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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 .
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5
6
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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.