Journal of Scientific & Industrial Research Vol. 58 , February 1999, pp 112-117

Conlputer-controlled Ultrasonic Hyperthermia System for Cancer Therapy

V R Singh

National Physical Laboratory, New Delhi 110012, India

Received: 14 May 1998; accepted: 08 October 1998

Cancer is serious disease and its proper treatment is required at proper stage. There are several techniques namely RF (radio­frequency), microwave, nuclear and chemotherapy which are currently used, but such techniques have their own limitations and

proper treatment is not assured. Focused ultrasound is used to raise the local temperature in the tumour or diseased cell for its

therapeutic treatment. A computer controlled ultrasonic hyperthermia system is developed for the treatment of, e.g., deep seated

tumours. Design, development and applications of the proposed system are described .

Introduction Cancer poses a serious problem. Majority of the

deaths reported are due to cancer. In our country, with increasing life expectancy, changing life styles con­comitant with development and progressive control of major communicable dl iseases , the morbidity and mor­tality due to cancer is steadily increasing. Presently, the cancer treatment is mainly done by using three modali­ties viz surgery, chemotherapy and radiotherapy. None of these has, however, been able to efficiently control cancer. Hyperthermia has come into use in the recent past 1-7 owing to the limitation of other techniques, com­puter controlled hyperthermia is discussed here.

Local Hyperthermia Treatment Technique Though there are many local heating modalities but

focal ultrasound with focusing mechanism is found to be more suitable for bettter penetration depth with better intensity in the focal zone.

Ultrasonic hyperthermia is the most suitable modality for tumour therapy. Some of the advantages of ultra­sonic hyperthermia are as follows :

(i) Deep seated tumours could be treated. (ii) Tumours absorb ultrasound energy better than the

normal tissues. (iii) Beam focusing devices are available, thereby

multiple beams are dire;;ted at deep seated target without much overheating of normal tissues.

Figure I describes various steps for executing deep tumour heat treatment, Treatment planning is divided into three parts, The first part, i.e., geometrical treatment planning, gives the dimensions and location of the target

volume, as well as the location of tissues, which are critical to the treatment outcome. The second part deter­mines the tissue properties that affect the ultrasonic properties and uses these properties to calculate and optimize the power deposition pattern. Finally, tempera-

GEOMETRICAL TREATMENT

PLANNING

THERMAL TREATMENT PLANNING

PROBE INSERTION

TREATMENT VOLUME

LOCATKlN

TREATMENT NON-INVASIVE

EXECUTION TEMPERATURE MEASUREMENT

Figure I - Local hyperthermia system

SINGH: COMPUTER-CONTROLLED ULTRASONIC HYPERTHERMIA SYSTEM 113

ture that results from the power deposition pattern is estimated. Before this can be done, thermal properties must be assigned for various tissues.

Thermal conduction , specific heat and density are well known in various tissues. In the probe insertion section, several temperature sensing probes are inserted into the target volume. For superficial tumours, palpa­tion and visible tumour boundaries are the guiding prin­ciples . When the tumour is deeper, imaging techniques are used to guide the probe into the desired locations. Imaging of the probe locations, after they have been

placed, verifies the temperature measurement or heating source locations with respect to the target volume. This information is useful during treatment.When deep tu­mours are heated using ultrasound energy sources, it becomes important to accurately locate the target vol­

ume with respect to the heating field . In an ideal situ­ation, an imaging modality is combined with the heating device in such a manner that the target volume can be imaged after the patient has been positioned on the treatment machine immediately prior to the treatment. During the treatment, the power is increased until the temperature in the target volume reach therapeutic lev­els or until patient's discomfort prevents the increase of

power. With ultrasound technique, the power is reduced to prevent overheating or increased to compensate for higher heat losses present at any location. Currently, the

techniques to control the deposition pattern as a response

LESION -~;.:;:.:.'---~

to the measured temperatures are already known . Com­puters are used to optimize the treatment.

Focused Ultrasonic Hyperthermia System

Figure 2 gives the block diagram of hyperthermia system based on focused ultrasound for the destructi on of tumour. The system consists of five main parts:

(i) Diagnostic and therapeutic focu sed transducers, (ii) RF generator with power amplifier,

(iii) Temperature monitoring system, (iv) Control sys­tem, and (v) Computer system giving treatment tem­perature and patient's data.

Materials and Methods

(a) Ultrasonic Transducers

(i) Diagnostic Transducers

Diagnostic transducers are used for the scanning or diagnosis of various tissue abnormalities . In the present investigation, diagnostic transducers used for the scan­ning of tumour show the construction of a typical transducer used by the author. The backing material is chosen as a mixture of tungsten powder and araldite. The compromise is between pulse duration and sensitivity, the shorter the pulse, the lower the sensitivity . A thin

layer of thickness 5/4A of the same backing material is also used at the face plate of the transducer to prevent direct contact of the crystal with the subject under ex-

_TtiER IMOC:OU' LE OUTPUT LEAD

Figure 2 - Focused ultrasonic hyperthermia system

114 ] SIC IND RES VOL 58 FEBRUARY 1999

~COAXIAL CABLE

ALUMINIUM CASING

~---vt-WIRE

PZTDISC

Figure 3 - Ultrasonic probe

R.F COAXIAL CABLE-~i:~~===-BAKELITE

METALLIC SPRING

t--__ -:::3'----M ETALLIC RING I

___ I ~--TRANSDUCER

METALLIC RING 11

v-----I-·....,.--'--METALLIC RING 1ll

1:::;;±~:1---WATER INSERTION --I---:.-I----RUBBER CONDOM ~~~+---LENS

Figure 4 - Focal ultrasonic therapy transducer

am ination. This also serves the purpose of protecti on

from moisture at the re onance frequency (Figure 3).

(ii) Focused Ultrasonic Therapy Transducer

Schematic di agram of focused therapy transducer is

shown in Figure 4, the assembly empl oys PZT-4 ( lead

zirconate titanate) ceramic disc with 50 mm di ameter.

The probe head is essent iall y a water proof housing

clamp and is energized as the a ir backed transduce r, the

ex posed surface of which is silvered and held at the earth

pote nti al. The other surface is coupled by a brass spring

to the high voltage electrodes of the coaxial outpUit cable

from the RF generator. Solid lenses are used to focus ultrasound beam. Ultrasound je lly or sa line soluti on is used as the coupling medium.

(b) Radio Frequency Generator

High power ultrasound is generated by the applica­ti o n of I MHz RF pulses to a pi ezoe lec tric plate transducer. These pulses are generated by radi o-fre­quency generator. Thi s arrangement provides an elec tri ­cally maintained mechanical vibrator e mitting sound waves of fixed frequency. The connecting flexibl e co­axial cable and the crystal are the part of the output tank of the generator (Figure 5).

(c) Temperatllre Mon itoring /n Ultrasonic Hyperthermia

(i) Invasive Technique

For the measurement of ti ssue te mperature distribu­tion in the human body, various techniques a re used such

as thermi stor, thermocouple and fibre optic probes. These modalities are invasive, which have many disad­vantages in clinical setting, like (i) viscous forces act ing between object and tissue, causes an additional local ri se in temperature, ( ii) interfe res w ith the control and meas­ure ment of various re lated parameters, (iii) they may in certain instance be subjected to inte rference by heat ing technique, and (iv) the introducti on of probe into the living ti ssues leads to obvious incon ve niences to the

patient.

(ii ) Non-Inyasive Technique

In the present inves ti ga ti on, the technique of double probe through transmi ss ion is used for the measuremen t of ultrasoni c ve loci ty throug h samples and liquid s. The ultrasonic propagat ion ve locity measure ment has been carried out in various bi ologica l materi a ls. The tempera­ture dependence of velocity in a range of temperature suited for hyperthermia app lications has been studied . The temperature due to therapeutic effec ts of ultrasound has been utili zed.

(d) Control Systel1l

A technique of time domain control is incorporated in controlling the RF power source. S ince, the tempera­ture cann ot be measured properly in the presence of RF due to inte rference, the RF Ge nerato r i put off for at least 5 s to measure the temperature .In this process of cont ro l, the power is kept on for a proportional to the difference of tumour temperature and the des ired treat­ment temperature . l-lence, as the temperature of tumour rises, the duration for whi ch the power is de li vered reduces . In any situation, after a fixed duration, i.e. 50 s, in this case, the machine is put off for temperature

SI GH: COMPUTER-CONTROLLED ULTRASONIC HYPERTHERMIA SYSTEM

O. 2!1)JF

IOJ) 17011

IOOt1j lOW

~--~2N350~l-----~t-----------------~t---t-----~f-t:~ __ ~~

22V

220V

-'-n / 5 W 2

O.!I.n..

1 N 1124

JN1124

1Nlf24

Figure 5 - Ultrasonic generator circuit

IMING SIGNAL REED RELAY GENERATOR t--_-'--~ (MUlTI POINT)

FOR CONTROL

T IMl'IG StGNAL. GENERATOR

FOR TEMPERATURE READING ·

REED RELAY

CONTROL FUNCTION GENERATOR

Figure 6 - Hyperthermia control system

l

SOUD STATE POWER RELAY

115

11 6 J SIC IND RES VOL 58 FEBRUARY 1999

measurement. After a gap of 5 s during which the thermocouple probe cools down sufficiently, the tem­perature is monitored for 5 s more. Hence, one full cycle of heating and temperature monitoring is made up of 60 s. A functional control diagram of the system is shown in (Figure 6).

Results and Discussion A new computer controlled modality based on fo­

cused ultrasound is studied and developed by using various physical parameters, measured here, as design parameters for the system. The present focusing transducer system is capable of obtaining an in tensity gain deep enough for cancer treatment. The results ob­tained by us ing the present focused transducer at I MHz frequency are shown (Figure 7). It is observed that with an increase in focal length and radius of curvature, the intensity generated by the therapy probe decrease in all materials used for the lenses. The focal intensity, as one of the factor is controlled for a particular beam intensity and specific duration, in order to ach ieve proper impact or crushing strength determined from physical measure­ments to destroy tumour. The lenses prepared from

200 A

B

180 C

CURVE A POLYETHYLENE

D CURVE B POLYSTYRENE

160 CURVE C TEFLON

f 140

E CURVE D ACRYliC CURVE E ALUMINIUM CURVE F BERYWUM

F CURVE G BRASS N CURVE H IRON

E G CURVE 1 STEEL ~ 120 ~

H ,;.:t->- 100 1 l-CJ)

~ 80 I-z ...J <t 60 U 0 'u..

40

20

0 ...l--14

FOCAL LENGTH (cm)-

Figure 7 - Focal intensity vs foca l lengths (M Hz)

plastic polyethylene in this case, are found to be most appropriate because of the acoustic impedance of tu­mour tissues which minimizes the reflection factor. The lenses, thus prepared from polyethylene, perspex and polystyrene are recommended. An externally generated focused ultrasound wave enters the body and propagates without interference because there is virtually no di ffer­ence in the acoustic impedance between the body ti ssues and water. At the tissue, by partial reflection of focused waves, a high power is establi shed, which destroys the tumour.

When focu sed waves come in contact with an inter­face, the sound impedance changes so that the compres­sion phase or tensile phase is reflected which further depends upon the acoustical qual ity of thi s in terface. At the point where the focal wave exceeds the strength of the material, mechanical destruction occurs. The present ultrasonic hyperthermia system is successfully imple­mented in brain tumours in vitro.

The non-invasive measurement of temperature is made in in vitro tumour (Figure 8), brai n tumour in thi s case. The temperature rise perceived in the case of

2 -INTENSITY (W/CM )

5 .0 4 .5 4 .0 2.5 f.o I.!i 42

40 /0

38

t 36

oU

~34 ::::> I-<t ~ 32 a.. ::?: W I- 30

~ 28

26 1565 1645 1725 1805 1885 1965 2045 2125

VELOCITY (m Isec)-

Figure 8 - Non-invasive temperature measurement in brain tumour

SINGH: COMPUTER-CONTROLLED ULTRASONIC HYPERTHERMIA SYSTEM 117

tumour sample is non-linear and slow with the increase

in ultrasonic intensity. This is possibly due to the het­

erogeneous structure of tumour tissues which precludes

uniform temperature rise. Here, the propagation velocity

increases with the rise in temperature. Hence, by meas­

uring the velocity and the corresponding temperature,

the heat dose is maintained in a desirable fashion by

interpolating and adjusting the ultrasonic intensity at

required temperature.

Conclusions In the present investigation, use of ultrasound for

diagnostic as well as for therapeutic purposes is dis­

cussed. Design aspects of computer controlled focused

ultrasonic hyperthermia system are described, in detail.

Intensity distribution with various lens systems, thermal

model, and utility of this modality in hyperthermia are

studied.

References I Hynynen K & Edwar D K, Temperature Measurements During

Ultrasound Hyperthermia, Med Phys, 16(4) (1989) pp 618-626.

2 Singh V R & Shriwastava M, Ultrasonic Hypertherima for Cancer Treatment , Def Sci J, 43(3) (1993) pp 235-241 .

3

4

5

6

7

Singh V R & Shriwastava M, Brain Tumour Destruction by High Power Focused Ultrasound, J ACOIlSI Soc India, 21(4) (1993) pp 241-245.

Singh V R, Shriwastava M & Sharma J K, Design of Focusing Lenses for Ultrasonic Hyperthermia, Innoval Technol Bioi Med(France), 15(1) (1994) pp 107-113.

Shriwastava M & Singh V R, A Focused Ultrasonic Transducer for Local Hyperthermia Treatment of Brain Tu­mours, 1111 Calif Recenl Adv Biomed Eng, (1994) pp 229-232.

ter Haar G Rivens ), Chen L & Ridder S, High Intensity Focused Ultrasound for the Treatment of Rat Tumours, Phys Med Biology, 36 (II) (1991) pp 1495-1501.

Yadav S, Singh V R, Singh R P,Ahmed A & Agarwal R, Design of a Focused Ultrasound System for Tumour Therapy, J AcolIsl Soc India, 16 (1988) pp 10 I-I 07.