HEATING SOURCE TREATMENT MALIGNANT BRAIN TUMOURS

Electrocomponent Science and Technology1974, Vol. 1, pp. 91-96

Gordon and Breach Science Publishers Ltd.Printed in Great Britain

INDIRECT HEATING SOURCE FOR TREATMENT OFMALIGNANT BRAIN TUMOURS

PHILIP C. THACKRAY and ZVI H. MEIKSIN

Department of Electrical Engineering, University of’ttsburgh, ’ttsburgh, Pennsylvania 15261, USA

and

SIDNEY K. WOLFSON and ROBERT G. SELKER

Department of Neurosurgery, School of Medicine, University of Pittsburgh Laboratory of SurgicalResearch, Montefiore Hospital, Pittsburgh, Pennsylvania 15213, USA

(Received March 20, 1974)

The design of an indirect heating source for the treatment of malignant brain tumors is presented. A high Q resonanttank working at 25 kHz generates a magnetic field of 16,000 ampere-turn/meter (peak) which is used to heatmetallic implants by a combination of hysteresis and induced current heating. The resonant tank is used in afeedback loop of the power driver to maintain the driver at the resonant frequency, thus minimizing the powerlosses that inevitably occur in open loop systems due to reference oscillator drifts and/or varying load and tankconditions. Because of the high field strengths required and the relatively small power dissipation that occurs in themetallic implants, the overall system design differs substantially from standard induction heating applications.

INTRODUCTION

This paper discusses the development of a specialpurpose high magnetic field rf energy source for thetreatment of malignant brain tumors. The biomedicalbackground will be briefly reviewed to help clarifythe special requirements and constraints of thsystem.

It is well established that reduced body tempera-ture (hypothermia) lowers the metabolic rate in bodytissues and organ systems. In cases where accessibletumors exist they have been experimentally treatedby a method which involves hypothermia of thesurrounding healthy tissues while the tumor is eitherheld at normal body temperature (normothermia) orat an elevated temperature relative to the normalbody temoerature (hyperthermia).,2 If the malig-nant tissue is subjected to applications of a toxicchemotherapeutic agent (antimetabolite), the healthytissue will be protected from the effects of theantimetabolite by its lower metabolic rate, thecancerous tissue being attacked in a normal way.

]-Supported in part by ACS institutional grant No. 58M.

The application of this hypo-hyperthermic tech-nique to the treatment of brain tumors is beingexplored in these laboratories (RGS and SKW). Sincedirect hyperthermia of a deep-seated tumor is diffi-cult, a method involving the magnetic hysteresis andinduced current heating by an external oscillatingmagnetic field of small stereotaxically implantedmetal pieces is being studied. In conjunction withmoderate total body hypothermia, this results in theestablishment of a temperature gradient between thevolume of brain in the immediate vicinity of theimplants and the surrounding brain tissue. Themagnitude of this gradient depends upon the mass ofmetal implanted and the intensity of the magneticfield. Present experiments involving live squirrelmonkeys with small (10 mm x 1.6 mm) low carbonsteel implants have produced temperature gradientsof 5C/mm in a reproducible fashion. A sharpfall-off in temperature 2-3 mm from the implantedmetal has been noted, thereby facilitating control ofthe area to be heated.

Having created a sufficient temperature differen-tial, indirect access by chemotherapeutic agents tothe brain tumor can be achieved by perfusion into thebrain’s vascular system. As mentioned, the healthy

91

92 P.C. THACKRAY et al.

tissues are protected from the antimetabolite by theirlower metabolic rate. The addition of a technique oftotal circulatory arrest during hypothermia wouldincrease the effectiveness of the above methods byallowing greater temperature differentials andreduced diluting effect of the toxic agent by normalblood flow in the brain.4

The previous work was carried out with a 5.5 cm(2.75") i.d. coil working at 37 kHz with an inputpower of kW. The coil and driver circuits wereprovided by the Rawland-Borg Corporation ofChicago, Illinois, and designed primarily for hysteresisheating of particles of Fe2 03, 0.02-0.1/a in size.3,s

Experiments with squirrel monkeys have determinedthat a field strengthf of 16,000 At/m (peak)issufficient to achieve the required temperature gradi-ents in living brain tissue. However, implementationof the ideas discussed in the previous paragraph areawaiting the construction of a greater diameter fieldgenerator so that larger experimental animals, e.g.baboons, can be accommoaatea, in the tollowlngsections the design and construction of a 0.15 m(6") i.d. system is discussed.

2 DESIGN

2.1 General Considerations

The power dissipation in the implanted metallic pieceswill be only a few watts. However, the creation of a16,000 At/m fidd in a 0.15 m diameter coil willrequire an input power on the order of kW due tolosses in the coil. As already noted, this situation is insharp contrast to the standard induction heatingapplication where a large percentage of the power isdelivered to the work piece and losses in the workcoil are almost negligible. Consequently, rf inductionheaters are optimized for their ability to deliverpower to the load and their open coil field strengthsare much less than 16,000 At/m. In the present case,loading is negligible and therefore load matchingrequirements are not applicable. The essence of theproblem is the creation of very strong high frequencyfields where no loading is assumed.

2.2 The Resonant Tank

The use of a resonant tank consisting of an inductorand a capacitor will be the most efficient circuit for

]’A current of ampere flowing in a ring meter indiameter creates a field of ampere-turn/meter (abbre-viation: At/m).

this basically inefficient (’- 1%) system. In the limitas the tank series impedance goes to zero, therewould be unlimited tank current and an infinite fieldwith zero input power. This idealization serves todefine the engineering approach: design a high Qair core inductor-capacitor resonant tank to obtain ahigh field strength to input power ratio.

2.2.1 Tank requirements The requirements forthe tank are:

a) Physical size-The coil diameter must be0.15 m to accommodate the range of baboon headsizes, and must be sufficiently long so that a uniformfield will be generated throughout a large enoughvolume. If the length is set to be 0.15 m also, a fieldwill be set up which does not fall more than 10%below its axial value in a volume of about 0.3 liternear the center of the coil. The additional fielduniformity which would be obtained by a Helrnholtzcoil arrangement would not justify the lower efficiencyin this application.

b) To avoid any heating of normal tissue whichwould offset the hypothermia and yet maintainsufficient induced heating of the metallic particles,25 kHz was chosen as a compromise for theseexperiments. Furthermore, at this frequency a largerpercentage of the heating effect will be due tomagnetic domain motion (hysteresis heating) in theimplant material. This is desirable because theamount of hysteresis heating is dependent only onthe quantity of metal and not on the size andorientation of the implants geometry in the field as isthe case with induced current heating. As the fieldfrequencies approach the megahertz range, inducedcurrent heating predominates in the metallic implantsand normal tissue heating becomes significant.

c) Field strength- Preliminary work has shownthat a field strength of 16,000 At/m is needed tocreate the required temperature gradient.

2.2.2 Tank components For power driver match-ing requirements discussed below, the parallel tankarrangement, rather than the series tank, was chosen.The tank is illustrated in Figure 1. Relationshipsbetween the tank parameters are given by thefollowing equations:

1Resonant frequency f "tLt.)2rr------ (1)

27rfLQ factor Q (2)Rs

INDIRECT HEATING SOURCE 93

FIGURE 1tance shown).

V

RS

RpL

_L

Basic resonant tank (equivalent parallel resis-

Equivalent parallel resistance Rp RsQ2 (3)Necessary input power Pin I2Rs (4)

VTank current I (5)

2zrjZ

Central axial magnetic field

H -d- (d 2 + 12f/2 At/m (6)

where L inductance (henries), C capacitance(farads), Rs coil resistance (ohms), coil length(meters), d =coil diameter (meters) and N=coilnumber of turns.

From Eq. (6) we find that for l- d--0.15 m andH 16,000 At/m, the product NI 3400 At (peak).The choice of N and I should be dictated by theminimum input power requirement. The input poweris given by Eq. (4) where the series resistance Rsdepends on the number of turns and coil configur-ation. If there existed a simple functional relationshipbetween Rs and N, an optimum value for N could bederived analytically. Such a simple relationship, how-ever, does not exist. If the coil turn spacing is large,then Rs is a linear function of N. However, as Nincreases, the coil spacing decreases to maintain afixed coil length, andR becomes a rapidly increasingfunction of N whose exact form depends on the con-ductor geometry. This change is caused by theincreased coupling between adjacent turns resulting indecreased utilization of conductor cross-section (skineffectS.

The design optimization was done empirically atreduced currents as follows. It was decided to use1/2" o.d. copper tubing for the solenoid to allow for

water cooling. The tubing was flattened in a rollingunit to a 1/4" thickness and wound edgewise on a0.15 m mandrel. A 25 kHz current was applied to thesolenoid and the field strength and input power weremeasured as a function of turn spacing while main-raining the length of the coil constant. A maximumvalue of the ratio of the field strength to input powerwas found to exist for a spacing of 0.87 turn per cm.This resulted in a coil consisting of 13 turns with alength and diameter of 0.15 m. The measured valueof inductance was 18.5/H. At 25kHz, the seriesresistance was 25 mr2, and the Q factor was 105. Fora peak field strength of 16,000 At/m the peak coilcurrent, from Eq. (6), is 260 A, and from Eqs. (4)and (2) the maximum rms input power required is900 W.

To complete the tank, a capacitor must be chosen.From Eqs. (1) and (2) it is found that a 2.5capacitor rated at 190 Arms, 500 V rms with Qfactor 105 is needed. This capacitor was made upof 30 parallel 0.085/F polystyrene units each ratedat 10 A rms, 1000 V rms with a minimum Q 10,000at 25 kHz. Thus, the circuit Q is determined only bythe coil. The parallel input impedance of the tank atresonance was measured to be 288 2 and from Eq.(5) it follows that the tank voltage will be +700 Vpeak for a field strength of 16,000 At/m. By tappinginto the resonant tank, the required drive voltage andinput impedance can be reduced so that a solid statedriver can be used.

The tapping was accomplished by placing a secondcapacitor C2 in series with the original capacitor C1,see Figure 2. The input voltage VT and the inputimpedance Rin are related to the tank voltage and theequivalent parallel resistance Rp by the following

vin --- 2.5/=tRp

c2f

la.sFhL

FIGURE 2 Tapped resonant tank.


equations"

Zc..Vin VT

Zcl + Zc2 Ca + C

Rin Ca + C Rtwhere Vr is the tank voltage, Zc and Zcz are theimpedances of capacitors C and C2, respectively andthe other symbols were defined earlier. LettingC/(C2 + Cl) 0.1, then C2 10C 25 F. Therequired drive voltage will be -+70 V and the inputimpedance will be about 2.5 2. C2 is composed offive parallel 5 F polystyrene units each rated at50 Arms and 300 V rms. The equivalent series resis-tance of the bank is 100/fZ at 25 kHz. If theinductor had been tapped, there would have beenvery few choices for the tap point and due to poorcoupling additional losses would occur. The capacitortap is virtually lossless. A picture of the completedtank appears as Figure 3.

2. 3 Power DriverThe power driver must be capable of delivering kWto the resonant tank. With a tank Q of 105 input

requirements of the tank will change rapidly withdeviations from the resonant frequency. For example,a 0.5% deviation will cut the magnitude of the inputimpedance by 1/2. However, if the tank is used in afeedback loop of the power driver, changes in theresonant frequency due to varying load and/or tankconditions will be compensated. Such is not the casein standard induction heating devices where, becauseof extremely low Q, the load appears resistive over alarge range of frequency. Consequently, these systemscan be driven by reference oscillators with nofeedback from the work coil itself.

2.3.1 Driver design The input impedance at thetap point of the resonant tank will be purely resistiveonly at the resonant frequency. If the power driver isa trans-conductance amplifier (i.e. characterized bythe equation/out gVin where lou is the outputcurrent, Vin is the input voltage, and g is thetransconductance of the amplifier), see Figure 4, thenthe output voltage when driving the resonant tank,will be in phase with the input voltage only at theresonant frequency. If the output voltage is fed backto the noninverting input via a zero phase shift scalingcircuit then we have an oscillator whose frequency isthe frequency of the tank. In Figure 4, resistors

FIGURE 3 Resonant tank.

INDIRECT HEATING SOURCE 95

R7

/ / 2 / R6

C5

_1_

FIGURE 4 Power driver and resonant tank.

R6-R7 and R2-R1 are two voltage dividers whichfeed a fixed percentage of the output voltage back tothe noninverting input. The resistive values are chosenso that a loop voltage gain slightly greater than unityis achieved. If the input resistance of the tank atresonance is R 2.8 Z, then the forward voltage gainis:

Vout-gR 75 f2 -1 X 2.8 fZ 210.

If a feedback attenuation of 1/200 is chosen, then thetotal loop gain will be

210 x 1.05.200

This assures that oscillations will begin, and theoutput level will increase until the branch composedof R9, R o, D1 and D2 begins to shunt current awayfrom divider R2-R1 thereby lowering the loop gain.The equivalent small signal resistance of the diodes is26 mV/la, where lcl is the diode current, so theresistance of this branch is a decreasing function ofthe voltage at the top of R9. Thus, the shuntingeffect is voltage sensitive and variable resistordetermines the voltage at which this shunting effectwill be significant. A stable output is obtained andR o determines the output voltage swing.

Resistor R provides 100% d.c. voltage feedbackto maintain the d.c. component of the output at theground level. For a.c., Cs shunts this feedback toground so that no overall negative feedback is used atthe resonant frequency.

Figure 5 shows the details of the transconductanceblock along with the feedback loops just discussed.The amplifier /.t715 provides voltage gain and estab-lishes good inverting and noninverting inputs. A unityvoltage gain current amplifier, LH0002, couples the715 to the input of the power predriver stage.Transistor Q1 establishes the quiescent biasing con-ditions in the remaining stages and in conjunctionwith C4 couples the input drive to the base of Q.

t3 R5

05’ Q6

165

IllR 2

FIGURE 5 Power driver.


Potentiometer R is adjusted to set a 50 mA d.c. biascurrent in each output transistor. This eliminatescrossover distortion and ensures that sufficient gainexists for the small noise voltages that are necessaryto start oscillations.

Positive input signals are inverted and level shiftedby Q2. This stage has unity gain, a 2 k2 inputimpedance, and a 50 2 output impedance. Thisvoltage is used to drive the emitter follower Qswhich supplies the necessary current to drive theparalleled bases of the output transistors Q4-Q6. The0.5 2 resistors in the output transistor emittersestablish the transconductance characteristic of theamplifier: the collector current in each output deviceis just the input voltage divided by the 0.5 2 emitterresistor. Q7 tlarougla Qll perform a symmetric func-tion on negative signals.

The amplifier must be sufficiently linear to mini-mize the power lost when harmonic distortion cur-rents are shunted to the high Q resonant tank. In thisdesign no overall negative feedback is used, butsufficient (<2% distortion) linearity is obtained byusing large amounts of feedback at each stage. Thisavoids the stability problems associated with overallfeedback and allows the use of relatively inexpensivesilicon audio power transistors to obtain full powerresponse at 25 kHz.

All of the power transistors (Q2-Q11) in thedriver are physically mounted on a water cooledcopper plate. Water passages are located directlybelow the chip center in the TO3 package. With anamplifier designed to deliver kW, each of the sixoutput devices will dissipate 100 W (although thismaximum dissipation occurs at an output power lessthan kW). With this cooling arrangement, casetemperatures never exceed 50 at 100W/device andthe corresoonding maximum junction temperaturefor these 200 watt devices ls:

0.875 C/W x 100 W + 50C 130C,which leaves a safety margin of:

200C_ 130C80 W/device.

0.875 C/W

The total output into 2.5 2 is +28 A (peak)and +70V (peak) at 25 kHz.

In the three phase power supply (Figure 6) thethree transformer primaries are delta connected. Eachsecondary winding is center tapped and uses a full

+_ eov

SUPPLY

1.5 KW

+80V

24,000,u.f

24,00oFf

-80V

FIGURE 6 Power supply.

wave bridge. This results in a +d.c. supply with 360Hz ripple on each supply. The 24,000 /aF filtercapacitors are constructed from 4-6000/2F units. The30 A half-wave current pulse drawn at 25 kHz fromeach supply cause a V pp ripple. The 360 Hz rippleis 4 V pp.

3 DISCUSSION

The original 5.5 cm diameter system requires an inputpower of kW to produce a field of 16,000 At/m in across-sectional area of 24 cm2 The system justpresented uses the same input power to produce asimilar field over a crossectional area of 178 cm2

This represents an increase in flux production effici-ency of 7.44 times. Greater electrical efficiency couldhave been obtained by using super conducting coils,but the cost efficiency of such an arrangement wouldbe very much less and the overall system complexityand size would be greatly increased.

REFERENCES

1. V. P. Popovic, and R. Maskoni, "Effect of generalhypothermia on normothermic tumors." Am. J. Physiol,211. 462 (1966).

2. V. P. Popovic, and R. Masironi, "Enhancement of 5flurouracil action on normothermic tumors by general-ised hypothermia," Cancer Res., 26, 2353 (1966).

3. R. G. Selker, S. K. Wolfson, Jr., R. Medal, and M.Miller, "Creation of a chemothermal gradient in treatmentof brain tumors," Surgical Forum, 24,461--463 (1973).

4. S. K. Wolfson, ana R. G. Selker, "Carotid perfusionhypothermia for brain surgery usin cardiac arrest withoutbypass," J. Surg. Res. 14,449-458 (1973).

5. R. Medal, et al., "Controlled radio frequency generator forproduction of localized heat in intact animal," Arch.Surg., 79,427-431 (1959).

International Journal of

AerospaceEngineeringHindawi Publishing Corporationhttp://www.hindawi.com Volume 2010

RoboticsJournal of

Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014


Active and Passive Electronic Components

Control Scienceand Engineering

Journal of



RotatingMachinery


Hindawi Publishing Corporation http://www.hindawi.com

Journal ofEngineeringVolume 2014

Submit your manuscripts athttp://www.hindawi.com

VLSI Design



Shock and Vibration


Civil EngineeringAdvances in

Acoustics and VibrationAdvances in



Electrical and Computer Engineering

Journal of

Advances inOptoElectronics

Hindawi Publishing Corporation http://www.hindawi.com

Volume 2014

The Scientific World JournalHindawi Publishing Corporation http://www.hindawi.com Volume 2014

SensorsJournal of


Modelling & Simulation in EngineeringHindawi Publishing Corporation http://www.hindawi.com Volume 2014


Chemical EngineeringInternational Journal of Antennas and

Propagation




Navigation and Observation



DistributedSensor Networks


Documents

HEATING SOURCE TREATMENT MALIGNANT BRAIN TUMOURS