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Description  |
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BACKGROUND OF INVENTION
This invention relates to hyperthermia therapy in which the temperature of
living tissue is increased for therapeutic purposes, and particularly to
apparatus and method for microwave hyperthermia treatment.
Hyperthermia treatments have for many years been used for treatment of
cancers. It is known that raising of the temperature of cells to above
about 43.degree. to 45.degree. C. for sufficient time causes necrosis, and
temperatures below about 41.5 generally do not affect cells. Some types of
malignant cells reportedly can be destroyed by raising their temperatures
to levels slightly below those injurious to most normal cells. One of the
techniques which has been used for hyperthermia is heating of the blood of
a patient by an external apparatus, thereby raising the temperature of the
entire body or a portion thereof to the therapeutic temperature. This
procedure risks substantial injury to the patient if temperature is not
carefully controlled, and may fail to raise the temperature of the
malignant cells sufficiently for destruction. Any malignant cells which
remain undestroyed may cause a recurrence of the tumor, growth or
malignancy (hereinafter tumor).
Some surface tumors may be successfully treated by application of surface
heat from a heated object. Deeply located tumors, however, are difficult
to heat to therapeutic temperatures without destruction of the overlying
tissue.
Another hyperthermia technique uses electromagnetic radiation to heat
tissue. The electromagnetic radiation is often in the form of radio
frequency (RF) or microwave radiation because of the ease of generating,
controlling and directing microwaves, and also because of the absorption
characteristics of tissue at microwave frequencies. At the current state
of the art, microwave hyperthermia is usually at frequencies in the range
of 100 MHz to 5 GHz. Microwave hyperthermia when applied to tissue
containing a tumor generates heat within the tissue which raises the
temperature of the tissue generally. It has been found that tumors tend to
have a limited blood supply by comparison with healthy tissue. Thus, the
circulation of blood through a tumor is low by comparison with circulation
through healthy tissue. At any microwave power density, the tumor will
usually be hotter than the surrounding healthy tissue because the more
ample flow of blood in the healthy tissue provides cooling of the healthy
tissue. Thus the tumor may be heated by microwave hyperthermia to a
therapeutic temperature without significant effect on surrounding healthy
tissue.
It has been found that microwave hyperthermia when used in conjunction with
either radiotherapy or with chemotherapy provides more consistent success
than either alone. A course of treatment may include several radiotherapy
treatments each week, interspersed with microwave hyperthermia treatments.
Widespread practical application of such combined therapy depends upon the
availability of convenient and predictable microwave hyperthermia methods
and apparatus.
U.S. Pat. No. 4,448,198 issued May 15, 1984, to Turner describes an
invasive hypertherapy arrangement in which a plurality of microwave
applicators are inserted into body tissue. The surgical implantantion
requires the use of an expensive operating room and the services of a
skilled surgeon, which is not convenient. The applicators provide numerous
potential sites for infection and at least require care by the patient.
The implanted applicators may interfere with concurrent radiotherapy.
Since the dielectric constant of the tumor may differ from that of the
surrounding tissue, the energy from the microwave applicators may be
partially reflected by the tumor if the applicators are implanted in
healthy adjacent tissue, and this may result in an undesirable temperature
distribution.
Noninvasive microwave hyperthermia relies upon heating from applicators
placed outside the patient's body. This is particularly convenient for
small surface tumors, the extent of which can be readily seen. The
applicator is often held in contact with the surface being treated to
avoid excessive spreading of the energy. For small tumors, a single
applicator may be used. The center of the applicator is directed towards
the tumor, and the power is applied. Adjacent normal tissue is likely to
be at a lower temperature than the temperature at the tumor because a
simple applicator such as a horn has a power distribution which decreases
away from the center or axis. The temperature of the tumor may be
monitored by a small sensor inserted into the tumor. However, if the
temperature sensor is electrically conductive it may itself be heated,
thereby providing an erroneous indication that the tumor is being heated
Also, the electrically conductive temperature sensor may perturb the
field, for example by signal reflection, and therefore cause constructive
interference at a location away from the axis of the application. This may
undesirably damage normal tissue. If the probe is thermally conductive it
may undesirably cool the tumor.
Large tumors are more difficult to treat. When an applicator such as a horn
with a single aperture is used, the power distribution across the aperture
of the applicator may heat the center of the area to too high a
temperature, and thereby cause burning, or may not heat outlying portions
of the tumor to therapeutic temperatures. Failure to sufficiently heat
portions of the tumor allows regrowth of the tumor. Burned areas subject
to radiation therapy tend to heal slowly or not at al. Ordinarily,
radiation therapy is discontinued if the area to be irradiated is injured.
Any burning of a part of the tumor by microwave hyperthermia is therefore
undesirable, as it may limit therapeutic options. Other variables include
surface phenomena such as reduction of surface temperature by
perspiration, reflection of microwave energy by bone structures, and the
use of heating or cooling pads applied to the surface being treated. A
major cause of temperature differences is variation of blood flow to
various portions of the tissues being heated. Thus, the treatment of large
tumors presents difficulties not found in small tumors.
One known technique for hyperthermia treatment of large tumors is to use a
"blanket" applicator which is large enough to cover the entire area to be
treated. Such large area applicators are ordinarily made up of an array of
a number of relatively small antennas. While such an applicator is
theoretically plausible, there are practical difficulties. Since the
antennas are spaced one from another on the blanket, those portions of the
surface to be treated which lie immediately under an antenna element
receive substantially more power than those areas lying between antenna
elements and therefore tend to be heated more than outlying areas.
Attempts to improve the power distribution by phasing the antennas (as in
the Turner patent) to provide constructive reinforcement of the
hyperthermia energy at points between antenna elements often fail. The
failure comes about because the effective path length of the hyperthermia
power passing through a dielectric medium depends upon the dielectric
constant of the medium. When the medium is tissue, the dielectric constant
varies from point to point and also depends upon the type of tissue (fat,
muscle, etc.) through which the field passes. This results in a relatively
random distribution of heating, and in the occurrence of hot spots at
which burning of the tissue may occur, and also in cold spots at which
therapeutic temperatures are not obtained. Such burns may not be visible
and may undesirably remain unhealed for long periods if concurrent
radiotherapy takes place.
An applicator for providing a uniform microwave field over a relatively
large area is described in U.S. Pat. No. 4,271,848 issued June 9, 1981, to
Turner. Ideally, such a field should provide uniform heating of a region
of tissue. The heating effect will not be uniform, however, because of
differences in the amount of absorption of power from the field by various
different types of tissue. Even assuming that the heating attributable to
the applicator is uniform over the surface to be treated, therapeutic
results are not likely to be optimum, because of differences in the
vascularization (number and size of bood vessels) and blood flow of
various portions of the tissue or surface being heated. A plentiful supply
of blood vessels and plentiful supply of blood to one portion of the
tissue may result in much lower equilibrium temperatures during
hyperthermia than an adjacent area with a paucity of blood vessels and
poor supply of blood. Thus, the combination of uneven heating of the
tissue by the applicator and of variable amount of cooling by the blood
supply results in widely varying temperatures across the surface or
throughout the tissues being treated.
A method for treating large tumors is described in U.S. Pat. No. 4,397,314
issued Aug. 9, 1983, to Vaguine. This technique implants temperature
sensors in the tumor and in the surrounding tissue. A microwave generator
under control of the temperature sensors is coupled to a plurality of
external applicators and controls the energy applied to each applicator to
provide therapeutic temperatures inside the tumor with an overriding
protection of the surrounding healthy tissue. Individual microwave
applicators are evaluated during the hyperthermia treatment to determine
their effect on the overall heating pattern for optimizing the heating
pattern. Besides being invasive, this arrangement has the disadvantage
that implanted temperature sensors may have to be moved during the course
of the treatment as the tumor size is reduced and healthy tissue replaces
it. Since the size of the tumor and the physiological condition of the
patient change during the course of the therapy, the optimization of the
applicators must be done anew during each session of therapy. This is
labor-intensive, and the optimization is subject to human error.
SUMMARY OF THE INVENTION
A hyperthermia method by mechanically scanning an antenna and a
noncontacting temperature sensor together along a predetermined path over
the surface of that portion of the patient to be treated. The amount of
electrical signal coupled to the antenna is controlled in response to the
temperature sensed to maintain a predetermined temperature. An apparatus
which may be used to perform the method includes an antenna and a
noncontacting temperature sensor mounted on a mechanical scanner
controlled to make recurrent scans in a predetermined path over the
patient. The electrical signal or power from a generator is applied to the
antenna by way of a controllable attenuator. The attenuator is controlled
by a controller in response to a comparison of a signal from the
temperature sensor and a reference signal representing the desired
temperature.
DESCRIPTION OF THE DRAWING
FIG. 1a is a diagram, partially in block and partially in pictorial from,
of a hyperthermia apparatus according to the invention, and
FIG. 1b illustrates a rectilinear scanning path;
FIG. 2 is a plot of surface temperature versus position along a path over
the surface of part of the thigh muscle of a dog after hyperthermia
performed according to the invention;
FIG. 3 illustrates a source of error in temperature sensing;
FIG. 4 is a simplified isometric view of the antenna and temperature sensor
assembly illustrated in FIG. 1, partially cut away to illustrate the
interior;
FIG. 5 is a plot of field distribution and heating for an antenna such as
that illustrated in FIG. 4;
FIGS. 6a, b and c are more detailed cross-sectional, end and exploded views
of the assembly of FIG. 4;
FIGS. 7 and 8a are diagrams, partially in block and partially in pictorial
form, of other embodiments of the invention, and, FIG. 8b illustrates a
scan pattern associated with FIG. 8.
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1a illustrates an apparatus according to the invention. In FIG. 1a a
portion of tissue to be treated by hyperthermia is designated as 12 and
has a skin surface 13. A scanning head assembly designated generally as 14
including an antenna 16 illustrated as a loop and a noncontacting
temperature sensor 18 is mechanically scanned over the surface of tissue
portion 12 by an X-Y driver 20 and mechanical drive 22 designated together
as mechanical scanner 19. The scanning path over which the scanning head
assembly 14 is driven is controlled by a controller 24. Within the limits
of mechanical drive 22, controller 24 may preselect any portion of the
tissue for scanning. As illustrated in FIG. 1a, the scanning range is
illustrated by dimensions x and y. The rectilinear scanning path is
illustrated in FIG. 1b, together with the x-y limits established by
controller 24. As illustrated, the scanning path includes a plurality of
scans 80, 80', . . . 80'" separated by steps 82, 82', 82" . . . 82'" for
stepping the antenna from one scan position to the next scan position. At
the end of scan 80"', the antenna assembly returns from end position 84 to
starting position 86 along a path 88, to begin another scan. Thus, antenna
assembly 14 is scanned relatively rapidly over the surface in close
proximity to, but not touching, the surface being treated.
Antenna 16 and temperature sensor 18 are coupled to a temperature control
loop designated generally as 30. Antenna 16 receives power from an
electrical signal generator or radio frequency power generator 32 by way
of a controllable attenuator 34 and a transmission line 36. The power
produced by generator 32 is selected to be great enough to provide more
than the required amount of power for hyperthermia treatment of surface
tissue portion 12. Attenuator 34 is controlled by temperture sensor 18 in
a feedback manner by temperature control loop 30 so as to provide
moment-to-moment or instantaneous control of the amount of power flowing
from generator 32 to antenna 16 to compensate for variations from point to
point in the vasculature of tissue portion 12 and for variations in the
absorption of energy from the antenna field by the various types of tissue
which may be encountered in tissue portion 12. As mentioned above, such
variations from point to point in the absorption and in the amount of
cooling would prevent a uniform temperature in tissue portion 12 if the
amount of electrical power applied from point to point were uniform.
Feedback loop 30 includes noncontacting temperature sensor 18, which
produces a signal on conductor 40 representative of the instantaneous
temperature of the tissue portion heated by antenna 16. The temperature
indicative signal is applied to a temperature sensing and display
electronics illustrated as a block 42 which includes a readout 44 for
displaying the indicated temperature. Sensing and display electronics 42
also produces an output signal which is representative of the temperature
sensed by sensor 18 which is applied to an input terminal 46 of a
difference amplifier or comparator 48 by way of a differential amplifier
50. Comparator 48 compares the signal applied to input terminal 46 with a
reference signal applied to input terminal 52 which represents the
temperature to which the surface tissue portion 12 is to be raised. As
illustrated, the desired temperature setting is derived from a tap 54 on a
potentiometer 56 coupled to an appropriate power supply (not illustrated).
Comparator 48 produces a control signal on a conductor 58 which is applied
to an attenuator drive amplifier 60 for driving the active portion,
illustrated as a PIN diode 62, of attenuator 34. PIN diode attenuators are
known in the art. Temperature control loop 30 variably attenuates or
reduces the amount of power flowing from generator 32 to antenna 16 moment
by moment during the scanning of head assembly 14 over tissue portion 12
in order to maintain the desired temperature.
In a particular embodiment of the invention, the mechanical scanner 19 is a
commercially available Hewlett-Packard Model 9872A x-y plotter. This
computer controlled mechanical arm 19 can move the assembly 14 to any
location within a 28.times.40 cm rectangular field. This plotter is
compatible with a Model 85 Hewlett-Packard computer, also commercially
available, and the combination is capable of large numbers of
predetermined motions, one of which is illustrated in FIG. 1b.
In one embodiment of the invention, temperature sensor 18 is the sensing
head of a model C-600M biotherm noncontacting infrared thermometer
manufactured by Linear Laboratories, a Division of Linear Corporation, 445
South San Antonio Road, Los Altos, Calif. 94022. This instrument has a
temperature range of 10.degree. to 50.degree. C., a sensitivity of
0.1.degree. C. and an accuracy of 0.5.degree. C. The target diameter is
0.25"(0.6 cm) at 0.75" (1.9 cm). The infrared sensor used in the C-600M is
optically filtered to limit the response of the instrument to the infrared
spectral band from 8 to 14 microns. This head senses temperature at and
near the surface 13 of tissue portions 12 with a speed of response of
about 1/10 of a second. The circuit portions 42 of the C-600M produce an
output signal which changes one millivolt per degree centigrade of
indicated temperature. Because of the fast response of the temperature
sensor and of the remainder of control loop 30, relatively uniform
temperatures are achieved in the tissues being treated.
In a particular embodiment of the invention, generator 32 operated at a
frequency of 2450 megahertz (MHz) with a power of 100 watts. In a
particular test, the antenna and temperature sensor assembly 14 was
scanned in a pattern as illustrated in FIG. 1b over a rectangular area
having an x dimension of 7.62 cm and a y dimension of 7.62 cm, broken into
4 transverse scans 82 each having a length of 19.05 mm. The antenna 16 of
head assembly 14 was typically one to two cm above the treatment area.
Separate tests were conducted with the apparatus as so far described on
the thigh muscle of a dog and on a muscle equivalent phantom consisting of
68% H.sub.2 O, 30% gelatin, 1% NaCl, and 1% Formalin. The time required
for one complete scan over the area being treated was 11 seconds. After
heating was completed by recurrent scans, surface temperatures were
measured with the infrared sensor in steps at points separated by 6.35 mm
along an x scan lying in the center of the area treated. A maximum
temperature rise of 7.8.degree. C. uniform to within .+-.0.25.degree. C.
was obtained on the muscle equivalent phantom over a length of 4.2 cm of
the center of the x scan. FIG. 2 is a plot of the surface temperature
along a centered x scan after the heating of the thigh muscle of a dog.
The temperature is within .+-.0.1.degree. C. over a length of 4.4 cm.
FIG. 3 illustrates a problem which can occur when performing an x-y scan as
described in conjunction with FIG. 1a when the antenna, (illustrated as a
crossed dipole 316) is offset from the field of view axis 330 of the
temperature sensor, illustrated as 318. Tissue portion 312 is illustrated
in two positions, a close position 312' and a relatively remote position
312". When axis 330 of the field of view of temperature sensor 318
intersects surface 312' relatively close to antenna 316, surface 312'
receives maximum heating from antenna 316 at a position 332 on surface
312'. Position 332 corresponds with the position being viewed or monitored
by temperature sensor 318, and therefore the feedback control of
temperature will attempt to control the temperature at point 332 to the
desired temperature. When tissue portion 312 is in position 312" somewhat
more distant from antenna 316, the point on surface 13 receiving the
maximum amount of power from antenna 316 corresponds to point 334 on
surface 312". The position being viewed by sensor 318, however, is
position 336 at the intersection of axis 330 and surface 312". This
position does not correspond to the position receiving the maximum amount
of energy, so the feedback loop will attempt to control the power applied
to antenna 316 in order to maintain point 336 at the desired temperature.
This will result in points corresponding to 334 being raised to
excessively high temperature. This is undesirable, for reasons described
above.
FIG. 4 illustrates in simplified form the arrangement of the antenna 16 and
temperature sensor 18 in scanning head assembly 14. Basically, antenna 16
consists of a loop or convolution designated 407 formed by a first
elongated conductive element 410 formed into a semicircle and a second
elongated conductive semicircular element 412 formed into a complementary
semicircle, with a small gap therebetween in a feed region gap designated
generally as 422. Such loop antennas are well known in the art. Major
differences among various loop antennas include the method of applying
feed signal across feed point or gap 422 for energizing the loop, and in
the method for supporting the loop. As illustrated in FIG. 4, a cavity 413
is defined by a conductive housing 414 and a loop 407 is supported at the
opening of cavity 413 by a portion 416 of rigid coaxial cable (coax)
having an outer conductor 420 and a center conductor 424. Coax portion 416
passes through and is in turn supported at an aperture 418 in the closed
end of cavity 413. In order to feed signals to feed gap 422 of loop 407,
conductive semicircular element 410 is formed as the outer conductor of an
extension of coax portion 416, extending from a right angle bend at a
location 409 to feed gap 422. In order to clearly differentiate the
conductive outer portion of the outer conductor from the coaxial
transmission line within portion 410, the coaxial portion within
conductive loop portion 410 is designated 411. Coaxial cable portion 416
receives the hyperthermia electrical signals at its input end 420 and
couples them past bend 409 and through the interior portion 411 of
semicircular coaxial element 410 to loop feed gap 422. At feed gap 422
loop portion 410 ends, and its inner coaxial portion 411 also ends. The
center conductor 424 of coax portion 411 passes across gap 422 and
connects to solid semicircular conductive loop 412. This arrangement
drives the ends of conductive elements 410 and 412 near feed point 422
with mutually out-of-phase signals. The end of semicircular loop portion
412 remote from feed gap 422 is electrically connected to the outer
conductor 420 of coaxial element 416 at bend 409 as by a solder connection
illustrated as 426. This creates planar conductive loop 407 including
conductive portions 410 and 412, interrupted only by gap 422.
When the dimensions of loop antenna 16 are relatively small by comparison
with a wavelength at the frequency of the applied electrical signal, the
mutually out-of-phase drive signals at feed gap 422 create currents around
the loop which are in the same circumferential direction and relatively
uniform in their magnitude. Under these conditions, the magnetic fields
are directed generally in the direction of axis 408 in the region within
loop 16. Variations in magnetic flux due to the loop drive signal do not
cause a magnetic flux which crosses (is at right angles to) the length of
portion 432 of probe sensor 18. The variation of magnetic flux causes a
variation of intensity of that portion of the magnetic field coaxial with
probe portion 432, which produces relatively little in | | |
