Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N7/00—Ultrasound therapy
  • A61N7/02—Localised ultrasound hyperthermia
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
  • A61B8/44—Constructional features of the ultrasonic, sonic or infrasonic diagnostic device
  • A61B8/4444—Constructional features of the ultrasonic, sonic or infrasonic diagnostic device related to the probe
  • A61B8/4461—Features of the scanning mechanism, e.g. for moving the transducer within the housing of the probe
• • 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
  • A61B90/36—Image-producing devices or illumination devices not otherwise provided for
  • A61B90/37—Surgical systems with images on a monitor during operation
  • A61B2090/378—Surgical systems with images on a monitor during operation using ultrasound

Definitions

• the present invention relates to a device for treatment of an organ or tissue of a living being with ultrasound, preferably high intensity focused ultrasound (HIFU) waves, according to claim 1.
• ultrasound preferably high intensity focused ultrasound (HIFU) waves
• Treatment with ultrasound waves is well known in the art. It is espe ⁇ cially used for treatment of tumours of the thyroid, breast, uterus and prostate. Tumours are thereby destroyed by means of thermal energy. The necessary heat is generated by focussing high intensity ultrasound waves onto a focal point. As an acous ⁇ tic wave propagates through the tissue, part of it is absorbed and converted to heat. At the focal point, due to the signifi ⁇ cant energy concentration, the temperature within the tissue rises to 65° to 85°C, destroying the diseased tissue by coagula ⁇ tion necrosis.
• HIFU high intensity fo ⁇ cused ultrasound
• HIFU treatment devices usually comprise a treatment head with a HIFU transducer.
• the treatment head is placed on the tissue to be treated or on tissue adjacent to the organ to be treated.
• Such devices are sold e.g. by EDAP TMS under the trademark Ab- latherm® or by Theraclion under the name TH-One.
• the ultra ⁇ sound waves When treating an internal organ, such as the thyroid, the ultra ⁇ sound waves generally travel through a layer of healthy tissue before reaching the focal zone.
• the travelling ultrasound waves also generate heat within this healthy tissue, which may accumu ⁇ late, leading to damage or even necrosis. This can be avoided by delivering the ultrasound radiation in short pulses separated by a blanking period which allows the healthy tissue to cool down between pulses thus avoiding heat damage.
• heat generated by the pulses in the focal zone is high enough to produce tissue damage, despite of the cooling phases between two pulses. Nonetheless, even with such a pulsed treatment, damage to healthy tissue is frequent, see for example LI Jian-Jun et al . ("Complications of High Intensity Focused Ultrasound for Pa ⁇ tients with Hepatocellular Carcinoma", Technology in cancer re ⁇ search & treatment 2009, vol. 8, no3, pp. 217-224) .
• US 6,425,867 teaches a HIFU device with both a scanning and a therapeutic transducer as well as a method for real time ultra ⁇ sound imaging during HIFU treatment. Synchronization of the therapeutic ultrasonic transducer system relative to the scan ⁇ ning ultrasonic transducer system is provided such that any noise within the imaging data arising from the therapeutic waves is shifted away from the image of the treatment site. Thus, a noise-free image of the treatment site is provided.
• US 6,425,867 also describes an ultrasound device having synchronization means to synchronize both transducers according to the method.
• Such a method provides for good simultaneous imaging of the tar ⁇ get area and thus helps focussing the HIFU waves into the tar ⁇ get .
• WO 03/008041 describes an ultrasound treatment head comprising a probe body which is mounted in rotation around an axis, a treat ⁇ ment transducer with a focussed ultrasound acoustic emission axis which is more or less the same as the probe body rotation axis and an imaging transducer.
• a head has the advantage of implementing treatment and imaging means on the same device.
• the visualization and treatment acoustic axis are more or less the same with the rotation axis, thus ensuring that even when the probe body is rotated, the focal point of the treatment transducer remains at the same spot as well as within the visu ⁇ alization plane of the imaging transducer.
• Rotation of the probe body is mainly used to acquire images of the target organ or tissue. Treatment of target organs is carried out by shooting short pulses of ultrasound to one spot of the target and then moving on to another spot of the target until the whole target area has been treated.
• One big disadvantage of the known ultrasound heads is that even though short pulses are used for HIFU treatment, damage to healthy tissue between the skin and the target organ may still occur .
• the invention concerns a device for treatment of an organ or tissue of a living being.
• the device comprises at least one treatment transducer for emission of ultrasound waves, prefera ⁇ bly high intensity focused ultrasound (HIFU) waves, focused on a focal point within or on the surface of said organ or tissue.
• the device further comprises rotating means to rotate said treatment transducer as well as synchronization means for synchronizing the rotation of the treatment transducer with at least the emission of ultrasound waves from said treatment transducer and/or an additional imaging transducer, whereby the focal point is not moved by the rotation.
• “Rotation” as understood herein means a movement around a de ⁇ fined axis. Said movement may be at a constant speed or a chang ⁇ ing speed, such as acceleration. Said movement may happen in both directions around said defined axis.
• the treatment transducer is rotatable about a central propagation axis.
• this axis is identical to the symmetry axis of the transducer.
• the treat ⁇ ment transducer will therefore revolve around itself. The cen ⁇ tral propagation axis as well as the focal point will not move.
• Central propagation axis as used herein is an axis intercepting the centre of the transducer and the focal point.
• the centre of the transducer as understood herein is the geometrical centre of the surface area of the transducer.
• the treatment transducer is rotatable about an axis which is angled in relation to said central propa ⁇ gation axis and which intersects said focal point.
• the treatment transducer will therefore follow a precession motion. Since the rotation axis intercepts the focal point, said point will not move.
• the axis can be angled in any angle ⁇ 90°, but preferably will be angled in an angle ⁇ 45°.
• the angle can be fixed or the device can provide for means of adapting this angle according to treatment need.
• the adapting means must ensure that the rotation axis will always intersect the central propagation axis of the transducer at the focal point.
• the transducer may be fixed to an arcuate arm having a rotation axis. By moving the transducer about such an arm it is possible to vary the angle of the central propagation axis of the transducer to the rotation axis .
• the treatment transducer is rotatable about an axis which is perpendicular to said central propagation axis and which intersects said focal point.
• the treatment trans ⁇ ducer will therefore follow a tilting or pivoting motion. Since the rotation axis intercepts the focal point, said point will not move.
• the device can comprise an arcuate holder on which the treatment transducer may be moved back and forth.
• the probe head is also ro ⁇ tatable around the central propagation axis.
• the probe head is also ro ⁇ tatable around the central propagation axis.
• rotation about both axes is synchronized with emission of treat ⁇ ment and/or imaging ultrasound waves.
• the space between a membrane covering the probe head may be filled with varying volumes of a coupling and/or cooling liquid.
• a coupling and/or cooling liquid By increasing the pressure of the liquid, the membrane will bulge out thus increasing the volume of liquid be ⁇ tween the skin of the patient and the transducer, thus moving the focal point.
• Such a pressure increase as well as a pressure decrease can be synchronized with the rotation and/or the emis ⁇ sion of ultrasound waves.
• Such an embodiment allows for treat ⁇ ment of a target area with varying depth with reduced risk of heat induced damages to healthy tissue.
• the treatment device preferably further comprises an imaging transducer, such as an ultrasound probe.
• This imaging transducer is thereby co-rotatable with the treatment transducer and has an imaging plane intersecting the focal point of the treatment transducer .
• the imaging transducer may be of any suitable kind, such as X- ray, but is preferably an ultrasound probe.
• the treatment device preferably comprises ad ⁇ ditional means to determine the angular position of the trans ⁇ ducer and to transmit said position information along with the imaging data.
• a co-rotatable imaging transducer may also be used to detect and/or compensate patient motion when rotated around said rotation axis
• the rotation axis may be represented as a line in the imaging plane. The ultrasound signal along this line remains constant throughout the rotation if no motion occurs, so that changes in the signal may be interpreted as a sign of unwanted motion .
• the treatment device may comprise means for generating a 3-dimensional image based on 2-dimensional images acquired by the imaging transducer during rotation. Multiple images acquired during rotation of the transducer may be assembled and processed to a 3-dimensional representation of the target area.
• tissue motion occurs in a plane.
• respira ⁇ tory motion occurs in the sagittal plane.
• the 3-dimensional representation of the object calculated from im ⁇ ages acquired during the rotation will be distorted.
• a correc ⁇ tion scheme is described hereafter.
• at least one im ⁇ age is taken in the direction of the plane of motion before the beginning of the treatment.
• signals from the line representing the rotation axis are compared with signals from lines parallel to the line representing the parallel axis from the at least one image taken before the beginning of the treatment. This allows to detect any displacement of signals.
• This displacement information can be used to correct the ac ⁇ quired image thus yielding an undistorted 3-dimensional image.
• Having a 3-dimensional representation of the target area can help monitor the treatment and asses its efficacy. It may also be used to determine the next spot to which the focal point has to be directed to. 3D representation also helps the practitioner to identify the target, to better compare size and aspect of the target before and after the HIFU treatment.
• a 3-dimensional representa ⁇ tion of the target area is further processed in order to compare its actual position relative to a previously acquired 3- dimensional representation. This processing allows to determine a displacement estimator of the target area.
• the displacement estimator is then used to determine whether the focal point of the ultrasound is still within the target area. If this is not the case, an appropriate warning may be given.
• the treatment device is provided with means to input a maximal displacement value prior to treatment. If the dis ⁇ placement estimator exceeds this value during treatment, the de ⁇ vice may warn the operator.
• the treatment and imaging transducer, along with the rotation means are mounted on a robotic table allowing for certain degrees of free ⁇ dom of the transducer.
• Displacement estimation can be used to compute commands for the robotic table in order to realign the focal point within the target area.
• displacement estimation is performed during HIFU treatment itself by synchro ⁇ nizing the pulses of treatment and imaging ultrasound with rota ⁇ tion of the transducers.
• the treatment device additionally pro ⁇ vides means to interrupt the emission of treatment ultrasound if the focal point moves out of the target area and/or to realign the focal point with the target area by means of the robotic ta ⁇ ble .
• calculation of displacement estimates may be done using a very sparse representation of the target area, starting from only two 2-dimensional images.
• the displacement estimator may be calculated in a progressive way, using data from 2-dimensional images se ⁇ quentially acquired during treatment to improve the accuracy of the displacement estimator.
• Another aspect of the present invention is directed to a method for operating a treatment device having a rotatable treatment transducer .
• the method comprises the steps of:
• Synchronization means thereby synchronize the rotation of the treatment transducer with the emission of the ultrasound pulse.
• the synchronization means are preferably in the form of an inte ⁇ grated circuit comprising a microchip or in the form of a computer, such as a workstation or a microcomputer.
• the synchronization means more preferably further comprise input means such as to allow an operator to change certain parameters or to chose a specific mode of synchronization.
• the treatment transducer is rotated about the central propagation axis of the transducer. In other words, the treatment transducer will revolve around itself. Thereby the central propagation axis as well as the focal point will not move .
• the treatment transducer is rotated about an axis which is perpendicular to said central propagation axis and which intersects said focal point.
• the treatment transducer will therefore follow a tilting motion. Since the rotation axis intercepts the focal point, said point will not move.
• the treatment transducer is rotated about an axis which is angled in relation to said central propa ⁇ gation axis and which intersects said focal point.
• the treatment transducer will therefore follow a precession motion. Since the rotation axis intercepts the focal point, said focal point will not move.
• An integrated imaging transducer will in most cases be arranged somewhere on or within the treatment transducer, thereby creat ⁇ ing an area where no treatment ultrasound waves will be gener ⁇ ated or where they will be masked. By rotating the treatment transducer, this area will also be rotated. This will subject tissue which would have been shielded by this area to be also subject to ultrasound emission.
• the co-rotatable imaging transducer allows the 3- dimensional acquisition to be less prone to tissue motion.
• an additional ultrasound pulse from an imag ⁇ ing transducer maybe emitted. Emission of this imaging pulse is synchronized with at least one of the rotation of said imaging transducer, rotation of said treatment transducer and/or emission of said treatment pulse.
• Intermittent imaging pulses allow visualizing the target zone and/or the focal point during treatment. This helps assessing the efficacy of the treatment and finding new points to focus the ultrasound to. Synchronizing these imaging pulses with the rotation of the treatment and/or imaging transducer or with the emission of ultrasound pulses from the treatment transducer al ⁇ lows for optimal acquisition of images.
• n is thereby any number >0.
• n is preferably any integer >0, such as 1, 2, 3, 4 etc. But n may also be any floating-point number such as 0.75, 1.5, 2.2 etc. Most preferably n is 1, 2 or 4, resulting in a respec ⁇ tive rotation of the head by 90°, 180° or 360° during one ultra ⁇ sound pulse.
• the treatment transducer may be rotated by n*90° in one direction around the rotation axis and back to its initial position during one pulse.
• n is any integer >0, such as 1, 2, 3, 4 etc.
• n may also be any floating-point number such as 0.75, 1.5, 2.2 etc.
• Most preferably n is 1, 2 or 4, resulting in a respective rotation of the head by 90°, 180° or 360° in one direction and back to its initial position during one pulse.
• m ultrasound pulses are emitted from the treatment transducer and/or the imaging transducer during one rotation through 90°.
• m is any integer >0, such as 1, 2, 3, 4 etc.
• m is 16, resulting in the emission of 16 pulses during rotation of the head by 90°.
• the treatment transducer may be rotated about 45° in each direction.
• the transducer may move from a predefined angle to a second prede ⁇ fined angle.
• the ultrasound pulse is emitted while the probe head moves from the first predefined an ⁇ gle to the second predefined angle and back during one pulse.
• a multitude of pulses may be emitted.
• each pulse from the treatment transducer one pulse or a series of pulses from the imaging transducer may be emitted. This allows for acquisition of multiple images during rotation, which may be processed to a 3-dimensional representa ⁇ tion of the target area and/or the area around the focal point.
• the rotation speed of the head and/or pulse emis ⁇ sion can be optimized in view of the characteristic cooling rate of the treated tissue. For example, if the treated tissue has a characteristic cooling rate of 30s - meaning that the over- temperature is reduced by roughly 2/3 after 30s - rotation of the head and/or emission of ultrasound can be synchronized in such a way that any volume of tissue outside of the focal point is not subjected to treatment waves for at least 30s.
• skin temperature is moni ⁇ tored, e.g. with an infrared thermometer or with ultrasonic thermography, and rotation and/or emission of ultrasound is synchronized in such a way that the skin temperature does not in ⁇ crease above a certain value.
• the rate of temperature increase and decrease can be monitored and the rotation and/or emission of ultrasound waves synchronized ac ⁇ cording to the measured temperature changes.
• the average acoustic intensity of the waves is mapped over the surface of the transducer, thereby approximating the actual exposure of tissue to ultrasound energy.
• Rotation of the head can then be synchronized to the emission of ultrasound in such a way that a certain average acoustic intensity is not exceeded .
• this invention also provides for a treatment method for an organ or tissue by irradiating said organ or tissue with ultrasound pulses from a treatment device as described.
• This treatment method provides for a non-invasive ablation treatment of an organ or tissue, thereby minimizing the risk for the patient. Moreover injury to healthy tissue between the treatment transducer and the focal point is reduced in compari ⁇ son with known HIFU treatments, therefore further minimizing the risks for the patient.
• this method is used to treat the thyroid gland, the parathyroid glands, the breast, the uterus or the prostate.
• Fig. 1 An embodiment of a treatment device according to the present invention where the rotation axis is identi ⁇ cal with the central propagation axis
• Fig. 2a Another embodiment of the treatment device with a ro ⁇ tation axis which is perpendicular to the central propagation axis
• Fig. 2b The treatment device of Fig. 2a rotated about a cer ⁇ tain angle
• Fig. 3 A further embodiment of the treatment device having a rotation axis which is angled in relation to the central propagation axis
• Fig. 4a Simulated heat distribution on the surface of a pa ⁇ tient's skin without rotation of the treatment trans ⁇ ducer
• Fig. 4b Simulated heat distribution on the surface of a pa ⁇ tient's skin with rotation of the treatment trans ⁇ ducer
• FIG. 5 Schematic representation of the control and synchro ⁇ nization arrangements of a treatment device
• FIG. 1 shows an embodiment of a treatment device 1 according to the present invention.
• the treatment device 1 comprises a probe head 2 with central propagation axis 8.
• Probe head 2 com ⁇ prises a treatment transducer 3 and an imaging transducer 4, both of which are incorporated into probe head 2.
• a membrane 5 is wrapped around the probe head 2.
• the space between membrane 5 and probe head 2 may contain a cooling and/or a coupling liquid. The amount on cooling and/or coupling liquid may be used to ad ⁇ just the distance between treatment transducer 3 and the tissue to be treated or the skin 27 of a patient. Adjustment of this distance allows for movement of focal point 7 along central propagation axis 8.
• Focal point 7 lies in the target area 6, which usually will be cancerous cells or a tumour.
• rotation axis 29 is identical to the central propaga ⁇ tion axis 8 of probe head 2.
• rotation axis 29 intersects focal point 7.
• treatment transducer 3 is a HIFU transducer hav ⁇ ing a concave and spherical configuration, thereby focusing the emission of treatment ultrasound waves 9 towards focal point 7.
• Treatment transducer 3 may also have any other suitable shape allowing focusing the emission of treatment ultrasound waves 9 towards focal point 7.
• imaging transducer 4 is arranged within the concave sphere of treatment transducer 3 symmetrical to central propagation axis 8. Imaging transducer 4 is of rectangular shape. Imaging waves 10 encompass focal point 7, but preferably imaging transducer 4 is configured to acquire images along the entire diameter of the spherical treatment transducer 3.
• FIG. 2a and 2b a second embodiment of a treatment device 1 according to the present invention is shown.
• rotation axis 29 is perpendicular to central propagation axis 8.
• Figure 2a shows the probe head 2 in neutral position.
• Figure 2b shows probe head 2 rotated about a certain predefined angle around rotation axis 29. Since rotation axis 29 intercepts focal point 7, focal point 7 does not move during rotation of probe head 2.
• rotation axis 29 is perpendicular to the plane of the figure.
• rotation axis 29 can have any other suitable orientation. However, for the focal point 7 not to move during rotation, rotation axis 29 must al ⁇ ways intercept focal point 7.
• Probe head 2 may be rotated to any angle in both directions around axis 29.
• probe head 2 will preferably not be rotated more than 45° in any direction.
• One treatment ultrasound wave may be emitted during rotation of the probe head from one predefined angle to a second predefined angle.
• one pulse may be emitted during rotation of the probe head 2 from one predefined angle to a sec ⁇ ond predefined angle and back to the first angle.
• dur ⁇ ing the rotation motions described above, a multitude of pulses may be emitted.
• rotation of the probe head 2 around axis 29 is synchronized with emission of treatment ultrasound waves from transducer 3 and/or imaging waves from imaging transducer 4.
• the plane of imaging is perpendicular to the rotation axis.
• Figure 3 shows yet another embodiment of a treatment device 1 of the present invention.
• probe head 2 is ro ⁇ tated about a rotation axis 29 which is angled in relation to the central propagation axis 8. Probe head 2 will therefore fol ⁇ low a precession motion around axis 29. Since rotation axis 29 intercepts focal point 7, said focal point 7 will not move dur ⁇ ing rotation of probe head 2.
• probe head 2 is thereby mounted on an arcuate arm encompassing the rotation axis 29. Probe head 2 may be slidably mounted on said arm, such that the angle may be varied depending on the tissue and/or organ to be treated. Alternatively, probe head 2 may be moved about said arm during rotation about said axis, resulting in a coupled rotation about two axes. Such motions must be synchronized as well as synchronized to the emission of treatment as well as imaging waves .
• FIGS. 4a and 4b simulated heat distribution on the skin of a patient is represented. Darker shades represent higher tem ⁇ peratures. Both half circles seen on figure 4a represent the heat generated by treatment ultrasound waves when the transducer is not rotated. The white area in between both half circles is the location of the imaging transducer, which was simulated to have a rectangular shape stretching over the entire diameter of the circularly shaped treatment transducer.
• Figure 4b represents the heat distribution when the treatment transducer is rotated by 90° during emission of a treatment ultrasound pulse. As is readily apparent, heat is now distributed more homogenously over the entire circular area of the treatment transducer. This con ⁇ siderably reduces the risk of heat induced damages to healthy tissue between the transducer and the focal point.
• FIG. 5 shows a schematic representation of a treatment device according to the present invention.
• Probe head 2 comprises treatment transducer 3 and imaging transducer 4.
• Motor 12 is coupled to probe head 3 via coupling 26.
• Coupling 26 preferably is a direct mechanical coupling, but may alternatively also be in the form of a gear, such as a worm gear or the like.
• Head rotation controller 11 provides motor rotation signals 25 to motor 12 and transmits information about head position 20, especially the angular position of the transducers, to central control unit 15.
• Central control unit 15 comprises a user interface as well as synchronization means for the rotation of the probe head 2 and emission of both treatment transducer 3 and imaging transducer 4.
• central control unit 15 comprises a computer or similar electronic control device and a user interface device such as keyboard, mouse and/or trackball. Preferably it further comprises an optical output device such as a screen.
• Central control unit 15 provides imaging scanner control signals 22 to ultrasound imaging scanner 14 as well as treatment ultrasound control signals 21 to frequency generator 13.
• Used frequencies for the treatment waves are in the range of 1 to 20MHz, preferably 1 - 3MHz .
• Frequencies generated in genera ⁇ tor 13 are transmitted to treatment transducer 3 via power cable 24.
• Treatment transducer 3 then generates HIFU treatment waves.
• Ultrasound imaging scanner 14 controls imaging transducer 4 via imaging control signal 28.
• Imaging signals 23 are transmitted back to ultrasound imaging scanner 14, which processes the sig ⁇ nals to a 2-dimensional representation which may in turn be dis ⁇ played on the optical output device of central control unit 15. Control and synchronization of rotation of probe head 2, acqui ⁇ sition of imaging data as well as generation of HIFU treatment waves is done by central control unit 15.
• syn ⁇ chronization between imaging and emission of HIFU treatment waves could be achieved by means of a power detector 17 provid ⁇ ing a gating signal 18 to ultrasound imaging scanner 14 when frequencies are transmitted to treatment transducer 3 via power cable 24, said gating signal preventing ultrasound imaging scanner 14 to acquire images.
• ultrasound imaging scanner 14 provides a gating signal to radiofrequency generator 13 during image acquisition to prevent emission of HIFU treatment waves.
• the treatment device according to the present invention may ex- emplarily be used for the ablation of an enlarged parathyroid gland.
• the method may comprise the following steps: a) the treatment head is positioned on the patient neck, such that the focal point is located at the center of the para ⁇ thyroid gland
• the treatment transducer emits a 3 MHz, 25W acoustic wave, concentrated on the focal point, during 8 s
• the treatment head In synchronization, with the pulse, the treatment head is made to rotate 90°C around its axis during the 8 seconds e) The treatment head is moved 2 mm sideways and rotated back by -90°
• another exemplary method of treatment using the treatment device according to the present invention may comprise the following steps:
• the treatment head is positioned on the patient neck, such that the focal point is located at the center of the para ⁇ thyroid gland
• the treatment transducer emits a 8 s, 3 MHz, 25W concen ⁇ trated acoustic waves.
• the ultrasound image is compared to the 3 dimensional rep ⁇ resentation. If unwanted motion has occurred, the head is translated to compensate for that motion h) the head is translated by 2mm so the focal point is located next to the first position
• Steps e) to h) are repeated until the whole gland is

Landscapes

• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Biomedical Technology (AREA)
• Animal Behavior & Ethology (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Veterinary Medicine (AREA)
• Radiology & Medical Imaging (AREA)
• Engineering & Computer Science (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Heart & Thoracic Surgery (AREA)
• Molecular Biology (AREA)
• Surgery (AREA)
• Medical Informatics (AREA)
• Biophysics (AREA)
• Physics & Mathematics (AREA)
• Pathology (AREA)
• Surgical Instruments (AREA)

Priority Applications (5)

Applications Claiming Priority (2)

Publications (1)

Family

ID=42103041

Family Applications (1)

Country Status (5)

Cited By (2)

Families Citing this family (26)

Citations (6)

Family Cites Families (2)

• 2009
  • 2009-12-10 EP EP09178640A patent/EP2332614A1/en not_active Withdrawn
• 2010
  • 2010-12-07 KR KR1020177030383A patent/KR20170120215A/ko not_active Application Discontinuation
  • 2010-12-07 US US13/514,326 patent/US9033886B2/en active Active
  • 2010-12-07 EP EP10787758.1A patent/EP2512599B1/en active Active
  • 2010-12-07 CN CN201080056198.5A patent/CN102781516B/zh active Active
  • 2010-12-07 WO PCT/EP2010/069014 patent/WO2011069985A1/en active Application Filing
  • 2010-12-07 KR KR1020127016100A patent/KR20120123034A/ko active Application Filing

Patent Citations (7)

Non-Patent Citations (1)

Also Published As

Similar Documents

Legal Events