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CA1291221C - Method and apparatus for hyperthermia treatment - Google Patents

Method and apparatus for hyperthermia treatment

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Publication number
CA1291221C
CA1291221C CA000553681A CA553681A CA1291221C CA 1291221 C CA1291221 C CA 1291221C CA 000553681 A CA000553681 A CA 000553681A CA 553681 A CA553681 A CA 553681A CA 1291221 C CA1291221 C CA 1291221C
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conductor
applicator
coaxial
array
antenna
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French (fr)
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Ronald H. Crooker
Raymond S. Kasevich
James F. Mcqueeney
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KASEVICH ASSOCIATES Inc
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KASEVICH ASSOCIATES Inc
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • A61B18/1815Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using microwaves

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  • Biomedical Technology (AREA)
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  • Physics & Mathematics (AREA)
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Abstract

METHOD AND APPARATUS FOR HYPERTHERMIA TREATMENT
Abstract of the Disclosure A microwave collinear antenna array applicator for in situ or in vivo treatment of tumors and/or other materials by hyperthermia is disclosed. The array consists of a plurality of harmonically related resonant coaxial antenna elements connected electrically in series to provide uniform heating along the entire length of the array. At the distal end of the array, a resistor may be provided at the inner conductor for steering the heating pattern.
At the proximal end of the array, an impedance matching dielectric structure is provided to enable maximum power transfer to the array and to minimize stray leakage currents along the outside of the coaxial transmission line. The array may be made longer or shorter without changing frequency and therefore depth of penetration by simply adding or subtracting half wave resonant elements or sections of coaxial transmission line. A lossy sleeve member may be provided around the applicator to provide a localized source of heat.

Description

~2~

Technical Field This invention relates to a microwa~e antenna for treatment of deep-seated caneerous tumors by hyperthermia and other biomedical and geologieal applieations involving the use of dielectric heating for trea-tment of materials.
Background Art The use of elevated temperatures, i.e., hyperthermia, to repress tumors has been under eon-tinuous investigation for many years. When normalhuman cells are heated to 41-43C, DNA synthesis is reduced and respiration is depressed. At about 45C, irreversible destruc-tion of strueture, and thus funetion of ehromosome assoeiated proteins, oeeurs.
Autodigestion by the eell's digestive meehanism occurs at lower temperatures in tumor eells than in normal cells.
In addition, hyperthermia induces an inflam-matory response which may also lead to tumor destruc-tion. Cancer cells are more likely to undergo these ehanges at a partieular temperature. This may be due to intrinsie differenees, between normal eells and caneerous eells. More likely, the diffe~ence is assoeiated with the low pH ~acidity), low oxygen eontent and poor nutrition in tumors as a eonsequence of decreased blood flow. This is confirmed by the faet that reeurrenee of tumors in animals, after hyperthermia, is found in the tumor marcJins; probably as a consequence of better blood supply to those areas.
Conventional methods of cancer treatment are surcJexy, radiation (X-ray) therapy and chemotherapy.
In radiation therapy and chemotherapy, there are important interaetions with hyperthermia. Aeidity, hypoxia ~low oxyclen tension) and deereased nutrition all lead to increased susceptibility to hyperthermia treatment. In contrast, these conditions lead to resistance to radiation therapy and chemotherapy.
Thus, hyperthermia has been suggested as an adjunct treatment to enhance the other two treatments.
The differences are fundamental. Radio-therapy chiefly affects cells in mitosis (cell divi-sion), while hyperthermia is most effective during the DNA synthesis phase. Heat impairs recovery from sublethal radiation damage. When heat and radiation are given together, or heat prior to radiation, there is thermal enhancement of radiation damage to both normal tissue and tumors. However, if radiation therapy is given prior to hyperthermia, thermal enhancement of radiation damage for tumors is greater than normal tissue.
Despite the ability to reasonably define radiation fields and the availability of accurate radiation dosimetry, damage to normal structures, which cannot be avoided, result in dose limiting factors in radiation therapy. Thus, the avoidance of significant hyperthermia to adjacent normal structures i5 cri~ical for hyperthermia to become a useful aajunct to radiation therap~.
Recent clinical studies support the proposi-tion -that radiation therapy and hyperthermia can be combined effectively. In addition, both in vivo and in vitro experiments show that the effects of chemo--therapy are also enhanced by hyperthermia. This enhancement may be due to increased membrane perme-ability at higher temperatures (drugs get into cells more easily) and inhibition of repair mechanisms for drug induced cellular damage. Since chemotherapy is given to -the entire body, precise localiza-tion of hyper~hermia i~ again essen-tial in combination with g~22~

chemotherapy to avoid significant damage to normal tissues.
A practical hyperthermia applicator must comply with the following criteria:
1. In order to treat tumors in all areas of the body, depth of penetration is essential.
The major limitation to many promising hyperthermia techniques is the inability to achieve high temperatures in deep struc-tures.
2. The applicator must have the ability to focus hyperthermia and quantitate absorbed heat in all areas of the tumor. Studies have shown that very high temperatures (approximately 50C) are most eEfective in cases where this temperature can be achieved. Me-thods that rely on temperature focusing, rather than on the ability of normal tissues to dissipate heat, allow these temperatures to be achieved.
3. The temperature throughout the tumor should be well-defined and uniform. The develop-ment of relative cool spots in a non-homogenous tumor may result in failure of cell kill and selection of cells with thermal tolerance (resistance to hyper-thermia) within that area. Sma]l differ-ences in temperature may produce large differences in cell kill.
The above criteria lead to the following requirements, which, i~ fulfilled, will allow the accurate measurements needed to develop dose response to therapy relationships which are necessary to provide uniform treatment for all patien-ts and evalu-ak:ion o~ cllniGal skudies.

~,-z9~ 2il 1. The technique should enable induction of hyperthermia to a well-defined volume. The fall-oEf of temperature beyond the tumor volume should be steep.
2. The level of hyperthermia should be precise-ly controllable.
3. Temperature distribution within the tumor volume should be uniform at therapeutic levels.
4. It should be possible to control the heat transferred in different regions of the tumor volume.
5. The therapist and not the changing charac-teristics of the heated tumor should control the temperature within the tumor volume, to avoid overheating a necrotic liquefied tumor center or underheating a well vascularized growing tumor edge.
6. In addition, one should be able to accurate-ly monitor temperature.
Applying these criteria to existing hyper-thermia devices, re~eals that while some devices have - advantages in some areas, all have limitations.
Non-invasive hyperthermia applicators, such as ultra-sound and electromagnetic radiation, are easier to use than invasive techniques, but are limited in depth of penetration. Ultrasound has poor penetration in bone and air. External microwave beam heating is limited by a shallow depth of penetration and the development of standing waves, creating hot and cold spots.
Consequentl~, more recently, investigations have been conducted into the feasibilit~ of using invasive applicators in the form of small diameter mlcrowave antennas or probes as a means of producing local hype~h~xmia in cancerous tissue. In -this form 2~

of therapy, antenna probes are inserted into the body through the esophagus or rectum, or directly into a tumor using a hollow plastic catheter.
Typically, these probes comprise a quarter-wavelength monopole antenna with frequencies in the 500 MHz to 3GHz range. These antennae are referred to by workers in the hyperthermia field as a dipole, or a sleeve dipole. A folded back quarter wave choke forms one-half of the antenna length (S. Silver, "Microwave Antenna Theory and Design", Dover Publication, Chapter 8, p. 241 and Electromagnetics, Vol. 1, No. 1, -January-March 1981, p. 58). The latter more nearly approximate a dipole antenna pattern.
These prior art dipole antennae suffer from a number of shortcomings, such as, poor impedance matching; high sensitivity to changes in the length of penetration of the probe into the body; poor uniform-ity in electric field and heating patterns produced;
and lack of beam steering and heat sensing capabili-ties. J. W. Strohbehn, et al., "An Invasi~e MicrowaveAntenna for Locally-Inducecl Hyperthermia for Cancer Therapy'`, Journal of Microwave Power, 14 (4), 197~, pp. 339-350; D. C. deSieyes, et al., "Optimization o~
an Invasive Microwave ~n-tenna for Local ~Iyperthermia Treatment of Cancer", Thayer School of Engineering, Dartmouth College, July 7, 1980; J. W. Stroh~ehn, et al., "Evaluation of an Invasive Microwave Antenna System for Heating Deep-Seated Tumors", presented at -the Third International Symposium: Cancer Therapy by Hyperthermia, Drugs and Radiation, Fort Collins, Colorado, June 22-26, 1980.
Disclosure of the Invention ~ ....... ......... ~
A construction in accordance with the present invention includes a microwave collinear an-tenna array applica-tor for hyperthermia -treatment 29~22~

comprising a plurality of harmonically related reson-ant coaxial antenna elements formed of an inner conductor and an outer coaxial conductor. The ele-ments are electronically connected in series to provide a uniform heating pattern of microwave radi-ation along the length of the applicator.
More specifically, the collinear antenna array is formed of a continuous inner conductor surrounded by dielectric material and an interrupted coaxial outer conductor wherein the interruptions are in the form of circumferential gaps periodically spaced along -the coaxial conductor at interrelated harmonic wavelengths to form a substantially uniform electromagnetic beam pattern about the periphery of the antenna.
In another aspect of the present invention, there is an adaptor for coupling the inner and outer conductors of small diameter coaxial line microwave hyperthermia applieators to larger diameter standard eoaxial line eables wherein the inner and outer eonduetors are separated by a dieleetrie core. The adaptor eomprises a transition pin adapted to fit over an extension of the inner eonductor for insertion into the inner eonduetor of the standard eable; an insula-tive sleeve fitted over an extension of the eore with a grooved spaee formed between the sleeve and the pin;
a metallie eonduetive ring affixed around the outer eonduetor over an extension thereof whieh abuts the sleeve; and an elastomerie eonduetive sleeve retaining member adapted to fit around the outer portion of the standard eable and the ring for retaining the appli-eator and eable in interlocking relationship.
A more speeifie embodiment of the present invention eomprises an invasive hyperthermia appli-eator for generating a well-defined uniform pa-ttern of ~ ~9~

electromagnetic radiation, preferably in the microwave frequency spectrum of 500 megahertz to 5 gigahertz, to produce well-defined temperatures throughou-~ a tumor.
The applicator is in the form of an elongate tubular member forming a collinear array of antennae fabri-cated from a common coaxial transmission line. In the preferred embodiment Oe the invention, a plurality Oe antennae, i.e., three, are formed from the coaxial transmission line by forming circumferential gaps in the outer conductor of -the transmission line.
These gaps serve as antenna feeds for subsequent antenna elemen-ts. The applicator has a proximal section and a clistal section. The three collinear antennas are located in the dis-tal section and a coaxial impedance matching transformer is providecl in the proximal sectic>n in the form of a circumferential volume of dielectric material with a conductor external to -the ou-ter coaxial line.
Progressin~ Erom the proximal section to the d:i~tal section, a first -three half wavelength col-linear antenna is provided. Then, two half waveleng-th antennas are prov:ided, which are harmonically related to the three halE wavelength antenna. 't'he comblned near Eie:Lcl radiat:ion pattern Oe the three antenna ,array procluces a un:ieorm temperatwre pattern a:Long the d~ ltr'lL sect.ion oE thc? appl:Lcator at a Erequenc~ which pro~uce~; rl In:inLmum in the ree.lectocl pOWeL' inc,icle the cotlx.i.r.l:l. tr,-lnsrrli~sion Lino.
'I'h~3 circllmEer~!nti.a:L cJap.4 in the outer 30 corldllctor Oe the tran.~rrlis;~ioll Line re~ult in u vo:Ltage ~oLrltJ ~Jene~ratecl ,acro~s the gap. '~'tle gap voltacJe e~xci.te~; unterln,l cllrr~rlt.; that E:Low on the outer corlcluctor oE tho tearl~ttli~,lon :I:ine, wh:ile the power EIJOW ln~i.cle~ the coaxial. tran~rtl:iss:ion line through -the cerlter concluctor, continue~ down the line to -the nex-t feed gap. The gaps thereby result in a radiation aperture. Preferably, the gap spacings from the distal end of the array are multiples of one-half of the antenna current wavelength. A standing wave of antenna current develops along the entire distal end of the array.
An outer plastic sheet or coating of di-electric material is provided around the collinear array, which may optionally include embedded therein, fiber optic sensor bundles, for measuring the tempera-ture at the delivery site.
Optionally, a sleeve of lossy, i.e., elec-tromagnetic energy absorbing material, such as fer-rite, may be disposed around the outer plastic sheet or coating at a predetermined location or locations along the distal length of the antenna array. Some of ; the electromagnetic energy radiated by the antenna is strongly absorbed by the ferrite sleeve which becomes hot and provides a source of localized heat ~or heating a tumor site. This heat source is independent of the electromagnetic energy absorbing properties of the tumor and produces hyperthermia range temperatures with significantly less power input than purely electromagnetic energy radiation permits. This sleeve tends to diminish the severity of the temperature gradient close to the antenna and thus permits more uniform temperatures near the antenna.
A method in accordance with the present invention of forming a small diameter electromagnetic radiàtion applicator having a distal section and a proximal section and comprised of an inner conduc-tor and an outer coaxial conductor comprises the steps of:
forming a dielectric inner core layer around the inner conductor; masking radial strips about the periphery of the dielectric layer with a thin metallic conduc-~ ~9~2Zl g tive layer to form the outer coaxial conductor;
forming an impedance matching transformer at the proximal section; and forming a protective dielectric sheath layer over the distal and proximal sections.
Brief Description of the Drawings Fig. 1 is a cross-sectional view of the applicator of the present invention showing in solid lines a cross-section of one-half of the far field antenna array pattern resulting from each of the three antenna elements and in dotted lines the near field heating pattern resulting from the superposition of the electromagnetic energy pattern generated by the three antenna elements.
Fig. 2 is a cross-sectional view through the applicator 10 of Fig. 1 along the lines 2-2.
Fig. 3 is a cross-sectional view of the applicator of Fig. 1 along the lines 3-3.
Fig. ~ is a cross-sectional view of the applicator of Fig. 1 along the lines 4-4.
Fig. 5 is a cross-sectional view of the applicator of Fig. 1 taken along the lines 5-5.
Fig. 6 is an illustration of an insulated dipole in an ambient medium used to depict the alge~
braic parameters needed f or calculating -the op timum transformer parameters.
Fig. 7 is a plot of frequency versus power ratio in decibels for the applicator of the invention.
Fig. 8 is a side view of an optional embodi-ment of the invention wherein a lossy sleeve 80 is provided over a selected portion of -the applicator.
Fig. 9 is a cross-sectional view of an alternate embodiment of the outermost end of the applicator 10 of Fig. 1.
Fig. 10 is an enlarged fragmented view of ~ig. 9.

~l2~

Fig. 11 is a cross-sectional exploded view of a flexible coaxial connector adaptor system 60 for use with the applicator of Fig. 1 shown in the process of being assembled.
~est Mode of Carrying Out the Invention I. APPLICATOR
Referring to Figs. 1-4, the invention will now be described in detail in connection therewith.
An applicator 10, for uniform heating of a tumor with well-defined temperatures throughout the tumor and without hot spots either within or outside the tumor volume, is shown in the form of a collinear array of three antennae fabricated from a coaxial transmission line comprising inner conductor ~0 and outer coaxial conductor 16 with an impedance matching element 26.
The three antennae are formed by providing circumferential gaps 5 in the outer conductor 16 to expose the dielectric core 18 of the transmission line structure. Preferably, the widths of the gaps 5 are about the same size as the distance between center conductor 20 and outer conductor 16. Core 18 may comprise a suitable solid dielectric insulator, such as PTF (polytetrafluoroethylene). The gaps 5 provide excitation feeds for more remo-te, i.e., more distal end, antenna sections and result in the equivalent o~
more than one antenna pattern being generated from the length of the center conductor. The electrical lengths of these antenna sections are harmonically relate~ to each other.
A dielectric outer envelope 14, containing fiber optic sensors 24, extends over the outer surface of the applicator 10. For antenna beam steering purposes, a resistor 22 is provided at the longi-tudinal axis of the applica-tor. In accordance with the -theore-tical and experimental teaching of ~1 29~2~1 Altschuler ("The Traveling-Wave Linear Antenna", E. E.
Altschuler, Cruft Laboratory, Harvard University, Cambridge, Massachusetts Scientific Report No. 7, May 5, 1960), an essentially traveling-wave distribution of current can be produced on a lineax antenna by inserting a resistance of suitable magnitude one-quarter wavelength from the end of the antenna. As shown in Fig. 21 from the above cited reference, the effect of such resistance is to significantly change the radiation pattern of the antenna and therefore, in the present application, its heating pattern for hyperthermia. The collinear array applicator 10 of the present invention is therefore provided with the appropriate value of resistance about one-quarter wavelength from the end of the distal section. By changing the applied frequency, or the location of the resistor, the distribution of heat around the appli-cator may therefore be changed or "steeredl' in many directions.
At the proximal end of the antenna array 10, a coaxial impedance matching transformer is provided in the form of a dielectric cylinder 26 concentric with and external to the outer conductor 16. The dielectric cylinder 26 is covered with a metallic cylinder 27 which is electrically shorted to outer conductor 16 at proximal end A. A dielectric outer envelope 14 extends over the full length of cylinder 27 and distal section B-E. The transformer minimizes the reflected power within the -feed transmission line and also prevents leakage of antenna currents along the outside of the array applicator 10. ~y judicious selec-tion of operating parameters, both func-tions (minimizing reflec-ted power and leakage prevention) occur at approximately the same operating frequency.
The operatlng parameters of -the coaxial impedance .~ 29~X2~

- 12 ~

matching transformer are based on the theoretical equations developed by R. W. P. King, "The Electro-magnetic Field of an Insulated Antenna in a Conducting or Dielectric Medium", R. W. P. King et al., IEEE
Transactions on Microwave Theory and Techniques, Vol.
MIT-31, No. 7, July 1983.
The transformer provides a load impedance at the proximal end of the collinear arrays for R.F.
power coupled from source 12 via lines 30 and 32 across the inner and outer conductors 20 and 16. This load impedance regulates the antenna current at the feed points or gaps 5 to more nearly match the 50 ohm impedance of the feed transmission line 30 and 32 with the input impedances of the collinear array 10. The distal section of applica-tor ~0 of Fig. 1 has an overall length B-E of 10 centimeters at a frequency of 915 megahertz. This length is a multiple of one-hal~
of the wavelength of the input frequency, (i.e. 5, ~L/2 sections) and is physically represented by a full-wav~ linear antenna (C-E) series connected to a three-halves wave linear antenna (s-c). This arrange-ment of antennae provides a uniform heatin~ pattern shown in the dotted lines labelled s4 of Fig. 1.
Note that heating pattern B4 is one-hal of a plane cut through the full cylindrical near field heating pattern extending from array 10, which is related to the superposi-tion o the three individual far field antenna patterns, Bl, B2 and ~3, shown in solid lines. If a shorter antenna array is desired, the frequency may be doubled and the length halved.
Alternatively, for the same frequency, section C-D can be removed to reduce the length to 8 cm or section B-C
can be removed to reduce -the length to 4 cm.

~.~9~L22~

I I . THEO~Y (:)F OPERATI~N
In operation, as the transmitted power from source 12 flows down the coaxial line, formed by inner and ou-ter conductors 20 and 16 separated by dielectric 18, voltage excites each antenna section and electro-magnetic energy is radiated from the applicator which is absorbed by the lossy tissue. The absorbed energy reduces the amplitude of the transmitted power. By increasing the number of elements at the distal end of the array (and decreasing the spacing between ele-ments), a higher sectional antenna gain is achieved, as compared to the more proximal section B-C, which will have a lower gain because it is a single (3 ~/2) element.
More specifically, the square of the elec-tric field for the half-wavelength(1), full wavelength linear( ) and 3/2 wavelength (3), antennas in free space, shown below, provides an indication of the radiated power distribution for the collinear array in lossy ma-terial (J. D. Jackson, "Classical Electro-dynamics", J. Wiley, 1975, Second Edition, pps.
402-403):

~1) For ~ Antenna: E a cos ( 2 (2) For ~ ~ntenna E2a ~ cos4 ( ~ cos~) s in2 0 (3) For 3~ ~ntenna: E ~ cos (3~/2 cos~) 2 sin20 wherein 0 is measured from the longitudinal axis of the antenna.
The ull wave antenna, distribution (C-E) can be considered as resulting from the coherent superposition of the ields of two collinearly adja-.. , ~

9~

cent half-wave antennae patterns B2 and B3 excited in phase; the power intensity at 9 = ~/2 is 4 times that of a half-wave length antenna and 4 times that of a three half wave length antenna. Thus, the extreme distal section (C-E) of two series connected half wave antennas radiates 6 dB more power per solid angle than the three half wave length section (B-C). Based on geometric reasoning, the total power radiated by the three half wave length antenna is about 60% of the total power delivered to the array (6 cm length compared with 4 cm length). Therefore, forty percent is left over for radiation by the series connected half wave antennae (C-E). The 6 dB gain of the 3 ~2 section compensates for this loss. The result is a nearly uniform heating pattern along the entire 10 cm length of the distal section B-E of array applicator 10 .
III. MANUFACTURING PROCESS
Preferably the collinear array applicator 10 is fabricated using standard AWG (American Wire Gauge) solid or stranded tin plated copper wire (AWG 26 for example) for inner conductor 20. The existing insula-tion of the copper wire may be increased in diameter by means of a thin wall plastic tube of PTF to form core 18. The outer surface of the -tube or core 18 is coated with a conductive ink or paint, such as silver, to provide the outer conductor 16 of a two conductor 50 ohm transmission line system. Etching of the tube may be required to insure adhesion of the silver paint. The gap location 5 are not covered with the conductive ink because they are masked off during the pain-t application process. ~ uniform PTF coating 14 is then applied over the entire distal section B-E.
The proximal section A-B is formed in a similar manner, except that prior to applica-tion of coating :,. :. ;.
. . . .

~.~9~2~

14, a dielectric sleeve or coating 26 of appropriate dielectric constant and loss tangent, is placed around the conductive ink 16 located at the proximal section.
The dielectric material may preferably be polyacryl-amide (See "The Polyacrylamide as a Phantom Material for Electromagnetic Hyperthermia Studies", M. G. Bini, et al., IE~E Transactions of Biomedical Engineering, Vol. BMD-31, No. 3, March 1984) ~rom which the appro-pria-te dielectric constant may be calculated for the proper transformer operation using the criterion that the complex propagation constant, kL of the trans-former dielectric is the same as the kL of the distal section. A uniform silver ink coating is then applied over the polyacrylamide material to form a second conductive layer 27. This second conductive layer 27 is present only over the length of the proximal section. It is applied in a manner to create a short circuit to the silver ink outer conductor 16 at proximal end A but leaves an open circuit between it and the outer conductor 16 at point B. The outer PTF
coating 14 is then applied over the proximal section A-B or continued from the distal section.
This coating 14 permits the probe to opera~e within wide limits of variations o~ temperature, tissue dielectric constant and electrical conductiv-ity. A 10 mil thick coating of PTF permits the array to maintain a constant heating pattern (ignoring the effects of heat loss or gain by conduc-tion or convec-tion) for a change in the dielectric constant of tissue from 30 to 80 which may occur during heat application.
Within the dielectric coating 14, fiberoptic thermometry sensors 24 may be embedded. A sensor, such as produced by the Luxtron Corporation ("16-Channel Fiberop-tic Thermometry ~ys-tem with 9~2~.
- 16 ~

Multisensor Arrays for Thermal Mapping", Wickersheim et al.) may be appropriately modified for application to the array 10. Several linear phosphor sensors 24 about 0.25 mm in diameter (10 mils) may be embedded in the outer dielectric 14. The phosphor sensors 24 utilize the temperature dependence of the fluorescent decay time of the phosphor to determine temperature.
This technique yields a simple, cost-effective multichannel system, which can support a number of small-diameter mul~i-sensor arrays.
IV. LOAD IMPEDANCE/TRANSFORMER LENGTH
AND DIELECTRIC CONSTANT
To determine the required value of the load impedance, the proper length of the transformer and its dielectric constant are theoretically determined from the complex propagation constant kL associated with the current on the- antenna, in the manner described below in connection with Fig. 6.
Consider a simple insulated dipole, Fig. 6, consisting of a central conductor (Region 1) with the half-length "h" and radius "a" surrounded by a cylin-der of dielectric which may consist of one (Region 2) or two layers ~Region 3)*, with the outer radii "b"
and "c", respectively. Outside this insulating sheath is the infinite ambient medium (Re~ion 4) which is a lossy or di.electric. The central conductor is suffi-c.iently highly conducting to be well approximated by a perfect conductor. The wavenumbers of the dielec-tric layers are:
3~ k ~ 1oE2)~ and k3 (~la~3) where 62 and ~3 are the relative dielectric cons-tants of regions 2 and 3, respectively, and are taken to be real since th~ dielec tXiGS actually used axe highly *Fo:r simplicity, only RegiQn 2 is shown in Fig. 6.

- ~ ~9~21 nonconducting and ~ = rela-tive permeability of free space and ~ = the radian frequency. The wavenumber of the lossy dielectric ambient medium is:

4 ~ ia4 ~t~0~4) ~ ~4 = ~4 + i~4/~;

wherein ~ = the phase constant in radians/meter; a =
the attenuation constant in Nepers/meter and ~ = the electrical conductivity in Siemens/meter.
The general theory of the insulated antenna applies when the wavenumber of the ambient medium ls large compared to that of the insulating sheath and the cross-section of the antenna is electrically small. That is ¦k4/k2¦2~> 1; j k~/k3~ 2~ 1; ~k2b)2c~ 1; (X3c)2CC 1. tl) Subject to these conditions and with the -time depen-dence e iwt, the current in the central conductor is I~z) = I(O) sin kL(h-¦z¦) L
I(O) = VOYo= VO~Zo (2a) where admittance is:

~i/2Zc)tan kLh. (2b) For a dielectric with two layers:

- `~
.29~

kL = k2 ~ ln(c/a1 ~ k [ :~ , %
ln(b/a)+n231n(clb n(c/a)~n24F

æc= (~OkL/2 ~ k2) [In(b/a) ~ n231n(c/~)~n where n23= k2 / k32~ n224= k22/ k42~
and F = Ho(l)(k4c)/k4cHl( )(k4c);

wherein Ho(l)(k4c) and Hl(1)(k4c) are zero and first order Hankel functions of the first kind.
These formulas can be simplified by the introduction of an effective wavenumber k2e and an effective permittivity ~2e for an equivalent di-electric composed of a single layer with the outerradius c, viz, k2e = k2 ~ ln(c/a) ln(b/a)+n231n(c/b) I ln(c~al ~ (5) E2e = 2 _ . ln(b~a)+n23ln(c/b) With (5), the above formulas become kL ~ k2~ ~ln(c/a) ~ F~ Lln(cla) ~ n24F] ~ (6) c ( ) L :1 1~here n2e4 = k2 jl 4 ~ 9~'~21 Equation (3) is the complex wave number for current on the surface of cylindrical structures embedded in electrically lossy media, such as tumors.
The input impedance of the bifurcated coaxial line matching transformer is given on page 59 of reference "Embedded Insulated Antennas for Communication and Heating" by R. W. P. King et al., Electromagnetics, Vol. 1, Number 1, January-March 1981. The phase constant of the dielectric inside the transforrner must match with ~L and ~L d - 1r/2 gives the required length of the transformer. ~ L is the real part of kL of Equation 6. The transformer length is the length of the proximal section. Proper imped-ance matching of the collinear antenna array is therefore dependent on the value of kL. For the proper choice of dielec-tric inside the transformer and length of transformer, a high value of impedance will exist at -the input (Section B). This will e~fectively isolate the array from the feed line and, with the proper location of the input of the transformer from gap 5, give a collinear array which is properly matched to the 50 ohm feed l:ine.
Fig. 7 shows the ratio of reflected power (Pr) to transmit-ted power (Pt) in decibels in the coaxial line for a 10 cm long, 3 gap, collinear array of 2 millimeter diameter made in accordan~e with the invention. The frequency fo is the frequency which yields the highest value of t~rminating impedance for the array wherein the elements of -the array are harmonically related. For the 10 cm device in the example, -the collinear array that achieves the uniform heating pattern consists of -the elements depicted in the dis-tal section B-E of ~ig. 1, wherein the fre-quency is 915 megaher-tz. ~he transformer length ls ~l %9~

about 1 centimeter with a PTF dielectric inside the transformer, having a dielectric constant of 40.
As shown in the optional embodiment of Fig.
8, a lossy sleeve 80 comprised of ferrite cores or beads formed in the shape of a cylinder with an inner bore may be disposed about the applicator 10 at the distal end thereof. Preferably, the inner diameter of the bore in sleeve 80 forms a press fit with the outer diameter of the applicator 10 and is held in place along the longi-tudinal length of the applicator by a suitable adhesive or other means. The sleeve may be used to modify the heat distribution near and around the applicator 10. We have found that by placing ferrite sleeves 80 around the antenna 10, a signifi-cant increase in heat close to the antenna and adja-cent to the sleeve is produced for the same power level into the collinear antenna array applicator 10 as compared to an applicator without the sleeve. The electromagnetic fields generated by the antenna applicator 10 produce currents in the ferrite material of sleeve 80 and the resultant heat is transferred by conduction to the surrounding tumor. Significantly less input power to create hyperthermia range tempera-tures near the applicator (40-44.5C) is required (1-2 watts as compared to 5 watts). The ferrite sleeve 80 therefore creates a source of heat for the tumor that is not dependent on the electrical proper-ties of the tumor. ~se of this sleeve provides a source of highly localized heat without requirin~ an electromagne-tic energy absorption capability of tissue~ The sleeve may also be used in conjunction with electromagnetic power dissipation in tissue to provide complex heat distribution patterns -that conform to the tumor geome-try. The Curie temperature o~ ferrite material d~t~rmin~ the upp~r t~mperatures beyond which the ~ 29~2~L

material becomes non-magnetic and hence non-lossy. sy selecting an appropriate Curie temperature for the ferrite sleeve, an upper limit on the temperature produced by the sleeve can be established.
An alternate embodiment for the extreme distal end of the applicator is shown in Figs. 9 and 10 wherein like items in Fig. 1 retain their numeral reference in Figs. 9 and 10. As may be seen more clearly in Fig. 10, in this embodiment, the outer conduccor 16 of the antenna array is terminated by a radially inwardly extending ring shown as section 16a and 16b. A beam steering resistor 22 may be disposed along the longitudinal axis of the antenna in the path of inner conductor 20, as shown. Alternatively, an equivalent beam steering resistor 21 may be formed as a circular ring embedded in outer insulator 1~.
The inner walls of ring sections 16a and 16b are insulated from resistor 22 or (in the event resistor 22 is not present) from inner conductor 20 by dielectric disk 62. The inner conductor is extended radially from the longitudinal axis by disk-like conductor member 18c which is integral with coa~ial conductor 18a encased in dielectric 14.
V. FLEXIsLE COAXIAL CONNECTOR
The collinear applicator array 10 may be connected to a commercially available coaxial cable, as shown in Fig. 11, by means of a flexible coaxial connector adaptor 60. This type of connector will eliminate the need of using expensive commercially available SMA connectors. In addition, the size of SMA connec-tors may be excessive in diameter for certain application, thereby creating the need of a special cOnnec-tQr whose diameter will conform to the diameter of -the collinear applicatox.

9~22~L

As shown in Fig. 11, the adaptor comprises a laminated metal conductive ring 40 or ferrule having an inner diameter conforming to the outer diameter of the outer conductor 16 of applicator 10 affixed around the outer conductor. The outer conductor 16, di-electric core 18 and inner conductor 20 of applicator 10 is allowed to extend longitudinally outward from the proximal end of the applicator, with the core 18 extending beyond the outer conductor 16 and the inner conductor 20 extending beyond the core 18. An insula-tive sleeve 64 is affixed around the extension of core 18. An adaptor pin 42 is secured around the extension of inner conductor 20 to provide an enlarged transi-tion from the outer diameter of inner conductor 20 to the outer diameter of standard coaxial cable inner conductors. For example, the O.D. of inner conductor 20 is preferably about 0.010 inches, the O.D. of pin 42 is 0.018 inches and -the O.D. of sleeve 64 is 0.050 inches.
Pin 42 is adapted to be inserted into tapered bore 51 formed within the inner conductor 50 of a standard SMA ca~le inner conductor having an O.D.
of 0.045 inches.
Dielectric insulator sleeve 64 is adapted to extend into coaxial channel 53 around inner conductor 50. The metal connector shell of the standard coaxial line slides over sleeve 64 and abuts ring 40. Conduc-tive plastic elastomeric extrusion 44 is bonded a-t one end by conductive epoxy to shell 46 and is held to ring 40 by friction.
CLINICAL UTILIZATION
The applicator of the invention can be made as described above with an outer diameter of about 0.050 inches. With this small diameter, it can be placed almost anywhere within a patient, with or ~ 29~2~L

without fiber optics, using current techniques and equipment, such as endoscopes, CT scanners, ultrasound imaging systems, and fluoroscopy units.
For example, in the hyperthermia treatment of urinary tract problems, access to this anatomic system for placement of the applicator could be obtained by any one of the following commonly prac-ticed procedures:
l. Angiographic techniques for access to arterial or venous components (using fluoroscopy);
2. Endoscopic techniques for access to the urethera, prostate, bladder, ureters, and renal pelvis via retrograde cannulation ~using fiber optic endo-scopy, i.e., cyrtoscopes);
3. Percutaneous techniques for direct access by way of a so-called antegrade nonsurgical approach through the flan]c or back to the renal pel~is, ureter and bladder (using CT, ultrasound, fluoroscopic or even endo-urologic equipment).
The currently available state-of-the-art imaging equipment (particu:larly ultrasound and CT) allows visualization and direet puncture of masses in the n~ck, abdomen, pelvis, and extremities. Under ultrasonic or CT guidance, long, small diameter needles (18-23 gauge) are easily introduced through the skin and into superficial or deep lesions. In a similar manner, the applicator probe lO could be easily introdueed into these lesions -through any number of widely available biopsy needles.
The same techniques and equipment can be used for -the relatively non-invasive (i.e., non-surgical) access and treatment of other anatomical sites. For example, the gastrointes-tinal tract, speci~ically, -the biliary system, is routinely ~ppro~ched by endoscopiG means (ERC~-endoscopic ~ 29~

retrograde cannulation of the pancreas), as well as percutaneously by direct intercostal puncture and catherization of the liver and bile ducts for diag-nosis and treatment of malignant and benign obstruc-tions (due to hepatic, biliary, pancreatic, and lymph node diseases). Other lesions of the GI tract, such as in the stomach, are now approached through gastro~
scopy. The relatively large size of the endoscope easily allows passage of a probe of the present size.
The small OD size of this probe, moreover, lends itself to intraoperative use, as is now being performed with small ultrasound probes in certain neurosurgical procedures.
Brain tumors are a potential area for application of the present probe in which hyperthermia may be able to play an immediate and important role.
Brain tumors are frequent in the population and histiological types with extremely poor prognosis can be identified. Failure to control local disease and not distant metastasis is by far the major cause of mortality, and clinical trials may be initiated with patients who have failed other modalities (surgery, radiation therapy, chemotherapy). In addition, relatively non-invasive techniques (such as through a burr hole) to guide placement and to monitor results are applicable. The lossy sleeve embodiment of Fig. 8 is capable of use for dissolving arterial plaque specifically for use in angiosurgery.
This completes the description of the preferred embodiment of the invention.
Equivalents While -the particular embodiment above described has been concerned mainly with the appli-cation oE hyperthermia Por -treatment o~ cancerous tumors in slku humans or animals, it also may ind - \
~ ;~.9~L~2~

application in treatment of materials, such as oil shales, tar sands, coal tar and the like. Hence, the invention is not to be construed as limited to the particular embodiment shown and described herein.
There are many equivalents -to these specific embodi-ments and such equivalents are intended to be covered by the following claims.

Claims (24)

1. A microwave collinear antenna array applicator for hyperthermia treatment comprising a plurality of harmonically related resonant coaxial antenna elements formed of an inner conductor and an outer coaxial conductor, said elements being electrically connected in series to provide a uniform heating pattern of microwave radiation along the length of the applicator.
2. The antenna array applicator of claim 1, wherein, at the proximal end of the array, an impedance matching dielectric structure is provided for enabling maximum power transfer to the antenna elements and minimizing stray leakage currents along the outside of the applicator.
3. The applicator of claim 1, in which the appli-cator is divided into a distal and a proximal end and wherein the proximal end includes an imped-ance matching means comprising a dielectric tube encircling the outer coaxial conductor and a conductive sheath around the dielectric tube in contact with the proximal end of the outer coaxial conductor.
4. The applicator of Claim 1 in which a resistor is provided at the longitudinal axis of the inner conductor about 1/4 .lambda. from the distal end thereof to provide directivity to the heating pattern.
5. The applicator of Claim 1 wherein a resistor is provided around the outer conductor about 1/4 .lambda. from the distal end to provide directivity to the heating pattern.
6. The applicator of Claim 1 in which the antenna elements are at least three in number, two of which are half wavelength antennae forming a one wavelength antenna and the third antenna element is three half wavelengths in length.
7. A hyperthermia device comprising a collinear antenna array formed of a continuous inner conductor surrounded by dielectric material and an interrupted coaxial outer conductor wherein the interruptions are in the form of circum-ferential gaps periodically spaced along the coaxial conductor at interrelated harmonic wavelengths to form a substantially uniform electromagnetic beam pattern about the periphery of the antenna.
8. The device of Claim 7 wherein the device has a proximal and distal section and the array is formed on the distal section and an impedance matching transformer is formed at the proximal section comprising a dielectric tube surrounding the coaxial conductor with a conductive sheath surrounding the tube and in contact with the proximal end of the coaxial conductor.
9. The device of claim 7, further including beam steering means in the form of a resistor of suitable impedance in the inner conductor about one-quarter wavelength from the distal end of the inner conductor.
10. The device of claim 7, wherein three gaps are formed, the first one of which is located about 1/4.lambda. from the distal end of the inner conductor, the second one is located 1/2.lambda. from the first and the third one is located 3/4.lambda. from the second.
11. The method of forming a small diameter electro-magnetic radiation applicator having a distal section and a proximal section and comprised of an inner conductor and an outer coaxial conductor comprising the steps of:
a) forming a dielectric inner core layer around the inner conductor;
b) masking radial strips about the periphery of the dielectric layer at harmonically related distances along the length of said inner conductor at the distal section thereof;
c) coating the unmasked portions of the di-electric layer with a thin metallic conduc-tive layer to form said outer coaxial conductor;
d) forming an impedance matching transformer at the proximal section; and e) forming a protective dielectric sheath layer over the distal and proximal sections.
12. The method of claim 11, wherein the transformer is formed by:
f) coating the proximal section after step (c) with an impedance matching layer of di-electric material, matched to the dielectric constant of the media in which the appli-cator will be used; and g) forming a metallic tubular layer over said impedance matching layer in contact at one end with said outer coaxial conductor.
13. The method of claim 12, wherein said impedance matching layer is formed of polyacrylamide.
14. The method of claim 11, wherein the masking strips are three in number and are located respectively one-quarter wavelength, three-quarter wavelength, and five-quarter wavelength from the distal end of the inner conductor.
15. The method of claim 11, wherein the frequency of the radiation is about 915 megahertz, the length of the transformer is about 1 centimeter and the length of the distal section is about 10 centi-meters.
16. The method of claim 11, wherein fiberoptic thermometry sensors are embedded in the sheath layer.
17. The method of claim 12, wherein the metallic layer is formed of silver.
18. In a microwave hyperthermia applicator having an inner conductor and an outer coaxial conductor;
the improvement comprising lossy material dis-posed adjacent or around said outer conductor in proximity thereto for absorbing microwave energy to form a localized source of heat.
19. The applicator of claim 18, wherein the lossy material is formed as a ferrite sleeve.
20. The applicator of claim 1 having a lossy sleeve extending longitudinally around a portion of the outer conductor.
21. The applicator of claim 18, wherein the appli-cator is used for in vivo application to human tissue and the Curie temperature of the lossy material is selected to be below the maximum desired temperature to which such tissue is to be exposed.
22. An adaptor for coupling the inner and outer conductors of small diameter coaxial line micro-wave hyperthermia applicators to larger diameter standard coaxial line cables wherein said inner and outer conductors are separated by a di-electric core, comprising:
a) a transition pin adapted to fit over an extension of the inner conductor for inser-tion into the inner conductor of the stan-dard cable;
b) an insulative sleeve fitted over an exten-sion of said core with a grooved space formed between said sleeve and said pin;
c) a metallic conductive ring afixed around the outer conductor over an extension thereof which abuts said sleeve; and d) an elastomeric conductive sleeve retaining member adapted to fit around the outer portion of said standard cable and said ring for retaining said applicator and cable in interlocking relationship.
23. A microwave collinear antenna array applicator having a proximal end which is adapted to be coupled to a source of microwave energy and an extended distal region for applying said energy for hyperthermia treatment comprising a plurality of harmonically related resonant coaxial antenna elements forming said distal region, said elements formed of an inner conductor having distal end in the distal region and an outer coaxial conductor with a distal end in the distal region, said elements being electrically connected in series to provide a uniform heating pattern of microwave radia-tion along the length of the distal region of the applicator and wherein the proximal end includes an impedance matching means comprising a dielectric tube encircling the outer coaxial conductor and a conductive sheath around the dielectric tube in contact with the proximal end of the outer coaxial conductor.
24. A hyperthermia device having a proximal section adapted to be coupled to a source of electro-magnetic energy and a distal section for radiating said energy comprising a collinear antenna array formed of a continuous inner conductor and a distal end in the distal section surrounded by dielectric material and an interrupted coaxial outer conductor longitudinally extending at one end from the proximal section to another end at the distal section and wherein the interruptions are in the form of circumferential gaps periodically spaced along the coaxial conductor at interrelated harmonic wavelengths to radiate a substantially uniform beam pattern of electro-magnetic energy about the periphery of the antenna and an impedance matching transformer formed at the proximal section comprising a dielectric tube surrounding the coaxial conductor with a conductive sheath surrounding the tube and in contact with the end of the coaxial conductor nearest the proximal section.
CA000553681A 1987-12-07 1987-12-07 Method and apparatus for hyperthermia treatment Expired - Fee Related CA1291221C (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117875550A (en) * 2023-12-28 2024-04-12 中国水产科学研究院长江水产研究所 A method for assessing fish resources in shallow water fisheries

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117875550A (en) * 2023-12-28 2024-04-12 中国水产科学研究院长江水产研究所 A method for assessing fish resources in shallow water fisheries

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