CA2116970A1 - Catheter depth, position and orientation location system - Google Patents
Catheter depth, position and orientation location systemInfo
- Publication number
- CA2116970A1 CA2116970A1 CA002116970A CA2116970A CA2116970A1 CA 2116970 A1 CA2116970 A1 CA 2116970A1 CA 002116970 A CA002116970 A CA 002116970A CA 2116970 A CA2116970 A CA 2116970A CA 2116970 A1 CA2116970 A1 CA 2116970A1
- Authority
- CA
- Canada
- Prior art keywords
- sensor
- probe
- coil
- signal
- magnetic field
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000000523 sample Substances 0.000 claims abstract description 82
- 230000004044 response Effects 0.000 claims abstract description 14
- 230000001939 inductive effect Effects 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims description 8
- 238000010586 diagram Methods 0.000 description 6
- 238000001514 detection method Methods 0.000 description 4
- 238000002594 fluoroscopy Methods 0.000 description 4
- 230000009977 dual effect Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 239000003990 capacitor Substances 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 239000004973 liquid crystal related substance Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000004065 semiconductor Substances 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 101000860173 Myxococcus xanthus C-factor Proteins 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000013307 optical fiber Substances 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- ACWBQPMHZXGDFX-QFIPXVFZSA-N valsartan Chemical class C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=NN1 ACWBQPMHZXGDFX-QFIPXVFZSA-N 0.000 description 1
- 229910000859 α-Fe Chemical group 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01V—GEOPHYSICS; GRAVITATIONAL MEASUREMENTS; DETECTING MASSES OR OBJECTS; TAGS
- G01V3/00—Electric or magnetic prospecting or detecting; Measuring magnetic field characteristics of the earth, e.g. declination, deviation
- G01V3/08—Electric or magnetic prospecting or detecting; Measuring magnetic field characteristics of the earth, e.g. declination, deviation operating with magnetic or electric fields produced or modified by objects or geological structures or by detecting devices
- G01V3/10—Electric or magnetic prospecting or detecting; Measuring magnetic field characteristics of the earth, e.g. declination, deviation operating with magnetic or electric fields produced or modified by objects or geological structures or by detecting devices using induction coils
- G01V3/104—Electric or magnetic prospecting or detecting; Measuring magnetic field characteristics of the earth, e.g. declination, deviation operating with magnetic or electric fields produced or modified by objects or geological structures or by detecting devices using induction coils using several coupled or uncoupled coils
- G01V3/105—Electric or magnetic prospecting or detecting; Measuring magnetic field characteristics of the earth, e.g. declination, deviation operating with magnetic or electric fields produced or modified by objects or geological structures or by detecting devices using induction coils using several coupled or uncoupled coils forming directly coupled primary and secondary coils or loops
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/06—Devices, other than using radiation, for detecting or locating foreign bodies ; determining position of probes within or on the body of the patient
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/06—Devices, other than using radiation, for detecting or locating foreign bodies ; determining position of probes within or on the body of the patient
- A61B5/061—Determining position of a probe within the body employing means separate from the probe, e.g. sensing internal probe position employing impedance electrodes on the surface of the body
- A61B5/062—Determining position of a probe within the body employing means separate from the probe, e.g. sensing internal probe position employing impedance electrodes on the surface of the body using magnetic field
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B34/00—Computer-aided surgery; Manipulators or robots specially adapted for use in surgery
- A61B34/10—Computer-aided planning, simulation or modelling of surgical operations
- A61B2034/107—Visualisation of planned trajectories or target regions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B34/00—Computer-aided surgery; Manipulators or robots specially adapted for use in surgery
- A61B34/20—Surgical navigation systems; Devices for tracking or guiding surgical instruments, e.g. for frameless stereotaxis
- A61B2034/2046—Tracking techniques
- A61B2034/2051—Electromagnetic tracking systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
- A61B90/39—Markers, e.g. radio-opaque or breast lesions markers
- A61B2090/3954—Markers, e.g. radio-opaque or breast lesions markers magnetic, e.g. NMR or MRI
- A61B2090/3958—Markers, e.g. radio-opaque or breast lesions markers magnetic, e.g. NMR or MRI emitting a signal
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B34/00—Computer-aided surgery; Manipulators or robots specially adapted for use in surgery
- A61B34/20—Surgical navigation systems; Devices for tracking or guiding surgical instruments, e.g. for frameless stereotaxis
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01F—MAGNETS; INDUCTANCES; TRANSFORMERS; SELECTION OF MATERIALS FOR THEIR MAGNETIC PROPERTIES
- H01F5/00—Coils
- H01F5/02—Coils wound on non-magnetic supports, e.g. formers
- H01F2005/027—Coils wound on non-magnetic supports, e.g. formers wound on formers for receiving several coils with perpendicular winding axes, e.g. for antennae or inductive power transfer
Abstract
A system for externally locating the depth and orientation of a catheter (9) in tissue with an external probe (12) which generates a virtual rotating magnetic field. The catheter (9) includes an inductive coil (30) for developing an induced signal in response to the virtual rotating magnetic field. An indicating device (6) such as a light bar display or digital readout indicates the strength of the induced signal for locating, independently of the relative angular orientation of the probe and the catheter, the depth in the tissue of the catheter.
Description
WO93/Oq628 PCT/VS92/07253 2116~)7U
CATHETER DEPTH, POSITION AND ORIENTATION
LOCATION SYSTEM
FIELD OF INVENTION
This invention relates to a system for locating the depth, orientation and position of a ca~heter inside biological tissue.
BACKGROUND OF INVENTION
In today's practice of medicine, catheters are routinely required to be positioned inside the human body. Catheters are frequently hollow tubes that infuse fluids into or extract fluids from body organs. Catheters may also contain conductive wires for delivering electrical impulses, such as pacemaker wires, or contain devices for sensing physiological fun~tions such as temperature, blood pressure! and cardiac output. Catheters may contain optical fibers for observing the interiors of body organs. A catheter may also be solid, :
such as a guide wire which is used~to direct other catheters into ~ody orifices,~incisions or vessels.
Typically, catheters may be~placed in the cardiovascular system, the dlgestive~tract,~the respiratory system, soft tissue, or other internal systems such as the excretory system. In~most instances, cathe~ers are placed using fluoroscopy or x-ray as a guide both during the procedure and as a confirmation that the device has been properly positioned.~ However, because of the cost of the equipment, fluoroscopy and x-ray are generally available only in the high~cost operating~room setting or in special procedure laboratories. Furthermore, there is a real concern about the ::
repeated exposure of physicians, nurses and technicians to ; excessive radiation because of the multiple exposures required during placement and confirmation.
W093/~628 PCT/VS92/072S3 2 ~
Two approaches to resolving these problems are disclosed in Van Steenwyck et al., U.S. Patent No. ~,173,228, and Strohl, Jr., et al., U.S. Patent No. 4,905,698. Van Steenwyck et al. disclose a catheter locating device which employs a sensing coil of wire embedded in the tip of a catheter tube, with the two coil wires brought out of the catheter to an external amplifier and detec~or circuit. The external probe contains two electromagnetic coi}s, one parallel to the skin (hereinafter called horizontal because the patient is generally ln a supine position) and the other perpendicular to the skin (hereinafter called vertical), each driven by an electronic oscillator so that a high frequency, time-varying magnetic ~fiéld is gènerated by either coil. The device has a switch for alternately energizing one or both of the coils. The~sen~sing coil in the catheter senses the strength of the magnetic field generated by the horizontal (parallel): external coil, and the phase of ~he field generated by the~vertical~ (perpendlcular) external coil. The field;strength at~the sensor coil is:inversel~related to the dist~nce between the~horizontal coil and the sensor coil.
The relative~phase between the~vertical coil drive signal and the sensèd signal: is indicatlve~of~the position of the vertical coil in~relation to the sensor coil; the:signals are ::in phase when the~vert1cal: coil is~ behind.the sensor coil, the signa:l~ are~out~of~phase when~the vertical coil is in front of the sensor coil, and there is no induced signal in the sensor coil;when the vertical coil is directly over the sensor coil.
Although:the Van~Steenwyck et~al. device can relatively ~ ::: :
accurately locate~the~or~lentation~and posltion of the ~: catheter, it has a number~of disadvantages which make it difficult and time consumlng to use in the clinical setting.
First, the device requires~repeated scans with the probe parallel, the~ p-rpendicular, ther rotated relative to the :
:
W093/04628 PCTtUS92/~72~3 211~70 marking several external probe positions on the patient's skin and drawing a connecting line between them in order to establish the position of the sensor. Finally, the device requires switching repeatedly between the two external coils in order to ~erify the position and direction of the catheter sensor coil. Between 8 and 12 separate steps are necessary in order to establish the catheter position and direction.
Furthermore, no quantitative indication of depth is given by the Van Steenwyck et al. device. The depth of the catheter below the surface of the skin can only be inferred from the signal strength displayed on the meter and from the setting of the range-selector switch.
;~
SUMMARY OF INVENTION
It is therefore an object of this invention to provide a system which is simple and easy to usé for externally locating the position, angular orientation and depth of a catheter.
It is a further object of this lnvention to provide such a~system which does not reguire repeated scans in a number of different directions.
It ~is a further~obj~ect of this invention to pro~ide such a system~which does not require marking probe positions on the patient's~skin.;~
-~ It is~a~further object~of~this i~vention to provide such a system whlch does not require the operator to switch between coils.
It is a~furthe~r ob~ect o;f this~invention to provide such a system wh~ich completely~ellminates~the need for x-ray or ~; ~ fluoroscopy guidance during catheter placement.
It is a further object of~this~invention to provide such a system which gives~a numerical~ display of the depth of the catheter below the skin,~and a displ~ay lndicating the direction in which the catheter is pointing.
W~g3/04~28 PCT/U~92~07253 2~ 1 ~97D
This invention accomplishes the above objects, that is, an effective, easy to use catheter location system, by providing a pair of mutually perpendicular, coplanar, horizontal (parallel to the skin) electromagnetic coils driven in quadrature (90 phase between alternating current supplied to each coil) to generate a rotating magnetic field which rotates once during each cycle of the driving frequency so that the strength of the signal induced in the catheter sensor coil is independent of the relative angle between the probe axis in its horizontal plane and the angle of the sensor coil axis in its horizontal plane, but is dependent on the distance between the probe and the sensor coil. When the probe is directly over the sensor, the strength of the signal induced in the sensor lS ~elated to the actual depth of the sensor below the probe.
This invention features a system for externally locating the depth and orientation of a catheter in tissue which includes an external probe having means for providing a ~irtual rotating magnetlc field, a sensor in the catheter for developing an induced~signal in response to the virtual rotating magnetic~field, and means for indicating the strength of the induced signal for locating, independently of the relative angle ~f orientation of the probe and the sensor, the depth~in the tissue of the catheter.
Preferablyj the virtual rotating magnetic field is provided by two mutually perpendicularly orlented electromagnetic coils in the pro~e which are horizontal ~parallel to the supine patent's skin~, coplanar, and wound on a unitary core. Those coils may then be driven in quadrature to accomplish a vlrtual rotating magnetic field of substantially constant strength.
The sensor preferably includes an inductive coil. The means for indicating the relative strength of the induced W093/046~ PCT/US92/~7253 2 1 1 ~ 9 1 O
signal may include a light bar display, a diyital display, or an audio output in which either the tone or volume is varied in relation to the induced signal strength. There may further be included a means for displaying the peak induced si~nal strength.
The system may also include means for resolving the relative angular orientation of the probe and the catheter, which may be accomplished by comparing the phase of a coil drive signal to the phase of the induced signal. Preferably, there are means for visually indicating the resolved angular orientation, which may be provided on the probe itseif. That may be accomplished by a plurality of lights arranged on the probe in a circular pattern ln which a single light indicative of the relative angular orientation of the probe and the sensor is lit.
The system may further include means for resolving the direction of the catheter in relation to the probe, which may be accomplished with a third, vertically oriented electromagnetic coil and means for driving that coil with an ~C signal to create time-varying magnetic field. The means for resolving the direction of the catheter may then further include means for comparing~the phase of the AC slgnal to the phase of the induced signal.~ There may be included means on the probe for visually lndicating the resolved direction of the catheter in relation to the probe.
The system may further includes means for multiplexing the coil pair vertical coil drive si;gnals to save power. In addition, the sensor may include a plurality af inductive coils spaced along the~cathete~r for separately developing induced signals to locate different portions of the catheter with~a single external probe.~ ~
W(:~ 93/04628 PCI'/US92/07253 2i 16~70 DISCLOSURE QF PREFERRED EMBODIMENT
Other objects, features and advan~ages will occur to those skilled in the art from the following description of a preferred embodiment and the accompanying drawings in which:
Fig. 1 is a schematic block diagram of the catheter locating system according to this invention;
Fig. 2A is a schematic diagram of the horizontal field generating coils and quadrature drive of the system of Fig.
l;
Fig. 2B is an overhead view of the horizontal field-generating coils and the catheter sensor coil;
Fig. 2C is a diagram of the h~rizontal field-generating coils, showing the rotating magnetic field and the induced sensor voltages;
Fig. 2~ is a three coil alternative to the coil set of Fig. 2A;
; Fig. 3 is a more detailed schematic diagram of the system of Fig. 1;
Fig. 4 is a~stlll more detailed~schematic diagram of an alternative embodiment of the system of this invention which additionally employs a vertical field generating coil for indicating whether the probe is in front of, directly over, or behind the~sensor coil;~
Fig. 5~ lS a slmp~Ilfled diagram of one form~of the probe of this invention in use, sensing the location of a catheter ~' with a plurality of sense coils;
Fig. 6 is a top~plan view, partially enlarged, of one form of a probe accordi~ng to the invention similar to that ~; ~ shown in Fig. 5; and ~ ~
Fig. 7 is a top plan view of an~alternative to the ; probe of Fiy. 6.
~ There is sho~n in Fig. 1 catheter depth and position :~ : :: :
W0~3/04~28 PCT/U~92/07253 ~116!~7~
locating system 10 according to this invention. System 10 includes cross-shaped coil set 12 on which are wound two mutually perpendîcular coils of wire driven by alternating high frequency curr~nt from generator 2 to generate a high-frequency magnetic field. The coils of coil set 12 are driven in ~uadrature to create a rotating magnetic field which rotates through 360 once during each cycle of the driving frequency to provide a field of essentially constant strength. As a result, the signal induced in sensor coil 30, coaxial with catheter 9, and~located below the level of skin 7, will have a strength dependent only on the distance from coil set 12, and independent of the axial direction of the coils of coil set 12 in relation to coil 30. The coils of coil set 12 may be wound over an~iron or ferrite core to stren~then the magnetic field~, or may~have no core.
The signal induced in~se~nsor coi~l 30 is fed to transformer/amplifier 8, which in turn sends the amplified signa~l to relative~angle indicator 4 and depth indicator 6.
The si~nal induced in coil 30 is a function o~f the strength of~the~field created by~the coils~of coll set 12, but is indepèndent of the relative~horizontai angle between coil set 12 and coil~30. ~Relative~angle~lndicator 4~indicates the relative angle~between~the àxis~of~one of the coils of set 12 nd~the axis of~c~o~il 30~in response~to the phase difference between one of the~coll~drive~signals and th~e sensed signal, as is further described below in conjunction with Fig. 3.
Coil set 12a, Fig. 2~ includes cross-shaped coil form 100 on~which are~wound perpendlcular;, coplanar coils 103 and OS. ;Coll 105 ls~driven~by~high~frequency alternating current source 106; coil 103;is~driven by the same source phase-shifted 90 to drive the coils~in quadrature for providing a virtual rotating~magnetic field whlch rotates 360 during each cycle of source 106. This arrangement is :
~: :
$~ ~ -essentially an electronic version of a rotating magnetic field created by a mechanically rotated bar magnet. ~he xesult is a field of essentially cons~ant strength, and so an induced signal of constant strength when the catheter is at a particular depth, regardless of the angle in the horizontal plane between the axis of either coil 103 or coil 105, and the axis of catheter coil 30, Fig. 1. Because the horizontal orientation of the probe is not significant, the catheter location procedure is greatly simplified over that described in U.S. Patent No. 4,173,228.
Fig. 2B shows a top view of the driven coil set 12 and the catheter 9 and the sensor coil 30, showing the relative horizontal angle between the axis of coil set 12 and sensor coil 3~.
; ~ Fig. 2C shows how the quadrature currents in mutually perpendicular coils 103 and 105 generate a rotating magnetic field. Approximately one cycle of the driving current is shown. At 0 the currents in coils 103 and 105 generate a field which points to the top of the page, inducing no voltage in sensor coil~ 30 when it is at angle A, but at so the sensor voltage is maximum positive, and at 270 is at maximum negative. When the sensor is physically at angle B
xelative to~coil 103~, the maximum posit1ve and negative induced voltage has the same value as at anyle A, but it is phase shifted in time by B-A degrees. Thus, the amplitude of the induced sensor voltage;is independent of angular orientation, but the phase of the induced voltage is directly related to the~physica~l angle between coil 103 and sensor ~` coil 30.
Although a cross~-shaped coil is 6hown in Fig. 2A, other shapes and configurations may occur to one skilled in the art. For example, a star-shaped coil form as shown in Fig.
2D could be driven by three alternating current sources (A,B
2116~7() and C) with B phase~shifted by 120 degrees and C by 240 degrees. This configuration would also produce a rotating magnetic field of constant strength.
One embodiment of system 10 of Fig. 1 is shown in Fig.
CATHETER DEPTH, POSITION AND ORIENTATION
LOCATION SYSTEM
FIELD OF INVENTION
This invention relates to a system for locating the depth, orientation and position of a ca~heter inside biological tissue.
BACKGROUND OF INVENTION
In today's practice of medicine, catheters are routinely required to be positioned inside the human body. Catheters are frequently hollow tubes that infuse fluids into or extract fluids from body organs. Catheters may also contain conductive wires for delivering electrical impulses, such as pacemaker wires, or contain devices for sensing physiological fun~tions such as temperature, blood pressure! and cardiac output. Catheters may contain optical fibers for observing the interiors of body organs. A catheter may also be solid, :
such as a guide wire which is used~to direct other catheters into ~ody orifices,~incisions or vessels.
Typically, catheters may be~placed in the cardiovascular system, the dlgestive~tract,~the respiratory system, soft tissue, or other internal systems such as the excretory system. In~most instances, cathe~ers are placed using fluoroscopy or x-ray as a guide both during the procedure and as a confirmation that the device has been properly positioned.~ However, because of the cost of the equipment, fluoroscopy and x-ray are generally available only in the high~cost operating~room setting or in special procedure laboratories. Furthermore, there is a real concern about the ::
repeated exposure of physicians, nurses and technicians to ; excessive radiation because of the multiple exposures required during placement and confirmation.
W093/~628 PCT/VS92/072S3 2 ~
Two approaches to resolving these problems are disclosed in Van Steenwyck et al., U.S. Patent No. ~,173,228, and Strohl, Jr., et al., U.S. Patent No. 4,905,698. Van Steenwyck et al. disclose a catheter locating device which employs a sensing coil of wire embedded in the tip of a catheter tube, with the two coil wires brought out of the catheter to an external amplifier and detec~or circuit. The external probe contains two electromagnetic coi}s, one parallel to the skin (hereinafter called horizontal because the patient is generally ln a supine position) and the other perpendicular to the skin (hereinafter called vertical), each driven by an electronic oscillator so that a high frequency, time-varying magnetic ~fiéld is gènerated by either coil. The device has a switch for alternately energizing one or both of the coils. The~sen~sing coil in the catheter senses the strength of the magnetic field generated by the horizontal (parallel): external coil, and the phase of ~he field generated by the~vertical~ (perpendlcular) external coil. The field;strength at~the sensor coil is:inversel~related to the dist~nce between the~horizontal coil and the sensor coil.
The relative~phase between the~vertical coil drive signal and the sensèd signal: is indicatlve~of~the position of the vertical coil in~relation to the sensor coil; the:signals are ::in phase when the~vert1cal: coil is~ behind.the sensor coil, the signa:l~ are~out~of~phase when~the vertical coil is in front of the sensor coil, and there is no induced signal in the sensor coil;when the vertical coil is directly over the sensor coil.
Although:the Van~Steenwyck et~al. device can relatively ~ ::: :
accurately locate~the~or~lentation~and posltion of the ~: catheter, it has a number~of disadvantages which make it difficult and time consumlng to use in the clinical setting.
First, the device requires~repeated scans with the probe parallel, the~ p-rpendicular, ther rotated relative to the :
:
W093/04628 PCTtUS92/~72~3 211~70 marking several external probe positions on the patient's skin and drawing a connecting line between them in order to establish the position of the sensor. Finally, the device requires switching repeatedly between the two external coils in order to ~erify the position and direction of the catheter sensor coil. Between 8 and 12 separate steps are necessary in order to establish the catheter position and direction.
Furthermore, no quantitative indication of depth is given by the Van Steenwyck et al. device. The depth of the catheter below the surface of the skin can only be inferred from the signal strength displayed on the meter and from the setting of the range-selector switch.
;~
SUMMARY OF INVENTION
It is therefore an object of this invention to provide a system which is simple and easy to usé for externally locating the position, angular orientation and depth of a catheter.
It is a further object of this lnvention to provide such a~system which does not reguire repeated scans in a number of different directions.
It ~is a further~obj~ect of this invention to pro~ide such a system~which does not require marking probe positions on the patient's~skin.;~
-~ It is~a~further object~of~this i~vention to provide such a system whlch does not require the operator to switch between coils.
It is a~furthe~r ob~ect o;f this~invention to provide such a system wh~ich completely~ellminates~the need for x-ray or ~; ~ fluoroscopy guidance during catheter placement.
It is a further object of~this~invention to provide such a system which gives~a numerical~ display of the depth of the catheter below the skin,~and a displ~ay lndicating the direction in which the catheter is pointing.
W~g3/04~28 PCT/U~92~07253 2~ 1 ~97D
This invention accomplishes the above objects, that is, an effective, easy to use catheter location system, by providing a pair of mutually perpendicular, coplanar, horizontal (parallel to the skin) electromagnetic coils driven in quadrature (90 phase between alternating current supplied to each coil) to generate a rotating magnetic field which rotates once during each cycle of the driving frequency so that the strength of the signal induced in the catheter sensor coil is independent of the relative angle between the probe axis in its horizontal plane and the angle of the sensor coil axis in its horizontal plane, but is dependent on the distance between the probe and the sensor coil. When the probe is directly over the sensor, the strength of the signal induced in the sensor lS ~elated to the actual depth of the sensor below the probe.
This invention features a system for externally locating the depth and orientation of a catheter in tissue which includes an external probe having means for providing a ~irtual rotating magnetlc field, a sensor in the catheter for developing an induced~signal in response to the virtual rotating magnetic~field, and means for indicating the strength of the induced signal for locating, independently of the relative angle ~f orientation of the probe and the sensor, the depth~in the tissue of the catheter.
Preferablyj the virtual rotating magnetic field is provided by two mutually perpendicularly orlented electromagnetic coils in the pro~e which are horizontal ~parallel to the supine patent's skin~, coplanar, and wound on a unitary core. Those coils may then be driven in quadrature to accomplish a vlrtual rotating magnetic field of substantially constant strength.
The sensor preferably includes an inductive coil. The means for indicating the relative strength of the induced W093/046~ PCT/US92/~7253 2 1 1 ~ 9 1 O
signal may include a light bar display, a diyital display, or an audio output in which either the tone or volume is varied in relation to the induced signal strength. There may further be included a means for displaying the peak induced si~nal strength.
The system may also include means for resolving the relative angular orientation of the probe and the catheter, which may be accomplished by comparing the phase of a coil drive signal to the phase of the induced signal. Preferably, there are means for visually indicating the resolved angular orientation, which may be provided on the probe itseif. That may be accomplished by a plurality of lights arranged on the probe in a circular pattern ln which a single light indicative of the relative angular orientation of the probe and the sensor is lit.
The system may further include means for resolving the direction of the catheter in relation to the probe, which may be accomplished with a third, vertically oriented electromagnetic coil and means for driving that coil with an ~C signal to create time-varying magnetic field. The means for resolving the direction of the catheter may then further include means for comparing~the phase of the AC slgnal to the phase of the induced signal.~ There may be included means on the probe for visually lndicating the resolved direction of the catheter in relation to the probe.
The system may further includes means for multiplexing the coil pair vertical coil drive si;gnals to save power. In addition, the sensor may include a plurality af inductive coils spaced along the~cathete~r for separately developing induced signals to locate different portions of the catheter with~a single external probe.~ ~
W(:~ 93/04628 PCI'/US92/07253 2i 16~70 DISCLOSURE QF PREFERRED EMBODIMENT
Other objects, features and advan~ages will occur to those skilled in the art from the following description of a preferred embodiment and the accompanying drawings in which:
Fig. 1 is a schematic block diagram of the catheter locating system according to this invention;
Fig. 2A is a schematic diagram of the horizontal field generating coils and quadrature drive of the system of Fig.
l;
Fig. 2B is an overhead view of the horizontal field-generating coils and the catheter sensor coil;
Fig. 2C is a diagram of the h~rizontal field-generating coils, showing the rotating magnetic field and the induced sensor voltages;
Fig. 2~ is a three coil alternative to the coil set of Fig. 2A;
; Fig. 3 is a more detailed schematic diagram of the system of Fig. 1;
Fig. 4 is a~stlll more detailed~schematic diagram of an alternative embodiment of the system of this invention which additionally employs a vertical field generating coil for indicating whether the probe is in front of, directly over, or behind the~sensor coil;~
Fig. 5~ lS a slmp~Ilfled diagram of one form~of the probe of this invention in use, sensing the location of a catheter ~' with a plurality of sense coils;
Fig. 6 is a top~plan view, partially enlarged, of one form of a probe accordi~ng to the invention similar to that ~; ~ shown in Fig. 5; and ~ ~
Fig. 7 is a top plan view of an~alternative to the ; probe of Fiy. 6.
~ There is sho~n in Fig. 1 catheter depth and position :~ : :: :
W0~3/04~28 PCT/U~92/07253 ~116!~7~
locating system 10 according to this invention. System 10 includes cross-shaped coil set 12 on which are wound two mutually perpendîcular coils of wire driven by alternating high frequency curr~nt from generator 2 to generate a high-frequency magnetic field. The coils of coil set 12 are driven in ~uadrature to create a rotating magnetic field which rotates through 360 once during each cycle of the driving frequency to provide a field of essentially constant strength. As a result, the signal induced in sensor coil 30, coaxial with catheter 9, and~located below the level of skin 7, will have a strength dependent only on the distance from coil set 12, and independent of the axial direction of the coils of coil set 12 in relation to coil 30. The coils of coil set 12 may be wound over an~iron or ferrite core to stren~then the magnetic field~, or may~have no core.
The signal induced in~se~nsor coi~l 30 is fed to transformer/amplifier 8, which in turn sends the amplified signa~l to relative~angle indicator 4 and depth indicator 6.
The si~nal induced in coil 30 is a function o~f the strength of~the~field created by~the coils~of coll set 12, but is indepèndent of the relative~horizontai angle between coil set 12 and coil~30. ~Relative~angle~lndicator 4~indicates the relative angle~between~the àxis~of~one of the coils of set 12 nd~the axis of~c~o~il 30~in response~to the phase difference between one of the~coll~drive~signals and th~e sensed signal, as is further described below in conjunction with Fig. 3.
Coil set 12a, Fig. 2~ includes cross-shaped coil form 100 on~which are~wound perpendlcular;, coplanar coils 103 and OS. ;Coll 105 ls~driven~by~high~frequency alternating current source 106; coil 103;is~driven by the same source phase-shifted 90 to drive the coils~in quadrature for providing a virtual rotating~magnetic field whlch rotates 360 during each cycle of source 106. This arrangement is :
~: :
$~ ~ -essentially an electronic version of a rotating magnetic field created by a mechanically rotated bar magnet. ~he xesult is a field of essentially cons~ant strength, and so an induced signal of constant strength when the catheter is at a particular depth, regardless of the angle in the horizontal plane between the axis of either coil 103 or coil 105, and the axis of catheter coil 30, Fig. 1. Because the horizontal orientation of the probe is not significant, the catheter location procedure is greatly simplified over that described in U.S. Patent No. 4,173,228.
Fig. 2B shows a top view of the driven coil set 12 and the catheter 9 and the sensor coil 30, showing the relative horizontal angle between the axis of coil set 12 and sensor coil 3~.
; ~ Fig. 2C shows how the quadrature currents in mutually perpendicular coils 103 and 105 generate a rotating magnetic field. Approximately one cycle of the driving current is shown. At 0 the currents in coils 103 and 105 generate a field which points to the top of the page, inducing no voltage in sensor coil~ 30 when it is at angle A, but at so the sensor voltage is maximum positive, and at 270 is at maximum negative. When the sensor is physically at angle B
xelative to~coil 103~, the maximum posit1ve and negative induced voltage has the same value as at anyle A, but it is phase shifted in time by B-A degrees. Thus, the amplitude of the induced sensor voltage;is independent of angular orientation, but the phase of the induced voltage is directly related to the~physica~l angle between coil 103 and sensor ~` coil 30.
Although a cross~-shaped coil is 6hown in Fig. 2A, other shapes and configurations may occur to one skilled in the art. For example, a star-shaped coil form as shown in Fig.
2D could be driven by three alternating current sources (A,B
2116~7() and C) with B phase~shifted by 120 degrees and C by 240 degrees. This configuration would also produce a rotating magnetic field of constant strength.
One embodiment of system 10 of Fig. 1 is shown in Fig.
3. System IOa includes alternating current signal generator 2a for driving perpendicular coils 103 and 105 in quadrature.
Generator 2a includes high frequency oscilla~or 14 which, in combination with inverter 16, flip-flops 18 and 20, and swîtches or current amplifiers 22 and 24j provides a high frequency alternating current signal to identical coils 103 and 105 to drive the coils in quadrature as explained above.
This magnetic field induces a signal in sensor coil 30 which is proportional to the lnverse cube of the distance of the sensor from transmitter coil 12. The sensor voltage is stepped up by transformer 32, which also provides safety isolation between patient and circuitry, and is amplified by amplifier 34. The amplified signal is provided both to relative angle indicator 4a and depth indicator 6a.
Depth indicator circuitry 6a~includes full wave rectifier 36 and low pass filter 38 which provide a dc voltage, inversely proportional to the cube of the distance of the sensor from the field generating coils, to one or more of the audio and visual outputs for indica~ing the actual or relative depth of the sensor coil 30 in relation to the field , generating coils 103 and~105. One aud~io output may be provided by employing logarithmic amplifier 40 for driving voltage controlled oscillator 42 whose output is applied to peàker 44 to provide an audible tone~ whose pitch increases as the probe gets closer to the sensor coil. The desirabillty of a logarithmic amplifler will be explained below. Another display can be LED or liquid-crystal light bar display 48, in which the length of the bar increases as the probe is brought closer to~the sensor coil.
: ~ :
W093/04628 PCT/~S92/07253 ,~
69~0 Display 48 preferably incorporates a logarithmic as opposed to a linear display of the sensor voltage to accommodate the wide range of sensor voltages. As an example, the depth of the sensor inside the body could vary ~rom less than l/2 inch to more than 7 inches, depending on the patient and the catheter location. Over this range, the amplified sensor output voltage could range, as an example, from less than 1 millivolt to over 500 millivolts, a range of 500 to 1~ Linear displays can adequately display a range of no better than about 30 to l; any voltage smaller than 1/30th of full scale would be barely visible. By using such a logarithmic display! the upper portion of the indicator is compressed and the lower portion expanded so that a voltage level of 1/500th of full scale would appear in the same poSitiQn as a level of 1/lOth of full scale on a linear dlsplay, thus allowing the locatlon apparatus to be usable over a larger range of catheter depths in the body. The light bar display~may be accomplished with drivers 50 and 54 .
which may be an LM3915 logarithmic~bar graph display driver made by National Semiconductor Corporation, each having ten outputs, for driving;LED~light bar displays 52 and 56. Each LED represents a change in sensor voltage of 3 decibels. 20 ::
LEDs~represents a 60 de~cibel~change, which `is a 1000 to l change in sensor~voltage.~ A~scale in inches or centimeters may be marked beside the LEDs, indicating the relative depth of sensor 30.
Likewise, the use of a logarithmic amplifier 40 to drive voltage-controlled oscillator 42 results in a smooth and gradual change in pitch~as the sensor signal varies over the range of 500 to l~
A third display may be created by having the signal-receiving circuitry generate a DC voltage related to the strength of the sensed signal, ~Jhich is then converted to .
W093/0462~ PCT/US92/07~53 2116~J70 digital form by analog-to-digital conver~er 58. The digital data is provided to a programmable read-only memory circuit 60, which acts as a 'llook-up table" and converts the digital data to a two or three digit numerical display representing the distance between the external probe coil and the catheter sensor coil, using drivers 62 and 64 which convert binary data to voltages that drive 7-segment numerical LED or Liquid Crystal displays.
Relative angle indicator 4a indicates the approximate relative angle in the horizontal plane between the axis of one of the two electromagnetic coils of field-generating coil set 12 and the axis of sensor coil 30 by applying the coil drive signal and the amplified sensed signal to phase detector 68. The output of phase detector 68 is filtered by low pass filter 70, ampllfied by amplifier 72, and provided to relative angle display 74 which includes display driver 76 for driving eight light-emitting diodes or lamps physically arranged around the periphery of a circle. Display driver 76 may be a LM3914, made by National Semiconductor, a bar graph display driver which~conv~erts an analog input voltage to discrete drive voltages for up:to 10:LEDs. Although only 8 LEDs are shown in:display~74, a larger number could be incorporated by adding more display drivers 76. The result, as shown with more partic~ularity below in conjunction with Figs. 6 and 7, is a visual indication of the approximate relative anigular orientation between the long axis of the probe housing colI set 12a and the axis of the catheter sensor coil, thereby allowing the person placing the catheter to determine the exact~positioll of the catheter tip without the use of fluoroscopy or x-ray during the positioning.
Fig. 4 depicts an;alternative embodiment of the system of this invention employing a vertically-oriented field-generating coil in conjunction with the horizontal coil W093/04628 ~CT/US92/07253 . ~
2~
pair described above for additionally providing the relative orientation between the external probe and the catheter sensor coil; that is, whether the field-generating coil is in front of, behind, or directly over the~sensor coil. In addition, Fig. 4 depicts multiplexing of the coil drive signals to save battery power.
The system of Fig. 4 combines the use of a vertically oriented field-generating coil for generating a phase-sensitive response in the catheter sensor coil, and a horizontally-oriented field-generating coil for creating an amp1itude-sensitive response in the sensor coil. In order to avoid switching manually between the~two techniques, a multiplexing scheme is employed, in which the horizontal and vertical field-generating coils are alternately energized.
Likewise, the received signals are al~ternately sampled-and-held in~synchronism with the field-generating coils so that two~separate DC signals are developed, one related to the phase~between the field of the vertical coil and the sensor signal, and the second proportional to the amplitude (intensity) of the field of the horiz~ontal coil as received by the sensor coil.
The~drive~s1gna1~mu1tip1ex1ng 1s~accomplished with low frequency~ 33 hert~z~square~wave~oscil1ator 124 which during its positive half cycle~enables~high-frequecy ~oscillator 130 ~and, through inverte~r 126,~enablès high-frequency oscillator 128 on the aIternate half cycle to drive the amplitude coils 12a and phase coil 122 at alternating 15 millisecond i~te~vals.~
Phase detection between vertical phase coil 122 and sensor coil 30 is accompl~ished by driv1ng MOSFET switch 144 with the output af osc111ator 128, preferably approximately 50 kilohertz. This output lS al~so provided as the phase referenc2~ slgnal inpu~ to ph~se sh1~ter 196, described below.
:
W093/04628 PCr/U~92/07253 2116~70 Switch 144 switches current to the resonant circuit comprising capacitor 140 and the ~ertical field-generating coiI 122.
The magnetic field created by coil ~22 induces a voltage in sensor coil 30. The sensor voltage is stepped-up by transformer 154, which also isolates the sensor from the remaining circuitry, and is then amplified 200 times by amplifier 156. The signal is amplified 20 times additionally by amplifier 192, and fed to the signal input of phase detector 194. The phase detector reference signal is fed from the output of switch 144 to the reference input of phase detector 194 through phase shifter 196, which is adjusted to compensate for phase shifting of the input signal created by the amplifier circuitry.
The output of phase detector 194 is a high frequency signal which is mostly high when the signals are in phase, and mostly low when the signals are out of phase, regardless of the signal strength. The phase detector output goes through low pass filter 198 which smoothes the high frequency signals to DC and then to sample and hold circuit 1'90, which is enabled by a del;ayed hold pulse from delay circuit 148 to ensure that the phase detec;tor output has settled to its final value before the sample and hold 190 is enabled. Unity gain amplifier 192 presents a high lmpedance to sample and hold 190. The signal is then passed to comparator 194 which iS supplied with two reference voltages. When the sensed and reference signaIs are ln phase, the output of amplifier 192 is ~igh and the output of comparator 194 at pin 8 goes high, causing inverter 196 to turn on the~red LED. When the field-yenerating coil position is changed such that the signals are 180 out of phase, the output of amplifier 192 is low, causing comparator 194 output to go high at pin 14, causing inverter 198 to turn~on yellow LED 202. When the .
211(i~7~
sensor output signal is very weak or non-existent, the output of amplifier 192 assumes a midway voltage so that neither comparator in comparator circuit 194 is tripped, and neither LED is lit. The result is that when the vertical phase coil 122 is beyond sensor coil 30, that is located somewhere along the length of the catheter not quite to its tip, the transmitted and sensed signals are in phase, causing the red LED to light. When the transmit coil is before the sensor coil, the yellow LED lights. When the device switches between the red and yellow LED, transmit phase coil 122 is directly over sensor coil 30.
Amplitude detection ~distance determination) of system 120 is accomplished as follows. Oscillator 130 drives flip-flops 132 and 134 such~that the square wave output of flip-flop 134 is shifted 90 from that of flip-flop 132. The square waves drive MOSFET switches 136 and 138 which switch current into the resonant circuit created by capacitor 140 and colinear amplitude coils L2 and L3, and the resonant circuit created by capaGitor 142 and collinear coils L4 and L5, which are coplanar~and perpendicular to coils L2 and L3 as shown above in conjunction~with Fig~ 2A to provide a rotating magnetic field rotating at the appraximately 50 kilohertz drive frequency. The amplitude of the signal induced in sensor coil 30 is thus proportional to the inverse cube of the distance between coils 12a and coil 30 regardless of the angular orlentation in the horizontal plane between either of the coils in coil 12a and coil 30.
The ampllfied se:nsor voltage is provided to full wave rectifier 158, and is then: filte~red and fed to sample and hold clrcuit 162. Sample and hold circuit 162 is enablèd by a delayed hold pulse from delay 152, which allows the rectified, filtered signal to settle to its final value before it is sampled and held to provide, at the output of :
W093J0462X PCT/US9~/07253 2116~7Q
unity gain amplifier 164) a DC voltage representative of the distance between the drive coil and the sensor coil. This DC
signal is applied to switch 168 and peak detector 166, whose output is supplied to switch 170. Switches 168 and 170 are driven by duty cycle adjust circuit 150 which provides signal C to switch 168 and the complementary signal to switch 170 so that switch 16~ is on approximately three times longer than switch 170, resulting in a brighter light intensity in li~ht bar display 172 for the currently-sensed amplitude l.ight bar than for the peak light bar. The peak remains lit at a low intensity so that the user may know the absolute peak encountered, and thus easily find the probe position in which the amplitude field-generating coils are closest to the sensor coil. The outputs are provided to lightbar display 172 which preferably includes 2Q LED segment outputs 180 and 182, each driven by drivers 176 and 178.
An alternative or additional audio output is accomplished by feeding the DC~signal from amplifier 164 to logarithmic amplifier 184 whose output is applied to voltage controlled oscillator 186, drivlng speaker 190 through amplifier 188. In this~case, the pitch of the speaker tone changes as the probe~coil is~moved in relation to the sense coil, with the highest pitch~indicating closest proximity.
The result of the system shown in Fig. 4 is the simultaneous detection of the~dept~l~of the sensor coil and the relative position of the probe and the sensor coil, allowing the user to locate the exact position and depth of the catheter tip ~y scanning in one dire~tion on the skin of the patient~, along the~estimat~ed direction of the catheter, until a signal maximum~is displayed, and then moving the probe along a line perpendicular to tne direction of the first scan until an ab`solute maximum is displayed, indicating the closest position f~om the probe to the sensor coil. If W093/04628 PCT/US92/072~3 the user moves the probe away from the point of maximum indication, the peak light bar segment will be dimly lit by the peak detector circuit, thereby informing the user to return the probe to the point of maximum indication. The phase detection in conjunction with the red and yellow lights is employed to confirm that the probe is directly over the catheter coil. The relative angular positioning of Fig. 3 may also be used to provide the relative direction of the sensor coil axis in relation to the probe axis so that the user may determine if the catheter tip is facing in the correct direction or has doubled back on itself.
Following is a Component parts list for the embodiment of Fig. 4:
Component No~ Description Type No.
U101 ~ Operational amplifier LF357 U102, U104 Op, amp., dual ~ TL052 Ul03, U13 :Phase detector,:Voltage-- controlled oscillator CD4046 : ~ :
Ul ~ Quad NOR gate:~ ~ CD4001-U2 : :~ Dual Oscillator : ~ ICM7556 , , .
U3, U4, U5 ~ ~Quad ~MOSFET~ VQ7254J
U6 : ~Dual :D Flip-Flop ~;: . CD4013 U7 ~ ~uad~NAN~gate~ ~ CD4011 U8, U11 Op.amp.,quad ~ : TL034 U9 ` ~nalog switch, guad: DG441 U10, U12 Not used ~
U14 ~ Inverter CD4049 176,178 Logarlthmlc Bar Graph Driver LM3915 One physical embodlme;nt of the probe and catheter system of this invention is sho~^Tn~in Fig. 5. Probe 220 may include :
:
W093/~4628 PCT/USg~/07253 21:~6~70 the power source and circuitry of the system and may have vertical coil 122 mounted proximate skin surface 221, with horizontal coil set 12 mounted direct~y ~hereabove. Catheter 212 ~ay include one or more of sensor coils 214, 216 and 21 for indicating the position of catheter 212 in relation to probe 220, specifically tip portion 223 of probe 220. When more than one sensor coil is employed in the catheter, the device may include a switch for manually switching from one sense coil to the next so that probe 220 may be used to detect not only the position of the ~ip of catheter 212, but also some distance along its length back from the tip to indicate the catheter path. Alternatively, ~he sensor coils may be multiplexed in some manner to alternately employ their outputs for the same purpose.
Figs. 6 and 7 depict in simplified form displays 222 of two different embodiments of the probe according to this invention. Probe 220a, Fig. 6, includes circular LED
display 78 for indicating the relative horizontal angle between the probe and sensor coil. Arrow 225 embossed on probe 220a is axially aligned with the one of the coils of horizontal coil 12 which is used to provide a phase de~ection reference signal as described above. Then, when one of the LEDs of display 78a, for~example LED 227, is lit, it indicates the relativ;e angle of the axis of the sensor coil in relation to the probe axis as~indicated by arrow 225.
Thus, in the example shown, the probe is indicating that the sensor coil, or catheter tip, is facing approximately northeast, or 45Q in a clockwise direction from the direction of arrow 225. Finer angular resolution would be achieved if a higher number of LEDs ~ere used. F~or example, with 20 LEDs each LED would represent an angular difference of 18 degrees.
Lightbar display 48a provides an indication of the depth of the sensor coil. A numerical scale, in inches or W093/04628 PCT/US92/072~3 211~370 centimeters, may be inscribed alongside display 48a to indicate the depth that each segment represents. Display 48a shows one segment brightly lit and ~he segme~t representing maximum sensor signal strength dimly lit.
An alternative display, probe 220b, Fig. 7, includes circular LED pattern 78b along with digital depth readout 66a of sensor depth, and red and yellow LEDs 200 and 202, respectively, for indicating the relative position of vertical coil 122, Fig. 5j in relation to the sensor coil as described above.
Although specific features of the invention are shown in some drawings and not others, this is ~or convenience only as each feature may be combined with any or all of the other features in accordance with the invention.
Other embodiments will occur to those skilled in the art and are within the following claims:
' : ::
:
,: :
:
:
:
Generator 2a includes high frequency oscilla~or 14 which, in combination with inverter 16, flip-flops 18 and 20, and swîtches or current amplifiers 22 and 24j provides a high frequency alternating current signal to identical coils 103 and 105 to drive the coils in quadrature as explained above.
This magnetic field induces a signal in sensor coil 30 which is proportional to the lnverse cube of the distance of the sensor from transmitter coil 12. The sensor voltage is stepped up by transformer 32, which also provides safety isolation between patient and circuitry, and is amplified by amplifier 34. The amplified signal is provided both to relative angle indicator 4a and depth indicator 6a.
Depth indicator circuitry 6a~includes full wave rectifier 36 and low pass filter 38 which provide a dc voltage, inversely proportional to the cube of the distance of the sensor from the field generating coils, to one or more of the audio and visual outputs for indica~ing the actual or relative depth of the sensor coil 30 in relation to the field , generating coils 103 and~105. One aud~io output may be provided by employing logarithmic amplifier 40 for driving voltage controlled oscillator 42 whose output is applied to peàker 44 to provide an audible tone~ whose pitch increases as the probe gets closer to the sensor coil. The desirabillty of a logarithmic amplifler will be explained below. Another display can be LED or liquid-crystal light bar display 48, in which the length of the bar increases as the probe is brought closer to~the sensor coil.
: ~ :
W093/04628 PCT/~S92/07253 ,~
69~0 Display 48 preferably incorporates a logarithmic as opposed to a linear display of the sensor voltage to accommodate the wide range of sensor voltages. As an example, the depth of the sensor inside the body could vary ~rom less than l/2 inch to more than 7 inches, depending on the patient and the catheter location. Over this range, the amplified sensor output voltage could range, as an example, from less than 1 millivolt to over 500 millivolts, a range of 500 to 1~ Linear displays can adequately display a range of no better than about 30 to l; any voltage smaller than 1/30th of full scale would be barely visible. By using such a logarithmic display! the upper portion of the indicator is compressed and the lower portion expanded so that a voltage level of 1/500th of full scale would appear in the same poSitiQn as a level of 1/lOth of full scale on a linear dlsplay, thus allowing the locatlon apparatus to be usable over a larger range of catheter depths in the body. The light bar display~may be accomplished with drivers 50 and 54 .
which may be an LM3915 logarithmic~bar graph display driver made by National Semiconductor Corporation, each having ten outputs, for driving;LED~light bar displays 52 and 56. Each LED represents a change in sensor voltage of 3 decibels. 20 ::
LEDs~represents a 60 de~cibel~change, which `is a 1000 to l change in sensor~voltage.~ A~scale in inches or centimeters may be marked beside the LEDs, indicating the relative depth of sensor 30.
Likewise, the use of a logarithmic amplifier 40 to drive voltage-controlled oscillator 42 results in a smooth and gradual change in pitch~as the sensor signal varies over the range of 500 to l~
A third display may be created by having the signal-receiving circuitry generate a DC voltage related to the strength of the sensed signal, ~Jhich is then converted to .
W093/0462~ PCT/US92/07~53 2116~J70 digital form by analog-to-digital conver~er 58. The digital data is provided to a programmable read-only memory circuit 60, which acts as a 'llook-up table" and converts the digital data to a two or three digit numerical display representing the distance between the external probe coil and the catheter sensor coil, using drivers 62 and 64 which convert binary data to voltages that drive 7-segment numerical LED or Liquid Crystal displays.
Relative angle indicator 4a indicates the approximate relative angle in the horizontal plane between the axis of one of the two electromagnetic coils of field-generating coil set 12 and the axis of sensor coil 30 by applying the coil drive signal and the amplified sensed signal to phase detector 68. The output of phase detector 68 is filtered by low pass filter 70, ampllfied by amplifier 72, and provided to relative angle display 74 which includes display driver 76 for driving eight light-emitting diodes or lamps physically arranged around the periphery of a circle. Display driver 76 may be a LM3914, made by National Semiconductor, a bar graph display driver which~conv~erts an analog input voltage to discrete drive voltages for up:to 10:LEDs. Although only 8 LEDs are shown in:display~74, a larger number could be incorporated by adding more display drivers 76. The result, as shown with more partic~ularity below in conjunction with Figs. 6 and 7, is a visual indication of the approximate relative anigular orientation between the long axis of the probe housing colI set 12a and the axis of the catheter sensor coil, thereby allowing the person placing the catheter to determine the exact~positioll of the catheter tip without the use of fluoroscopy or x-ray during the positioning.
Fig. 4 depicts an;alternative embodiment of the system of this invention employing a vertically-oriented field-generating coil in conjunction with the horizontal coil W093/04628 ~CT/US92/07253 . ~
2~
pair described above for additionally providing the relative orientation between the external probe and the catheter sensor coil; that is, whether the field-generating coil is in front of, behind, or directly over the~sensor coil. In addition, Fig. 4 depicts multiplexing of the coil drive signals to save battery power.
The system of Fig. 4 combines the use of a vertically oriented field-generating coil for generating a phase-sensitive response in the catheter sensor coil, and a horizontally-oriented field-generating coil for creating an amp1itude-sensitive response in the sensor coil. In order to avoid switching manually between the~two techniques, a multiplexing scheme is employed, in which the horizontal and vertical field-generating coils are alternately energized.
Likewise, the received signals are al~ternately sampled-and-held in~synchronism with the field-generating coils so that two~separate DC signals are developed, one related to the phase~between the field of the vertical coil and the sensor signal, and the second proportional to the amplitude (intensity) of the field of the horiz~ontal coil as received by the sensor coil.
The~drive~s1gna1~mu1tip1ex1ng 1s~accomplished with low frequency~ 33 hert~z~square~wave~oscil1ator 124 which during its positive half cycle~enables~high-frequecy ~oscillator 130 ~and, through inverte~r 126,~enablès high-frequency oscillator 128 on the aIternate half cycle to drive the amplitude coils 12a and phase coil 122 at alternating 15 millisecond i~te~vals.~
Phase detection between vertical phase coil 122 and sensor coil 30 is accompl~ished by driv1ng MOSFET switch 144 with the output af osc111ator 128, preferably approximately 50 kilohertz. This output lS al~so provided as the phase referenc2~ slgnal inpu~ to ph~se sh1~ter 196, described below.
:
W093/04628 PCr/U~92/07253 2116~70 Switch 144 switches current to the resonant circuit comprising capacitor 140 and the ~ertical field-generating coiI 122.
The magnetic field created by coil ~22 induces a voltage in sensor coil 30. The sensor voltage is stepped-up by transformer 154, which also isolates the sensor from the remaining circuitry, and is then amplified 200 times by amplifier 156. The signal is amplified 20 times additionally by amplifier 192, and fed to the signal input of phase detector 194. The phase detector reference signal is fed from the output of switch 144 to the reference input of phase detector 194 through phase shifter 196, which is adjusted to compensate for phase shifting of the input signal created by the amplifier circuitry.
The output of phase detector 194 is a high frequency signal which is mostly high when the signals are in phase, and mostly low when the signals are out of phase, regardless of the signal strength. The phase detector output goes through low pass filter 198 which smoothes the high frequency signals to DC and then to sample and hold circuit 1'90, which is enabled by a del;ayed hold pulse from delay circuit 148 to ensure that the phase detec;tor output has settled to its final value before the sample and hold 190 is enabled. Unity gain amplifier 192 presents a high lmpedance to sample and hold 190. The signal is then passed to comparator 194 which iS supplied with two reference voltages. When the sensed and reference signaIs are ln phase, the output of amplifier 192 is ~igh and the output of comparator 194 at pin 8 goes high, causing inverter 196 to turn on the~red LED. When the field-yenerating coil position is changed such that the signals are 180 out of phase, the output of amplifier 192 is low, causing comparator 194 output to go high at pin 14, causing inverter 198 to turn~on yellow LED 202. When the .
211(i~7~
sensor output signal is very weak or non-existent, the output of amplifier 192 assumes a midway voltage so that neither comparator in comparator circuit 194 is tripped, and neither LED is lit. The result is that when the vertical phase coil 122 is beyond sensor coil 30, that is located somewhere along the length of the catheter not quite to its tip, the transmitted and sensed signals are in phase, causing the red LED to light. When the transmit coil is before the sensor coil, the yellow LED lights. When the device switches between the red and yellow LED, transmit phase coil 122 is directly over sensor coil 30.
Amplitude detection ~distance determination) of system 120 is accomplished as follows. Oscillator 130 drives flip-flops 132 and 134 such~that the square wave output of flip-flop 134 is shifted 90 from that of flip-flop 132. The square waves drive MOSFET switches 136 and 138 which switch current into the resonant circuit created by capacitor 140 and colinear amplitude coils L2 and L3, and the resonant circuit created by capaGitor 142 and collinear coils L4 and L5, which are coplanar~and perpendicular to coils L2 and L3 as shown above in conjunction~with Fig~ 2A to provide a rotating magnetic field rotating at the appraximately 50 kilohertz drive frequency. The amplitude of the signal induced in sensor coil 30 is thus proportional to the inverse cube of the distance between coils 12a and coil 30 regardless of the angular orlentation in the horizontal plane between either of the coils in coil 12a and coil 30.
The ampllfied se:nsor voltage is provided to full wave rectifier 158, and is then: filte~red and fed to sample and hold clrcuit 162. Sample and hold circuit 162 is enablèd by a delayed hold pulse from delay 152, which allows the rectified, filtered signal to settle to its final value before it is sampled and held to provide, at the output of :
W093J0462X PCT/US9~/07253 2116~7Q
unity gain amplifier 164) a DC voltage representative of the distance between the drive coil and the sensor coil. This DC
signal is applied to switch 168 and peak detector 166, whose output is supplied to switch 170. Switches 168 and 170 are driven by duty cycle adjust circuit 150 which provides signal C to switch 168 and the complementary signal to switch 170 so that switch 16~ is on approximately three times longer than switch 170, resulting in a brighter light intensity in li~ht bar display 172 for the currently-sensed amplitude l.ight bar than for the peak light bar. The peak remains lit at a low intensity so that the user may know the absolute peak encountered, and thus easily find the probe position in which the amplitude field-generating coils are closest to the sensor coil. The outputs are provided to lightbar display 172 which preferably includes 2Q LED segment outputs 180 and 182, each driven by drivers 176 and 178.
An alternative or additional audio output is accomplished by feeding the DC~signal from amplifier 164 to logarithmic amplifier 184 whose output is applied to voltage controlled oscillator 186, drivlng speaker 190 through amplifier 188. In this~case, the pitch of the speaker tone changes as the probe~coil is~moved in relation to the sense coil, with the highest pitch~indicating closest proximity.
The result of the system shown in Fig. 4 is the simultaneous detection of the~dept~l~of the sensor coil and the relative position of the probe and the sensor coil, allowing the user to locate the exact position and depth of the catheter tip ~y scanning in one dire~tion on the skin of the patient~, along the~estimat~ed direction of the catheter, until a signal maximum~is displayed, and then moving the probe along a line perpendicular to tne direction of the first scan until an ab`solute maximum is displayed, indicating the closest position f~om the probe to the sensor coil. If W093/04628 PCT/US92/072~3 the user moves the probe away from the point of maximum indication, the peak light bar segment will be dimly lit by the peak detector circuit, thereby informing the user to return the probe to the point of maximum indication. The phase detection in conjunction with the red and yellow lights is employed to confirm that the probe is directly over the catheter coil. The relative angular positioning of Fig. 3 may also be used to provide the relative direction of the sensor coil axis in relation to the probe axis so that the user may determine if the catheter tip is facing in the correct direction or has doubled back on itself.
Following is a Component parts list for the embodiment of Fig. 4:
Component No~ Description Type No.
U101 ~ Operational amplifier LF357 U102, U104 Op, amp., dual ~ TL052 Ul03, U13 :Phase detector,:Voltage-- controlled oscillator CD4046 : ~ :
Ul ~ Quad NOR gate:~ ~ CD4001-U2 : :~ Dual Oscillator : ~ ICM7556 , , .
U3, U4, U5 ~ ~Quad ~MOSFET~ VQ7254J
U6 : ~Dual :D Flip-Flop ~;: . CD4013 U7 ~ ~uad~NAN~gate~ ~ CD4011 U8, U11 Op.amp.,quad ~ : TL034 U9 ` ~nalog switch, guad: DG441 U10, U12 Not used ~
U14 ~ Inverter CD4049 176,178 Logarlthmlc Bar Graph Driver LM3915 One physical embodlme;nt of the probe and catheter system of this invention is sho~^Tn~in Fig. 5. Probe 220 may include :
:
W093/~4628 PCT/USg~/07253 21:~6~70 the power source and circuitry of the system and may have vertical coil 122 mounted proximate skin surface 221, with horizontal coil set 12 mounted direct~y ~hereabove. Catheter 212 ~ay include one or more of sensor coils 214, 216 and 21 for indicating the position of catheter 212 in relation to probe 220, specifically tip portion 223 of probe 220. When more than one sensor coil is employed in the catheter, the device may include a switch for manually switching from one sense coil to the next so that probe 220 may be used to detect not only the position of the ~ip of catheter 212, but also some distance along its length back from the tip to indicate the catheter path. Alternatively, ~he sensor coils may be multiplexed in some manner to alternately employ their outputs for the same purpose.
Figs. 6 and 7 depict in simplified form displays 222 of two different embodiments of the probe according to this invention. Probe 220a, Fig. 6, includes circular LED
display 78 for indicating the relative horizontal angle between the probe and sensor coil. Arrow 225 embossed on probe 220a is axially aligned with the one of the coils of horizontal coil 12 which is used to provide a phase de~ection reference signal as described above. Then, when one of the LEDs of display 78a, for~example LED 227, is lit, it indicates the relativ;e angle of the axis of the sensor coil in relation to the probe axis as~indicated by arrow 225.
Thus, in the example shown, the probe is indicating that the sensor coil, or catheter tip, is facing approximately northeast, or 45Q in a clockwise direction from the direction of arrow 225. Finer angular resolution would be achieved if a higher number of LEDs ~ere used. F~or example, with 20 LEDs each LED would represent an angular difference of 18 degrees.
Lightbar display 48a provides an indication of the depth of the sensor coil. A numerical scale, in inches or W093/04628 PCT/US92/072~3 211~370 centimeters, may be inscribed alongside display 48a to indicate the depth that each segment represents. Display 48a shows one segment brightly lit and ~he segme~t representing maximum sensor signal strength dimly lit.
An alternative display, probe 220b, Fig. 7, includes circular LED pattern 78b along with digital depth readout 66a of sensor depth, and red and yellow LEDs 200 and 202, respectively, for indicating the relative position of vertical coil 122, Fig. 5j in relation to the sensor coil as described above.
Although specific features of the invention are shown in some drawings and not others, this is ~or convenience only as each feature may be combined with any or all of the other features in accordance with the invention.
Other embodiments will occur to those skilled in the art and are within the following claims:
' : ::
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Claims (35)
1. A system for externally locating a sensor in tissue, comprising:
an external probe including electronic means for providing a horizontal rotating magnetic field;
a sensor for placement in tissue, in which the sensor develops an induced signal in response to said rotating magnetic field;
means for determining the relative strength of said induced signal, independently of the relative angular orientation in the horizontal plane of said probe and said sensor; and means, responsive to said means for determining, for indicating the relative distance between said probe and said sensor.
an external probe including electronic means for providing a horizontal rotating magnetic field;
a sensor for placement in tissue, in which the sensor develops an induced signal in response to said rotating magnetic field;
means for determining the relative strength of said induced signal, independently of the relative angular orientation in the horizontal plane of said probe and said sensor; and means, responsive to said means for determining, for indicating the relative distance between said probe and said sensor.
2. The system of claim 1 in which said means for providing a horizontal rotating magnetic field includes two mutually-perpendicularly-oriented electromagnetic coils in said probe.
3. The system of claim 2 in which said coils are coplanar.
4. The system of claim 3 in which said coils are wound on a unitary core.
5. The system of claim 2 in which said means for providing further includes means for driving said coils in quadrature to accomplish a horizontal rotating magnetic field of substantially constant strength.
6. The system of claim 1 in which said sensor includes an inductive coil.
7. The system of claim 1 in which said induced signal has a peak and said means for indicating includes means for displaying the peak induced signal strength.
8. The system of claim 1 in which said means for indicating includes means for generating a light bar display.
9. The system of claim 1 in which said means for indicating includes means for generating an audio tone.
10. The system of claim 9 in which said induced signal has a strength and said means for indicating further includes means for varying the frequency of said audio tone in relation to the induced signal strength.
11. The system of claim 9 in which said induced signal has a strength and said means for indicating further includes means for varying the volume of said audio tone in relation to the induced signal strength.
12. The system of claim 1 further including means for resolving the relative horizontal angular orientation of said probe and said sensor.
13. The system of claim 12 in which said means for providing a horizontal rotating magnetic field includes at least one coil and a coil drive signal having a phase, and said induced signal has a phase, and said means for resolving includes means for comparing the phase of said coil drive signal to the phase of said induced signal.
14. The system of claim 12 in which said sensor has a longitudinal axis, and further including means for visually indicating the true direction of the sensor axis in the horizontal plane.
15. The system of claim 14 in which said means for visually indicating includes a plurality of lights arranged on said probe in a circular pattern, andmeans, responsive to said means for resolving, for lighting a single light whosedirection relative to the center of the circular pattern is indicative of the true direction of said sensor axis in the horizontal plane.
16. The system of claim 14 in which said sensor has a distal end along the longitudinal axis, and in which said means for visually indicating indicates thetrue direction of the sensor distal end along the longitudinal axis.
17. The system of claim 16 in which said means for visually indicating includes a plurality of lights arranged on said probe in a circular pattern, andmeans, responsive to said means for resolving, for lighting a single light whosedirection relative to the center of the circular pattern is indicative of the true direction of the sensor distal end along the longitudinal axis.
18. The system of claim 1 further including means for resolving the position of said sensor in relation to said probe.
19. The system of claim 18 in which said means for resolving includes a vertically-oriented electromagnetic coil in said probe, and means for driving said coil with an AC signal to create a time-varying magnetic field.
20. The system of claim 19 in which said AC signal and said induced signal have a phase, and said means for resolving further includes means for comparing the phase of said AC signal to the phase of said induced signal.
21. The system of claim 19 in which said means for providing a horizontal rotating magnetic field includes a field drive signal, and further including means for multiplexing the field drive signal and the vertical coil AC signal.
22. The system of claim 18 further including means on said probe for visually indicating the resolved position of said sensor in relation to said probe.
23. The system of claim 6 in which said sensor includes a plurality of inductive coils spaced along a catheter for separately developing induced signals to locate different portions of the catheter with a single external probe.
24. The system of claim 1 in which said means for indicating includes a scale of inches or centimeters on said probe to provide a numerical indication of the distance between said sensor and said probe.
25. The system of claim 1 in which said means for providing a horizontal rotating magnetic field includes three coils on a six-pointed coil form driven by a 3-phase alternating current.
26. A system for externally locating a sensing coil in tissue, comprising:
an external probe having an axis and including a horizontally-oriented pair of perpendicular electromagnetic coils;
means for driving said pair of coils in quadrature with a drive signal having a phase to create a horizontal rotating magnetic field of substantially constant strength;
?????/????3 an inductive sensing coil having a distal end and located along a longitudinal axis for developing, in response to said rotating field, an inducedsignal having a phase and strength;
means, responsive to said induced sensing coil signal, for indicating the strength of the induced signal as a measure of the relative distance between thesensing coil and the probe, independently of the relative horizontal angular orientation of said probe and said sensing coil;
means for comparing the phase of the drive signal for one of the pair of coils to the phase of the induced signal; and means, responsive to said means for comparing, for displaying the true direction of the sensor distal end along the longitudinal axis in the horizontalplane.
an external probe having an axis and including a horizontally-oriented pair of perpendicular electromagnetic coils;
means for driving said pair of coils in quadrature with a drive signal having a phase to create a horizontal rotating magnetic field of substantially constant strength;
?????/????3 an inductive sensing coil having a distal end and located along a longitudinal axis for developing, in response to said rotating field, an inducedsignal having a phase and strength;
means, responsive to said induced sensing coil signal, for indicating the strength of the induced signal as a measure of the relative distance between thesensing coil and the probe, independently of the relative horizontal angular orientation of said probe and said sensing coil;
means for comparing the phase of the drive signal for one of the pair of coils to the phase of the induced signal; and means, responsive to said means for comparing, for displaying the true direction of the sensor distal end along the longitudinal axis in the horizontalplane.
27. A system for externally locating a catheter in tissue, comprising:
an external probe having an axis and including a horizontally-oriented pair of perpendicular electromagnetic coils and a third, vertically-oriented electromagnetic coil perpendicular to said horizontally-oriented coils;
means for driving said pair of coils in quadrature with a drive signal having a phase to create a horizontal rotating magnetic field of substantially constant strength;
means for driving said third coil with an AC signal to create a time-varying magnetic field having a phase;
a catheter with a longitudinal axis and including an inductive sensing coil in the catheter tip for developing induced signals in response to said rotating and time-varying magnetic fields;
means, responsive to said sensing coil signal induced by said rotating field, for indicating the relative distance between the catheter sensing coil and the probe, independently of the relative horizontal angular orientation of said probe axis and said catheter axis;
PCT/U?9?/????3 means for resolving the phase difference between said time-varying magnetic field and the signal induced by said time-varying magnetic field;
means, responsive to said means for resolving, for indicating the position of the sensing coil in relation to the probe;
means for comparing the phase of the drive signal for one of the coils of the coil pair to the phase of the signal induced in response to said rotatingmagnetic field; and means, responsive to said means for comparing, for displaying the true direction of the catheter tip along the longitudinal axis in the horizontal plane.
an external probe having an axis and including a horizontally-oriented pair of perpendicular electromagnetic coils and a third, vertically-oriented electromagnetic coil perpendicular to said horizontally-oriented coils;
means for driving said pair of coils in quadrature with a drive signal having a phase to create a horizontal rotating magnetic field of substantially constant strength;
means for driving said third coil with an AC signal to create a time-varying magnetic field having a phase;
a catheter with a longitudinal axis and including an inductive sensing coil in the catheter tip for developing induced signals in response to said rotating and time-varying magnetic fields;
means, responsive to said sensing coil signal induced by said rotating field, for indicating the relative distance between the catheter sensing coil and the probe, independently of the relative horizontal angular orientation of said probe axis and said catheter axis;
PCT/U?9?/????3 means for resolving the phase difference between said time-varying magnetic field and the signal induced by said time-varying magnetic field;
means, responsive to said means for resolving, for indicating the position of the sensing coil in relation to the probe;
means for comparing the phase of the drive signal for one of the coils of the coil pair to the phase of the signal induced in response to said rotatingmagnetic field; and means, responsive to said means for comparing, for displaying the true direction of the catheter tip along the longitudinal axis in the horizontal plane.
28. The system of claim 1 in which said means for indicating includes an analog meter display.
29. The system of claim 1 in which said means for indicating includes a digital numerical display.
30. A system for externally locating a sensor in tissue, comprising:
an external probe including electronic means for providing a horizontal rotating magnetic field;
a sensor with a distal end located along a longitudinal axis, said sensor developing an induced signal in response to said horizontal rotating magnetic field; and means, responsive to said induced signal, for resolving the true direction of said sensor distal end along the longitudinal axis in a horizontal plane.
an external probe including electronic means for providing a horizontal rotating magnetic field;
a sensor with a distal end located along a longitudinal axis, said sensor developing an induced signal in response to said horizontal rotating magnetic field; and means, responsive to said induced signal, for resolving the true direction of said sensor distal end along the longitudinal axis in a horizontal plane.
31. The system of claim 30 in which said means for resolving is further responsive to said means for providing a horizontal rotating magnetic field.
32. A method of externally locating a sensor in tissue, comprising the steps of:
providing a horizontal rotating magnetic field generated electronically from a probe external to the tissue;
developing from a sensor in the tissue an induced signal in response to said horizontal rotating magnetic field;
determining the relative strength of said induced signal, independently of the relative angular orientation in the horizontal plane of said probe and said sensor; and indicating, in response to the induced signal, the relative distance between the probe and the sensor.
providing a horizontal rotating magnetic field generated electronically from a probe external to the tissue;
developing from a sensor in the tissue an induced signal in response to said horizontal rotating magnetic field;
determining the relative strength of said induced signal, independently of the relative angular orientation in the horizontal plane of said probe and said sensor; and indicating, in response to the induced signal, the relative distance between the probe and the sensor.
33. A method of externally locating a sensor in tissue, comprising:
placing in the tissue a sensor having a distal end located along a longitudinal axis;
providing from a probe external to the tissue a horizontal rotating magnetic field;
developing from the sensor within the tissue an induced signal in response to said horizontal rotating magnetic field; and resolving and displaying, in response to said induced signal, the true direction of the sensor distal end along the longitudinal axis in a horizontal plane.
placing in the tissue a sensor having a distal end located along a longitudinal axis;
providing from a probe external to the tissue a horizontal rotating magnetic field;
developing from the sensor within the tissue an induced signal in response to said horizontal rotating magnetic field; and resolving and displaying, in response to said induced signal, the true direction of the sensor distal end along the longitudinal axis in a horizontal plane.
34. The method of claim 33 in which the horizontal rotating magnetic field and the induced signal have phases, and in which resolving and displaying the true direction includes comparing the phase of the induced signal to the phase of the horizontal rotating magnetic field.
35. The method of claim 1 in which said sensor is located coaxially within a catheter.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US07/755,024 US5425367A (en) | 1991-09-04 | 1991-09-04 | Catheter depth, position and orientation location system |
US755,024 | 1991-09-04 |
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CA2116970A1 true CA2116970A1 (en) | 1993-03-18 |
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Application Number | Title | Priority Date | Filing Date |
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CA002116970A Abandoned CA2116970A1 (en) | 1991-09-04 | 1992-08-27 | Catheter depth, position and orientation location system |
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US (1) | US5425367A (en) |
EP (1) | EP0606253A4 (en) |
JP (1) | JPH07500979A (en) |
AU (1) | AU666672B2 (en) |
CA (1) | CA2116970A1 (en) |
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-
1991
- 1991-09-04 US US07/755,024 patent/US5425367A/en not_active Expired - Lifetime
-
1992
- 1992-08-27 CA CA002116970A patent/CA2116970A1/en not_active Abandoned
- 1992-08-27 JP JP5505284A patent/JPH07500979A/en active Pending
- 1992-08-27 AU AU25115/92A patent/AU666672B2/en not_active Ceased
- 1992-08-27 EP EP92918887A patent/EP0606253A4/en not_active Withdrawn
- 1992-08-27 WO PCT/US1992/007253 patent/WO1993004628A1/en not_active Application Discontinuation
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JPH07500979A (en) | 1995-02-02 |
AU666672B2 (en) | 1996-02-22 |
US5425367A (en) | 1995-06-20 |
EP0606253A4 (en) | 1995-08-23 |
AU2511592A (en) | 1993-04-05 |
WO1993004628A1 (en) | 1993-03-18 |
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FZDE | Discontinued |