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Description  |
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to heating human or animal tissue
(hyperthermia) and more particularly to electromagnetic radiation (EMR)
apparatus for heating local areas within such living body tissue.
2. Background Information
As is generally known, death, or necrosis, of living tissue cells occurs at
temperatures elevated above a normal cell temperature. Further, the death
rate of such heated tissue is a function of both the temperature to which
it is heated and the duration for which the tissue is held at such
temperatures.
It is also well known that the elevation of temperature of living tissue
can be produced with electromagnetic energy at frequencies greater than
about 10 kHz.
It has been reported that some types of malignant cells may be necrosed by
heating them to a temperature which is slightly below the temperature
injurious to most normal cells. In addition, some types of malignant cells
may be selectively heated and necrosed by hyperthermia techniques because
masses of these malignant cells typically have considerably poorer blood
flow and thus poorer heat dissipation properties than does the surrounding
normal tissue. As a result, when normal tissue containing such malignant
masses is heated by EMR (electromagnetic radiation), the resultant
temperature of the malignant mass may be substantially above that of
surrounding healthy cells.
Although some disagreement exists regarding exact temperatures, most
malignant cells have a relatively limited temperature range in which
hyperthermia is effective in causing necrosis. Below a thershold
temperature of about 41.5.degree. C. (106.7.degree. F.) insubstantial
thermal damage occurs even in those types of malignancies which have a
greater sensitivity to temperature than do normal cells. In fact, at
temperatures just below this threshold, growth of some types of
malignancies may be stimulated. At temperatures within or above 43.degree.
to 45.degree. C. (109.4.degree. to 113.degree. F.) thermal damage to most
normal cells occur. A discussion of hyperthermia in the treatment of
cancer is contained in "Physical Hyperthermia and Cancer Therapy" by J.
Gordon Short and Paul F. Turner in the Proceedings of the IEEE, Vol. 68,
No. 1, January, 1980 herein incorporated by reference.
Typically, EMR heating of body tissue is accomplished by holding an EMR
radiator, or applicator, adjacent to, or against, exterior portions of a
body, the EMR then penetrating and heating subsurface portions of tissue.
However, significant amounts of energy are absorbed by surface or
epidermis layers which may have to be cooled in order to prevent damage
thereto by overheating.
The amount of penetration, or the depth of which EMR causes effective
heating, is dependent upon the frequency of radiation.
For example, in accordance with an article by A. W. Guy, et al, published
in proceedings of the IEEE, Vol. 63, No. 1, January, 1974 entitled
"Therapeutic Application of Electromagnetic Power", the depth of
penetration in the human muscle and fat at 100 MHz is 6.66 cm (2.62
inches) and 60.4 cm (23.8 inches), respectively, while at 915 MHz the
depth of penetration is only 3.04 cm (1.2 inches) and 17.7 cm (6.97
inches), respectively.
In general, the lower the EMR frequency, the larger the applicator must be
in order to effectively radiate electromagnetic energy into the tissue
and, as a result, applicators for radiating electromagnetic energy below
one gigahertz tend to be large in size and cumbersome to handle.
Additionally, such applicators are not configured to selectively heat
tumors of various sizes and shapes located well beneath the surface layers
of the body being irradiated. Further, tumors, or other selected areas,
shielded by a layer of boney tissue such as a skull, are difficult to
effectively heat with externally applied EMR.
Invasive EMR applicators, that is, radiators which can be inserted into
body tissue to levels adjacent malignant tumors, or other localized
growths, for selective heating thereof, may cause nonuniform heating, or
"hot spotting" at or near the surface of such applicators because of
nonuniform field distributions. Such unwanted "hot spotting" is more
likely to cause serious overheating when such invasive applications are
operated at higher power levels in order to heat large localized growths
using a single applicator. Such growths may be many times the size of the
radiating area of an invasive type applicator.
An example of invasive EMR applicators are disclosed in U.S. Pat. No.
4,448,198 entitled "Invasive Hyperthermia Apparatus and Method" which
discloses the application of several invasive type applicators and a
method of using the apparatus to effectively heat relatively large
localized areas within living body tissue, without significant hot
spotting at or about the applicators.
Gammell discloses a similar apparatus in U.S. Pat. No. 4,346,715 which
issued Aug. 31, 1982 includes an array of contacting metal electrodes
operating the array with radio frequency energy in the range of 500 KHz in
a way to cause an isothermal rotating electric field which is confined to
the area of the tumor or lesion.
Doss et al. also developed an invasive electrode array described in U.S.
Pat. No. 4,016,886 in April of 1977 and which produced a heating field
from a fixed current field being established by connecting metal needles
directly contacting the tissue. Doss teaches the operation of this
apparatus at low radio frequencies below 1 MHz.
German Patent DAS No. 1143937 issued in February, 1963 describes a similar
two electrode array. This apparatus also placed metal electrodes in direct
contact with the body. With a grounded outer conductor, the heating field
may be 3 phased causing microwave energy to have current fields parallel
to, and perpendicular to the electrodes. The heating field would be
locally positioned at the tips of the electrodes.
German Patent DT No. 2815156 to convert describes an electromagnetic
radiating apparatus which is inserted into the tissue to apply HF (high
frequency) electromagnetic waves to heat living tissues. This apparatus or
probe is adapted to radiate the waves into the tissue like an antenna.
Also, multiple arrays of this probe may be used. This device operates at
higher frequencies (300-2000 MHz) than the other referenced devices
because the inner and outer coax conductors form a monopole type radiating
antenna. The earlier references operate as metal contact electrode pairs
or arrays which by virtue of their contact to the tissue can induce
currents to flow in the tissue. These tissue current fields terminate
perpendicular to the inserted electrode surfaces.
The current fields of current are substantially parallel to the radiating
shaft as is well known in the sciences for monopoles and dipoles.
Turner disclosed in U.S. Pat. No. 4,448,198 a similar apparatus and method
of radiating invasive monopoles was described. This apparatus also
operates at high frequencies.
The Oximetrics Corporation has developed a specially designed catheter
which has an internal hollow dielectric surrounded by a metal braid which
is coated with a removable outer dielectric layer. This enables the
clinician to remove segments of the outer dielectric coating to provide
selective contact between the metal braid and the surrounding tissues into
which the catheter is inserted. This technique applies 500 KHz currents
directly into the tissue to cause a local current field between electrode
referenced by a presentation at North American Hyperthermia Group by S. D.
Prionas, et al, "Interstitial RF Hyperthermia Plus Brachy Therapy of
Neoplasma," Stanford University School of Medicine. Clinical use in
stimulation of muscle and nerve tissues has shown that this apparatus
requires special precautions to shape the waveform or eliminating the
current field prior to switching active electrode pairs. These
observations have been reported by independent researchers who have shown
such stimulation is observed as high as 1 MHz. These researchers have
indicated such stimulation is potentially hazardous. Some of the hazardous
effects are obturator muscle spasm, cardiac ventricular fibrillation, and
pacemaker malfunction referenced by John R. LaCourse, et al., "Effect of
High-Frequency Current On Nerve and Muscle Tissue," IEEE transaction
BME-32, No. 1, January 1985, pp. 82-86.
This results in the stimulation threshold current increasing montonically
with increasing frequency. Therefore, the stimulation current at 50 MHz
would be expected to be about 50 times more than the stimulation current
at 1 MHz. Thus, for frequencies above 1 MHz tissue, destruction or
desiccation probably occurs before the stimulus threshold current can be
reached.
The use of frequency of approximately 10 MHz or more would eliminate this
potentially hazardous stimulation potential.
The apparatus and methods described by Gammell, Doss, and Oximetrics use
the lower frequencies near 500 KHz with contacting metallic electrodes.
That of Fritz also uses contacting metal electrodes but with higher
frequency microwave fields being radiated.
Convert and Turner methods patented earlier both use radiating
electromagnetic waves from each electrode or applicator acting like a
monopole antenna.
All these methods require metallic contact to the tissue and sterilization
of the electrode or applicator. This would be difficult for repeated use
since each has exposed material interfaces which would be difficult to
clean after use.
The method and devices of this invention includes the use of a sterile
catheter or dielectric tube placed into the tissue to enable the
applicator insertion therein. The catheter would either pass completely
through the tissue exposing both ends to the outside air, or the catheter
would have a closed tip. The use of the high frequency selective
capacitive coupling through the catheter is distinctly different from the
established prior art.
The procedure to install such catheters is quite common in radiation
therapy, where radioactive seeds or wire ribbons are inserted into a
number of these catheters to radiate a tumor from inside with ionizing
radiation. It has been shown that adding tissue heating to ionizing
radiation enhances tumor cell killing and regression. The method of using
the standard dielectric catheters (nylon or teflon) for local capacitive
heating inside the tumor should minimize treatment costs and improve
clinicians acceptance. This method is therefore a significant improvement
over the direct contact applicator methods and also different from these
methods.
It is the object of the present invention to provide an applicator for
inserting into body tissue through a dielectric catheter or sleeve for
locally heating these tissues.
It is further the object of the present invention to provide an enlarged
diameter metal section for more selective heating in the intended area
with reduced heating in the zones of smaller electrode diameters. This is
a result of larger capacitance from the enlarged metal section through the
catheter to the tissue than the capacitance of the smaller metal sections.
It is still further an object of this invention to provide a system to
provide UHF electromagnetic (EM) signals capable of flowing through the
catheter wall capacitive impedance.
It is still further an object of this invention to provide an applicator
and system which enables the temperature of the electrodes to be measured
with or without EM signals being applied to the applicator for the control
of the EM power to each applicator to achieve the desired elevation of the
tissue temperatures around each applicator.
SUMMARY OF THE INVENTION
In accordance with the present invention an applicator is provided for
capacitive coupling electromagnetic energy into local areas of body
tissue. The applicator includes an enlarged diameter metallic section for
selectively coupling electromagnetic currents into the body tissue and
further includes temperature sensing capability for providing an
indication of the adjacent body tissue temperature.
In one embodiment of the present invention, an applicator for capacitive
coupling electromagnetic energy into the local regions of body tissues is
provided that includes a coaxial cable having an outer conductor shorter
in length than the center conductor whereby the temperature sensing
apparatus is connected between the outer and inner conductors by two long
twisted wires. In this embodiment, the temperature sensing apparatus
includes thermistors each having an impedance at least 100 times greater
than the impedance of the applicator array at the electromagntic operating
frequency and distributed along the applicator to detect temperatures in
different regions. Also in this embodiment, one of these wires connects
the enlarged diameter metal coupling region to the coax center conductor
to increase the capacitance coupling of electromagnetic energy to the
surrounding tissue.
In a further embodiment, a method for operating the hyperthermia
electromagnetic capacitive coupling applicator is disclosed that includes
providing an electromagnetic field of energy to the application while
simultaneously providing a direct current to the applicator for
determining the surrounding tissue temperature.
Still further, a method for operating the hyperthermia electromagnetic
radiation applicator that includes a temperature sensing device for
indicating temperature variations in the surrounding body tissue is
provided that includes the steps of providing direct current energy while
simultaneously and intermittently providing high frequency electromagnetic
energy to the applicator. The voltage drop across the applicator is then
measured both during the time that the electromagnetic energy is being
applied and the time that the electromagnetic energy is absent. Since, in
this method, the temperature sensing device absorbs a portion of the
electromagnetic energy, the resulting measurements during the time that
electromagnetic energy is absent is used to determine the temperature of
the surrounding tissue. The measured voltage during the time of
application of electromagnetic energy is used to determine the high
frequency power output of the applicator.
In a still further embodiment of the present invention, an electromagnetic
hyperthermia apparatus is provided for heating local regions of body
tissue and includes a source of electromagnetic energy connected to a
plurality of electromagnetic energy capacitive applicators that are
inserted in the body tissue. A control apparatus is interconnected between
the electromagnetic power source and each applicator that controls the
amplitude and/or phase from each applicator in accordance with the
temperature indicated by the applicator and a desired heating pattern. In
operation, this control device varies the energy output from the
applicators in order to produce the desired heating pattern as indicated
by the temperature sensing devices in the applicators.
In one embodiment, the electromagnetic capacitive applicators are connected
to an applicator multiplexer which includes an attenuator controlled by
the control device. The multiplexer enables one of several groups of
applicators to be powered whereby the groups may include different numbers
of applicators.
BRIEF DESCRIPTION OF THE DRAWINGS
The novel features believed characteristic of this invention are set forth
in the appended claims; however, this invention can be best understood by
referencing the Detailed Description of the Embodiment together with these
drawings.
FIG. 1 is a block diagram of the capacitive coupling electromagnetic
hyperthermia apparatus.
FIG. 2 is a block diagram of the microwave thermometry multiplexer for
connecting the applicator electrodes.
FIG. 3 is a plan view of a capacitive coupling applicator, a catheter, and
a hyperdermic needle.
FIG. 4 is a partial sectional view of a capacitive coupling applicator.
FIG. 5 is a schematic diagram of a pair of capacitively coupled
applicators.
FIG. 6 is a software flow chart of the software used to calibrate the
temperature sensing thermistor of the capacitive coupled applicator, and
correct for any local thermistor heating resulting from RF potentials
across the thermistor.
DESCRIPTION OF THE PREFERRED EMBODIMENT
This invention relates to a system for the treatment of cancer by
hyperthermia. Specifically, the system includes several microwave or UHF
capacitive applicators that are inserted into living tissue in a
dielectric catheter in or around a cancerous growth. EM energy is then
distributed to these applicators which together provide a capacitive EM
field in the tissue which is used to heat the cancerous growth to a
temperature which destroys the cancerous growth but leaves the normal
living tissue surrounding the cancerous growth unharmed. In this
invention, the applicators include an enlarged diameter EM energy coupling
metal shaft at the tip and a temperature measuring capability enabling the
system to provide EM energy and determine the resulting heating of tissue
surrounding the applicators.
FIG. 1 is a system block diagram of a typical system of the present
invention. The system includes a microwave or UHF generator 12 that is
connected by an RF power transmission line 24 to a Balun line splitter.
The Balun splitter 18 distributes RF power between two coaxial lines 32
and 33 to the microwave thermometry multiplexer 13.
The multiplexer is connected to typically two to sixteen probes via RF
coaxial transmission lines. For instance, the microwave thermometry
multiplexer 13 is shown in FIG. 1 connected to eight RF transmission lines
37-44 that are respectively connected to eight applicators 45-52. The
applicators are inserted inside eight catheters 53 to 60 which have been
placed in the human tissue 100 around the area to be heated.
The amount of average power provided to each applicator is controlled by
its respective multiplexer switch setting. The control of the switch
position may be manual or may be controlled by a central processing unit
10. In FIG. 2, the 8 switches 61-68 are each connected to one of the two
opposing phase input lines A and B represented by lines 32 and 33. When
controlled by the CPU line 31 would actuate switches 61 to 68 as relays by
cable 31. In this manner, the central processing unit 10 may control the
amount of average RF power distributed to each of the applicators 45 to
52. It should be understood that the switches may also be replaced by any
means for regulating power distribution to the applicators such as
attenuators, amplifiers, mismatched tuning sections or the like.
The applicators 45-52 may include temperature sensors. The temperature
sensors are also connected to the microwave thermometry multiplexers 13
through the respective lead lines as shown. The output of the temperature
sensing devices is connected to the temperature interface circuitry 14 via
a cable represented by line 26 from the connected multiplexer as shown.
The temperature sensor information is then provided to the central
processing unit 10 via line 22. In practice, the output of the microwave
thermometry multiplexer may be a single multiplexed line for all the
sensors connected to the multiplexer or it may be individual discrete
lines from each of the applicators to the temperature interface circuitry
14. The central processing unit 10 will be able to adjust the amount of
average power to the applicators in accordance with the indicated
temperatures to treat the tissue area with a predetermined heating
pattern. During treatment, the central processing unit 10 will monitor the
indicated tissue temperatures from the applicators and make whatever
adjustments are necessary to the capacitively coupled EM power distributed
to the applicators.
The implementation of the timing of the RF power and temperature monitoring
is important to insure the accuracy of heating of the tissue. However, the
applicator can be designed to provide adequate temperature accuracy
without the need of special timing of RF power and temperature monitoring.
In one implementation, power is applied to the individual applicators while
temperature is measured. Power is then turned off to allow the temperature
sensors to cool wherein again temperature is measured. Since the tissue
requires more than two seconds to substantially cool, by turning the power
off the temperature may be accurately measured since the temperature
sensors will normally cool off much faster than the two seconds. By
switching RF power on and off from the microwave generator 12, the
temperature sensors may be calibrated to determine what portion of the
temperature increase during the power on is generated by the heating of
the temperature sensors themselves. The central processing unit 10 is then
used to regulate the amount of power applied to each of the applicators to
produce a specified heating pattern in the body tissue 100. If the
temperature sensors do not heat up sufficiently to result in a discrepancy
of reading during the application of RF power, the temperature measured
during the application of RF power to the body tissue 100 will be used to
control the resulting heating pattern. This characteristic can be obtained
by proper applicator design described in the applicator details.
A further system enhancement includes the independent control of amplitude
and phase to control the heat pattern. This would improve the capability
to provide the desired heat patterns. Since lines A and B (32 and 33) are
180 degrees out of phase the switches (61-68) shown for each applicator
can be connected to either line A or B or to an open connection.
MULTIPLEXER
Clinical use of this system of FIG. 1 will vary in the number of
applicators actually required for use. Typically, between 2 and 16
applicators will be used. To improve clinical use and speed of the
changing of the number of applicators. The probes will attach to a coax
quick disconnect connector to the multiplexers.
FIG. 2 is a block diagram of multiplexer 13. In practice, multiplexer 13
may contain many more applicator channels than shown. Each probe is
connected to an individual decoupling circuit such as 70 to 77 as shown.
The DC decoupling circuit includes a simple capacitance and inductance to
provide a DC direct current signal on the DC lines 78 to 85 which may be
multiplexed or discretely connected to the temperature interface circuitry
previously discussed. The DC coupling circuitry 70 further provides the RF
connection between the switch 61 via line 86 to the probe via line 101 as
shown. In this manner, the probe receives the RF power while providing a
direct current temperature sensing indication signal.
In the embodiment shown in FIG. 2, each of the switches 61-68 provide the
connection to a group of applicators. All applicator probe outputs need
not be connected for fewer operating applicators. At least one applicator
must connect to channel A and at least one must connect to channel B to
enable current to flow between channel A and B through the tissue to be
heated.
APPLICATOR
FIG. 3 illustrates the applicator 200 together with a catheter 212 and a
hypodermic needle 214. In the preferred embodiment, the catheter 212 is
dry catheter (i.e. closed tip) and will be inserted into the body tissue.
In practice, the catheter is a 16 gauge catheter. The applicator 200 will
then be inserted inside the catheter 212. The applicator 200 includes the
connection 202 and a coaxial cable shown as 204, and small wire twisted
lead section having an outside coating 206 and terminating with a tip 208.
The blunt tip hypodermic needle 214 is provided to indicate the relative
size of the applicator and catheter. The blunt tip needle can be used
inside the catheter to stiffen the catheter during insertion into the
tissue and then removed. The catheter can also be inserted by a larger
removable hollow hypodermic needle.
The interior of the applicator is illustrated in FIG. 4 as a partial
cross-sectional view. The connector 202 is connected to a lead line as
shown in FIG. 1. FIG. 4 illustrates that the applicator consists of two
lengths L1 and L2, where L1 is the length of the small diameter conductor
with an outer dielectric sleeve shown as 260 and L2 is the length of the
enlarged diameter tip conductor tube 252 portion including the metallic
tip connected to the center conductor 261. The conductor attaches to a
threaded or snap on connector 262 connected to the coax center conductor
261 and temperature sensing device 254 typically a thermistor. The coax
outer 210 is connected to a conductor 263 which is wrapped around and
insulated from the center dielectric 261. Wires 261 and 263 are connected
to the temperature sensor 254. These wires are insulated by a dielectric
sleeve 260.
Shown in this embodiment is a thermistor 254 that is connected to the outer
conductor 210 by a resistive conductor 263. A resistance of over 50
kilo-ohm will prevent a significant RF voltage across the thermistor with
typically a 5 megohms resistance at 25.degree. C. In practice, the
applicator provides EM capacitive coupling through the dielectric catheter
selectively from the enlarged tip 252 while providing a temperature
indication of the region from the resulting resistance of thermistor 254.
Here the outer conductor 210 is cut back from the tip to expose the small
diameter center conductor 261 as shown. The coaxial dielectric insulator
may be used to insulate the resistive conductor 263. The 5 megohms
thermistor 254 between the center conductor 261 and the lower resistance
(typically 100 kilo-ohms) resistive conductor 263 add in series to enable
the accurate measurement of temperature. In practice, the thermistor 254
is a microscopic chip that is inserted between the two leads conductor 261
and the resistive conductor 263 as shown. The resistance of the thermistor
254 changes as temperature changes. Therefore, by placing a DC voltage
across the outer conductor 210 and center conductor 261, the resulting
measured resistance indicates the temperature of the tip region.
The location of the thermistor inside the enlarged tip conductor enables
the small mass thermistor to remain basically at the metal tip region
temperature. If insufficient resistance is in lead 263 heating for the
thermistor may occur because of the presence of the RF field. However, by
determining the slopes of cooling, the heat resulting from the selective
RF power absorption of the thermistor may be distinguished from the
temperature of body tissue.
The approximate capacitance of the interface between the tissue and the
enlarged tip metal tube (252) can be determined by the following equation:
##EQU1##
Where E.sub.o is permittivity of space which is 8.85.times.10.sup.-12
farad/meter, E.sub.r is the dielectric relative permittivity, b is the
catheter outer diameter and a is the catheter inner diameter. The tip
(252) is assumed to fill the catheter opening. The capacitive coupling
impedance is:
##EQU2##
where .omega.c is radians per second. For standard 16 gauge teflon
catheter E.sub.r =2 b=0.066 inches and a =0.043 inches. So the capacitance
at the tip is 260 picofarad/meter of length. This is -j205 ohms at 100 MHz
for a 3 cm long tip.
The center conductor 261 for this size applicator is typically 0.008 inches
in diameter.
Assuming the dielectric sleeving 260 is also teflon and fills the inside of
the catheter, the capacitance from lead 261 and the tissue can also be
calculated using a modified value for a as 0.008 inches. The value of C
for lead 261 is 53 picofarads/meter. For the 100 MHz and 3 cm length
example this would be an impedance of -j 1,006 ohms. Some heating is to be
allowed in the tissue surrounding lead 261, but the intent of this
invention is to provide increased heating at the local tip zone defined by
a selectable length (L2) tip zone. The current flow from the applicator
into the tissue is divided inversely proportional to the total resistive
values loading the local applicator locations. As long as the tip 252 and
lead wire 261 lengths are much less than a quarter of a wavelength long,
the inductance of the lead will be small. This will place the lead 261 at
the same electrical potential as the tip (252).
FIG. 5 shows an equivalent schematic diagram representing the capacitance
of the tip region C.sub.c and the capacitance of the wire region C.sub.w.
Each are loaded by muscle tissue which has a complex dielectric constant
K* of 160-j72 at 100 MHz. The tissue resistivity is r=-j/K*E.sub.o
.omega., ohm-meters or r=0.42-j0.94, ohm-meters. For a 3 cm length this is
a tissue resistance R.sub.r of approximately R.sub.r =14-j31 ohms. Since
R.sub.r is so much lower than the impedance of C.sub.w and C.sub.c, the
amount of current flow along each capacitance C.sub.w and C.sub.c is
dominated by the capacitive impedance of C.sub.w and C.sub.c. In fact, the
current division is inversely proportional to these capacitive impedances.
Therefore, within a 3 cm tip section of enlarged diameter at 100 MHz the
impedance is -j205 ohms. The same distance for the conductor 261 provides
a -j1,006 ohms. The resulting current density ratio flowing into the
tissue from the tip compared to that of the wire 261 is 1,006/205=4.91.
Since the power absorption in the tissue is proportional to the current
squared, the power density is 24 times higher around the tip 252 for this
example than around conductive small diameter connection wire 261.
Therefore, selective heating of tissues around the enlarged tip region is
the result.
As frequency is increased or wire 261 lengthened, the inductance of the
small diameter can begin to increase, the inductance of this lead will add
in series with the lead connecting C.sub.w and C.sub.c on the diagram of
FIG. 5. This may result in some increase heating around conductor 261 with
a corresponding decrease around the tip 252. Therefore, dimensional limits
exist on the upper frequency that is permitted for a length L1 of
conductor 261. In practice, the maximum length L1 in inches is related
frequency in MHz by the following relationship.
L1<1350/f (MHz), inches
Other calculations have concluded that at 100 MHz | | |
