System and method for preparing an image corrected for the presence of a gravity induced distortion

Information

  • Patent Grant
  • 7277594
  • Patent Number
    7,277,594
  • Date Filed
    Monday, November 5, 2001
    23 years ago
  • Date Issued
    Tuesday, October 2, 2007
    17 years ago
Abstract
The present invention relates to an imaging system for obtaining an image correctable for the presence of a gravity induced image error. The imaging system includes an imager to obtain an image of an object and a position measurement device to obtain position data indicative of a gravity-induced deformation of the imager. The position data may include gravity vector data indicative of an orientation of a gravity vector.
Description
FIELD OF THE INVENTION

The invention relates to a system and method for obtaining an image of an object. In particular, the invention relates to a system and method for obtaining an image corrected for the presence of a distortion caused by a gravity induced deformation of an imager used to obtain the image.


BACKGROUND OF THE INVENTION

The use of measuring instruments and imaging appliances often necessitates changes in the position or orientation of the measuring instrument depending on the type of measurement to be taken. For example, imagers or for obtaining x-ray images, such as the mobile or swivel-mounted x-ray imagers commonly used in surgery may be used to obtain images with the apparatus at different positions. Image intensifiers and c-arm appliances are examples of such imagers.


With imagers, such as x-ray apparatuses used in surgery, the orientation of the imager relative to the gravitational field of the Earth may have an influence, due to material deformations, on the measurement and, consequently, on the digitization of the image. With x-ray imagers using magneto-optical image digitization, the orientation of the apparatus relative to the Earth's magnetic field may also have a negative effect on the x-ray photographs (images). A further possible deformation of these x-ray images may be due to the influence of optical deformations occurring in the receiver, depending primarily on the composition of the radiation source and on the nature of the receiver, which may arise, for example, during the transformation of electrons into photons or during a subsequent transformation of the photons into an electrical signal.


A system for detecting the position and orientation of a surgical instrument or device within an object and for simultaneously displaying previously generated images corresponding to the detected position and orientation is disclosed in U.S. Pat. No. 5,383,454 to Buchholz. The Buchholz patent discloses that the tip of a probe can be moved to a defined position within the object with the location of the probe being observable on a single display screen, which simultaneously displays a previously generated image of the object. The position of the probe is determined by means of a three-dimensional sound digitizer.


SUMMARY OF THE INVENTION

One embodiment of the present invention relates to an imaging system for obtaining an image, which is correctable for the presence of a gravity induced image error. The system comprises an imager, such as an x-ray apparatus, to obtain an image of an object and a position measurement device to obtain position data indicative of a gravity-induced deformation of the imager. An example of a gravity induced image error is an error caused by a gravity induced mechanical deformation of the imager. The mechanical deformation may change, for example, the position of an imager source with respect to an imager receiver. Such deformations, as well as the resulting image error, may differ depending upon the orientation of the imager with respect to a gravity vector local to the imager. The present invention is preferably configured to obtain a correctable image for each orientation of the imager.


The position data may comprise image position data indicative of a position and orientation of the imager, for example, the position and orientation of the imager receiver with respect to the imager source. The imaging device preferably comprises markers having a known spatial relationship with respect to the imager and the position measurement device preferably comprises receivers to determine a respective position of the markers. The position data may also comprise, alone or in combination with the imager position data, gravity vector data indicative of an orientation of a gravity vector in which case the system preferably comprises at least one inclinometer for determining the orientation of the gravity vector. A processor of the imaging system is preferably configured to perform a coordinate transformation between the position and orientation of the imager and the gravity vector data to determine the position and orientation of the imager with respect to the gravity vector.


The at least one inclinometer is preferably selected from the group consisting of spirit level inclinometers, gyration inclinometers, and inertial inclinometers. Alternatively, or in addition, an inclinometer with a movable body having a position indicative of the orientation of the gravity vector may be used.


The imaging system may be configured to prepare a corrected image, which is corrected for the presence of the gravity induced image error. In this case, the system further comprises a processor to prepare the corrected image by relating the gravity induced deformation and the gravity induced image error.


Another embodiment of the present invention relates to a system for preparing a reduced error image from image data obtained using an imager. A reduced error image is an image that has been corrected for the presence of a gravity induced image error. The system comprises a processor to receive the image data and position data indicative of a gravity induced deformation of the imager. The processor is configured to prepare a reduced error image from the image data by correcting an image error associated with the gravity induced deformation of the imager. The reduced error image is preferably essentially free of the error associated with the gravity induced deformation of the imager.


Yet another embodiment of the invention relates to a method for obtaining an image, which is correctable for the presence of a gravity induced image error. The method comprises imaging an object with an imager to obtain an image of the object and obtaining position data indicative of a gravity-induced deformation of the imager. The method may comprise the further step of preparing an image corrected for the presence of the gravity induced image error by relating the gravity induced deformation and the gravity induced image error.


The step of obtaining the position data may include determining a respective position of at least three markers each having a known spatial relationship with respect to the imager.


Another embodiment of the present invention relates to a method for preparing a reduced error image of an object. The method comprises providing image data of the object, wherein the image data was obtained using an imager, and providing position data indicative of a gravity induced deformation of the imager. The image data is preferably in electronic format, such as a digitized image. The position data is used to prepare a reduced error image from the image data by correcting an image error associated with the gravity induced deformation of the imager.


Another embodiment of the present invention relates to a device for detecting the position and orientation of an imager, which is preferably provided with at least three non-collinear markers, within at least one three-dimensional coordinate system. The device includes a position measurement device for locating the markers within the coordinate system and a computer for determining the position and orientation of the body based upon position data received from the position sensor. The position measurement device preferably includes at least two light sensitive elements having a respective optical axis. The optical axes intersect at a point displaced from the position measurement device. The device also includes a gravity vector determination device, which provides gravity vector data indicative of the direction of the gravity vector within the coordinate system.


The gravity vector detection device comprises at least one inclinometer, which is fixed with respect to the position measurement device. A preferred embodiment includes two inclinometers each having a respective axis. The respective axes are angularly offset, such as perpendicularly, to one another. The inclinometers can include, for example, spirit level inclinometers, gyration inclinometers having a space-based angular momentum vector, and inertial inclinometers.


In one embodiment, the inclinometer comprises a body, which includes at least two markers displaced from one another by a distance. The body is preferably free to assume a spatial position indicative of the alignment of the body with respect to the gravity vector. The position measurement device determines the body's spatial position. The computer is configured to determine the direction of the gravity vector based upon the position of the body.


The body may be suspended, such as by a thread, wire, or chain. Joints, which allow the body to move, such as Cardon joints or ball and socket joints, may also be used. The body may also be embedded within a flexible material, such as an elastomer, for example, silicone or foamed silicone rubber.


Movement of the body, such as movement tending to bring the body into alignment with the gravity vector may be damped, such as by shock-absorption. For example, the body may be contacted with a liquid, damped by mechanical means, such as springs, or damped by electromagnetic means. The shock absorption may be provided by friction or pneumatic shock absorbers.


Yet another embodiment of the invention relates to a method for preparing corrected image, such as a corrected x-ray image, from images including gravity induced errors. Gravity induced errors may arise because of, for example, mechanical deformations of an imager used to obtain the images. For example, gravity induced deformations may introduce errors into images obtained using x-ray apparatus comprising an x-ray source and a receiver. A example of a image is an x-ray image, such as an x-ray photograph, which is preferably digitized and stored electronically.


The method comprises obtaining gravity vector data indicative of the direction of the gravity vector within a three-dimensional coordinate system. Imager position data indicative of the position and orientation of the imager within the coordinate system are obtained, preferably by using a position measurement device in communication with a computer. The corrected image is prepared based upon the position and orientation of the imager with respect to the gravity vector.


The corrected image is prepared without placing a calibration instrument between the source and receiver of the imager, which eliminates errors caused by such instruments. In addition, the influences of gravity and of the Earth's magnetic field on the x-ray photographs may also be determined and the image corrected for either or both gravity or magnetic field-induced errors.


In one embodiment of an imaging system of the invention, the system comprises a position measurement device having at least two optoelectronic cameras, which are preferably equipped with CCD chips (charge-coupled device chips). The position measurement system is configured to determine the positions of markers, preferably infrared light-emitting diodes (IREDs), within a sensor based coordinate system. The markers have a known spatial relationship to an imager, which allows the position and orientation of the imager to be determined within the sensor based coordinate system.


The system further includes a gravity vector determination device for determination of a direction of a local gravity vector. The gravity vector determination device includes a first inclinometer defining an x-axis of a gravity-based, three-dimensional coordinate system, a second inclinometer defining a y-axis of the gravity-based, three-dimensional coordinate system, and a computer equipped with software permitting a three-dimensional, real-time display in a numeric or graphic form.


The inclinometer axes form a plane extending perpendicularly to a local gravity vector thereby forming a three-dimensional, gravity-based coordinate system. By means of an electronic transmission of the signals emitted by the inclinometers to the computer, it is possible to determine a deviation in parallelism between one axis of the sensor-based coordinate system and the corresponding axis of the gravity-based coordinate system, and, consequently, to determine the rotation, if any, of the sensor-based coordinate system relative to the gravity-based coordinate system. The computer is configured to perform a coordinate transformation between the sensor-based coordinate system and the space-based or gravity-based coordinate system. Based on the coordinate transformation, the position and orientation of the imager can be determined with respect to the local gravity vector.


Another embodiment of the present invention relates to a method for obtaining an image of an object. The method includes obtaining an image of the object using an imager. Position data indicative of the position and orientation of the imager with respect to the direction of the local gravity vector within a three-dimensional coordinate system are obtained. The position data preferably include gravity vector data indicative of the direction of the local gravity vector within the three-dimensional coordinate system and imager position data indicative of the position of the imager within the three dimensional coordinate system. The position data may be stored, such as in a computer memory, for processing. A corrected image is prepared from image based on the position data. The corrected image is preferably essentially free of error, such as a distortion, caused by gravity induced mechanical deformations of the imager.


In a preferred embodiment, the method comprises determining the direction of a normal extending perpendicular to the image with the three dimensional coordinate system based upon the imager position data. The normal extends between a source and receiver of the imager. A second corrected image is prepared by correcting the image for errors caused by deviation of the normal from the direction of the Earth's local magnetic field. The image is preferably an x-ray photograph generated by the receiver on a magneto-optical basis. Errors of the magneto-optical photograph caused by optical deformations occurring in the receiver may be corrected.





BRIEF DESCRIPTION OF THE DRAWINGS

The present invention is described below in reference to the drawings in which:



FIG. 1 shows an imaging device according to the invention;



FIG. 2 shows a position measurement device of the imaging system of FIG. 1; and



FIG. 3 shows a second position measurement device according to the invention.





DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

Referring to FIG. 1, an imaging system 50 includes an imager 28, which is configured to obtain one or more images of an object, such as a human 33 or other animal.


The images may include gravity induced errors, such as image distortions caused by gravity induced deformations of the imager, including mechanical deformations in the shape or position of the imager. According to the present invention, the gravity induced errors are correctable upon obtaining position data indicative of the position and orientation of the imager with respect to a gravity vector 19 local to the imager. The position data may include imager position data indicative of the position and orientation of imager 28 and gravity vector data indicative of the direction of gravity vector 19. A position measurement device 12 provides the imager position data and a gravity vector determination device 52, which may be integral with position measurement device 12, provides the in-situ gravity vector data. A computer 8 receives image data from imager 28 and the position data. Computer 8 prepares corrected image data from the image data based upon the position data.


Imager 28 includes a source 30 and a receiver 29, which are preferably movable between a plurality of positions, such as between first and second positions 60, 62, and configured to obtain an image of the object from each of the plurality of positions. For example, object images, which are preferably formed parallel to image planes 35, 64, may be obtained from an anterior-posterior direction and a lateral-medial direction, such that respective image axes 31,32, which are normal to respective image planes 35, 64 extend approximately vertically or horizontally, depending on the position of imager 28. Mechanical deformations of the imager differ depending on whether the imager is oriented horizontally or vertically.


Imager 28 may be an x-ray imager configured to obtain at least one x-ray image of the object. A rotatable or swivel-mounted x-ray imager configured to obtain x-ray images from different orientations is preferred. Source 30 may be an x-ray source and receiver 29 an x-ray receiver, which preferably cooperate to generate an x-ray image on a magneto-optical basis.


Imager 28 includes markers 21 to allow determination of a position and orientation of imager 28 by position measurement device 12. Markers 21 preferably emit energy. For example, markers 21 may comprise light sources, such as light emitting diodes, infrared light emitting diodes and reflectors configured to reflect light emitted from a light source displaced from the markers. Acoustic energy sources, such as acoustic transmitters, may be used. The markers may comprise magnetic field generating elements, such as electromagnetic coils.


Referring to FIG. 2, position measurement device 12 includes receivers to receive energy emitted by markers 21. In the embodiment of FIG. 2, markers 21 are light emitting diodes and each of the receivers is an optoelectronic camera 2, which preferably include linear charge coupled device (CCD) chips to detect light from markers 21. An example of a position measurement device comprising camera elements is the model OPTOTRAK 3020 System available from Northern Digital, Waterloo, Ontario. Receivers of alternative position measurement devices include other light sensitive elements, such as photodiodes; acoustic receivers, such as microphones; and magnetic field sensitive receivers such as Hall effect components. It should be understood that markers 21 may be configured as receivers rather than emitters and that position measurement device 12 may include emitters rather than receivers.


Position measurement device 12 outputs imager position data indicative of a position of markers 21. Because the position of markers 12 is known with respect to imager 28, the position data are also indicative of the position and orientation of imager 28. Computer 8 receives and processes the imager position data. Computer 8 is programmed, such as with software, to display the data received thereby. Data are preferably displayed real-time, such as in numeric form or graphically in three-dimensions on a display 10. To facilitate the reception and processing of the image data, system 50 includes a system control unit 9, which is preferably integral with the computer 8, cables 13, which connect computer 8 and position measurement device 12, and an interface card 11.


Gravity vector determination device 52 includes first and second inclinometers 3, 6, which are preferably fixed with respect to position measurement device 12. The inclinometers are configured to determine deviations from the gravity vector 19. A horizontal axis 4 of inclinometer 3 defines an x-axis of a gravity-based, three-dimensional coordinate system 5. A horizontal axis 7 of second inclinometer 6 extends at an angle, preferably perpendicularly, to horizontal axis 4 and forms the y-axis of coordinate system 5. An axis XK of a sensor-based, three-dimensional coordinate system 26 is aligned preferably parallel to the horizontal axis 4 of first inclinometer 3 and an axis YK of coordinate system 26 is aligned preferably parallel to horizontal axis 7 of second inclinometer 6. Optical axes 14-16 of cameras 2 intersect at a point 17 and define a plane 18, which extends at an angle, preferably perpendicularly, to gravity vector 19.


Imaging system 50 determines the presence of angular deviation between one or more of the sensor-based coordinate axes XK, YK and the corresponding axis 4, 7 of the respective inclinometer 3, 6. The angular deviation is preferably indicative of the angular deviation (rotation) of the sensor-based coordinate system 26 relative to the gravity-based coordinate system 5. Computer 8 is configured to perform a coordinate transformation between the sensor-based and gravity-based coordinate systems. Therefore, the image position data and gravity vector data allow the position and orientation of imager 28 to be determined with respect to the local gravity vector. Deformations of imager 28, which may depend on the orientation of imager 28 with respect to the local gravity vector, may be determined based on the position data, which may include image position data, gravity vector data, or a combination thereof. For example, the imager position data may be indicative of a deviation of image planes 35, 64 from a respective desired orientation of normal axes 31, 32. Such deviations may cause image errors of images obtained by imager 28. Computer 8 is configured to prepare a corrected image based on the position data.


Inclinometers useful with the present invention include, spirit level inclinometers including a liquid with associated gas bubble, gyration inclinometers, and inertial inclinometers. Inclinometers including magnetic elements analogous to a compass may also be used. Gyration and inertial inclinometers are preferably calibrated with respect to an initial orientation with respect to the gravity vector.


Referring to FIG. 3, a position measurement device 100 differs from position measurement device 12 in that determination of the direction of the gravity vector 19 comprises determining the alignment of a body 20 with respect to the gravity vector. Body 20 is preferably movable such that it tends to assume a position indicative of the direction of the local gravity vector. For example, body 20 may be suspended, such as by a thin thread or wire 22. Body 20 is equipped with at least two markers 121 displaced from one another by a distance A. Markers 121 are preferably configured to emit energy, such as light, as discussed above for markers 21.


Energy emitted by the markers 121 is detected by cameras 2 of position detector 112, which provides body position data indicative of the positions of the markers 121 in space. The spatial positions of body 20 and, therefore, markers 121 are influenced by the direction of gravity vector 19. Computer 8 is configured to determine the direction of gravity vector 19 based upon the body position data. In case of a deviation in parallelism between the sensor-based normal 23 extending perpendicularly to the plane 18 formed by the optical axes 14, 15, 16 of the cameras 2 and the gravity vector 19, the deviation is detected by position measurement device 112. The rotation of the sensor-based coordinate system 26 relative to the gravity-based coordinate system 5 is determined by computer 8 by processing of the signals corresponding to the deviation detected by the position measurement device 112.


The present invention also provides a method for obtaining an image, which is correctable for the presence of a gravity induced image error. An object is imaged, such as with imager 28, to obtain an image of the object. A gravity induced deformation of the imager is determined, such as by using a position measurement device of the invention. For example, the position and orientation of an x-ray source 30 and/or the receiver 29 may be determined by measuring positions of markers 21 having a known relationship to the x-ray source 30 and/or the receiver 29. Determining the position of respective sets of markers fixed with respect to the source and receiver, respectively, allows deviations in alignment between the source and receiver to be determined from the imager position data.


The direction (orientation) of the gravity vector 19 is determined within a three-dimensional coordinate system 5, 24, 26 using a position measurement device and computer. For example, a space-based coordinate system 24 may be determined by measuring the positions of at least three non-collinear markers 21 having a fixed position in space, while the determination of the gravity-based, three-dimensional coordinate system 5, which is equally space-based, may be realised by measuring the positions of axes 4, 7 of inclinometers 3, 6 and their point of intersection. Alternatively, the gravity based coordinate system may be determined by measuring the positions of at least three markers 21 associated with body 20.


The position and orientation of x-ray source 30 and/or the receiver 29 are determined within coordinate system 5, 24, 26 using a position measurement device such as by measuring the positions of the markers 21 fixed on the source 30 and/or the receiver 29.


Distortions of images obtained by the imager, due to gravity-induced, mechanical deformations of the imager 28, may be determined using computer 8. The distorted image may be corrected to provide a reduced error image using the computer 8.


The direction of the image plane normal 31, 32 extending perpendicularly to the image within coordinate system 5, 24, 26 may be determined from the position and orientation of the receiver 29. Image errors generated by the receiver 29 arising from the deviation of the respective normal 31, 32 of said photograph from the direction of the Earth's local magnetic field may be determined by means of the computer 8. The image may be corrected to provide a reduced error image corrected for the presence of magnetic field induced errors. Magnetic field induced errors may be present in, for example, x-ray photographs obtained on a magneto-optical basis. Distortions of the magneto-optical x-ray photograph caused by optical deformations occurring in receiver 29, which distortions are particularly affected, among other things, by the vertical or horizontal orientation of the x-ray apparatus 28, may be corrected using computer 8.


While the above invention has been described with reference to certain preferred embodiments, it should be kept in mind that the scope of the present invention is not limited to these. Thus, one skilled in the art may find variations of these preferred embodiments which, nevertheless, fall within the spirit of the present invention, whose scope is defined by the claims set forth below.

Claims
  • 1. An imaging system for obtaining a reduced error image that is correctable for the presence of a gravity induced image error, said imaging system comprising: an imager to obtain an image of an object, the objected being in a suspended state;at least two markers displaced from one another by a distance attached to the object;a position measurement device providing object position data indicative of positions of the markers; anda computer configured to determine a direction of a gravity vector based on the object position data,wherein deviation of parallelism between the gravity vector and a sensor-based normal is determined by the position measurement device,wherein the imager is rotated to eliminate the deviation of parallelism between the gravity vector and a sensor-based normal of a sensor-based coordinate system, andwherein the reduced error image of the objected is taken by the imager.
  • 2. An imaging system according to claim 1, wherein the imager includes multiple optical axes intersecting at a point to define a plane.
  • 3. An imaging system according to claim 2, wherein the sensor-based normal is perpendicular to the plane.
  • 4. An imaging system according to claim 1, wherein the markers are energy emitting markers having a known spatial relationship with respect to the imager.
  • 5. An imaging system according to claim 1, wherein the position measurement device comprises receivers to determine the positions of the markers.
  • 6. An imaging system according to claim 1, wherein the object is suspended by a wire.
  • 7. An imaging system according to claim 3, wherein an x-axis of a gravity-based three-dimensional coordinate system is aligned parallel with a horizontal axis of the imager.
  • 8. An imaging system according to claim 7, wherein an x-axis of a sensor-based three dimensional coordinate system is parallel to the plane.
  • 9. An imaging system according to claim 8, wherein the deviation of parallelism between the gravity vector and the sensor-based normal is based on an angular deviation of the sensor-based coordinate system relative to the gravity-based coordinate system.
  • 10. An imaging system according to claim 9, wherein the reduced error image is obtained by rotation of the sensor-based coordinate system relative to the gravity-based coordinate system as determined by the computer processing signals corresponding to the deviation of parallelism detected by the position measurement device.
  • 11. An imaging system according to claim 1, wherein the imager is an x-ray apparatus and the image is an x-ray image of an animal.
  • 12. A method imaging system for obtaining a reduced error image that is correctable for the presence of a gravity induced image error, said method comprising the steps of: attaching at least two markers displaced from one another by a distance onto an object to be imaged by an imager;suspending the objected such that the object is movable;obtaining object position data indicative of positions of the markers by a position measurement device;determining a direction of a gravity vector based on the object position data;determining a deviation of parallelism between the gravity vector and a sensor-based normal of a sensor-based coordinate system;rotating the imager to eliminate the deviation of parallelism between the gravity vector and a sensor-based normal of a sensor-based coordinate system; andtaking the reduced error image of the objected by the imager.
  • 13. A method according to claim 12, wherein the imager includes multiple optical axes intersecting at a point to define a plane.
  • 14. A method according to claim 13, wherein the sensor-based normal is perpendicular to the plane.
  • 15. A method according to claim 12, wherein the markers are energy emitting markers having a known spatial relationship with respect to the imager.
  • 16. A method according to claim 12, wherein the position measurement device comprises receivers to determine the positions of the markers.
  • 17. A method according to claim 12, wherein the object is suspended by a wire.
  • 18. A method according to claim 14, wherein an x-axis of a gravity-based three-dimensional coordinate system is aligned parallel with a horizontal axis of the imager.
  • 19. A method according to claim 18, wherein an x-axis of the sensor-based three dimensional coordinate system is parallel to the plane.
  • 20. A method according to claim 19, wherein the deviation of parallelism between the gravity vector and the sensor-based normal is based on an angular deviation of the sensor-based coordinate system relative to the gravity-based coordinate system.
  • 21. A method according to claim 20, wherein a reduced error image is obtained by rotation of the sensor-based coordinate system relative to the gravity-based coordinate system as determined by the computer processing signals corresponding to the deviation of parallelism detected by the position measurement device.
  • 22. A method according to claim 12, wherein the imager is an x-ray apparatus and the image is an x-ray image of an animal.
RELATED APPLICATIONS

This application is a continuation of National stage of application no. PCT/CH99/00183, May 3, 1999, which application is incorporated herein in its entirety.

US Referenced Citations (176)
Number Name Date Kind
3821469 Whetstone et al. Jun 1974 A
3983474 Kuipers Sep 1976 A
4058114 Soldner Nov 1977 A
4146924 Birk et al. Mar 1979 A
4182312 Mushabac Jan 1980 A
4204225 Mistretta May 1980 A
4209254 Reymond et al. Jun 1980 A
4262306 Renner Apr 1981 A
4341220 Perry Jul 1982 A
4358856 Stivender et al. Nov 1982 A
4396945 DiMatteo et al. Aug 1983 A
4418422 Richter et al. Nov 1983 A
4419012 Stephenson et al. Dec 1983 A
4437161 Anderson Mar 1984 A
4457311 Sorenson et al. Jul 1984 A
4465069 Barbier et al. Aug 1984 A
4473074 Vassiliadis Sep 1984 A
4485815 Amplatz et al. Dec 1984 A
4543959 Seponen Oct 1985 A
4571834 Fraser et al. Feb 1986 A
4583538 Onik et al. Apr 1986 A
4592352 Patil Jun 1986 A
4598368 Umemura Jul 1986 A
4602622 Bär et al. Jul 1986 A
4613866 Blood Sep 1986 A
4613942 Chen Sep 1986 A
4618978 Cosman Oct 1986 A
4638798 Shelden et al. Jan 1987 A
4649504 Krouglicof et al. Mar 1987 A
4651732 Frederick Mar 1987 A
4670781 Aubert et al. Jun 1987 A
4672564 Egli et al. Jun 1987 A
4674057 Caughman et al. Jun 1987 A
4729098 Cline et al. Mar 1988 A
4733661 Palestrant Mar 1988 A
4733969 Case et al. Mar 1988 A
4737032 Addleman et al. Apr 1988 A
4742815 Ninan et al. May 1988 A
4743770 Lee May 1988 A
4743771 Sacks et al. May 1988 A
4745290 Frankel et al. May 1988 A
4750487 Zanetti Jun 1988 A
4753528 Hines et al. Jun 1988 A
4760851 Fraser et al. Aug 1988 A
4761072 Pryor Aug 1988 A
4762016 Stoughton et al. Aug 1988 A
4763652 Brisson et al. Aug 1988 A
4764016 Johansson Aug 1988 A
4776749 Wanzenberg et al. Oct 1988 A
4779212 Levy Oct 1988 A
4782239 Hirose et al. Nov 1988 A
4791934 Brunnett Dec 1988 A
4793355 Crum et al. Dec 1988 A
4794262 Sato et al. Dec 1988 A
4803976 Frigg et al. Feb 1989 A
4821200 Öberg Apr 1989 A
4821206 Arora Apr 1989 A
4822163 Schmidt Apr 1989 A
4825091 Breyer et al. Apr 1989 A
4829373 Leberl et al. May 1989 A
4835710 Schnelle et al. May 1989 A
4836778 Baumrind et al. Jun 1989 A
4841967 Chang et al. Jun 1989 A
4869247 Howard, III et al. Sep 1989 A
4875478 Chen Oct 1989 A
4896673 Rose et al. Jan 1990 A
4907252 Aichinger et al. Mar 1990 A
4943296 Funakubo et al. Jul 1990 A
4945914 Allen Aug 1990 A
4955891 Carol Sep 1990 A
4970666 Welsh et al. Nov 1990 A
4987488 Berci Jan 1991 A
4991579 Allen Feb 1991 A
5016639 Allen May 1991 A
5027818 Bova et al. Jul 1991 A
5047036 Koutrouvelis Sep 1991 A
5050608 Watanabe et al. Sep 1991 A
5059789 Salcudean Oct 1991 A
5078140 Kwoh Jan 1992 A
5080662 Paul Jan 1992 A
5086401 Glassman et al. Feb 1992 A
5094241 Allen Mar 1992 A
5097839 Allen Mar 1992 A
5099846 Hardy Mar 1992 A
5107839 Houdek et al. Apr 1992 A
5119817 Allen Jun 1992 A
5142930 Allen et al. Sep 1992 A
5178164 Allen Jan 1993 A
5186174 Schlöndorff et al. Feb 1993 A
5197476 Nowacki et al. Mar 1993 A
5198877 Schulz Mar 1993 A
5207223 Adler May 1993 A
5211164 Allen May 1993 A
5211165 Dumoulin et al. May 1993 A
5230338 Allen et al. Jul 1993 A
5230623 Guthrie et al. Jul 1993 A
5249581 Horbal et al. Oct 1993 A
5251127 Raab Oct 1993 A
5257998 Ota et al. Nov 1993 A
5274551 Corby, Jr. Dec 1993 A
5278756 Lemchen et al. Jan 1994 A
5295483 Nowacki et al. Mar 1994 A
5299288 Glassman et al. Mar 1994 A
5300080 Clayman et al. Apr 1994 A
5305203 Raab Apr 1994 A
5309913 Kormos et al. May 1994 A
5325855 Daghighian et al. Jul 1994 A
5350351 Saffer Sep 1994 A
5383454 Bucholz Jan 1995 A
5389101 Heilbrun et al. Feb 1995 A
5394457 Leibinger et al. Feb 1995 A
5408409 Glassman et al. Apr 1995 A
5445166 Taylor Aug 1995 A
5479597 Fellous Dec 1995 A
5483961 Kelly et al. Jan 1996 A
5494034 Schlöndorff et al. Feb 1996 A
5517990 Kalfas et al. May 1996 A
5588430 Bova et al. Dec 1996 A
5617857 Chader et al. Apr 1997 A
5622170 Schulz Apr 1997 A
5630431 Taylor May 1997 A
5631973 Green May 1997 A
5662111 Cosman Sep 1997 A
5676673 Ferre et al. Oct 1997 A
5682886 Delp et al. Nov 1997 A
5711299 Manwaring et al. Jan 1998 A
5729129 Acker Mar 1998 A
5732703 Kalfas et al. Mar 1998 A
5735278 Hoult et al. Apr 1998 A
5748767 Raab May 1998 A
5755725 Druais May 1998 A
RE35816 Schulz Jun 1998 E
5769078 Kliegis Jun 1998 A
5769789 Wang et al. Jun 1998 A
5769861 Vilsmeier Jun 1998 A
5772593 Hakamata Jun 1998 A
5795294 Luber et al. Aug 1998 A
5799099 Wang et al. Aug 1998 A
5800352 Ferre et al. Sep 1998 A
5807252 Hassfeld et al. Sep 1998 A
5810008 Dekel et al. Sep 1998 A
5829444 Ferre et al. Nov 1998 A
5848967 Cosman Dec 1998 A
5880976 DiGioia III et al. Mar 1999 A
5995738 DiGioia, III et al. Nov 1999 A
6002859 DiGioia, III et al. Dec 1999 A
6021343 Foley et al. Feb 2000 A
6112113 Van Der Brug et al. Aug 2000 A
6120465 Guthrie et al. Sep 2000 A
6122341 Butler et al. Sep 2000 A
6135946 Konen et al. Oct 2000 A
6149592 Yanof et al. Nov 2000 A
6165181 Heilbrun et al. Dec 2000 A
6167145 Foley et al. Dec 2000 A
6167295 Cosman Dec 2000 A
6167296 Shahidi Dec 2000 A
6198794 Peshkin et al. Mar 2001 B1
6205411 DiGioia, III et al. Mar 2001 B1
6216029 Paltieli Apr 2001 B1
6224613 Hofstetter May 2001 B1
6226548 Foley et al. May 2001 B1
6236875 Bucholz et al. May 2001 B1
6246898 Vesely et al. Jun 2001 B1
6256529 Holupka et al. Jul 2001 B1
6259943 Cosman et al. Jul 2001 B1
6275725 Cosman Aug 2001 B1
6285902 Kienzle et al. Sep 2001 B1
6298262 Franck et al. Oct 2001 B1
6332891 Himes Dec 2001 B1
6341231 Ferre et al. Jan 2002 B1
6351659 Vilsmeier Feb 2002 B1
6351662 Franck et al. Feb 2002 B1
6739752 Sabczynski et al. May 2004 B2
20010007919 Shahidi Jul 2001 A1
20010027271 Franck et al. Oct 2001 A1
20010039421 Heilbrun et al. Nov 2001 A1
Foreign Referenced Citations (19)
Number Date Country
195 06 197 May 1996 DE
195 36 180 Jun 1997 DE
297 04 393 Jul 1997 DE
0 062 941 Oct 1982 EP
0 326 768 Aug 1989 EP
0 591 712 Apr 1994 EP
0 647 428 Apr 1995 EP
0 832 609 Apr 1998 EP
2 094 590 Sep 1982 GB
WO 9005494 May 1990 WO
WO 9107726 May 1991 WO
WO 9423647 Oct 1994 WO
WO 9424933 Nov 1994 WO
WO 9515729 Jun 1995 WO
WO 9531148 Nov 1995 WO
WO 9611624 Apr 1996 WO
WO 9729685 Aug 1997 WO
WO 9729709 Aug 1997 WO
WO 9747240 Dec 1997 WO
Related Publications (1)
Number Date Country
20020109705 A1 Aug 2002 US
Continuations (1)
Number Date Country
Parent PCT/CH99/00183 May 1999 US
Child 09985585 US