CA1077573A - Apparatus for heating tissue - Google Patents

Abstract

ABSTRACT

Apparatus is described for heating tissue and which is particularly useful for treating tumors in humans and ani-mals. An electric field is produced across two electrodes or one electrode and ground, and is passed through both the tumor and the surrounding tissue. The polarity of the electric field is varied at radio frequency. The power of the electric field is efficiently coupled into the tissue being heated. Direct current inverse feedback means enable close control of tissue temperatures.

Description

~7~73 .", . . .
This invention relates generally to the treatment of tissue. More parti-cularly, the invention relates to appara~us for heating tumors in humans and ~nimals to a higher temperature than the surrounding tissue.
One of the ~nown characteristics of certain types .0 of tumors is that the blood circula~ion rate therein is sig-nificantly less than that in normal ~r healthy tissue. ~See ~ncyclopedia Britannica pa. 769 - "Cancer"). For example, certain types of tumors have a blood circulation rat:e which is aF~ low as one half tha~ of normal surroun~ing healthy L5 ti~su~. This fact is considered to be the ca~tse o~ a con-tributory factor in the selective heat sensitivity of many types o~ malignant tumors.
The treatment of tumors by selective heating has been reported in the literature. ~See Surgery, Gynecology and Obstetrics, Volume 14~, No. 3, March, 1975, Results of Hy~erthermic Per~usion for Melanoma of the Extremities, Stehlin, Jr., Giovanella, I~olyi, ~luenz, and ~nderson.).
Techniques for selective heating h~v~ included hyper~hermic perfusion, diathermy t and the induction of fever.
For various reasons, however, success in the treat-ment of tumors and in particular malignant tumors has becn limit~d. For example, in the case of hyperthermic perfusion,

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~ 1~77573 some undesirable damage to healthy tissue has often resulted and the technique is only suitable for the treatment of tumors in limbs. Although a form of diathermy has been used success-fully to treat tumors near the skin surface, specifically the use of a probe or stylus inside the rectum to produce a small area of electrically induced heating in the treatment of rectal tumors, tumors any substantial distance below the sur-face of the skin have typically been untreatable. Finally, although fever has caused remission in some cases, prolonged induction of fever may have considerable undesirable side effects~
Experiments conducted at the Royal Victoria Infirmary, Newcastle-Upon-Tyne/ England, durin~ the late 1930's have been reported in th~ American Journal o~ C~ncer, Vol. 28, November, lS 1936, pp. 603-620; Vol. 30, ~une, 1937, pp. 3~1-35~; and Vol. 38, 1940, pp. 533-550. These experiments succeeded in ~estroying tumors in rats and mice through the u6e of radio frequency electric fields. Treatment, however was limited for the most part to relatively small volumes of tissue, and success was generally limited to surface tumors. In many cases the skin was damagcd as well as the tumor. Moreover, very high field d~nsities were employed in the aforementioned experiments resulting in little if any selective heating between the tumor and the surrounding ti~sue. Finally, the frequencies used in the experiments and the type of appara~us employed resulted in poor coupling of the,power of the apparatus into the tissue being heated and poor control over power levels.

~J:i 77~73 The basic elements described above are disclosed by the prior art. Thus ~appler U. S. Patent No. 1,480,353, January 8, 1924, shows the use of a pair of padded capacitive plates attached to handles and used to apply high frequency currents to human tissue for medical or th~erapeutic purposes.
Carpenter et al, "Production of Fever in Man by Short Wave Radio Waves", Science, ~ay 2, 1930, LXXI, 450-2, discuss the production of artificial fever in man by short radio waves to whole body temperature of 104F to lOSF for therapeutic pur-poses. A frequency of 104 MHz was used with capacitive plates 28 x 18 inches covered by rubber insulation. The vacuum tube oscillator had an output of 500 watts at 3,000 volts. Comment-ing on the Carp~nter et al work in 1933, Schereschewsky, J. W., Radiology 20:2~6, 1933, noted the dif~erence between electro-static heating and convenkional diathermy where there was an actual flow of current between the electrodes. Schereschewsky suggested the use of high frequency condenser fields to raise the temperature of deep-seated organs to a considerable degree without, at the same time, overheating the subcutaneous tissue.
Although the production of a high frequency electric field is relatively simple from an enyineering point of view, the above reports suggest considerable lack o sophistication in the apparatus used. The mere connection of a pair of capacitive plates to the combination of an oscillator and amplifier does not provide the degree of control over heating rates and temperatures needed for a truly effective tumor treatment.

, ` ` ~077573 It is an object of the present invention ~o provide an improved apparatus for the treatment of tumors.
Another object of the invention is to provide an improved apparatus for heating tumors witllout adverse effects to surrounding tissue.
A further object of the invention is to provide apparatus for heating tumors to a higher temperature than the surrounding tissue.
- Other objects of the invention will become apparent to those skilled in the art from the following description, taken in connection with the accompanying drawings wherein:
FIGU~ 1 is a schematic block diagram of apparatus constructed in accordance with the invention;
FIGURE 2 is a circu~t dia~ram illustxatincJ one form of a portion of th~ apparatus of the invention; and FIGU~E 3 is a ~ross sec*ional schematic view illustratiny another manner in which the invention may be employed.
Very generally, the apparatus of the invention comprises radio frequency oscillator means and amplifier means coupled to the output of the radio frcquency oscillator means for producing an ampli~ied radio frequeney output signal.
Electxode means are coupled to the amplifier means and include at least one capacitive electrode having a configuration adapted to pass an electric field through both the tumor and the surrounding tissue. Means are provided for controlling the power of the amplifier means to avoid heating the ~ ~977573 surrounding tissue beyond a preselected temperature level while allowing the tumor to heat beyond the preselected tem- !
perature level. The controlling means incLude direct current inverse feedback means connected from the amplifier means to the oscillator means for stabilizing the OlltpUt current.
The higher sensitivity of maliqnant tumors to heat has been taken advantage of in a number of techniques as previously mentioned. One such technique is the use of ~o-called diathermy in which m~gnetic fields produced by suitable coils of the type used for physical therapy have been used to attempt to heat malignant tumors. The results of such attempts, however, have produced very limited, if ~ny, success. ~ttempts to heat tumors ~ypically resulted in dam~ye to the skin, wi~hout succ~ssful results in destroyinc3 the tumor.
The present invention results from a recognition that diathermy techniques for the treatment of malignan~ tumors did not succeed because of skin effects inheren~ with live tissue in electromagnetic fields, and also the very limited volume of the effective electromagnetic field (that is an ef~ective field only in close proximity to the coil itself).
More particularly, any tissue which has a resistivity of approximately 50 ohrns per cubic centimeter, when placed in an electroma~netic field, will have eddy curren~s generated close to its surface. These eddy currents operate in the same manner as the eddy currents in a conductive shield sur-rounding a vacuum tube or the like, preventing penetration 11~77573 of the elec~romagnetic field below the region in which the eddy currents are generated. Typically in the case o~ the human body such eddy currents are generated in a more highly conductive subcutaneous layer lying slight:Ly beneath th~ sur-face of the skin. Eddy currents are usually not generated inthe skin surface because the surface cells of the skin are dead and of substantially less conductivity.
In accordance with the invention, the field utilized for treating the tumors is an electric field, some-1~ times referred to by those skilled in the art as an E-field or an electrostatic field. Unlike an electromagnetic field, the lines of force of an electric field are typically un closed on each other and, when the field is formed between substantiall~ parallel plates as in a capacitor, the lines lS o force typically run approximately parallel with each other between the plates. By passing such a field through a malignant tumor and the surrounding tissue approximately uniformly, and by varying such field at a radio frequency, heating of the tumor and the surrounding tissue will occur.
Because the circulation rate and hence the cooliny effect in the tumor is substantially lo~er than that in the healthy surrounding tissue, the tumor heats to a higher temperature.
Some observations have indicated that the higher temperature of the tumor may also result in a further decrease in circula-tion within the tumor, and it is estimated that temperatureincrease within the tumor can be as much as 2 to 3 times as great as in the surrounding tissue. By selecting a ~77573 predetermined uT~per temperature limit for the surrounding tissue ~Id/or the bo~y as a whole~ for ex.~nple 109F as measured orally, the power of the elec~rif field may be regulated such th~t the surrounding ti.ssue does not exceed the predetermined temperature but the temperature of ~he tumor heing treatfcl does exceed the predetermined tempera-ture. Because the temperature of the tumor typical.ly exceeds ~he predeter~in~d temperature ~y a substctntial magnitude, by maintaining this temperature differenti.al for a sufficie.nt period o~ time, the tumor may be killed.
nlr~her, the treatment of tumors with a comb:irl~-tion of hf~at: ~rld chf.~!notherapy or heat and rad.iatioll hcls been ~xt~llr,iv~ly r~E~ori:e~d i.n the~ e~al:ure~ ~Xee Cancer E~e~earc~h, 30: ]'u2:~-lfi:~l, 1.370, rl~ect~ of .E'lc~vate~ 'X'f~mper t~ro~; arl(~
lS r~ru~ on the Vi.abili~y of L1210 I,eu]semia Cells; or Euro~ean ~. Canc~rt ~: 573~576, 1972~ Irlvesti~ations of IL the Action of Coïnbirled f3eat ~ Roer,t~en Treatment on a Transplanted Mouse _ _ . .
Mammary Carc~inoma~. Thi5 inven~ion may be used tf.~ heat tumors ~in cor.junction wi.t~. treatment by chemot.herapy or Roentgen radia'-:io-l ir. such a way ;lS t.o enhance t:he effec~iveness o thes~ txe~t;nent:s.
As previ.ously rnentione(l, elect~ic field.s have ~een used in t~le past in at~empts to trea1: tumors. Such fields, howevex, have been utilized in such a way that the pheno~nenon of di~ferent cixcula~ion rates between t~mors and he~lthy ti~;sue has not been taken advan~a~e of. The p~esent inventioll enables utilization v~ electric ~ields .~or l:he purpose oi~ taking advan~aye of the aforem~ntioned , .~

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7~7~

difference in circulati~Jl rates by ef~iciently coupling the electric field to the tissue being txeated while at : the same tinto providing the abi~ity ~v e~fectively and closely control the power being applied to the tissue.
Referring now more p~rticularly to FIG~
apparatus for perfcnnilt~ the method of the inverlti.on i.
illustrated~ The apparatus includes a radio frequency oscillator 11 of any suitable type for providing a radio frequenc~ outp~t. ~or rec~sons which c~re eY~plained below, this fxequency should be less than about 40 ~-lz and greater than about 2 M~lz. ~he Federal Cor~nun.ications Commission in the U. S. ~ t~ allc~-,ated l~. 56 ~ . o:c t~le Se(`Olld C)r th.i~d mu1.tipl~: ~hereoi- as the :Ere~3uenci~t3; t:,o be 119C'Cl in di~-~tthol-lny ecltt.i.i~m~ t, ~nd 13.'j6 ~1% .i~ \ref~rre(l ~vel th~
higher multiple~.
1~he output of the oscillator 11 is coupled to a radi.o frequency ampj.ifier 13. Both the osci.lla~or ancl th2 ampli~ier are pol,7ered by a s:uitable pc~wer supp].y 15, and feedback circui.t 17 .i5 provided from the ampliE.;.ex ~o khe oscillcator ;lS a stal)ilizing device. The amplifier is pro-v:;dccl with two OU;:p~.ltS in~i.c~tc~ at :1.9 and ~l. Or~e of tl~e outpuks may be u~ed alone to e~;~ablic;h an RF output between the attached electrode and ground a5 dc:scr.ibed below in connection with FIGIJRE 3 or both the outputs 21 and 19 rnay be utilized tosether to provide an ~F output tnerebetween.
As illust~ated in FIGU~ l, a radio ~requency coaxial plug 23 is ~ltilized to connect 2 coaxial ~able 25 ,' , .

_9_ 1~77573 to the output 21 of the amplifier 13. Suitable ground connectiOnS 27 are provided to the sheath or shield of the cable 25 as is known in the art. The coa~ial cable 25 is connected to a coil or choke 2g to connect the ou~put from the terminal 21 of the amplifier 13 to a conductive plate 31.
Similarly, a radio frequency coaxial plu~ 22 is utilized to connect a coaxial cable 24 to the output i9 of the amplifier 13. Suitable ground connections 26 are provided to the shield of the cable 25 as is known in the art. The coaxial cable 24 is connected to a coil or choke 28 to connect the output from the terminal 22 o~ the amplifier 13 to a conductive plate 32.
In addition, the sheaths of the cables 24 and 25 are interconnected by a flexible jurnper cable 39, also co-axial. The cable 39 is connccted by both ce~ntral conductor and sheath to the sheaths o the cables 2~ and 25 a~ the ends of the cables 2~ and 25 just inside of the handles 33 and 34.
The jumper lead 39 has the unction of reducing the voltage drop between the open ends of the cable sheath, that i5 be-tween the ends farthest from the power source. It also reduces the voltage drop between the power ground and the open ends of the she~th by providing a return path for the ground~side currcnts. The power coupling to the paddle~ or electrodes 31 and 32 is improved by a ratio o~ two to three times over the case where a jumper cable is not employed. The flexibility of the cable 39 allows freedom of positioning of the electrodes 31 and 32 while maintaining good coupling into the tissue as electrode sizes and corresponding spaces change.

: , ` 1077573 The plates 31 and 32 are of a shape suitable for the purpose of applying an electric ~ield of the desired configuration. Preferably, their diameter is about ten to twenty percent greater than the maximum d:imension of the tumor in a plane perpendicular to ~he fie:Ld. Insulation 30 may be provided over the entire surface of the plates 31 and 32 including the edges to prevent shorting of the plates to the tissue being treated. The thickness of the insulation 30 is shown in FIGURE 1 exaggerated but is sufficiently thick so as to prevent direct conductive contact between the conductive plates and the skin. However, the thickness should not be so great as to inhibit coupling of the electric field to the tissu~ being treated. Accordingly, it is preferred that the in~ulation layer b~ a thin layex of low 105s dielectric mater~
1~ ial such as polyurethane. The thickness of the plates 31 and the material thereof are selected to provide substantially uniform field density between their larger surfaces. Thus, a material having good electrical conductivity, such as copper or aluminum is used.
In a typical application, the plates 31 and 32 are circular discs, subst~ntially flat, and are provided with in-sulating handles 33 and 3~ to assist in manual placement o~
the plates 31 and 32. The coils or chokes 2~ and 28 are contained within the handles 33 and 34, respectively, and are selected to have an inductance to couple the plates 31 and 32 to the driving ampli~ier and oscillator 13 and 11.
More particularly, the sizes of the chokes 28 and 29 are ,, , 1~775'7;~

selected such that the resulting inductive reactance provided in $he circuit approYimately balances and cancels out the capaci~ive reac~ance of the circuit: pr~vided by the plates, thereby ensuring that ~ood couplin~ of the electric field into the tissue will result.
The insulation layer 30 on each o~ the electrodes is for the purpose of preventing low frequency transient voltage pulses from reaching the tissue being treated. When the radio frequency power source is turned on or off, frequen-cies are present in the circuitry, as may be shown by F'ourierseries analysis, which may extend down to d-c. The insulation in series with the electrode and the tissue has such an in-heren~ly low capacitancc ~less than ~000 pF) that it inhibits very low ~requencies ~ld d-c from reaching the tis~ue~
lS It should be noted, however, that the lo~akion of the capacitance for inhibiting low frequencies and d-c from reaching the tissue need not be physically located on the sur-face of the electrodes themselves. Another loGation, which has several advantages, is in the handles. To this end, high voltage highly stable capacitors 28a and 29a may be located in the handles 34 and 33, respectively. The capacitors 28a and 29a are, respectively, connected in series with the coils 28 and 29 in the handles. By choosing an inductance in the handles as de~ermined by the coils 28 and 29 equal to the capacitance as before, only with the capacitance this time being determined by the capacitors 28a and 29a, significant advantages accrue. In other words, the capacitive reactance ~&177573 of the capacitor 2~a or 29a is substantially equal to the inductive reactance of the coils with which it is in series (and 180 out of phase). The electrodes 31 and 32 may then be polished metal, rather than insulated, avoiding the pos-sibility of the coated electrode developing scratches throughwhich current could pass. A stable accurately known eapaci-tance is provided in the handles which does not vary in eapacitanee as compared with variations in the eapacitance of the eoating on the electrodes as the eoating varies in thickness with fabrication. Also, with very small electrodes, where the surface capacitance of the electrode coating is very small, the requirement for a large inductance is avoided, avoiding the corresponding very high volta~e developcd Across both the eoil and the electrode insulation.
lS The tissue into whieh the electrie field is bein~
eoupled, is indicated substantially in cross section at 36 which may represent, for example, a portion of a human body.
A tumor may be located at 38. Where surface irregularities exist, such as the undulations illustrated, coupling may be assisted by using a eonductive deformable material 37, such as copper "wool", between the plates 31 and 32 and the un-dulating sur~aces 35. Thus, irregularities such as those produced by ribs and other bony structures or by a protrud-ing tumor are easily accommodated. A further improvement ~S in coupling results if the skin surface is coated with a conductive paste, such as the jelly used for attaching the electrodes of an eleetrocardiogram machine.

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```- 11~775'73 In applying the field, the plates or paddles 31 and 32 act as the plates of a capacitor, bet~7een which the tissue is placed~ Each of the paddles may have RF vol~age applied thexeto, 180~ out of phase, or one of the paddles S may be grounded. Thus, for example, the paddle 31 may al-ternately become positive and negative with respect to ground, and the paddle 32 may become neyative and positive, respectively; or the paddle 32 may instead remain at ground.
Another possible configuration is to use only a single paddle and place the tissue on a grounded conductive plate, such as a metal examination table 40 tied electrically to the chassis of the apparatus. This is illustrated in FIGURE 3. The con-figur~tion of ~IGU~E 3 is typic~lly pr~ferr~cl wher~ the tumor is much closex to on~ ~ur~ace than the oth~x, as ~hown.
It is pre~erred that the conductive plates or paddles 31 and 32 be as close to the skin or tissue surface as possible to minimize the air gap between the plates and the surface. The copper wool or other deformable conductive material 37, as previously mentioned, takes up the irregular-ities and improves coupling fxom the electrodes into the ti~sue. A flexible electrode may be an alternative pos-~i~ility or the use of ~ mesh of wire5 or a conductive coating on skin may also make it possible to couple the field into the tissue. The smaller the size of the region of coupling, the greater the impedance in the circuit, and this means more reactive power is wasted and therefore less useful power is applied to the tissue. However, the reactive impedance may 1~77~73 be cancelled by using inductive coils such as coils 28 and 29 in FIGURE 1. In addition, higher voltages are required with poorer ~oupling in o~-der to carry the cur-rent, and the current density will also be correspondingly higher with a consequent hi7her risk of damage to the skin or the healthy tissue. Moreover, with higher current den-sities and higher voltage levels, control over the power being applied to the tissue is more difficult.
The shape of the conductor, as previously mentioned, may be circular, but other shapes are pos-sible within the scope of ~he invention. The shape pximarily depends upon the shape and location of the tu,mor be,ing treated bu~ in every case it is significant that the electric fi~ld b~ as un~orm as possible and that the tumor be fully included within the uniform por-tion of the electric field. To th'is end,'the electrodes ' or paddles may be held in place by any suitable means ,' such as by hand, by an external me,chanical structure t by adhesive tape, or by a conductive adhesive on the surface ,' 20 of the tissue.
As pre~iou~.ly mention~d, the frequency at which the apparatus operates should be less than about 40`M~1z and greater than about 2 ~Iz. At frequencies greater than about 40 ~z, the electrodes or paddles, and some other structural items, begin to act as , antennae and radiate in all directions. Above 40 MHz, this radiation becomes significant and results in a ~77573 significant wasting of power and therefore a substantially less efficient apparatuS Moreover, above about 40 MHz frequency, the surface of the tissue has a tendency to heat undesirably. This can be dangerous, especially to eye tissue. Other undesirable affects of operation at relatively high frequencies is that losses in a coaxial cable increase with increasing frequencies and that heat dissipation internally of the RF oscillator or amplifier may present a problem~ Na~urally, considerations of a:Llo-1~ cation of frequencies by government agencies is also asignificant factor. Further difficulty with relatively higher frequencies include increased cost of manufacturing the app~ratus, dif~iculty in controlling and measuring the actu~l RF current going to the tissuc, and a wand~riny o~
the electric field at higher ~requencies.
More significant, however, from a practical standpoint is the limitation that frequency places upon the length of coaxial cables which may be employed. The longer the coaxial cable length is relative to the wave-length at the frequency used, the more sensitive the circuitbecomes to variables such as the resistive and capacitive loads and the electrode config~ration. This is because any shunt capacitive load at the end of a coaxial cable sub-~ stantially increases its "electrical" length. Thus, a ; 25 substantial increase in control problems results where ; the coaxial cable length is long relative to the wavelength at the paxticular frequency selected.

1~77573 As a practical matter, it has been determined that the total length o~ the coaxial cables, including the length inside of the apparatus itself, should not e~ceed about one-twentieth of the wavelength at the frequency being used. At the 13.56 MHz allocated for diathermy equipment, the wavelength is about 14.6 meters. Using the above criterion, a total coaxial cable length o~ about 73 centimeters or less is desirable. Since as much as 20 centimeters or more of coaxial cable may be utilized in-side the apparatus itself, the length of the coaxial cableleads 24 and 25 at this frequency should be no more than ~bout 50 centimeters. This is about as short as the leads can be and still enable the electrodes ~o be prop~rly posi-~ioned. Thus, as a practic~l matter/ it may be ex~remel~
difficult to devise means or coupling an electric field ;. into a human patient where the frequency used is much higher than about lS ~z.
As previously mentioned, the lower limit on the frequency utilized .is about 2 MHz. Below this frequency, any significant amount of bone in the ield may cause problems in providing adequate coupling of the field to the ~issue More-over, with lower frequencies, the coils .in the apparatus and in the handles of the paddles must be correspondingly larger and at frequencies lower than about 2 MHz may become so bulky as to be impractical. Maturally, the frequency used should also be above that of any neuromuscular reaction. A lower limit of about 2 MHz assures this. Experiments on simulated tissue at frequencies extending over the range of about 2 MHz to about 15 MHz indicate very lit~le variation in heating efficiency between different ~requencies in the range.
In applying the electric field to tissue in accordance with the invention, it is important to prevent excessive damage to the healthy tissue whi:Le at the same time maintaining a high enough temperature in the tumor over a sufficient period of time so as to kill the twnor.
The fact that the maintenance of a high enouyh temperature over a sufficiently long period of time will kill many types of tumors is, as previously mentioned, documented in the priox art. ~pplicant's in~ention has pro~ided a method and mcan~ or ~ccomplishin~ this throu~h the u~e o~ an elecl:ric field wherein it is possible to closely control the amount of energy being applied to the tissue and thus closely xegulate the temperatures inaccordance with the desired treatment. The use of frequencies in the range previously specified, together with the avoidance of high loss factors, make it possible to employ electric fields in such a way as to destroy tumors without signiicant damage to the sur rounding healt}ly tissue. Using a heating rate of about 20 minutes for a 5~E' rise in the healthy tissue surrounding the tumor, the temperature inside a tumor has been observed to increase from two to three times as much as the temperature in the surrounding healthy tissue.
Referring now more particularly to FIGURE 2, there is illustrated a schematic diagram of circuitry for use as : ~77573 the RF oscillator 11 and the amplifier 12. A 60 c.p.s.
117 V. or other suitable a-c supply is applied to the primary winding 43 of a power transformer ~5, the primary being bypassed to ground through a capacitor 47. Included . 5 in the power transformer 45 is a secondary winding 49 to which are connected the filaments of the vacuum tubes de-scxibed below. The secondary winding 51 of the power trans-former 45 is connected across a diode bridge rectifier 53.
Completing the diode circuitry are a pair of resistors 57 and 59 connected across opposite corners of the bridge, capac.itors 61 and 63 in parallel therewith, respectively, .;~ and a capacitor 65 connected in parallel with the capacitors 61 and 63. The junction between the capaci,tors 57 and 59 is connected to the junction between the capacitors 61 and 63 lS A center tnp 67 on the secondary windin~ 51 is connected through a diode 69, a resistor 71, a filter capa-citor 9 to yround, and resistors 73 and 75 to the screen of a tetrode 77. The resistors 73 and 75 are connected to ground through a capacitor 76. The tetrode 77 functions as the RF oscillator element in the oscillator 11, having its grid connected to a bias source terminal 79 through a resistor ~7 and a tank circuit. ~r~,e tank circuit includes a quartz crystal 81, a coil 83 and a resistor 85 in series with the coil 83. The plate of the tetrode 77 is connected to the choke 105 and through a plate capacitor 89, to the resistors 115, 117 and 119, in the control ~rids of tetrodes 109, 111 and 113. Coupled to the low side of the choke 91 ~77573 is a capacitor 95 and a pair of series resistors 97 and 99 connected in parallel w.ith the capacitor to ground. The cathode of the t~trode 77 is grounded through a capacitor 101 and parallel resistor 103. The bias source is from 79.
The RE output of the tetrode 77 at the plate .;
thereof is coupled through a tuned circuit: including a coil 105 and a variable capacitor or tuning capacitor 107 to a parallel amplifier including three tetrodes 109, 111 and 113. RF drive and grid bias for the three amplifier tubes is provided through resistors 115, 117 and 119, res-pectively. Plate voltage for the tetrode 109 is supplied throucJh a choke coil 127 and the P~ra] 1e1 combination of a resis~or 129 and a coil 131 from ~he diod~ bridge rectifier 53. The parallel combination of the resistor 133 and coil 135 supplies the plate voltage for the tube 111 and the parallel combination of the resistor 137 and the coil 139 provides the plate voltage for the tube 113. The tubes 109, 111 and 113, therefore, operate in parallel to amplify the output of the R~' oscillations of the tube 77.
The contacts 123 of a relay 125 axe interposed between the resistor 1~1 and the plate o.~ the tetxode 77.
One side of the relay 125 is connected to growld through a normally closed reset switch 12~. The other side of the relay 125 i5 connected through a resistor 126 to the cathode of the tube 77.
The amplified oscillations of the RF oscillator-~nplifier 11 are developed across an output transfo~ner ~20-having a primary winding 145 in series with the capacitor 147 and having a variable capacitor 149 connected there-across. The smaller secondary winding 151 of the output transforrner passes its signals through a shielded coaxial cable 153 having a ~uning capacitor 15~, through a coupling capacitor 157 to the a~nplifier 13.
The amplifier 13 includes a pair of parallel triodes 159 and 161. The grids of the triodes are grounded and the input from the RF oscillator 11 is coupled to the 10 cathodes of the triodes 159 and 161 through the coupling capacitor 157. The plate output circuit of the triode 159 includes a parallel combination of a coil 165 and resistor 167. The plate output circuit o:E the triode 161 includes the parallcl combination of a coil 169 and a resistor. 171.
The d-c voltAge is provided ~rom a. hiyh voltage 1~erminal 175 through a choke coil 177 and a furtller choke coil 179.
A capacitor 181 bypasses the coils 177 and 179 to ground.
A capacitor 172 couples the plate RF output o~
the parallel triode amplifiers :L59 and 161 through an auto-transformer 173. The autotransformer 173 includes a tap 183 which is ~rounded. A further winding on the trans:Eoxmer 173 has a tap 185 which is connected to a terminal 187. A tap 189 toward the higher voltage end o the transformer 173 is connected to a terminal 191. A further tap 193 closer to the input end of the transformer 173 than the tap 189 is connected to a terminal 195. The transformer 173 is tuned by a variable capacitor 197.

77~73 .

The output of the amplifier 13 is derived through a relay with one contact 201 fox a left ~hannel and a second contact 203 for a right channel. The relay contact 201 in the illustrated position connects to a grounded terminal 205 and is for the purpose of operating the apparatus in the mode - illustrated in FIGURE 3. In this condition, the relay contact 203 connec'cs with the terminal 195, ~hereby supplying a radio frequency signal between the tap 193 and ground. This signal is applied through a meter 207 to the output socket or terrninal 21. In the event two electrodes or paddles are used, as in FIGURE 1, the relay contacts 201 and 203 are moved to the terminals 187 and 191, respectively, when the output from the terminal 1~7 is applied throug}l a meter 209 to the left ~ocket or outpuk terminal 19.
For the purpose of stab.ilization and control, a d-c coupled servo loop or feedback loop is prov.ided. The servo loop includes a voltage doubler diode 211 in which the left-hand one of the plates is coupled throuyh a pair of capacitors 213 and 215 to the terminal l9S. A variable capa-citor 217 is connected between that plate and its correspond-ing grounded cathode for adjusting the power level at which the apparatus is being operated. The right-hand plate of the diode 211 is connec~ed through a resistor 219 and a diode 221 to the coil 83 of the grid xe~urn of the tetrode oscillator tube 77 in the oscillator-amplifier 11. The signal thus applied is developed across the parallel combination of the resistor 223 and capacitor 225 in the oscillator 11. The ~C)77573 plate signal is develoPed across a capacitOr 227 connecting the plate side of the resistor 219 to ground. A capacitor 225 connects the opposite side of the resistor 219 to ground.
A capacitor 231 is connected to ground from the opposite side of the diode 221 from the resistor 219. The right-hand ;`
cathode of the doubler diode 211 is connected to the left-hand plate such that the dual diodes of the tube 211 are coupled in series. Adjustment of the capacitor 217 sets the power level at which the apparatus operates by adjusting the grid voltage on the tube 77, and is capable of an approx-imate fifteen fold variation.
'~he above discussed circuit configuration permits the apparatus to be operated by a single control adjusting the capacitor 217. There i8 no ne~ed or the operator of thc apparatus to do any tunincJ of the circuit. This is beaause the direct current inverse feedback provided b~ the circuit 17 stabilizes the current at any given control setting even if the resistive and/or capacitive loads vary. Thus, for example, if the apparatus is utilized to treat a lung tumor, and if the electric field passes through the lung, the cur-rent i6 stabilized at the control setting even though the air path in the lung ~hrough which the field passes varies in length with the breathing of the patient.
In the event that the doubler diode 211 fails, power output may tend to increase dangerously. To prevent this, the relay 125 is set to open the contacts 123 when the cathode current of the tube 77 increases beyond a preselected ~i :J17~S~3 level. When the relay switch or contacts 123 open, screen bias to the tubes 109, 111 and 113 is removed, cutting off the R~ power.
For the purpose of illus~rating the apparatus of the invention, the following examples are given. It is not intended, however, that the inven~ion be ~Limited in any way to the specific parameters or procedures set forth in the examples .
Example 1~ To demonstrate the unifonmity of heating and absence of skin eddy currents, apparatus con-structed in accordance with the invention was utilized to pass an electric field through a bag containin~ three litexs o~ salt-a~ar jelly. Vsing a radio frcquency of 13~56 M~lz, power levels o~ 300 to ~00 watts were used. Tempern1:ure~
wer~ measured adjacent to opposite sides of the jelly and in the center of the jelly using highly accurate centigrade thermometers. With an increase in temperature of over 30~C
the maximum observed difference in temperature readings was 6.5C. Where conditions and the configuration of the appar-atus were carefully controlled, temperatures were maintainedwithin 2C and in most cases substantially le~,s. ~ore im-portantly, however, there was no indication of a tendency for greater heating near the surace than in the center demonstrating that the degree of heating was uniform regardless of depth and was not affected by the presence of eddy currents in the s~in as is the case typically in connection with electromagnetic fields.

~77573 Example 2. A "terminal" patient having a malignant tumox in the right lung complained of constant pain before treatment and pain in the xight shoulder when thP right arm was moved. The pa~ient was treated using apparatus constructed in accordance with the invention using a single electrode and a grounded ta~le. The fol-lowing indicates the procedure:

Approximate Time After Skin Surface Temp.Power Output Startinq Treatment at Electrode ~C.in Watts 100 min. 35.65 50 1 min. 37.10 50 2 min. 37.1 60

3 min. 37.1 60 min. 37.35 60 6 min. 37.5 60 8 min. 3~.35 60 10 min. Shut o~ ~pparatus to further scdate patient.
re~art 37.7 50 2 rnin. 38.6 50 ~53 min. 3~.7 50

4 min. 3~-7 50 6 min. 38.35 50 8 min. 38.2 45 10 min. 38.2 After treatment, the patient indicated that he felt no pain and had increased mobility in his right arm. Several weeks a~ter treatment, the patient was discharged from the hospital.
Exam~le 3. A patierlt having a malignant turnor in the let lung considered ~erminal was treated using apparatus constructed in accordance with the invention usin~ two electrodes as follows:

1~775~3 Approximate Time After Skin Sur~ace Temp. Power Output - Starting Treatment at Chest Elec~rode ~C. in Watts 0 min. 37 7 50 2 min. 37.8 50

5 min. 38.2 50 7 min. 38.6 60 9 ~in. 39.0 60 11 min. 39.0 60 13 min. 39.0 60 14 min. 39.1 60 17 min. 39.1 S0 19 min. 39.2 70 21 min. 39.3 70 Several weeks after treatment, the patient was discharged from the hospital.
Example 4. A male patient having a hard mal:ignant tumor about the size of a baseball on the front of his throat was treated using apparatus constructed in accordance with the invention. For ~ long period before treatment, the patiellt hud di~iculty in breathing such that it was necessary to pro-vide him constantly with oxygen, and he was unable to ~peak.
A single electrode was used and the table upon which the patient was lying was grounded. Copper wool was shaped to conform to the approximately~spherical external shape of the tumor. The treatment was carried out for approximately 45 minutes utilizing a power of approximately 200 watts. The oxal t~mperature was ~hecked repeatedly during treatment and it did not exceed 10~F (40C).
Approximately six hours after cessation of treat-ment, the patient was ex~nined and it was noted that the tumor had decreased in size and was soft. Less than 24 hours later, it was no longer necessary to provide the patient with oxygen and the patient was beginning to whisper. The twnor was . .
. :

~377573 further reduced in size. One week after treatment, the tumor had reduced ~o a size of "about a silver half-dollar". Biopsies performed on the material taken from the area of the tumor be-fore the treatment showed the tumor ~o be malignant while a S biopsy taken one week after treatment showed nothing but dead tissue and no malignant cells.
It may be seen, therefore, that the invention provides an effective apparatus for treating tumors by caus-ing the tumors to increase in temperature substantially above that of the surrounding healthy tissue. It is believed that such procedure causes the tumor to be deskroyed in many cases, and that the resulting rise in temperatllre i5 du~ to the suh-stan~ially reduced circulation present in malign~nt tumors.
Thc invention is al30 capable o~ heating other types of tissue which have a substantially lower circulation rate than surrounding tissue to temperatures higher than the surrounding tissue.
Va~.ious modifications of the invention in addition to those shown and described herein will become apparent to those skilled in the art from the foregoing description and accompanying drawings. Such modi~ications are intended to fall within the scope o the appended claims.

!

Claims (13)

WHAT IS CLAIMED IS:
1. Claim 1. Apparatus for treating tumors in humans and animals, comprising, radio frequency oscillator means, amplifier means coupled to the output of said radio frequency oscillator means for producing an amplified radio frequency output signal, electrode means coupled to said amplifier means, said electrode means including at least one capacitive electrode having a configuration adapted to pass an electric field through both the tumor and the surrounding tissue, and means for con-trolling the power of said amplifier means to avoid heating the surrounding tissue beyond a preselected temperature level while allowing the tumor to heat beyond the preselected temperature level, said controlling means including direct current inverse feedback means connected from said amplifier means to said oscillator means for stabilizing output current.
2. Claim 2. Apparatus according to Claim 1 including coaxial conductor means connecting said amplifier means to said electrode means, said coaxial conductor means having a total length of less than about one-twentieth of the wave-length of the radio frequency output signal.
3. Claim 3. Apparatus according to Claim 1 wherein said capacitive electrode is insulated with a low-loss di-electric material.
4. Claim 4. Apparatus according to Claim 1 wherein said electrode means-comprise-two capacitive plates.
5. Claim 5. Apparatus according to Claim 1 including inductance means in series with said electrode means having an inductive reactance substantially equal to the capacitive reactance of said electrode means.
6. Claim 6. Apparatus according to Claim 5 including capacitance means in series with said inductance means having a capacitive reactance substantially equal to the inductive reactance of said inductance means.
7. Claim 7. Apparatus according to Claim 1 wherein said oscillator means and said amplifier means are constructed to provide an output signal at a frequency of between about 2 MHz and about 40 MHz.
8. Claim 8. Apparatus according to Claim 1 including coaxial cable means connecting said amplifier means to said electrode means, said coaxial cable means having a total length of less than about one-twentieth of the wavelength at the frequency of the output signal of said amplifier means.
9. Claim 9. Apparatus according to Claim 8 including jumper means connecting the open ends of the sheaths of said coaxial cable means and providing a return path for ground currents.
10. Claim 10. Apparatus according to Claim 1 including cut-off circuit responsive to an output power level of said amplifier means exceeding a predetermined amount to cut off power to said apparatus.
11. Claim 11. Apparatus for treating tumors in humans and animals comprising, radio frequency oscillator means, amplifier means coupled to the output of said radio frequency oscillator means for producing an amplified radio frequency output signal, said oscillator means and said amplifier means being constructed to provide an output signal at a frequency of between about 2 MHz and about 40 MHz, electrode means coupled to said amplifier means, said electrode means including at least one plate having a configuration adapted to pass an electric field through both the tumor and the surrounding tissue, coaxial cable means connecting said amplifier means to said electrode means, said coaxial cable means having a total length of less than about 1/20th of the wavelength at the frequency of the output signal of said amplifier means, and means for controlling the power of said amplifier means to avoid heating the surrounding tissue beyond a preselected temperature level while allowing the tumor to heat beyond the preselected temperature level.
12. Claim 12. Apparatus according to Claim 11 wherein said controlling means include direct current inverse feed-back means connected from said amplifier means to said oscillator means for stabilizing output current.
13. Claim 13. Apparatus for treating tumors in humans and animals, comprising, radio frequency oscillator means, amplifier means coupled to the output of said radio frequency oscillator means for producing an amplified radio frequency output signal, electrode means coupled to said amplifier means, said electrode means including at least one plate means having a configuration adapted to pass an electric field through both the tumor and the surrounding tissue, capacitance means and inductance means series connected with said electrode means proximate thereto, said capacitance means having a capacitive reactance substantially equal to the inductive reactance of said inductance means, and means for controlling the power of said amplifier means to avoid heating the surrounding tissue beyond a preselected temperature level while allowing the tumor to heat beyond the preselected temperature level.