Method and Apparatus for Hyperthermia Treatment

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 super position 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. 4 is a cross-sectional view of the applicatior of FIG. 1 along the lines 4--4.

FIG. 5 is a cross sectional view of the appliator of FIG. 1 taken along lines 5--5.

FIG. 6 is an illustration of an insulated dipole in an ambient medium used to depict the algebraic parameters needed for calculating the optimum 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 embodiment 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 FIG. 9.

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.

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 20 and outer coaxial conductor 16 with an impedance matching element at the array proximal end.

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 (polytetrafluorethylene). The gaps 5 provide excitation feeds for more remote, i.e., more distal end, antenna sections and result in the equivalent of more than one antenna pattern being generated from the length of the center conductor. The electrical lengths of these antenna sections are harmonically related 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 longitudinal axis of the applicator. In accordance with the theoretical and experimental teaching of 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 linear antenna by inserting a resistance of suitable magnitude one-quarter wavelenth 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 applicator may therefore be changed or "steered" 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 (cylindrical, layer 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 minimized the reflected power within the feed transmission line and also prevents leakage of antenna curents along the outside of the array applicator 10. By judicious selection of operating parameters, both functions (minimizing reflected power and leakage prevention) occur at approximately the same operating frequency. The operating parameters of the coaxial impedance matching transformer are based on the theoretical equations developed by R. W. P. King, "The Electromagnetic 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 applicator 10 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-half of the wavelength of the input frequency, (i.e. 5, .lambda..sub.L /2 sections) and is physically represented by a full-wave linear antenna (C-E) series connected to a three halves wave linear antenna (B-C). This arrangement of antennae provides a uniform heating pattern shown in the dotted lines labelled B4 of FIG. 1.

Note that heating pattern B4 is one-half of a plane cut through the full cylindrical near field heating pattern extending from array 10, which is related to the superposition of the three individual far field antenna patterns, B1, B2 and B3, 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.

In operation, as the transmitted power from source 12 flows down the coaxial line, formed by inner and outer conductors 20 and 16 separated by dielectric 18, voltage excites each antenna section and electromagnetic 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 elements), 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.lambda./.sub.2) element.

More specifically, the square of the electric field for the half-wavelength (1), full wavelength linear (2) 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 material (J. D. Jackson, "Classical Electrodynamics", J. Wiley, 1975, Second Edition, pps 402-403): ##EQU1## wherein .theta. is measured from the longitudinal axis of the antenna.

The full wave antenna, distribution (C-E) can be considered as resulting from the coherent superposition of the fields of two collinearly adjacent half-wave antennae patterns B.sub.2 and B.sub.3 excited in phase; the power intensity at .theta.=.pi./2 is 4 times that of 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-F). The 6 dB gain of the 3.lambda./.sub.2 section compensates for this loss. The result is a nearly uniform heating pattern along the entire 10 cm length of distal section B-E of array applicator 10.

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 insulation 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 reguired 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 paint application process. A 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 application of coating 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 polyacrylamide (See "The Polyacrylamide as a Phantom Material for Electromagnetic Hyperthermia Studies", M. G. Bini, et al., IEEE Transactions of Biomedical Engineering, Vol. BMD-31, No. 3, March 1984) from which the appropriate dielectric constant may be calculated for the proper transformer operation using the criterion that the complex propagation constant, k.sub.L of the transformer dielectric is the same as the k.sub.L 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 operate within wide limits of variations of temperature, tissue dielectric constant and electrical conductivity. 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 conduction or convection) 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 Fiberoptic Thermometry System with 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 multi-sensor arrays.

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 k.sub.L 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 cylinder 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 (Region 4) which is a lossy or dielectric. The central conductor is sufficiently highly conducting to be well approximated by a perfect conductor. The wavenumbers of the dielectric layers are:

where .epsilon..sub.2 and .epsilon..sub.3 are the relative dielectric constants of regions 2 and 3, respectively, and are taken to be real since the dielectrics actually used are highly nonconducting and .mu.=relative permeability of free space and .omega.=the radian frequency. The wave number of the lossy dielectric ambient medium is:

wherein

.beta.=the phase constant in radians/meter;

.alpha.=the attenuation constant in Nepers/meter and

.sigma.=the electrical conductivity in Siemens/meter.

The general theory of the insulated antenna applies when the wavenumber of the ambient medium is large compared to that of the insulating sheath and the cross-section of the antenna is electrically small. That is

Subject to these conditions and with the time dependence e.sup..fwdarw.iwt, the current in the central conductor is ##EQU2## where admittance is:

For a dielectric with two layers: ##EQU3## where n.sub.23.sup.2 =k.sub.2.sup.2 /k.sub.3.sup.2, n.sub.24.sup.2 =k.sub.2.sup.2 /k.sub.4.sup.2, and F=H.sub.o.sup.(1) (k.sub.4 c)/k.sub.4 cH.sub.1.sup. (1) (k.sub.4 c); wherein H.sub.o.sup.(1) (k.sub.4 c) and H.sub.1.sup.(1) (k.sub.4 c) are zero and first order Hankel functions of the first kind.

These formulas can be simplified by the introduction of an effective wavenumber K.sub.2e and an effective permittivity .epsilon..sub.2e for an equivalent dielectric composed of a single layer with the outer radius c, viz, ##EQU4## With (5), the above formulas become

where n.sub.2e4.sup.2 =k.sub.2e.sup.2 /k.sub.4.sup.2.

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 "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 transformer must match with .beta..sub.L and .beta..sub.L d.perspectiveto..pi./2 gives the required length of the transformer. .beta..sub.L is the real part of k.sub.L of Equation 6. The transformer length is the length of the proximal section. Proper impedance matching of the collinear antenna array is therefore dependent on the value of k.sub.L. For the proper choice of dielectric inside the transformer and length of transformer, a high value of impedance will exist at the input (Section B). This will effectively 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 line.

FIG. 7 shows the ratio of reflected power (P.sub.r) to transmitted power (P.sub.t) in decibels in the coaxial line for a 10 cm long, 3 gap, collinear array of 2 millimeter diameter made in accordance with the invention. The frequence fo is the frequency which yields the highest value of terminating 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 distal section B-E of FIG. 1, wherein the frequency is 915 megahertz. The transformer length is 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 inplace along the longitudinal 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 significant increase in heat close to the antenna and adjacent 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 temperatures near the applicator (40.degree.-44.5.degree. C.) 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 properties of the tumor. Use of this sleeve provides a source of highly localized heat without requiring an electromagnetic 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 geometry. The Curie temperature of ferrite material determines the upper temperatures beyond which the material becomes non-magnetic and hence non-lossy./By 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 conductor 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 eguivalent beam steering resistor 21 may be formed as a circular ring embedded in outer insulator 14.

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 coaxial conductor 18a encased in dielectric 14.

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 connectors may be excessive in diameter for certain applicaton, thereby creating the need of a special connector whose diameter will conform to the diameter of the collinear applicator.

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, dielectric 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 insulative 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 transition 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 0.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 cable 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. Conductive plastic elastomeric extrusion 44 is bonded at one end by conductive epoxy to shell 46 and is held to ring 40 by friction.

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 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 practiced procedures:

1. 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 endoscopy, i.e., cyrtoscopes);

3. Percutaneous techniques for direct access by way of so-called antegrade nonsurgical approach through the flank or back to the renal pelvis; ureter and bladder (using CT, ultrasound, fluoroscopic or even endo-urologic equipment).

The currently available state-of-the-art imaging equipment (particularly ultrasound and CT) allows visualization and direct puncture of masses in the neck, 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 10 could be easily introduced 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 gastrointestinal tract, specifically, the biliary system, is routinely approached by endoscopic means (ERCP-endoscopic retrograde cannulation of the pancreas), as well as percutaneously by direct intercostal puncture and catherization of the liver and bile ducts for diagnosis and treatment of malignant and benign obstructions (due to hepatic, biliary, pancreatic, and lymph node diseases). Other lesions of the GI tract, such as in the stomach are now approached through gastroscopy. 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 beinq 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 capables of use for dissolving arterial plaque specifically for use in angiosurgery.

This completes the description of the preferred 10 embodiment of the invention.

While the particular embodiment above described has been concerned mainly with the application of hyperthermia for treatment of cancerous tumors in situ humans or animals, it also may find 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 embodiments and such equivalents are intended to be covered by the following claims.