti l •M. Bullo, M. Chiampi, F . Dughiero, E. Sieni and L. Zilberti, Numerical prediction of currents produced in human models by induction cooking appliances , Proc. International Symposium on Heating by Electromagnetic Sources, SGEditoriali, Padova, 67‐74 , May 19‐21, 2010. •Di Barba, F . Dughiero, E. Sieni, Synthesizing a nanoparticle distribution in magnetic fluid hyperthermia, Proc. International Symposium on Heating by Electromagnetic Sources, SGEditoriali, Padova, 483‐490 , May 19‐21, 2010. •Sieni E., Candeo A., Dughiero F ., A simplified 3d approach for the evaluation of the SAR and temperature distribution in magnetic nanoparticles hyperthermia, Proc. ESHO 2009 ‐ oral presentation appeared on Visual Journal of Medicine, 13 Ottobre 2009, www . vjmed.net Abstract book pp. 13‐14 •P. Di Barba, F. Dughiero, E. Sieni Magnetic Field Synthesis in the Design of Inductors for Magnetic Fluid Hyperthermia, IEEE Trans on Magn, 2010 •P . Di Barba, F . Dughiero, E. Sieni, A. Candeo, Coupled Field Synthesis in Magnetic Fluid Hyperthermia, in press IEEE Trans on Magn P . Di Barba, F . Dughiero, E. Sieni, A. Candeo, Coupled Field Synthesis in Magnetic Fluid Hyperthermia, in press IEEE Trans on Magn •E. Sieni, F. Dughiero, M. Forzan, Simple 3D fem models for evaluation of EM exposure produced by welding equipments, To be appear on IOSPress 2010 •F Dughiero M Forzan E Sieni A numerical evaluation on Electromagnetic fields exposure on real human body models until 100 kHz In press on COMPEL •F . Dughiero, M. Forzan, E. Sieni A numerical evaluation on Electromagnetic fields exposure on real human body models until 100 kHz, In press on COMPEL
Transcript
Page 1: Sieni

Biomedical applications of electromagnetic fields: human exposure, hyperthermia and cellular stimulationTitolo: Biomedical applications of electroypElisabetta Sieni hyperthermia and cellular stimulatElisabetta SieniAnno: 2011Anno: 2011Supervisore: Prof Fabrizio Dughiero

Ph.D. candidate: Elisabetta SieniSupervisore: Prof. Fabrizio Dughiero

Year: 2011

Supervisor: Prof Fabrizio DughieroSupervisor: Prof. Fabrizio Dughiero

Ph.D. School Director: Prof. Matteo Bertocco

ABSTRACTABSTRACTElectromagnetic fields are spread in the environment because a lot of the modern devices areElectromagnetic fields are spread in the environment because a lot of the modern devices aresupplied by means of an electric current and others equipments use electromagnetic waves Itsupplied by means of an electric current and others equipments use electromagnetic waves. Itis well known that electromagnetic fields can interact with metal structures, then withis well known that electromagnetic fields can interact with metal structures, then withelectrical conductor material, inducing a temperature increasing by means of Joule effect or, g p g yenergy deposition.gy pSince electromagnetic fields can interact with electrical conductors, they might induce also thesame effects on the human body structures. In fact, with the same mechanisms theelectromagnetic fields can induce current density or heat in the human body. Theseinteractions can be studied in order to prevent adverse effects, but also to use them in medical

h h b d h b d f h d ftreatments. For instance, the human body tissue heating can be used for the reduction ofd th th i ht h th ti ff t h i thsome cancer mass and, then, they might have a therapeutic effect, whereas in some case they

might induce muscles contractions or nerve stimulationmight induce muscles contractions or nerve stimulation.Finite Element Analysis has been used to solve electromagnetic and thermal problems inFinite Element Analysis has been used to solve electromagnetic and thermal problems instructure with electric and thermal characteristics like the human body tissue whereasstructure with electric and thermal characteristics like the human body tissue, whereasoptimizations techniques have been used to design a medical deviceoptimizations techniques have been used to design a medical device.Example on the electromagnetic field exposure, Magnetic Fluid Hyperthermia (MFH) cancerExample on the electromagnetic field exposure, Magnetic Fluid Hyperthermia (MFH) cancertreatments and electric field distribution in the brain when a voltage difference is applied tog ppthe skull bone have been presented and solved by means of the above mentioned techniques.p y q

A. Electromagnetic fields in medical applications: MFH as tumor therapyThe MFH provides the heating of cancer lesions up to a temperature that can damage

tumor tissues. In this therapy the nanoparticles (NPs), injected in the human tissues, areheated by means of a time‐varying magnetic field which should be as much as possibleuniform in the treatment area.I h d i f h i fi ld h i fi ld if i fi d hIn the design of the magnetic field source the magnetic field uniformity at first and the

lti t t if it th t i t t bj ti f ti Th iresulting temperature uniformity are the most important objective functions. Then, inaddition the temperature rate in a predefined time interval that allows a temperature riseaddition, the temperature rate in a predefined time interval that allows a temperature riseup to the therapeutic value (e g 42°C in mild hyperthermia or 60°C in the thermal ablation)up to the therapeutic value (e.g. 42 C in mild hyperthermia or 60 C in the thermal ablation)is be another plausible objective functionis be another plausible objective function.

tThermal and magnetic uniformity solutions

stopStartVariable values

A. Thermal  1,8E‐02

2,0E‐02

UM_M

Thermal inhomogeneityVariable values

optimization1,4E‐02

1,6E‐02 UM_ T

M optimum

Thermal  1,0E‐02

1,2E‐02

UM

p

T optimum

New variable valuesSet magnetic problem post‐process 6,0E‐03

8,0E‐03

Magnetic computation Thermal computation2,0E‐03

4,0E‐03

Magnetic computation Thermal computation 0,0E+00

0,0E+00 2,0E‐02 4,0E‐02 6,0E‐02 8,0E‐02

Set thermal problemMagnetic

UT

Thermal MagneticMagnetic field H   Computation of the NP power density

Magnetic post‐process 

Thermal uniformity

Magnetic uniformity

ip y

Magnetic inhomogeneity B Magnetic

y yMain coilMagnetic inhomogeneity B. Magnetic 

optimizationcoil

stop Controlled regionControlled region(Tumor)(Tumor)(Tumor)(Tumor)

Fl h f h i d h l l d i i iCorrecting

Flow chart for the magnetic and thermal coupled optimization and results optimization (Evolution Stratyegy algorithms) g

coilC il iti f th t ti i ti t t i

and results optimization (Evolution Stratyegy algorithms)Search the thermal and magnetic field uniformity Coils position for the two optimization strategies. g f f y

Both the magnetic fluid drug and the magnetic field source must be opportunely designedBoth the magnetic fluid drug and the magnetic field source must be opportunely designedusing optimization techniques in order to shape the magnetic field source and for the choiceusing optimization techniques in order to shape the magnetic field source and for the choiceof the magnetic fluid parameters.

0,08

of the magnetic fluid parameters.

0,07 conc_ 0,1%

M lti l Designi of the magnetic fluid (NP size and0,06

K/s]

conc_ 0,2%

conc 0 3%

Multiple solutions!!

Designi of the magnetic fluid (NP size and concentration):

0,05

 rate [ conc_ 0,3%

conc_ 0,5%

solutions!!!

)Design of the temperature rate‐Multiple solutions 

0 03

0,04

rature

conc_ 1% Ill-posed tTttT −Δ+ΩΔ

)()()( 11

0 02

0,03

empe

r

0 015 [K/s]synthesis problem t

tTttTT mmT Δ

Δ+=ΩΔ

)()()( 11

0,01

0,02te 0.015 [K/s] problem tΔOptimization 

0,00

0,0

|*)(|),( TTDF T Δ−ΩΔ≡φ function

0 10 20 30 40 50

l d [ ]nanoparticle diameter [nm]

Developed designs by evolution strategyS•Eeffect of the 

p g y gyalgorithms:

••

ff fposition of NPs 

g•electromagnetic source based on magnetic

•Sinjections. and thermal field uniformity; the solution of a•SNot uniform NPs

coupled electromagnetic and thermal problem•2

Not uniform NPs distribution . • heating source focusing some aspects of a

h ••

therapeutic treatment;NP i j ti it f i th th l d •

•• NPs injection sites focusing the thermal andthe therapy design problems •the therapy design problems.

magnetic fields: human exposure, tion

B Human exposure to magnetic fieldsB. Human exposure to magnetic fieldsHuman models have been used in order to compute the induced current density in theHuman models have been used in order to compute the induced current density in the

human body tissues generated by means of a magnetic field at frequency under 100 kHzhuman body tissues generated by means of a magnetic field at frequency under 100 kHz.Some examples of evaluation of the magnetic field effects rising from welding equipments areSome examples of evaluation of the magnetic field effects rising from welding equipments arereported.reported.

18 mA/m2 27 mA/m2H b d d l18 mA/m2 27 mA/m Human body modelbuilt from real CTbuilt from real CTdata segmentingdata segmentingeach slice in ordereach slice in orderto distinguish theto distinguish thedifferent organsdifferent organsand discretized byytetrahedralelements for FiniteElement Analysis.

Induced current density in huma body model due to resistance welding equipment

The numerical computation of induced current density is important in cases where themagnetic flux density overcomes prescribed limits. Since in some practical cases thecurrent that supplies the device can be so high that the magnetic flux density overcomesli i h i d d d i b l d i d d id if ilimits, the induced current density must be evaluated in order to decide if equipmentti fi fi ld li it t d b t d dsatisfies field limits suggested by standards.

C Electromagnetic fields in medical applications: electric field applicationsC. Electromagnetic fields in medical applications: electric field applicationsElectric field can be used to stimulate brain cells In this example an evaluation of theElectric field can be used to stimulate brain cells. In this example an evaluation of the

possibility to reach the internal structure of the brain with an electric field enough intense topossibility to reach the internal structure of the brain with an electric field enough intense toallow the cell stimulation is proposed The electric field can be applied by means of two orallow the cell stimulation is proposed. The electric field can be applied by means of two ormore electrodes on the surface of the head.

P1

more electrodes on the surface of the head.

P0 P0P1P0

P1P0

P1

Si CSi BElectric field model and some P2Electric field for different electrodeSim A Sim CSim BElectric field model and some 

computation resultsP1

Electric field for different electrode voltage 

computation resultsg

Vn 0 VVn 0 V

ossoosso

osso

l f ld h h d f d ff fElectric field in human head for different position of the electrodesthe electrodes

Numerical analysis on real models of the head has been conducted in order to evaluateythe effect on different positions of the electrodes on the skull in order to induce an electricfield in the brain structures. It is to be noted that electrical characteristics of the tissues area function of the frequency, and then a time‐varying electric field have a different behavior

35

30

25

20m]

15E [V/m

10

5SimA simB

Si C E00

SimC E0

0,00 0,05 0,10 0,15 0,20Electric field in human head

x [m]Electric field in human head

Some papers•F Dughiero M Forzan E Sieni Numerical FEM models for the evaluation of EM fields exposure near welding machines Proc COMPUMAG 2009•F. Dughiero, M. Forzan, E. Sieni Numerical FEM models for the evaluation of EM fields exposure near welding machines, Proc. COMPUMAG 2009•E. Sieni, F. Dughiero, M. Forzan Evaluation of the exposure to magnetic field generated by welding equipment with reference to induced current density, Cedrat News, 2010M B ll M Chi i F D hi E Si i d L Zilb ti N i l di ti f t d d i h d l b i d ti ki li P I t ti l•M. Bullo, M. Chiampi, F. Dughiero, E. Sieni and L. Zilberti, Numerical prediction of currents produced in human models by induction cooking appliances , Proc. InternationalSymposium on Heating by Electromagnetic Sources, SGEditoriali, Padova, 67‐74 , May 19‐21, 2010.•Di Barba, F. Dughiero, E. Sieni, Synthesizing a nanoparticle distribution in magnetic fluid hyperthermia, Proc. International Symposium on Heating by ElectromagneticSources, SGEditoriali, Padova, 483‐490 , May 19‐21, 2010.•Sieni E., Candeo A., Dughiero F., A simplified 3d approach for the evaluation of the SAR and temperature distribution in magnetic nanoparticles hyperthermia, Proc. ESHO2009 ‐ oral presentation appeared on Visual Journal of Medicine, 13 Ottobre 2009, www.vjmed.net Abstract book pp. 13‐14p pp , , j pp•P. Di Barba, F. Dughiero, E. SieniMagnetic Field Synthesis in the Design of Inductors for Magnetic Fluid Hyperthermia, IEEE Trans on Magn, 2010•P. Di Barba, F. Dughiero, E. Sieni, A. Candeo, Coupled Field Synthesis in Magnetic Fluid Hyperthermia, in press IEEE Trans on MagnP. Di Barba, F. Dughiero, E. Sieni, A. Candeo, Coupled Field Synthesis in Magnetic Fluid Hyperthermia, in press IEEE Trans on Magn•E. Sieni, F. Dughiero, M. Forzan, Simple 3D fem models for evaluation of EM exposure produced by welding equipments, To be appear on IOSPress 2010•F Dughiero M Forzan E Sieni A numerical evaluation on Electromagnetic fields exposure on real human body models until 100 kHz In press on COMPEL•F. Dughiero, M. Forzan, E. Sieni A numerical evaluation on Electromagnetic fields exposure on real human body models until 100 kHz, In press on COMPEL