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Attempts to localize a carcinoma of the endometrium with the use of short radio waves
Attempts to localize a carcinoma of the endometrium with the use of short radio waves A. INGELMAN-SU:"iDBERG. M.D. E. ODEBLAD, M.D. Stockholm. Sweden
T H E ll E T E R M I N AT I 0 N of the location and spread of an endometrial ca~o11Ja before treatment is of great prognostic and therapeutic importance. When searching for methods allowing such a determination, om· interest was focused on the possibility of using the absorption of radiofrequency radiation in tissues. The absorption of radiofrequency in tissues can, schematically, be classified into two types. The first type is the frequency-nonspecific dielectric absorption due to tissue water. Macromolecules cause, in general, a moderate increase in the apparent dielectric constant of aqueous solutions, mainly in the frequency range below 10 megacycles per second. In the frequency range between 10 and 1,000 megacycles per second, differences might bP expected to exist between tissues, due to tht-ir water contents. The second type of absorption is frequency-specific. This type of absorption has been much less investigated and, to date, very little information is available in literature. Bach, Luzzio, and Brownell~- " havr presented strong indications for specific absorption at about 13.3 megacycles per second
m human gamma globulin. Hellt>r' has reported that migration direction of protozoa can be influenced by radiofrequency ! RF 1 fields between 1 and 100 megacycles per se~· ond, and Saito, Sher, and Schwan' ha\'t' made theoretical and experimental studies on the effects of radiofrequency ( RF) fields on microscopic and submicroscopic particles. 'Ve d('cidcd to investigate the nonspecific absorption and to search for absorption hands from normal and malignant tissue in the frequency region 10-1 00 megacycles per second, using techniques similar to those used in nuclear magnetic resonance. Convenient detection systems for nuclear magnetic resonance were already available in our laboratory for this frequency range, and could easily be adapted to both in vitro and in ,j,·o in\TStigations. Materials and methods
In vitro. The measurements of RF absorption were undertaken with a marginal oscillator being a modificationr. of previously existing ones.-, The oscillator operates bv capacitative feed-back from anode to !!,riel in a pentocle.* The oscillation frequency j,; determined by the coil inductance and total capacitance of the grid circuit. The anodt· circuit is untuned. If increased energy absorption occurs in the sampie inside the coiL the oscillation amplitude is depressed. This results in an alteration of the anode voltage which is recovered, amplified, and recorded.
From the Department of Obstetrics and Gynecology and its Isotope and Spin Resonance Laboratory, Sabbatsbergs Ho;pital, Karolinska Institute!. Supported by a Grant from the Swedish Society for Cancer Research, Project No. 64:'10. Guest address, presented at the Thirty-first Annual Meeting of the Pacific Coast Obstetrical and Gynecological Society, Santa Barbara, California, N 01'. 4-7, 1964.
*E180F, special quality pt~ntodc, a hi~h gain and hl~h stability broad band pentodc manufactured hy J>hilips J.teL
592
Fig. 1. Front view, showin g the control panel of the RF spectrometer unit for in vitro recording of absorption. The sample tube, to the right, is surrounded by the oscillator coil , which is soldered to the RF leads and can be dipp ed into a water bath of 37° C. The oscilloscope screen to th(' left.
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July I. 1111i'•
lngelman-Sundberg and Odeblad
\m.
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()h.,.L & ( ;ynt·r
Fig. 2. Equipment for intrauterine radiofrequency investigations in vivo at curettage. The RF generator (Philips) GM 2893, bottom) is connected to the exploration unit (top). This is made up of a box (left) and the intrauterine sound (right). Between the sound an d the RF generator is seen the unit, carrying the batteries for the transistor supply and th e microammeter.
Frequency-nonspecific absorption effects were directly read on a meter after radiofrequency detection. In order to display the specific absorption bands on an oscilloscope screen, the oscillation frequency was sinusoidally varied by about 1 per cent at 50 cycles per second in synchronism with the time axis of an oscilloscope. The frequency modulation was brought about with the a.id of the variable capacitance diode BA 101 (Telefunken) .* By changing the bias of the *Voltage
dependence
capacitor,
silicon
diode
capacitance depends on the applied backward voltage.
\Vhm;c
diode, the frequency could be slowly varied over a frequency range of about :+:30 per cent of the middle frequency. Different frequency intervals were covered by interchange of sample coils. In this way a complete frequency range between 10 and 108 megacycles per second could be investigated. Fig. 1 shows a view of the spectometer unit. The calibration of frequency was made by interference with standard quartz crystals, using the ground frequencies and overtones. The calibration of the magnitude of absorption was made by comparison with proton
Volume 92 :i
Short radio waves and endometrial carcmoma location
Num lu~r
595
Fig. 3. Inside view of the box of the RF exploration unit (shown in Fig. 2, top, left). From left to right, contact for RF intrauterine sound, twin-T bridge (shown in part), transistor RF amplifier, diode detector, and contacts to batteries and to microammt>ter.
magnetic resonance lines at 10.6, 25.1, 47.0, and 104.5 megacycles per second, using the permanent magnetic resonance in our laboratory. By insertion of proton samples with different proton magnetic relaxation times, some approximate information on the radiofrequency intensity inside the sample could also be obtained. The calibration of the widths of absorption lines was performed with a standard variable frequency oscillator* in connection with a frequency multiplier. Myometrium, endometrium, and carcinoma of the edometrium from patients were investigated. The samples were obtained at operation. Endometrium, myometrium, liver tissue, fat tissue, and blood were also obtained from mice and rabbits. Control runs with distilled water and saline were frequently undertaken. In vivo. On the basis of the in vitro investigations, recordings were undertaken in *GM 2893, a commercial manufactured by Philips Ltd.
radiofrequency
oscillator
vivo at fixed frequencies ( ll.6 or 13.3 megacycles per second), selected for working with both frequency-specific and -nonspecific radiofrequency absorption. The equipment for the in vivo studies consisted of a frequency generator and a RF exploration unit (Fig. 2). This, in turn (Fig. 3), consisted of a twin T-bridge 8 of a simplified construction and high stability/ a transistorized RF amplifier, and a diode detector. The bridge was preset at the frequency to be used, the final adjustment being performed at the operation. General anesthesia (pentothal + oxygen + nitrous oxide) was used. The cervical canal was dilated to the size of a Hegar 9 and the RF sound with the coil near the top was introduced into the uterine cavity (Fig. 4). The cavity and the cervical canal were then explored by successive scanning and the rectified voltage appearing at the detector diode was recorded. A drop in this voltage reflected an increased magnitude of tissue absorption of radio wave energy.
596
lngelman-Sundberg and Odeblad . \111 ,
Fig. 4. RF sound introduced into an extirpated uterus (Case RliS/63). To the left, in fundus uteri, there is the residual cance r remaining after radium trea tment, which preceded the operation.
The clinical material consisted of 12 patients; 7 of them underwent hysterectomy after the scannings (Table II'!. Results In vitro. Frequency-nonspecific absorption of water a nd saline was found between 10 and 105 megacycles per second. The magnitude of this absorption was rather large, about 400 parts per million (ppm ) of the RF energy over the whole frequency range. The frequency-nonspecific absorption of myometrium and endometrium was not, as expected, smaller, due to the lower water contents, but significantly higher (Fig. 5 ) . It was also observed that there occurred a shift of the oscillator frequency, when different tissues or water were introduced into the RF spectromete r. Frequency-specific absorption bands were found at about 11.6 and 13.3 megacycles per second . They were absent in pure water and ranged in tissues from 0 to 80 parts per million of RF energy. An example of a record, and some average RF absorption curves are shown in Fig. 6. Fig. 6 shows values of RF absorption of carcinomatous and norma l tissues from Case 9108/63. Endometrium shows a strong absorption, adeno-
.f
July 1 I ~11; :, Oh"t.. &
< ;yrrt·c.
carcinoma a moderate one and myometriuu1 a weak absorption around 1:Ll megacycle-; per second. Typical average results are also given in Table I, obtained on rabbit tissues . The results on human and mouse tissues arc of the order of size and occur at about tilt' same frequencies. In vivo. The results from l 2 cases ·;uh jected to intrauterine RF absorp tion measuremen ts are given m Table I L The measurements were undertaken with special reference to right-left asymmetry of RF absorption (Fig. 7 ·), because the electroni c sources of error are nearly ey ua l at such measurements. The difference between n~ad ings for the left and right sides of tht• uterine cavity are given, lower readings to the ldt thus giving negative values. The values givu 1 are in parts per million of RF energy and include the bridge balance facto r ' about 2,·<10 "i. It must be pointed out. that rht· bridge balance factor may wl'il vary hv :~o a nd <50 per cent. The average recorded difference for 9 patients. ~utTering from various gynecological diseases. was b "- ~ :\ parts per million \ standard deviation'. Thn'<' cases of carcinoma showed the fig ures 86. -•19+. and +ljO parts per million. wt'll outside the statistica l confidence limits for significamT. Table I. Magnitude of peak absorp tion of RF eneq,ry for some different samples obtained from rabbits. Each va lue represents the average of 3 or -+ recordings of the type shown in F ig. 6. Frequency (meg a-
cycle\ Myomeper sec- i trium and) [ (ppm)
lUi
- - --- --
· Serum
L iver
(ppm)
( ppm)
1 7
30 40
20 :10
20
+O
:Ill
g
:w
·Hl .')()
:HI :Hl
J-(l
]1_1
Ill
+O
BO g()
20
')
. ------·
1 metrium
( PPm)
9
I :1 .3
I En do-
')
6 7 15
:15
15
Short radio waves and endometrial carcinoma location
Volume 92 Number 5
ppm
1000
500
)(
•
597
:. water "myometrium
...
0 ::endometrium 0 0
0
••
•• •
0
X
X
0
•
• •
•
o•
•
•
0
• X
X X
xx
X
)(
X
X
X
X
X X
0+-----T-----~----~----~----r-----r-----r-----r-----r---~ 20 60 30 0 70 40 10 50 90 80 TOO Me/sec
Fig. 5. Frequency-nonspecific RF absorption in water, myometrium and endometrium from rabbits, investigated in vitro. Abscissa, oscillator frequency. Ordinate, approximate ppm scale for RF energy absorption. Calibration by comparison with proton nuclear magnetic resonance absorption signals at 10.6, 25.1, 47.0, and 104.5 megacycles per second.
ppm
9108/63
50
Adenocarcinoma
25 Myometrium
/
13.2
13.3
--~---1·-
1}.4
________.____ l'J/'I
~
--:
I
I
Me/sec
-!jf}
r
Fig. 6. Record of frequency-specific RF absorption band in endometrium (patient K3/63), obtained by phase sensitive detection. Average curves of specific tissue radiofrequency absorption in tissues from Patient 9108/63, read directly on the oscillograph screen.
598
lngelman-Sundberg and Odeblad
July 1, J% '1 .\m . j . Obst. & ("";y •n:c.
Fig. 7. Extirpated. bisected ut<> rus from Case 910H/ 63 ( ri g ht \ . ~ bowin g the uutrcaH·d endometrial carcinoma to the right in fundus. To the left a schematic drawing of the utt>rin e c;l\·ity with the absorption figur es in parts per million obtained a t intrauterine scanning t the zt' ro point a rbitrarily chosen) .
Figs. 4 and 7 illustrate two of the cases of endometrial cancer studied. Comment
In vitro. The largest part of the RF absorption in vitro is frequency-nonspecific and has been shown to occur within the whole frequency range investigated. It certainly corresponds to the dielectric dipole absorption of tissue water as mentioned in introduction. It was, however, observed, that the RF absorption in complex tissues largely exceeded what was expected from the water contents. This finding is currently being studied in more detail. The shift of the oscillation frequenc y is also the subject of extended investigations. The specific absorption bands constitute comparatively small effects. The question m ay be raised as to whether these are false effects. The presence of the effects in watercontaining tissues and their absence in fat tissue, pure water, and saline justifies the conclusion that they are real and present in the protein-rich tissues. It is of interest to point out, that the absorption bands occur
at about the same frequencies in samples from different species. Another important observation is the magnitude of the absorption, that ranges from 0 to 80 parts per million of the total RF energy. These two observations indicate, that physicochemical basis underlying the absorption bands is of similar nature in different tissues, but may differ quantitatively. It is not possible to give a satisfactory explanation for the absorption bands. Bach, Luzzio, and BrownelF· " have suggested unfolding of protein helices as the basis for absorption. They have also suggested , that the active frequencies should form a harmonic series with the fundamental frequencies between about 6 and 7.5 megacycles per second. Such suggestions are not in contradiction to our observations. In vivo. When perfonning the measurements in vitro, the geometrical rela tions between sample and coil arc constant and optimal, as the sample is localized inside the co:J. In the uterine cavity the conditions arc different, as the tissues lie outside the coil. To date, the measurements have been
Short radio waves and endometrial carcinoma location
Volume 92 Number 5
599
Table II. Clinical material and results of measurements of intrauterine RF absorption difference between contralateral symmetrical points
Patient identification R!IS/63 8178/63 K3/63 E4/63 T50d/63 9108/63 K80d/63 5663/64 7780/64 6273/64 6768/64 10939/63
Average asymmetry of radiofrequency absorption (ppm)
Hysterectomy performed
Carcinoma of the corpus uteri (radiotract) Polyp of the corpus uteri Myoma of the uterus
- 86
Yes
- 10 - 36
No Yes
Endometritis Dysmenorrhea Carcinoma of the corpus uteri Functional bleeding Carcinoma of the corpus uteri Tuberculous endometritis Myoma of the uterus Myoma of the uterus + atypical epithelium of the uterus
0 + 22 +194
No No Yes
10 +150
No Yes
- 16 - 34 + 32
No Yes Yes
-
Yes
Diagnosis
undertaken with an axially oriented coil, which does not allow separate recording of absorption in the anterior and posterior uterine walls. For the same reasons the direction and depth of malignant infiltration cannot be determined, but indications may be obtained on the surface spread. The resolution of the detection coil is also rather indefinite, of the order of i em. Special and high-resolution sounds are, however, being constructed. Gross capacitance and inductance factors may also come into play in vivo, when the sound is oriented in different directions in the body. By making symmetrical measurements bctvveen left and right these sources
of error are brought to a minimum and small absorption differences between symmetrical points apparently can be detected, as indicated by our results on the three localized endometrial cancers, when compared to the other cases with essentially symmetrical intrauterine conditions. Summary
Biological samples have been examined in vitro for radiofrequency absorption, when
4
In vitro spectrometry of tissues
Endometrium, polyp Endometrium, cervix, myoma, myometrium Endometrium Cancer, endometrium, myometrium Endometrium
introduced in the coil of a marginal oscillator, working in the range of 10 to 105 megacycles per second. Frequency-nonspecific absorption was present in the whole range, of an order exceeding the value expected from the contents of tissue water. Localized, weak absorption bands were, in addition, found at 11.6 and 13.3 megacycles per second. The samples examined consisted of blood serum, endometrium, myometrium, liver, and fat tissue from rabbits and mice and carcinomatous endometrium and normal uterine tissues from humans. No absorption bands were found in fat tissue, distilled water, and saline. The magnitude of the absorption bands increased in the order; 1nyon1etriurn, carcinomatous endometrium, normal endometrium, liver, and serum, i.e., nearly in the order of increasing water contents. In addition, shifts of oscillation frequency occurred, when different tissues were introduced in the coil. Clinical intrauterine measurements were performed in 12 cases at 1 L6 and 13.3 megacycles per second with a coil placed at the top of a perspex sound. The coil formed a part of a twin-T + amplifier + diode exploration unit. In 3 of these cases there was a
600
lngelman-Sundberg and Odeblad
carcinoma of the uterus, which in all cases gave rise to significant RF absorption differences between contralateral symmetrical points. The results were fully confirmed at
july L 1%:, Arn .
.f.
Ohst. & Cvnt·c.
hysterectomy. By intrauterine RF scanning it appears, therefore, possible to determine the surface spread of an endometrial carcinoma.
REFERENCES
1. Allgen, L. G.: Acta physiol. scandinav. (Suppl.) 22: 76, 1950. 2. Bach, S. A., Luzzio, A. ]., and Brownell, A. S.: Proc. Fourth Conf. Bioi. Effects Micro-Wave Rad. 1: 117, 1961. 3. Bach, S. A., Luzzio, A. ]., and Brownell, A. S.: Am. ]. Med. Electron. 1: 9, 1961. 4. Heller, ]. H.: Twelfth Conference on Electrical Technology, Medicine and Biology, Winner, New York, 1959, p. 56.
'i. Hopkins, N. ].: Rev. Sc. Instruments 20: 401, 1949. 6. Odeblad, E.: Unpublished work, 1964. 7. Saito, M., Sher, L. D., and Schwan, H. P.: 1961 International Conference of Medical Electronics, 1961. p. 154. H. Tuttle, W. :\1.: Proc. Inst. Radio Engrs. 28: 2:1, 19·to.
T H E ll E T E R M I N AT I 0 N of the location and spread of an endometrial ca~o11Ja before treatment is of great prognostic and therapeutic importance. When searching for methods allowing such a determination, om· interest was focused on the possibility of using the absorption of radiofrequency radiation in tissues. The absorption of radiofrequency in tissues can, schematically, be classified into two types. The first type is the frequency-nonspecific dielectric absorption due to tissue water. Macromolecules cause, in general, a moderate increase in the apparent dielectric constant of aqueous solutions, mainly in the frequency range below 10 megacycles per second. In the frequency range between 10 and 1,000 megacycles per second, differences might bP expected to exist between tissues, due to tht-ir water contents. The second type of absorption is frequency-specific. This type of absorption has been much less investigated and, to date, very little information is available in literature. Bach, Luzzio, and Brownell~- " havr presented strong indications for specific absorption at about 13.3 megacycles per second
m human gamma globulin. Hellt>r' has reported that migration direction of protozoa can be influenced by radiofrequency ! RF 1 fields between 1 and 100 megacycles per se~· ond, and Saito, Sher, and Schwan' ha\'t' made theoretical and experimental studies on the effects of radiofrequency ( RF) fields on microscopic and submicroscopic particles. 'Ve d('cidcd to investigate the nonspecific absorption and to search for absorption hands from normal and malignant tissue in the frequency region 10-1 00 megacycles per second, using techniques similar to those used in nuclear magnetic resonance. Convenient detection systems for nuclear magnetic resonance were already available in our laboratory for this frequency range, and could easily be adapted to both in vitro and in ,j,·o in\TStigations. Materials and methods
In vitro. The measurements of RF absorption were undertaken with a marginal oscillator being a modificationr. of previously existing ones.-, The oscillator operates bv capacitative feed-back from anode to !!,riel in a pentocle.* The oscillation frequency j,; determined by the coil inductance and total capacitance of the grid circuit. The anodt· circuit is untuned. If increased energy absorption occurs in the sampie inside the coiL the oscillation amplitude is depressed. This results in an alteration of the anode voltage which is recovered, amplified, and recorded.
From the Department of Obstetrics and Gynecology and its Isotope and Spin Resonance Laboratory, Sabbatsbergs Ho;pital, Karolinska Institute!. Supported by a Grant from the Swedish Society for Cancer Research, Project No. 64:'10. Guest address, presented at the Thirty-first Annual Meeting of the Pacific Coast Obstetrical and Gynecological Society, Santa Barbara, California, N 01'. 4-7, 1964.
*E180F, special quality pt~ntodc, a hi~h gain and hl~h stability broad band pentodc manufactured hy J>hilips J.teL
592
Fig. 1. Front view, showin g the control panel of the RF spectrometer unit for in vitro recording of absorption. The sample tube, to the right, is surrounded by the oscillator coil , which is soldered to the RF leads and can be dipp ed into a water bath of 37° C. The oscilloscope screen to th(' left.
::J
co
0...
::J
0
II>
11>
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~
o·
0...
0
g_
:r
(/l
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(5"
e.
0C'l
a
3
0
::J
6.
..., a
o·
~
3
0... 0
~·
594
July I. 1111i'•
lngelman-Sundberg and Odeblad
\m.
J.
()h.,.L & ( ;ynt·r
Fig. 2. Equipment for intrauterine radiofrequency investigations in vivo at curettage. The RF generator (Philips) GM 2893, bottom) is connected to the exploration unit (top). This is made up of a box (left) and the intrauterine sound (right). Between the sound an d the RF generator is seen the unit, carrying the batteries for the transistor supply and th e microammeter.
Frequency-nonspecific absorption effects were directly read on a meter after radiofrequency detection. In order to display the specific absorption bands on an oscilloscope screen, the oscillation frequency was sinusoidally varied by about 1 per cent at 50 cycles per second in synchronism with the time axis of an oscilloscope. The frequency modulation was brought about with the a.id of the variable capacitance diode BA 101 (Telefunken) .* By changing the bias of the *Voltage
dependence
capacitor,
silicon
diode
capacitance depends on the applied backward voltage.
\Vhm;c
diode, the frequency could be slowly varied over a frequency range of about :+:30 per cent of the middle frequency. Different frequency intervals were covered by interchange of sample coils. In this way a complete frequency range between 10 and 108 megacycles per second could be investigated. Fig. 1 shows a view of the spectometer unit. The calibration of frequency was made by interference with standard quartz crystals, using the ground frequencies and overtones. The calibration of the magnitude of absorption was made by comparison with proton
Volume 92 :i
Short radio waves and endometrial carcmoma location
Num lu~r
595
Fig. 3. Inside view of the box of the RF exploration unit (shown in Fig. 2, top, left). From left to right, contact for RF intrauterine sound, twin-T bridge (shown in part), transistor RF amplifier, diode detector, and contacts to batteries and to microammt>ter.
magnetic resonance lines at 10.6, 25.1, 47.0, and 104.5 megacycles per second, using the permanent magnetic resonance in our laboratory. By insertion of proton samples with different proton magnetic relaxation times, some approximate information on the radiofrequency intensity inside the sample could also be obtained. The calibration of the widths of absorption lines was performed with a standard variable frequency oscillator* in connection with a frequency multiplier. Myometrium, endometrium, and carcinoma of the edometrium from patients were investigated. The samples were obtained at operation. Endometrium, myometrium, liver tissue, fat tissue, and blood were also obtained from mice and rabbits. Control runs with distilled water and saline were frequently undertaken. In vivo. On the basis of the in vitro investigations, recordings were undertaken in *GM 2893, a commercial manufactured by Philips Ltd.
radiofrequency
oscillator
vivo at fixed frequencies ( ll.6 or 13.3 megacycles per second), selected for working with both frequency-specific and -nonspecific radiofrequency absorption. The equipment for the in vivo studies consisted of a frequency generator and a RF exploration unit (Fig. 2). This, in turn (Fig. 3), consisted of a twin T-bridge 8 of a simplified construction and high stability/ a transistorized RF amplifier, and a diode detector. The bridge was preset at the frequency to be used, the final adjustment being performed at the operation. General anesthesia (pentothal + oxygen + nitrous oxide) was used. The cervical canal was dilated to the size of a Hegar 9 and the RF sound with the coil near the top was introduced into the uterine cavity (Fig. 4). The cavity and the cervical canal were then explored by successive scanning and the rectified voltage appearing at the detector diode was recorded. A drop in this voltage reflected an increased magnitude of tissue absorption of radio wave energy.
596
lngelman-Sundberg and Odeblad . \111 ,
Fig. 4. RF sound introduced into an extirpated uterus (Case RliS/63). To the left, in fundus uteri, there is the residual cance r remaining after radium trea tment, which preceded the operation.
The clinical material consisted of 12 patients; 7 of them underwent hysterectomy after the scannings (Table II'!. Results In vitro. Frequency-nonspecific absorption of water a nd saline was found between 10 and 105 megacycles per second. The magnitude of this absorption was rather large, about 400 parts per million (ppm ) of the RF energy over the whole frequency range. The frequency-nonspecific absorption of myometrium and endometrium was not, as expected, smaller, due to the lower water contents, but significantly higher (Fig. 5 ) . It was also observed that there occurred a shift of the oscillator frequency, when different tissues or water were introduced into the RF spectromete r. Frequency-specific absorption bands were found at about 11.6 and 13.3 megacycles per second . They were absent in pure water and ranged in tissues from 0 to 80 parts per million of RF energy. An example of a record, and some average RF absorption curves are shown in Fig. 6. Fig. 6 shows values of RF absorption of carcinomatous and norma l tissues from Case 9108/63. Endometrium shows a strong absorption, adeno-
.f
July 1 I ~11; :, Oh"t.. &
< ;yrrt·c.
carcinoma a moderate one and myometriuu1 a weak absorption around 1:Ll megacycle-; per second. Typical average results are also given in Table I, obtained on rabbit tissues . The results on human and mouse tissues arc of the order of size and occur at about tilt' same frequencies. In vivo. The results from l 2 cases ·;uh jected to intrauterine RF absorp tion measuremen ts are given m Table I L The measurements were undertaken with special reference to right-left asymmetry of RF absorption (Fig. 7 ·), because the electroni c sources of error are nearly ey ua l at such measurements. The difference between n~ad ings for the left and right sides of tht• uterine cavity are given, lower readings to the ldt thus giving negative values. The values givu 1 are in parts per million of RF energy and include the bridge balance facto r ' about 2,·<10 "i. It must be pointed out. that rht· bridge balance factor may wl'il vary hv :~o a nd <50 per cent. The average recorded difference for 9 patients. ~utTering from various gynecological diseases. was b "- ~ :\ parts per million \ standard deviation'. Thn'<' cases of carcinoma showed the fig ures 86. -•19+. and +ljO parts per million. wt'll outside the statistica l confidence limits for significamT. Table I. Magnitude of peak absorp tion of RF eneq,ry for some different samples obtained from rabbits. Each va lue represents the average of 3 or -+ recordings of the type shown in F ig. 6. Frequency (meg a-
cycle\ Myomeper sec- i trium and) [ (ppm)
lUi
- - --- --
· Serum
L iver
(ppm)
( ppm)
1 7
30 40
20 :10
20
+O
:Ill
g
:w
·Hl .')()
:HI :Hl
J-(l
]1_1
Ill
+O
BO g()
20
')
. ------·
1 metrium
( PPm)
9
I :1 .3
I En do-
')
6 7 15
:15
15
Short radio waves and endometrial carcinoma location
Volume 92 Number 5
ppm
1000
500
)(
•
597
:. water "myometrium
...
0 ::endometrium 0 0
0
••
•• •
0
X
X
0
•
• •
•
o•
•
•
0
• X
X X
xx
X
)(
X
X
X
X
X X
0+-----T-----~----~----~----r-----r-----r-----r-----r---~ 20 60 30 0 70 40 10 50 90 80 TOO Me/sec
Fig. 5. Frequency-nonspecific RF absorption in water, myometrium and endometrium from rabbits, investigated in vitro. Abscissa, oscillator frequency. Ordinate, approximate ppm scale for RF energy absorption. Calibration by comparison with proton nuclear magnetic resonance absorption signals at 10.6, 25.1, 47.0, and 104.5 megacycles per second.
ppm
9108/63
50
Adenocarcinoma
25 Myometrium
/
13.2
13.3
--~---1·-
1}.4
________.____ l'J/'I
~
--:
I
I
Me/sec
-!jf}
r
Fig. 6. Record of frequency-specific RF absorption band in endometrium (patient K3/63), obtained by phase sensitive detection. Average curves of specific tissue radiofrequency absorption in tissues from Patient 9108/63, read directly on the oscillograph screen.
598
lngelman-Sundberg and Odeblad
July 1, J% '1 .\m . j . Obst. & ("";y •n:c.
Fig. 7. Extirpated. bisected ut<> rus from Case 910H/ 63 ( ri g ht \ . ~ bowin g the uutrcaH·d endometrial carcinoma to the right in fundus. To the left a schematic drawing of the utt>rin e c;l\·ity with the absorption figur es in parts per million obtained a t intrauterine scanning t the zt' ro point a rbitrarily chosen) .
Figs. 4 and 7 illustrate two of the cases of endometrial cancer studied. Comment
In vitro. The largest part of the RF absorption in vitro is frequency-nonspecific and has been shown to occur within the whole frequency range investigated. It certainly corresponds to the dielectric dipole absorption of tissue water as mentioned in introduction. It was, however, observed, that the RF absorption in complex tissues largely exceeded what was expected from the water contents. This finding is currently being studied in more detail. The shift of the oscillation frequenc y is also the subject of extended investigations. The specific absorption bands constitute comparatively small effects. The question m ay be raised as to whether these are false effects. The presence of the effects in watercontaining tissues and their absence in fat tissue, pure water, and saline justifies the conclusion that they are real and present in the protein-rich tissues. It is of interest to point out, that the absorption bands occur
at about the same frequencies in samples from different species. Another important observation is the magnitude of the absorption, that ranges from 0 to 80 parts per million of the total RF energy. These two observations indicate, that physicochemical basis underlying the absorption bands is of similar nature in different tissues, but may differ quantitatively. It is not possible to give a satisfactory explanation for the absorption bands. Bach, Luzzio, and BrownelF· " have suggested unfolding of protein helices as the basis for absorption. They have also suggested , that the active frequencies should form a harmonic series with the fundamental frequencies between about 6 and 7.5 megacycles per second. Such suggestions are not in contradiction to our observations. In vivo. When perfonning the measurements in vitro, the geometrical rela tions between sample and coil arc constant and optimal, as the sample is localized inside the co:J. In the uterine cavity the conditions arc different, as the tissues lie outside the coil. To date, the measurements have been
Short radio waves and endometrial carcinoma location
Volume 92 Number 5
599
Table II. Clinical material and results of measurements of intrauterine RF absorption difference between contralateral symmetrical points
Patient identification R!IS/63 8178/63 K3/63 E4/63 T50d/63 9108/63 K80d/63 5663/64 7780/64 6273/64 6768/64 10939/63
Average asymmetry of radiofrequency absorption (ppm)
Hysterectomy performed
Carcinoma of the corpus uteri (radiotract) Polyp of the corpus uteri Myoma of the uterus
- 86
Yes
- 10 - 36
No Yes
Endometritis Dysmenorrhea Carcinoma of the corpus uteri Functional bleeding Carcinoma of the corpus uteri Tuberculous endometritis Myoma of the uterus Myoma of the uterus + atypical epithelium of the uterus
0 + 22 +194
No No Yes
10 +150
No Yes
- 16 - 34 + 32
No Yes Yes
-
Yes
Diagnosis
undertaken with an axially oriented coil, which does not allow separate recording of absorption in the anterior and posterior uterine walls. For the same reasons the direction and depth of malignant infiltration cannot be determined, but indications may be obtained on the surface spread. The resolution of the detection coil is also rather indefinite, of the order of i em. Special and high-resolution sounds are, however, being constructed. Gross capacitance and inductance factors may also come into play in vivo, when the sound is oriented in different directions in the body. By making symmetrical measurements bctvveen left and right these sources
of error are brought to a minimum and small absorption differences between symmetrical points apparently can be detected, as indicated by our results on the three localized endometrial cancers, when compared to the other cases with essentially symmetrical intrauterine conditions. Summary
Biological samples have been examined in vitro for radiofrequency absorption, when
4
In vitro spectrometry of tissues
Endometrium, polyp Endometrium, cervix, myoma, myometrium Endometrium Cancer, endometrium, myometrium Endometrium
introduced in the coil of a marginal oscillator, working in the range of 10 to 105 megacycles per second. Frequency-nonspecific absorption was present in the whole range, of an order exceeding the value expected from the contents of tissue water. Localized, weak absorption bands were, in addition, found at 11.6 and 13.3 megacycles per second. The samples examined consisted of blood serum, endometrium, myometrium, liver, and fat tissue from rabbits and mice and carcinomatous endometrium and normal uterine tissues from humans. No absorption bands were found in fat tissue, distilled water, and saline. The magnitude of the absorption bands increased in the order; 1nyon1etriurn, carcinomatous endometrium, normal endometrium, liver, and serum, i.e., nearly in the order of increasing water contents. In addition, shifts of oscillation frequency occurred, when different tissues were introduced in the coil. Clinical intrauterine measurements were performed in 12 cases at 1 L6 and 13.3 megacycles per second with a coil placed at the top of a perspex sound. The coil formed a part of a twin-T + amplifier + diode exploration unit. In 3 of these cases there was a
600
lngelman-Sundberg and Odeblad
carcinoma of the uterus, which in all cases gave rise to significant RF absorption differences between contralateral symmetrical points. The results were fully confirmed at
july L 1%:, Arn .
.f.
Ohst. & Cvnt·c.
hysterectomy. By intrauterine RF scanning it appears, therefore, possible to determine the surface spread of an endometrial carcinoma.
REFERENCES
1. Allgen, L. G.: Acta physiol. scandinav. (Suppl.) 22: 76, 1950. 2. Bach, S. A., Luzzio, A. ]., and Brownell, A. S.: Proc. Fourth Conf. Bioi. Effects Micro-Wave Rad. 1: 117, 1961. 3. Bach, S. A., Luzzio, A. ]., and Brownell, A. S.: Am. ]. Med. Electron. 1: 9, 1961. 4. Heller, ]. H.: Twelfth Conference on Electrical Technology, Medicine and Biology, Winner, New York, 1959, p. 56.
'i. Hopkins, N. ].: Rev. Sc. Instruments 20: 401, 1949. 6. Odeblad, E.: Unpublished work, 1964. 7. Saito, M., Sher, L. D., and Schwan, H. P.: 1961 International Conference of Medical Electronics, 1961. p. 154. H. Tuttle, W. :\1.: Proc. Inst. Radio Engrs. 28: 2:1, 19·to.