Source: https://patents.justia.com/patent/10368893
Timestamp: 2019-10-20 00:59:50
Document Index: 537693654

Matched Legal Cases: ['Application No. 61', 'art 20', 'art\n20080146924', 'artz\n20100198040', 'Application No. 11833950', 'Application No. 117822476', 'Application No. 117847822', 'Application No. 11782221', 'Application No. 11782222', 'Application No. 11782221', 'Application No. 11833950', 'Application No. 11782223', 'Application No. 11785792', 'Application No. 11782222', 'Application No. 11782476', 'Application No. 201180060741', 'Application No. 201180060741', 'Application No. 11833950', 'art, 98', 'Application No. 11782222', 'Application No. 201180060862', 'Application No. 201180060862', 'Application No. 2013', 'Application No. 11833950', 'Application No. 11782221', 'Application No. 11782222', 'Application No. 2013', 'Application No. 11782222', 'Application No. 15862313']

US Patent for Ultrasound transducer and uses thereof Patent (Patent # 10,368,893 issued August 6, 2019) - Justia Patents Search
Justia Patents MethodsUS Patent for Ultrasound transducer and uses thereof Patent (Patent # 10,368,893)
Ultrasound transducer and uses thereof
Feb 26, 2014 - CardioSonic Ltd.
According to some embodiments there is provided a method for controlling a treatment effect on blood vessel tissue during an ultrasonic treatment, the method comprising positioning an ultrasonic transducer device in the blood vessel lumen; controlling a treatment effect by controlling fluid flow, wherein controlling comprises deploying a fluid restrictor at a location relative to the transducer effective to block at least a portion of fluid flowing upstream, downstream or adjacent the transducer. According to some embodiments there is provided an ultrasonic transducer device sized for placement in a body lumen, and comprising a fluid restrictor effective to block at least a portion of fluid flowing upstream, downstream or adjacent the transducer. In some embodiments, the fluid is blood.
Latest CardioSonic Ltd. Patents:
Ultrasound transceiver and cooling thereof
This application is a division of U.S. patent application Ser. No. 13/049,013 filed Mar. 16, 2011, which claims the benefit of priority under 35 USC 119(e) of U.S. Provisional Patent Application No. 61/393,947 filed Oct. 18, 2010. The contents of the above applications are all incorporated by reference as if fully set forth herein in their entirety.
The present invention relates to an ultrasound transducer device and uses thereof and, more particularly, but not exclusively to such a transducer device modified for use in surgical procedures.
A problem arises in providing the ultrasound transducer close to the tissue that requires the procedure. It is known to put small ultrasound sensors in the blood vessels but it is difficult to ensure that the sensor is looking at the tissue that requires the procedure. A further problem involves providing the ultrasound power beam sufficiently close to the tissue requiring ablation, and controlling the beam given a) the difficulty in correctly directing the sensor and b) generally controlling factors that affect efficiency of the ablation beam.
The present embodiments may provide a transducer in which sensing and ablation are combined on a single transducer device that can be placed in a blood vessel or the like.
According to one aspect of the present invention there is provided a dual use ultrasonic transducer device for combined sensing and power transmission, the power transmission for tissue ablation, comprising:
a first piezoelectric transducer sized for placement in a body lumen;
a power unit enabling an ultrasonic power beam for tissue ablation in a tissue ablation region; and
a sensing unit enabling an ultrasonic sensing beam for sensing at said tissue ablation region.
In an embodiment, said first piezoelectric transducer comprises a piezoelectric surface, said piezoelectric surface being electrically connected to a mounting; the mounting comprising damping for said piezoelectric surface, the mounting being configured such as to provide a first region of said piezoelectric surface with a first relatively high level of damping and a second region of said piezoelectric surface with a second relatively low level of damping, thereby to enable said ultrasonic sensing beam from said first region and said power transmission beam from said second region.
An embodiment may comprise at least a second piezoelectric transducer also sized for placement in a body lumen, the first piezoelectric transducer being provided with a first, relatively high level of damping and the second piezoelectric transducer being provided with a second, relatively low, level of damping, and enabling said ultrasonic sensing beam from said first piezoelectric transducer and said ultrasonic power beam from said second piezoelectric transducer.
In an embodiment, said ultrasonic power beam and said ultrasonic sensing beam are enabled through said first piezoelectric transducer.
In an embodiment, said body lumen is a blood vessel.
An embodiment may comprise with a catheter for placing within said blood vessel.
In an embodiment, said sensing is usable in a control system to control treatment efficacy or device efficiency.
In an embodiment, said first piezoelectric transducer is configured to provide said power transmission as a non-focused beam.
In an embodiment, said first region comprises a first surface part of said piezoelectric surface and said second region comprises a second surface part of said piezoelectric surface, and a non-focused beam is provided from throughout said second surface part.
In an embodiment, said power transmission is configured to provide a thermal effect to surrounding tissues and said sensing is configured to provide imaging of said thermal effect.
In an embodiment, said thermal effect comprises denaturation of collagen and said sensing comprises detection of a change in reflected signal, or in backscatter.
An embodiment may provide said power transmission in bursts having gaps and transmit separate sensing transmissions during said gaps.
An embodiment is configured to be placed in said body lumen and said sensing region is configured to detect a lumen wall and to provide a signal to control for distance to the lumen wall and thereby ensure that the device does not touch said lumen wall.
In an embodiment, said mounting comprises an air pocket and a plurality of contact points.
In an embodiment, said mounting is provided with a surface tension sufficient to maintain said air pocket when said device is immersed in liquid.
An embodiment may comprise a matching layer for acoustic impedance matching placed on said piezoelectric surface wherein said matching layer comprises pyrolytic graphite.
The device may have a resonance and an anti-resonance, and may advantageously be used at a working frequency equal to said anti-resonance.
According to a second aspect of the present invention there is provided a method of online testing of efficiency or treatment efficacy of an ultrasound transducer to detect changes in said efficiency, said efficiency being a ratio between ultrasound energy and heat generated in said transducer, said method comprising applying an impulse to said ultrasound transducer, measuring a response of said ultrasound transducer to said impulse, and inferring changes in said efficiency or said efficacy from said measured response.
In an embodiment, said inferring said changes in efficiency comprises inferring from at least one member of the group comprising: a shape of said measured response; an envelope of said measured response, a duration of said measured response, amplitudes of said measured response, and a damping factor of said measured response.
In an embodiment, said transducer has a resonance and an anti-resonance and said online or offline testing comprises inferring a change in at least one of said resonance and said anti-resonance.
Usage of the embodiment may involve placing said transducer in a liquid-filled body lumen and carrying out said online testing while said transducer is in said body lumen.
The embodiments extend to the device when placed in a liquid within a body lumen.
According to a third aspect of the present invention there is provided a method of using an ultrasonic transducer for simultaneous heating and monitoring of a target, the method comprising providing a relatively high power ultrasonic transmission in bursts for heating said target, said bursts having gaps, and sending relatively low power ultrasonic sensing transmissions during said gaps for monitoring said target.
An embodiment may comprise using a surface of a piezoelectric sensor to produce said relatively high power and said relatively low power ultrasonic transmissions, said piezoelectric sensor surface comprising a first relatively high damping region and a second relatively low damping region, the method comprising using said first region for said monitoring and said second region for said heating.
An embodiment may comprise placing said transducer in a liquid-filled body lumen and carrying out said simultaneous heating and measuring while said transducer is in said body lumen.
An embodiment may involve testing an efficiency of said transducer or a treatment efficacy, said testing comprising applying an impulse to said transducer and measuring a response of said transducer to said impulse.
According to a fourth aspect of the present invention there is provided a method of online testing of efficiency of an ultrasound transducer to detect changes in said efficiency, said efficiency being a ratio between ultrasound energy and heat generated in said transducer, said method comprising measuring an impedance of said transducer at a current working frequency, and inferring changes in said efficiency from changes in said measured impedance.
According to a fifth aspect of the present invention there is provided a method of online testing of efficiency of an ultrasound transducer to detect changes in said efficiency, said efficiency being a ratio between ultrasound energy and heat generated in said transducer, or for testing treatment efficacy, said transducer being for placement in a liquid flow and having a temperature sensor positioned for measurement of flowing liquid downstream of said transducer, said method comprising measuring a temperature of said flowing liquid downstream of said transducer, and inferring a decrease in said efficiency or a change in said efficacy from an increase in said measured temperature.
According to a sixth aspect of the present invention there is provided a method of online testing of treatment efficacy and safety of the device of claim 1, comprising placing the device in said lumen at a distance from a lumen wall, measuring liquid flow between the device and the wall and using changes in said flow measurement as an indicator of said treatment efficacy or said safety.
FIG. 1 is a simplified schematic diagram of a first embodiment of an ultrasound transducer in which sensing and ablation are combined onto a single device according to the present invention;
FIG. 2 is a simplified schematic diagram showing a modification of the transducer of FIG. 1;
FIG. 3A is a simplified flow chart illustrating a method for monitoring operation of an ultrasound transducer according to embodiments of the present invention;
FIG. 3B is a flow chart showing a method of monitoring efficacy or operation of an ultrasound transducer according to further embodiments of the present invention;
FIG. 4 is a simplified flow chart illustrating a method for ablating tissue using high power pulses, and measuring during gaps in the pulse, according to embodiments of the present invention;
FIG. 5 is a simplified schematic diagram of a system using the air-backed ultrasound transducer of FIG. 1;
FIG. 6 is a simplified schematic diagram showing a cross-section of the construction of an ultrasound transducer according to the embodiment of FIG. 1;
FIGS. 7A-7C are simplified schematic diagrams illustrating variant shapes of a piezoelectric element for the transducer of FIG. 1;
FIG. 8A is a side view of a series of piezoelectric elements mounted on a single mounting according to an embodiment of the present invention;
FIG. 8B is a view from above of an arrangement of piezoelectric elements mounted in two rows according to embodiments of the present invention;
FIG. 9 is a simplified schematic diagram illustrating a construction of a PCB for mounting PCB elements that includes grooves for air bubble formation according to an embodiment of the present invention;
FIG. 10 is a simplified schematic diagram that illustrates a series of angles and positions in relation to a body vessel and a catheter, in which the transducer can be placed by navigation;
FIG. 11 is a histology slide using H&E stain, and showing the thermal effect in a pig carotid artery;
FIG. 12 is a histology slide using H&E stain, and showing the thermal effect in a pig renal artery;
FIG. 13 is a histology slide wherein analysis and marking of the thermal damage area to a pig Carotid Artery is made by a trained pathologist;
FIG. 14 is a histology slide wherein analysis and marking of the thermal damage area to a pig Renal Artery is made by a trained pathologist;
FIG. 15 is a histology slide showing analysis and marking of the blocked Vasa-Vasorum, with arrows placed by a trained pathologist in a pig Carotid Artery Vasa-Vasorum in the adventitia; and
FIG. 16 shows two histology slides with analysis and marking of the thermal damage, or nerve degeneration area, made by trained pathologist, for a pig renal artery, and nerves in adventitia.
The present embodiments comprise an ultrasound transducer device and uses thereof and, more particularly, but not exclusively, such a transducer device modified for use in surgical procedures. The transducer device combines imaging and ablation into a single device.
The single device may include multiple transducers or a single transducer having multiple regions. The regions may provide respective power beams and measuring beams and methods are provided for estimating changes in efficiency while in use.
Reference is now made to FIG. 1, which is a simplified diagram showing a dual use ultrasonic transducer device 10 for combined sensing and power transmission. The transducer comprises a piezoelectric surface 12 of a piezoelectric element. The element is mounted using mounting points 14 to a printed circuit board 16. The combination of the PCB 16 and the mounting points 14 form a mounting.
The piezoelectric element is electrically connected to the printed circuit board. For example the mounting points may be comprised of conductive glue, or may include wire connections. The piezoelectric element is vibrated in use by the electrical input to transmit a beam and also vibrates in the presence of a beam to sense ultrasound echoes. Thus the mounting comprises damping for the piezoelectric element in order to manage the vibrations. The mounting may provide different levels of damping to various parts of the piezoelectric element so as to provide different regions on the surface which are distinguished by their different levels of damping. A highly damped region is good for sensing since an acoustic beam can be transmitted and the returning echo can be reliably read by a surface whose vibrations have already died down. On the other hand power transmission benefits from the vibrations mounting up so that an undamped surface may be considered, and on the contrary, a mounting that actually multiplies vibrations would be better.
Thus the embodiment of FIG. 1 may provide the two different levels of damping to two different parts of the surface, shown as 18 for the highly damped low power sensing region and 20 for the low damping high power transmission region, so that one part is optimized for power transmission and the other part is optimized for sensing. The two regions are connected using different electrodes so that their operation is kept separate.
The low damped, high power region 20 may be configured to provide the power transmission as a non-focused beam.
The non-focused beam may be provided from throughout the surface part 20, that is to say from throughout the body of the low damping high power region.
The power beam may provide a thermal effect to surrounding tissues, thus carrying out ablation. Different parts of the surrounding tissues may have different sensitivities to the non-focused power beam. The sensing may provide imaging of the heating effect. Since, in the present embodiment, the surface doing the imaging is an extension of the surface providing the power beam, the sensing surface is necessarily correctly directed for sensing.
In an alternative embodiment, the same sensor surface may be used for both the power and imaging.
In a third embodiment different transducers may be placed on the device. Each transducer produces either a power beam or a measuring beam. Example configurations are shown below in FIGS. 8A and 8B.
The thermal effect that is used may comprise denaturation of collagen. The sensing may specifically involve detection of an increase in amplitude of the ultrasonic reflection over the transmitted beam, which increase in amplitude is an indicator of the denaturation of the collagen.
The power beam may be transmitted in bursts. The gaps in between the bursts may then be used to transmit separate sensing transmissions at lower power and allow detection without interference from the power beam.
The device is designed to be placed in a body lumen. The sensing region may detect the wall of the lumen, and this can be used to provide a signal that can be used in a control loop to control for distance to the lumen wall. The control loop can thus be used to ensure that the device does not touch the lumen wall.
The body lumen is generally liquid. The mounting, as discussed, includes gaps 26 between the contact points 14. The device may be designed so that gaps remain air filled even when the device is in the lumen. Thus the gaps 26 become air pockets which lie between the multiple contact points 14.
Reference is now made to FIG. 2 which is a variation of the device of FIG. 1.
As discussed, the air pocket may be maintained by surface tension. The mounting may be designed with a surface tension sufficient to maintain the air pocket when the device is immersed in liquid, and this may be due to the materials themselves, or, if not sufficient, then suitable coatings 22 and 24 may be applied.
In an embodiment, a matching layer 28, for acoustic impedance matching, may be placed on the piezoelectric surface 20. A suitable material for the matching layer is pyrolytic graphite, due to its combination of heat conducting ability and biological compatibility. Specifically pyrolytic graphite has little effect on platelets and thus does not increase the risk of clot formation.
In operation, electrical waves are applied to the acoustic surfaces 18 and 20, which causes the surfaces to vibrate. The surfaces have resonant and anti-resonant frequencies, and the working frequency at which the device is typically operated is an anti-resonance. The anti-resonance was found empirically to provide a highest efficiency in terms of a ratio of conversion of electrical energy to sound as opposed to conversion of electrical energy to heat.
Reference is now made to FIG. 3A, which is a simplified flow diagram illustrating a method for monitoring operation of the transducer in order to control efficiency of the device of the present embodiments, or to control efficacy of the treatment, as will be explained hereinbelow. The device efficiency may change during use, typically leading to a danger of overheating. The problem is believed to lie with materials from the blood stream, particularly clots, getting attached to the device and changing the vibration dynamics. The anti-resonant frequency changes as a result but, unless this is detected, the device continues to work at the predefined working frequency. Thus the efficiency drops and the device heats up.
To help solve the above problem the present embodiments may provide a way of online testing of efficiency of the ultrasound transducer to detect changes in its efficiency. As mentioned above, the efficiency is a ratio between ultrasound energy and heat generated in the transducer. As shown in FIG. 3, the method involves applying an impulse to the ultrasound transducer—box 30, and then measuring a response of the ultrasound transducer to the impulse, as shown in box 32. Changes in a property of the response may then be used in decision box 34 to infer changes in the efficiency of the device.
If such changes are detected then in box 36 an action is taken. The action may be stopping of the device. Alternatively it may involve changing the applied duty cycle and/or the applied power or alternatively the change may involve modifying the working frequency of the device. Subsequently, the efficiency is tested again so that the device can rapidly converge on a new efficient working frequency. If no changes are detected then a delay 38 may be introduced and the test repeated.
The test may be carried out continuously during use.
In the test, the changes in efficiency can be inferred from a change in a property of the impulse response, as shown in FIG. 3A. However alternatives for the test include scanning the device impedance against frequency, measuring the applied power and measuring the impedance during a pulse.
In the case of the impulse test, the property may be a shape or envelope of the measured response. Alternatively the property may be a duration of the measured response, typically the time the response falls to a predetermined minimal threshold. The property may alternatively be an amplitude of the measured response, and as a further alternative the property may a damping factor, which is derived from the measured response.
As described above, the transducer device has both a resonance and an anti-resonance. Indeed the device may have several resonant frequencies and several anti-resonances formed from local maxima on the efficiency graph. The online testing may involve inferring changes in any of these maxima and minima and thus in either a resonance or an anti-resonance.
The efficiency testing is a form of test which can be carried out in situ in the liquid-filled body lumen since the impulse response can be monitored remotely via the contact points 14.
As an alternative, the impedance of the transducer device can be tested. A fall of say ten percent in the impedance can be taken as a signal to move the working frequency or to stop the treatment.
Reference is now made to FIG. 3B, which is a simplified diagram illustrating a more detailed control loop for the transducer device. In FIG. 3B, changes in power, current, voltage, impedance, and temperature are used together or as alternatives and changes are looked for. In the case of current, voltage, and impedance, changes of 10 percent are looked for. In the case of temperature a measurement in excess of 43 degrees is looked for. A pulse cycle using a given power P at a duty cycle of D % is applied and over excitation leads to the device stopping. Blood flow and acoustic feedback are also obtained.
Returning now to FIG. 2, and the ultrasonic transducer device, may have an acoustic matching layer 26 comprising pyrolytic graphite as discussed. The matching layer has a thickness 40, which is advantageously a quarter of a wavelength of the power beam transmitted by the ultrasonic transducer. As mentioned the working frequency could be the anti-resonance of the device so that the thickness 40 is a quarter of a wavelength of the working frequency.
Reference is now made to FIG. 4, which illustrates a method of using an ultrasonic transducer of the present embodiments for simultaneous heating and monitoring of a target. The method comprises a box 50 for providing a relatively high power ultrasonic transmission in bursts for heating the target. The bursts have gaps, as discussed above, and the method uses the gaps to send relatively low power ultrasonic sensing transmissions—box 52—for monitoring the target. The measurements are then read—box 54. As discussed, the high power and low power beams may be provided from different parts of the same surface of a piezoelectric sensor which are differentially damped, at working frequencies which are anti-resonances of the transducer. Alternatively they may be provided from the same surface. Alternatively high power and low power beams may be provided from different transducers on the device.
The present embodiments are now considered in greater detail. The present embodiments relate generally to devices, parameters and methods for the treatment of tissue using ultrasonic waves in particular for heating, at a target area such as in the wall of a tube or cavity, located in the living body, The treatment may involve excitation using high power acoustic energy.
The treatment method may be applied by creating a gradient of different temperatures in the tissue by the combined effects of: heating the tissue with high power ultrasound and cooling of the tissue using conduction and convection. The convection could be of natural fluid, for example blood flow, or by artificial injection of cooling liquid, for example cold saline injection. Additional temperature effects that are widely elaborated in other sources may also simultaneously influence the temperature gradient, for example—capillary blood perfusion.
The heating control is performed by controlling the parameters of the ultrasonic field and the transmission protocol, including: transmission frequency, power, duration and duty cycle, as will be described in greater detail herein.
Simultaneously with the transmission the cooling effect is achieved by liquid flow in the vessel or fluid present (for example urine, lymphatic liquid, bile) or liquid active ejection.
The present embodiments may provide the possibility of transmitting the energy without touching the cavity all. By not touching it is possible to increase protection for both the elements and the non target tissue by allowing fluid to flow on the cavity walls and on the transducer surface. The liquid provides for cooling. The present embodiments may also allow for easier operation by not restricting the transducer location.
Echoe sampling and recording and or processing for measurement and monitoring can be performed simultaneously with the treatment. Such simultaneous treatment and analysis can increase the level of control of the treatment in real time and help ensure achievement of the desired results.
An ultrasonic transducer may be placed on the skin, with an internal catheter and transmission to the outer side of the cavity.
Possible target tissues for the device include one or more of the following and their nearby tissues to douse cavities: arteries, veins, lymph vessels, intestine, esophagus, CNS, urine lumen, gall lumen, Stomach, and Tear Trough.
A point to note is that the attenuation of the ultrasound field is smaller in the fatty tissue around the nerves than in the nerves themselves at the device frequencies. Furthermore the fatty tissue, due to its low heat conduction, isolates the heat created in the nerves. Such phenomena increase the selectiveness of the treatment.
Mechanical blocking of the vasa-vasorum or\ and the lymph capillary;
Transmission frequency: 5-30 MHz;
imaging frequency 5-60 MHz;
Reference is now made to FIG. 5, which is a simplified block diagram of a system according to an embodiment of the present invention. In FIG. 5, the system 110 may contain one or more of an acoustic transducer 112, a power supply unit 114, a control unit 116, a pumping or circulation unit, shown as perfusion unit 118, a balloon control unit 120, and a navigating shaft 122.
The navigating unit allows the acoustic element to navigate to the location or locations at which it is needed. The balloon control unit controls a balloon for supporting the lumen as needed. The perfusion unit provides injection substances as necessary.
Reference is now made to FIG. 6, which is a schematic illustration of the acoustic element 112 of FIG. 1. The acoustic element 112, typically an ultrasonic element, includes a piezoelectric element 124 which converts electrical energy into an acoustic beam. The piezoelectric element is mounted on PCB board 126, for example via air gap 128. The PCB in turn is mounted on housing 130 which protects the acoustic element.
The ultrasonic element typically includes one or more ultrasonic transducers including a piezoelectric material 24 or a MEMS element.
Electrodes may provide power to the transducer. The housing 30 protects the assembly, and an electrical connection may be provided between the electrodes and the catheter wires.
Reference is now made to FIGS. 7A, 7B and 7C which illustrate designs for the ultrasonic element 112. FIG. 7A illustrates a series of shapes where the depth cross-section is rectangular as shown in element 132. The remaining elements in FIG. 7A are viewed from above. Element 134 is rectangular as seen from above. Element 136 is a hexagon. Element 138 is an irregular quadrilateral. Element 140 is a flattened circle. Element 142 is a trapezium. Element 144 is a bullet shape. Element 146 is a trapezium having a shorter dimension between its parallel sides than the trapezium of element 142. Element 148 is a comb shape having a narrow tooth at a first end followed by three wider teeth. Element 150 is a “W” shape, again with a narrow tooth projection at a first end.
FIG. 7B illustrates a closed ring shaped element 152 and an open ring shaped element 154.
FIG. 7C illustrates four variations on a cylindrical element. Element 156 is a filled cylinder. Element 58 is a cylinder with a removable sector. Element 160 is a hollow cylinder having an opening 161 in the lower wall, and element 162 is a hollow cylinder having an open part of the cylinder wall along its length.
In addition the element 112 may be spherical.
Reference is now made to FIGS. 8A and 8B which illustrate examples for multi-elements transducers. FIG. 8A is a side view showing five piezoelectric elements 170 mounted on a curved PCB 172. FIG. 8B is a view from above showing two rows of piezoelectric elements 174 and 176.
The housing 130 can made from one or more of the following materials: metals, ceramics, PZT, PIEZO-electric ceramics, glass, polymers or carbons.
Reference is now made to FIG. 9, which illustrates an embodiment of a printed circuit board 16 for mounting of the acoustic transducer 12. The printed circuit board may include different thickness to provide the gaps for the air pockets referred to above.
As mentioned above, an air pocket may be maintained between the PCB and the peizoelectric element.
Air pockets may be formed by the use of trenches in the PCB structure as illustrated with reference to FIG. 9. or by providing a mounting as shown in FIG. 1 where a gap is defined between the ultrasonic element and the PCB.
Hydrophobic coatings, including praline, may be used to enhance the surface tension effect in order to prevent the water medium from penetrating into the air volume, as mentioned in respect of FIG. 2.
The ultrasonic element may use different anti-resonance values for the working frequency when available. For example one anti-resonance may be used for moderate heating of the tissue, another for power heating of the tissue and yet another for monitoring.
The navigation unit may also mechanically hold and place the ultrasonic elements in different locations and at different desired angles, as per FIG. 10. In FIG. 10 a ring configuration 180 may be used, or an angle configuration 182, or a cylindrical configuration 184 or a side configuration 186 or a front configuration 188, each in relation to the catheter.
Other materials can be used, say in drug exuding balloons, and may include materials that are used for bio-degradable stents, anti-Inflammatory materials, medications that may be better presented locally to the tissue than systemically, anti-thrombotic materials, such as Heparin, Aspirin, Ticlopidine, and Clopidogrel, and materials that can cause damage or death to target tissues. Thus materials that can cause nerve death may be supplied for renal denervation.
It is possible to add micro-bubbles to the fluid material in order to help with detection of presence of the material in the target tissue. Micro-bubbles may be detected using ultrasound and sub-harmonic imaging. Micro-bubbles may also improve heating of the target tissue under ultrasonic energy, due to higher absorption of the ultrasonic energy in the tissue volume where they are located.
Applying a thermal effect in the tissue may cause the capillaries to be blocked mechanically or by blood coagulation.
Ultrasound energy applies mechanical force on particles that are present in a liquid, when there is a difference in the acoustic impedance, which is a function of the density multiplied by the speed of sound, between the particles and the liquid. The applied force then pushes particles along the direction of the traveling ultrasonic waves. The mechanical force phenomenon can be used to ensure that required substances arrive at the treatment site.
The ultrasonic transducer may be positioned in a tissue liquid cavity such as a blood vessel, near the target tissue, while ensuring a liquid spacing between the target tissue and the ultrasonic transducer irradiating face. As mentioned above a control loop can be used to ensure that the transducer does not touch the vessel wall and damage epithelium cells.
The required material may be released into the tissue liquid cavity in a way that will cause some of the particles to enter the spacing between the target tissue and the ultrasonic transducer irradiating face. One way of doing this is to coat the face of the ultrasonic transducer with the required material, such that the operation of the ultrasonic transducer may cause particles of the required material to be released into the surrounding liquid.
Another possibility is to add micro-bubbles to the required material fluid in order to detect the material presence in the target tissue. Micro-bubbles may be detected using ultrasound and sub-harmonic imaging.
Yet another possibility is to activate the ultrasonic transducer so as to apply force on the required material particles to push the particles into the blood vessel wall near the ultrasonic transducer irradiating face, using the pushing effect mentioned above.
Another possibility is to apply the ultrasonic energy in short high power pulses with long separations between each pulse. This may apply mechanical force, as per the phenomenon discussed above, to the particles to push them into the tissue wall, without heating the tissue wall extensively.
A further possibility is that activation of the captured required material can be achieved by applying additional ultrasonic energy or some other kind of external energy such as a magnetic field on Ferro-electric particles, or an ultrasonic shock-wave to the particles
The present embodiments may be used for the treatment of renal denervation. The transducer is simply positioned at 1, 2 or more treatment points, and there is no need for tip manipulation or accurate positioning. The total energizing duration may be between two seconds and two minutes. Real-time feedback of treatment progress may be provided. The advantages of ultrasonic treatment include directional, localized and remote target tissue effects with minimal damage to other closer tissues, possibly reducing pain, preservation of endothelium and elastic lamina structure and function, sot that there is no post treatment stenosis, or at least reduced post treatment stenosis, the avoidance of any mechanical contact on the blood vessel wall, and overall a more robust treatment effect due to real-time feedback.
The following table is a summary of currently contemplated clinical applications.
Currently Contemplated Clinical Applications
# Application Name Anatomy Target
1. Renal sympathetic nerve Renal artery Renal sympathetic nerves modulation 2. Carotid sympathetic nerve Carotid artery Carotid sympathetic nerves modulation 3. Vagus sympathetic nerve Aorta Vagus sympathetic nerve modulation 4. Peripheral sympathetic nerve Peripheral blood Peripheral sympathetic nerves modulation vessels 5. Pain nerve modulation Spinal cord cannel Pain nerves 6. Restenosis decrease All relevant arteries Artery media and adventitia 7. Vulnerable plaque All relevant arteries Artery media and adventitia stabilization 8. Atherosclerosis All relevant arteries Artery media and adventitia passivation 9. Plaque volume All relevant arteries Artery media and adventitia decrease 10. Plaque thrombosis All relevant arteries Artery media and adventitia decrease 11. Tetanic limb muscle Limb arteries or veins Peripheral motor nerves tonus decrease 12. Atrial fibrillation Right atria Pulmonary vain insertion prevention 13. Cardiac arrhythmia Coronary arteries Cardiac tissue pathology prevention 14. Liver tumor necrosis Inferior vena cava Tumor 15. None-malignant Urethra Sick prostate tissue prostate treatment 16. Malignant prostate Urethra Sick prostate tissue treatment 17. Artery aneurysms All relevant arteries Aneurysm wall stabilization 18. Aortic aneurysms Aorta Aneurysm wall stabilization 19. Berry aneurysms Brain arteries Aneurysm wall sealing 20. Erectile dysfunction Internal Iliac Artery media and adventitia treatment
Table 2 below summarizes embodiments of the technology and uses.
TABLE 2 Summary of Technology
1.1. The ultrasonic transducer:
1.1.1. Very small: 1.5 × 8 [mm] 1.1.2. Very thin: 0.8 [mm] 1.1.3. Very high ultrasonic intensity output: 100 [W/cm{circumflex over ( )}2] continuous 1.1.4. Relatively high work frequencies: 10-25 [MHz]. 1.1.5. Biocompatible coating: Perylene
1.2. The catheter
1.2.1. Ultrasonic transducer cooling: vessel blood/liquid flow + catheter breading as heat sink 1.2.2. Very flexible treatment tip: 10 mm stiff length. (Pass through 8Fr “hokey-stick” guide catheter) 1.2.3. Precise and easy torque following 1.2.4. Standard 0.014 OTW 1.2.5. Relatively small diameter: 6 Fr
1.3. Distancing fixture
1.3.1. Distancing transducer face from artery wall to prevent contact damage, with minimal mechanical forces on artery wall
2. Technology functionality
2.1. Non-focused ultrasonic beam-like ultrasonic emission
2.1.1. Simple anatomic 2.1.2. Big treatment volume cross-section, the size of the transducer face (differing from focused ultrasound with small treatment volume) 2.1.3. Relatively even spread of ultrasonic energy in beam cross-section (No need to precise anatomic positioning like in focused ultrasound)
2.2. Treatment maneuverability and directionality
2.2.1. Simple maneuvering with nearly 1:1 torquability. 2.2.2. Simple treatment beam directivity feedback and control from standard angiograph (0, 90, 180, 270) 2.2.3. No need for high operator skills 2.2.4. No problem to use contrast agent during treatment
2.3. Ultrasonic imaging using the unique transducer - Continuous measurement of distance to artery wall
2.3.1. Treatment tip real positioning measurement (not possible only from angiography) 2.3.2. Feedback to prevent high power operation of the transducer while touching the artery wall.
3. Tissue treatment
3.1. Very fast treatment:
3.1.1. Treatment duration of 30-5 sec per treatment point. 3.1.2. Possibly 4 treatment point per artery for renal denervation
3.2. Remote and localized effect
3.2.1. Thermal effect volume in the tissue far from the transducer face: media, adventitia, Vasa-Vasorum, peri-adventitia, adventitia nerves, peri- adventitia nerves, peri-adventitia capillaries. 3.2.2. Targeting tissues in varying distances from transducer face according to treatment parameters (not possible in most focused ultrasonic catheter designs) 3.2.3. Possibility to apply thermal effect in tissues located 5 mm from the lumen wall. Relevant for peripheral nerves blocking from peripheral arteries. 3.2.4. Non targeted tissues on the beam path to the target tissue are not damaged. 3.2.5. Importantly no damage to the endothelium, basal membrane and internal elastic lamina.
3.3. Tissue selectivity
3.3.1. Highly selective remote thermal effect in nerve bundles that are covered with thick fat tissue. (most relevant to Renal Denervation in the Renal artery ostium)
3.4. Treatment special features for Renal Denervation
3.4.1. Working very close to artery ostium: <10 [mm] 3.4.2. Working in short arteries: <20 [mm] 3.4.3. Working in small arteries: 4-3 [mm]
4.1. The temperature of the blood that flows over the ultrasonic transducer does not go over 50 C. while working in the maximal allowed operation intensity level 50 [W/cm{circumflex over ( )}2]. 4.2. The temperature of the blood that flows over the ultrasonic transducer does not go over 43 C. while working in the therapeutic operation intensity level 30 [W/cm{circumflex over ( )}2]. No need to add external cooling saline injection. 4.3. The therapeutic treatment on the blood vessel wall is done with no mechanical contact with the vessel wall. No danger of damaging the vessel wall or disrupting any pathologies on the wall (Atherosclerosis plaques) 4.4. Localized and controlled effect specifically in the targeted treatment volume. No non-controlled energy effects in other tissues (unlike in RF treatment). 4.5. No blocking of the blood flow during the treatment
5. Possible implications
5.1. Much less pain in treatment: fast blocking of nerves with no electric excitation of the target nerve and no effect on other nerves (In contrast with Unipolar RF treatment)
Reference is now made to FIGS. 11-16 which illustrate experimental results following use of the device.
FIG. 11 is a histology slide, using H&E stain, and showing the thermal effect in a pig carotid artery. The border of the thermal effect region in the tissue is marked with a dashed line and noted as “Thermal Damage”. The setup used was an ultrasonic catheter from inside the blood vessel.
FIG. 12 is a histology slide, using H&E stain, and showing the thermal effect in a pig renal artery. The border of the thermal effect region in the tissue is marked with a dashed line and noted as “Thermal”. A necrotic nerve inside the thermal effect region is marked with an arrow and “necrotic nerve” text. The setup involved an ultrasonic catheter from inside the blood vessel.
It is noted that the embodiments cause thermal damage in target tissues far from the lumen internal wall, while causing no thermal damage in the lumen wall internal layer.
Specifically in blood vessels it was shown that thermal damage was achieved in the adventitia or media layers, without causing any apparent damage in the intima layer, either the endothelium or the elastic lamina.
It is believed that the reason for this effect is that the ultrasonic energy heats the artery wall all along the beam, but the blood flow in the lumen cools the tissue that is close to the blood flow, thus the endothelium wall never heats sufficiently to be damaged. It is possible to find a setting for the treatment parameters so to cause heating above 55 C of the tissues far from the blood flow, while the temperature of the intima layer is kept below 55 C.
Exemplary results are shown in FIGS. 13 and 14 which are histology slides wherein analysis and marking of the thermal damage area to a pig Carotid Artery and a Pig Renal Artery respectively, is made by a trained pathologist.
Heating the adventitia or media can cause blocking of the flow inside the small capillaries (called Vasa-Vasorum) in the blood vessel media and adventitia, for example by mechanical crimping due to the shrinking of the connective tissue due to collagen denaturation, or due to thrombotic blocking by a thrombus that is formed in the Vasa-Vasorum because of the thermal damage (the blood flow in these vessels is very low so it can not cool the blood vessel).
FIG. 15 illustrates exemplary results for the above. A histology slide shows analysis and marking of the blocked Vasa-Vasorum with arrows placed by a trained pathologist in a pig Carotid Artery Vasa-Vasorum in the adventitia.
The treatment is intended to provide extensive thermal damage to specific target tissues while keeping nearby tissues undamaged.
It is believed that the ultrasonic energy absorption is different for different kinds of tissue and, and furthermore, the content of collagen fibers may differ.
Specifically it was shown that in nerve fibers that are wrapped by fat tissue, it is possible to cause extensive thermal damage to the nerve tissue, while there is no significant thermal damage in the fat tissue or/and to the tissue surrounding them.
FIG. 16 illustrates two histology slides with analysis and marking of the thermal damage, or nerve degeneration area made by a trained pathologist, for a pig renal artery, and nerves in adventitia.
1. A method for controlling a treatment effect on blood vessel tissue during a non-focused ultrasonic treatment, comprising
positioning a non-focused ultrasonic transducer device which generates one or more non-focused ultrasonic beams with frequency in a range of 8 MHz-30 MHz for generating a treatment effect in target tissue outside of the inner wall of said blood vessel, said device positioned in the blood vessel lumen in a manner which prevents contact of said transducer with the inner wall, wherein said transducer faces said target tissue;
controlling said treatment effect by controlling fluid flow, wherein said controlling comprises deploying a fluid restrictor at a location relative to said transducer effective to block at least a portion of fluid flowing upstream, downstream or adjacent said transducer; and wherein said deployed fluid restrictor allows natural blood flow between said transducer and said inner wall of said blood vessel to cool said inner wall.
2. The method according to claim 1, wherein said fluid is blood.
3. The method according to claim 1, wherein said restrictor is deployed to block the flow upstream relative to said transducer device to load the vasa vasorum with a liquid material.
4. The method according to claim 3, wherein said liquid material comprises micro bubbles to increase energy absorption in the target tissue.
5. The method according to claim 1, wherein said restrictor is deployed to block the flow downstream relative to said transducer device to allow drug delivery to target tissue areas treated by said transducer device.
6. The method according to claim 5, wherein said drug is one or more of:
restenosis prevention drug, anti-inflammatory drug, anti-thrombotic drug.
7. The method according to claim 1, wherein said deploying comprises inflating a balloon.
8. The method according to claim 1, wherein said fluid is a cooling fluid effective to cool said transducer device.
9. The method according to claim 1, wherein said deploying comprises ensuring a fluid spacing between an irradiation face of said ultrasonic transducer device and target tissue.
10. The method according to claim 1, wherein said treatment effect comprises cell necrosis.
11. The method according to claim 1, further comprising estimating said treatment effect according to an echo received on said transducer.
12. The method according to claim 1, wherein said controlling said treatment effect comprises controlling fluid flow according to real-time feedback from the tissue.
13. The method according to claim 1, wherein said fluid restrictor blocks only a portion of fluid flowing downstream said transducer.
14. The method according to claim 13, wherein a portion of said fluid flowing downstream which is not blocked by said fluid restrictor comprises said natural blood flow.
15. The method according to claim 1, wherein said deployed fluid restrictor is in the form of a wire or a thin plastic sheet.
16. The method according to claim 1, wherein said fluid restrictor is deployed at a location around said non-focused ultrasonic transducer device and allows natural blood flow on said non-focused ultrasonic transducer device outer surface.
17. The method according to claim 1, wherein said non-focused ultrasonic transducer device is positioned at a distance from said inner wall of said blood vessel when generating said treatment effect while mechanically ensuring a liquid space between said inner wall and said transducer.
18. The method according to claim 1, wherein said non-focused ultrasonic transducer device is flat.
19. The method according to claim 1, further comprising treating said target by said one or more non-focused ultrasonic beams without affecting said inner wall of said blood vessel, and wherein said controlling comprising controlling fluid flow in said blood vessel during said treating.
20. The method according to claim 19, wherein said target tissue is located at least 5 mm from said blood vessel lumen.
21. The method according to anyone of claim 19 or 20, wherein said target tissue comprises nerve tissue which resides outside of said blood vessel wall.
22. The method according to claim 1, wherein said frequency is in the range of 10 MHz-30 MHz.
23. The method according to claim 1, wherein said fluid restrictor is effective to block a portion of said fluid which is large enough so as to change said treatment effect.
24. The method according to claim 1, wherein said inner wall of said blood vessel comprises the intima, and said target tissue comprises at least one of the media and adventitia of said blood vessel.
25. A non-focused ultrasonic transducer device comprising:
a non-focused flat piezoelectric transducer configured to generate one or more non-focused ultrasonic beams and sized for placement in a body lumen in which blood naturally flows, wherein said piezoelectric transducer is configured to be placed in said body lumen in a manner which prevents contact of said piezoelectric transducer with the inner wall of said body lumen, wherein said transducer faces target tissue located outside of the inner wall of said body lumen;
a controller which electrifies said piezoelectric transducer to generate a non-focused ultrasonic power beam with frequency in a range of 8 MHz-30 MHz, total energy and for a time period suitable for treating said target tissue; a power unit enabling said ultrasonic power beam for tissue ablation; and
a fluid restrictor effective to block at least a portion of fluid flowing upstream, downstream, or adjacent said piezoelectric transducer; wherein said fluid restrictor, when deployed, is shaped and positioned to allow at least some of said natural flow of blood between said transducer and said inner wall of said body lumen to cool said inner wall enough to prevent thermal damage to said inner wall.
26. The device according to claim 25, wherein said fluid restrictor is a balloon.
27. The device according to claim 25, wherein said fluid restrictor is a wire, a net, or a thin sheet.
28. The device according to claim 25, wherein said device further comprises a control unit configured to activate deployment of said fluid restrictor.
29. The device according to claim 28, wherein said device further comprises a flow sensor, and said control unit is configured to monitor fluid flow in the region of treatment based on an indication from said flow sensor.
30. The device according to claim 25, further comprising a perfusion unit configured for ejecting substances into the vessel.
31. The device according to claim 25, wherein said fluid restrictor serves as a placing element for positioning said transducer in the vessel.
32. The device according to claim 25, wherein said device further comprises a temperature sensor and said fluid restrictor is positioned to allow the sensor to detect a temperature of fluid flowing passed said transducer.
33. The device according to claim 25, wherein said piezoelectric transducer is protected by a housing, said housing shaped to affect fluid flow within a lumen around said piezoelectric transducer.
34. The device according to claim 25, wherein said fluid restrictor blocks only a portion of fluid flowing downstream said transducer to allow for at least some of said natural flow of blood between said transducer and an inner wall of said body lumen.
35. The device according to claim 25, wherein said fluid restrictor is shaped and positioned to (1) restrict blood flow on said non-focused flat piezoelectric transducer, and to (2) prevent contact of said non-focused flat piezoelectric transducer with said inner wall of said body lumen.
36. The device according to claim 25, wherein said frequency is in the range of 10 MHz-30 MHz.
37. A method for controlling a treatment effect on blood vessel tissue during an ultrasonic treatment, comprising
positioning an ultrasonic transducer device in the blood vessel lumen, wherein said transducer faces target tissue located outside of an inner wall of said blood vessel;
treating said target tissue by one or more non-focused ultrasonic beams with a frequency in a range of 10 MHz-30 MHz for generating a treatment effect, generated by said ultrasonic transducer without damaging a surface of said inner wall;
controlling a treatment effect by controlling fluid flow, wherein said controlling comprises deploying a fluid restrictor in the form of a wire or a thin plastic sheet, at a location relative to said transducer effective to block at least a portion of fluid flowing upstream, downstream or adjacent said transducer; wherein said deployed fluid restrictor allows natural blood flow between said transducer and said inner wall of said blood vessel to cool said innerwall; and
monitoring said fluid flow using a flow sensor.
38. A method for controlling a treatment effect on blood vessel tissue during an ultrasonic treatment, comprising
treating said target tissue by one or more non-focused ultrasonic beams with a frequency in a range of 10 MHz-30 MHz for generating a treatment effect, generated by said ultrasonic transducer without damaging a surface of said inner wall; and
controlling a treatment effect by controlling fluid flow, wherein said controlling comprises deploying a fluid restrictor at a location around said transducer effective to block at least a portion of fluid flowing upstream, downstream or adjacent said transducer; and wherein said deployed fluid restrictor allows natural blood flow between said transducer and said inner wall of said blood vessel to cool said inner wall.
39. A method for controlling a treatment effect on blood vessel tissue during an ultrasonic treatment, comprising
positioning a non-focused ultrasonic transducer device in the blood vessel lumen, at a distance from an inner wall of said blood vessel, wherein said transducer faces target tissue outside of said inner wall of said blood vessel, while mechanically ensuring a liquid space between said inner wall and said non-focused ultrasonic transducer device;
treating said target tissue by one or more non-focused ultrasonic beams with a frequency in a range of 10 MHz-30 MHz generated by said non-focused ultrasonic transducer without damaging a surface of said inner wall; and
controlling a treatment effect by controlling fluid flow, wherein said controlling comprises deploying a fluid restrictor at a location relative to said transducer effective to block at least a portion of fluid flowing upstream, downstream or adjacent said transducer; and wherein said deployed fluid restrictor allows natural blood flow between said transducer and said inner wall of said blood vessel to cool said inner wall.
5699804 December 23, 1997 Rattner
5707367 January 13, 1998 Nilsson
6077225 June 20, 2000 Brock-Fisher
6428477 August 6, 2002 Mason
6511436 January 28, 2003 Asmar
6527759 March 4, 2003 Tachibana
6645147 November 11, 2003 Jackson et al.
6953460 October 11, 2005 Maguire et al.
6955173 October 18, 2005 Lesh
7001336 February 21, 2006 Mandrusov et al.
7037271 May 2, 2006 Crowley
7084004 August 1, 2006 Vaiyapuri et al.
7220258 May 22, 2007 Myhr
7220261 May 22, 2007 Truckai et al.
7285116 October 23, 2007 De la Rama et al.
7341583 March 11, 2008 Shiono et al.
7460369 December 2, 2008 Blish, II
7479106 January 20, 2009 Banik et al.
7538425 May 26, 2009 Myers et al.
RE40815 June 30, 2009 Kudaravalli et al.
7540846 June 2, 2009 Harhen et al.
7563260 July 21, 2009 Whitmore et al.
7655005 February 2, 2010 Bhola
7704212 April 27, 2010 Wckcll et al.
7713210 May 11, 2010 Byrd et al.
7819868 October 26, 2010 Cao et al.
7824348 November 2, 2010 Barthe et al.
7850683 December 14, 2010 Elkins et al.
7883506 February 8, 2011 McIntyre et al.
7940969 May 10, 2011 Nair et al.
8216216 July 10, 2012 Warnking et al.
8221402 July 17, 2012 Francischclli et al.
8419729 April 16, 2013 Ibrahim et al.
8540662 September 24, 2013 Stehr et al.
8568403 October 29, 2013 Soltesz et al.
8585695 November 19, 2013 Shih
20010014780 August 16, 2001 Martin et al.
20020002371 January 3, 2002 Acker et al.
20020022833 February 21, 2002 Maguire et al.
20020026127 February 28, 2002 Balbierz et al.
20020048310 April 25, 2002 Heuser
20020055754 May 9, 2002 Ranucci et al.
20020077643 June 20, 2002 Rabiner et al.
20020188218 December 12, 2002 Lipman
20030013968 January 16, 2003 Fjield et al.
20030092667 May 15, 2003 Tachibana
20030151417 August 14, 2003 Koen
20030181901 September 25, 2003 Maguire et al.
20030199747 October 23, 2003 Michlitsch
20030199768 October 23, 2003 Cespedes
20040019687 January 29, 2004 Ozawa
20040073660 April 15, 2004 Toomey
20040102769 May 27, 2004 Schwartz et al.
20050015079 January 20, 2005 Keider
20050020967 January 27, 2005 Ono
20050096542 May 5, 2005 Weng
20050215946 September 29, 2005 Hansmann et al.
20050240170 October 27, 2005 Zhang et al.
20060009753 January 12, 2006 Fjield et al.
20060052774 March 9, 2006 Garrison et al.
20060058711 March 16, 2006 Harhen et al.
20060079816 April 13, 2006 Barthe et al.
20060084966 April 20, 2006 Maguire et al.
20060173387 August 3, 2006 Hansmann et al.
20060241442 October 26, 2006 Barthe et al.
20060241739 October 26, 2006 Besselink et al.
20070043297 February 22, 2007 Miyazawa
20070088346 April 19, 2007 Mirizzi et al.
20070142831 June 21, 2007 Shadduck
20070142879 June 21, 2007 Greenberg et al.
20070203479 August 30, 2007 Auth et al.
20070225619 September 27, 2007 Rabiner et al.
20070233057 October 4, 2007 Konishi
20070249997 October 25, 2007 Goodson, IV et al.
20080039745 February 14, 2008 Babaev
20080077202 March 27, 2008 Levinson
20080086073 April 10, 2008 McDaniel
20080114354 May 15, 2008 Whayne et al.
20080125829 May 29, 2008 Velasco et al.
20080139971 June 12, 2008 Lockhart
20080146924 June 19, 2008 Smith et al.
20080179736 July 31, 2008 Hartwell et al.
20080183110 July 31, 2008 Davenport et al.
20080195000 August 14, 2008 Spooner et al.
20080214966 September 4, 2008 Slayton et al.
20080228111 September 18, 2008 Nita
20080249518 October 9, 2008 Warnking et al.
20080300655 December 4, 2008 Cholette
20080312643 December 18, 2008 Kania et al.
20090018446 January 15, 2009 Medan et al.
20090036914 February 5, 2009 Houser
20090093737 April 9, 2009 Chomas et al.
20090149782 June 11, 2009 Cohen et al.
20090163807 June 25, 2009 Sliwa
20090216246 August 27, 2009 Nita et al.
20090254078 October 8, 2009 Just et al.
20090281478 November 12, 2009 Duke
20100036293 February 11, 2010 Isola et al.
20100081933 April 1, 2010 Sverdlik et al.
20100114082 May 6, 2010 Sharma
20100125198 May 20, 2010 Thapliyal et al.
20100130892 May 27, 2010 Warnking
20100152625 June 17, 2010 Milo
20100168649 July 1, 2010 Schwartz
20100198040 August 5, 2010 Friedman et al.
20100210946 August 19, 2010 Harada et al.
20100228162 September 9, 2010 Sliwa et al.
20100331686 December 30, 2010 Hossack et al.
20110009779 January 13, 2011 Romano et al.
20110028962 February 3, 2011 Werneth et al.
20110034809 February 10, 2011 Eberle et al.
20110066217 March 17, 2011 Diller et al.
20110106132 May 5, 2011 Barbut
20110112400 May 12, 2011 Emery
20110178441 July 21, 2011 Tyler
20110201973 August 18, 2011 Stephens et al.
20110257563 October 20, 2011 Thapliyal et al.
20110270247 November 3, 2011 Sherman
20110282203 November 17, 2011 Tsoref
20110282249 November 17, 2011 Tsoref et al.
20110319765 December 29, 2011 Gertner
20120016273 January 19, 2012 Diederich
20120053577 March 1, 2012 Lee et al.
20120065494 March 15, 2012 Gertner
20120095335 April 19, 2012 Sverdlik et al.
20120095371 April 19, 2012 Sverdlik et al.
20120123270 May 17, 2012 Klee et al.
20120209116 August 16, 2012 Hossack
20120215106 August 23, 2012 Sverdlik et al.
20120232436 September 13, 2012 Warnking
20120265227 October 18, 2012 Sverdlik et al.
20120268886 October 25, 2012 Leontiev et al.
20120283605 November 8, 2012 Lewis, Jr.
20130072928 March 21, 2013 Schaer
20130131668 May 23, 2013 Schaer
20130197555 August 1, 2013 Schaer
20130204167 August 8, 2013 Sverdlik et al.
20130204242 August 8, 2013 Sverdlik et al.
20130207519 August 15, 2013 Chaggares et al.
20130211292 August 15, 2013 Sverdlik et al.
20130211396 August 15, 2013 Sverdlik et al.
20130211437 August 15, 2013 Sverdlik et al.
20130218054 August 22, 2013 Sverdlik et al.
20130218068 August 22, 2013 Sverdlik et al.
20130267875 October 10, 2013 Thapliyal et al.
20130296836 November 7, 2013 Barbut et al.
20140039286 February 6, 2014 Hoffer
20140039477 February 6, 2014 Sverdlik et al.
20140074076 March 13, 2014 Gertner
20140276135 September 18, 2014 Agah
20140359111 December 4, 2014 Hilmo
20150073400 March 12, 2015 Sverdlik et al.
20150112234 April 23, 2015 McCaffrey
20160059044 March 3, 2016 Gertner
20160113699 April 28, 2016 Sverdlik et al.
20160374710 December 29, 2016 Sinelnikov
1279595 January 2001 CN
101610735 December 2009 CN
101820820 September 2010 CN
1384445 January 2004 EP
1424100 June 2004 EP
1799302 March 2006 EP
1769759 April 2007 EP
2218479 August 2010 EP
2455133 May 2012 EP
07-227394 August 1995 JP
09-122139 May 1997 JP
10-248854 September 1998 JP
2008-536562 September 2008 JP
2010-517695 May 2010 JP
WO 91/10405 July 1991 WO
WO 99/16366 April 1999 WO
WO 00/67648 October 2000 WO
WO 2004/054448 July 2004 WO
WO 06/022790 March 2006 WO
WO 06/041881 April 2006 WO
WO 2006/041847 April 2006 WO
WO 2006/042163 April 2006 WO
WO 2007/001981 January 2007 WO
WO 2007/078997 July 2007 WO
WO 2007/115307 October 2007 WO
WO 2007/127176 November 2007 WO
WO 2008/003058 January 2008 WO
WO 2008/098101 August 2008 WO
WO 2008/102363 August 2008 WO
WO 2010/009473 January 2010 WO
WO 2010/118307 October 2010 WO
WO 2011/053757 May 2011 WO
WO 2011/060200 May 2011 WO
WO 2012/052920 April 2012 WO
WO 2012/052921 April 2012 WO
WO 2012/052922 April 2012 WO
WO 2012/052924 April 2012 WO
WO 2012/052925 April 2012 WO
WO 2012/052926 April 2012 WO
WO 2012/052927 April 2012 WO
WO 2012/061713 May 2012 WO
WO 2013/030743 March 2013 WO
WO 2013/111136 August 2013 WO
WO 2013/134479 September 2013 WO
WO 2013/157009 October 2013 WO
WO 2013/157011 October 2013 WO
WO 2013/162694 October 2013 WO
WO 2014/188430 November 2014 WO
WO 2016/084081 June 2016 WO
Applicant-Initiated Interview Summary Dated Jan. 24, 2014 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/449,539.
Communication Pursuant to Article 94(3) EPC Dated Nov. 4, 2014 From the European Patent Office Re. Application No. 11833950.6.
Communication Pursuant to Article 94(3) EPC Dated Jun. 10, 2014 From the European Patent Office Re. Application No. 117822476.3.
Communication Pursuant to Article 94(3) EPC Dated Jun. 10, 2014 From the European Patent Office Re. Application No. 117847822.2
Communication Pursuant to Article 94(3) EPC Dated Apr. 14, 2014 From the European Patent Office Re. Application No. 11782221.3.
Communication Pursuant to Article 94(3) EPC Dated Sep. 26, 2014 From the European Patent Office Re. Application No. 11782222.1.
Communication Pursuant to Article 94(3) EPC Dated Oct. 30, 2014 From the European Patent Office Re. Application No. 11782221.3.
Communication Pursuant to Rules 70(2) and 70a(2) EPC Dated Mar. 28, 2014 From the European Patent Office Re. Application No. 11833950.6.
Communication Under Rule 71(3) EPC Dated Apr. 24, 2014 From the European Patent Office Re. Application No. 11782223.9.
International Preliminary Report on Patentability Dated May 2, 2013 From the International Bureau of WIPO Re. Application No. PCT/IB2011/054634.
International Preliminary Report on Patentability Dated May 2, 2013 From the International Bureau of WIPO Re. Application No. PCT/IB2011/054635.
International Preliminary Report on Patentability Dated May 2, 2013 From the International Bureau of WIPO Re. Application No. PCT/IB2011/054636.
International Preliminary Report on Patentability Dated May 2, 2013 From the International Bureau of WIPO Re. Application No. PCT/IB2011/054638.
International Preliminary Report on Patentability Dated May 2, 2013 From the International Bureau of WIPO Re. Application No. PCT/IB2011/054639.
International Preliminary Report on Patentability Dated May 2, 2013 From the International Bureau of WIPO Re. Application No. PCT/IB2011/054640.
International Preliminary Report on Patentability Dated May 2, 2013 From the International Bureau of WIPO Re. Application No. PCT/IB2011/054641.
International Preliminary Report on Patentability Dated Aug. 7, 2014 From the International Bureau of WIPO Re. Application No. PCT/IL2013/050068.
International Preliminary Report on Patentability Dated Oct. 30, 2014 From the International Bureau of WIPO Re. Application No. PCT/IL2013/050339.
International Preliminary Report on Patentability Dated Oct. 30, 2014 From the International Bureau of WIPO Re. Application No. PCT/IL2013/050341.
International Search Report and the Written Opinion Dated Feb. 7, 2012 From the International Searching Authority Re. Application No. PCT/IB2011/054641.
International Search Report and the Written Opinion Dated Oct. 11, 2013 From the International Searching Authority Re. Application No. PCT/IL2013/050341.
International Search Report and the Written Opinion Dated Sep. 19, 2013 From the International Searching Authority Re. Application No. PCT/IL2013/050068.
International Search Report and the Written Opinion Dated Nov. 20, 2014 From the International Searching Authority Re. Application No. PCT/IL2014/050457.
International Search Report and the Written Opinion Dated Jun. 22, 2012 From the International Searching Authority Re. Application No. PCT/IB2011/054640.
International Search Report and the Written Opinion Dated Jan. 23, 2012 From the International Searching Authority Re. Application No. PCT/IB2011/054635.
International Search Report and the Written Opinion Dated Jan. 25, 2012 From the International Searching Authority Re. Application No. PCT/IB2011/054636.
International Search Report and the Written Opinion Dated Jan. 27, 2012 From the International Searching Authority Re. Application No. PCT/IB2011/054634.
International Search Report and the Written Opinion Dated Jan. 27, 2012 From the International Searching Authority Re. Application No. PCT/IB2011/054638.
International Search Report and the Written Opinion Dated Oct. 29, 2013 From the International Searching Authority Re. Application No. PCT/IL2013/050339.
International Search Report and the Written Opinion Dated Jan. 31, 2012 From the International Searching Authority Re. Application No. PCT/IB2011/054639.
Invitation Pursuant to Rule 137(4) EPC Dated Apr. 4, 2014 From the European Patent Office Re. Application No. 11785792.0.
Invitation Pursuant to Rule 137(4) EPC Dated Apr. 8, 2014 From the European Patent Office Re. Application No. 11782222.1.
Invitation Pursuant to Rule 137(4) EPC Dated Apr. 10, 2014 From the European Patent Office Re. Application No. 11782476.3.
Invitation to Pay Additional Fees Dated Sep. 3, 2013 From the International Searching Authority Re. Application No. PCT/IL2013/050339.
Invitation to Pay Additional Fees Dated Sep. 4, 2014 From the International Searching Authority Re. Application No. PCT/IL2014/050457.
Invitation to Pay Additional Fees Dated Aug. 5, 2013 From the International Searching Authority Re. Application No. PCT/IL2013/050341.
Invitation to Pay Additional Fees Dated Apr. 17, 2012 From the International Searching Authority Re. Application No. PCT/IB2011/054640.
Invitation to Pay Additional Fees Dated Jul. 24, 2013 From the International Searching Authority Re. Application No. PCT/IL2013/050068.
Notice of Allowance Dated Oct. 6, 2014 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/880,061.
Notice of Allowance Dated Nov. 7, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/049,013.
Notice of Allowance Dated Jun. 21, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/049,151.
Office Action Dated Jul. 30, 2014 From the State Intellectual Property Office of the People's Republic of China Re. Application No. 201180060741.3 and Its Summary in English.
Official Action Dated Nov. 4, 2014 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/879,400.
Official Action Dated Nov. 5, 2014 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/049,022.
Official Action Dated Oct. 7, 2014 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/880,109.
Official Action Dated May 8, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/462,956.
Official Action Dated Sep. 10, 2014 From the US Patent and Trademark Office Re. U.S. Appl. No. 14/049,238.
Official Action Dated Apr. 14, 2014 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/879,400.
Official Action Dated Jul. 17, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/049,013.
Official Action Dated Dec. 19, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/049,022.
Official Action Dated Mar. 20, 2014 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/449,539.
Official Action Dated Apr. 23, 2014 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/880,061.
Official Action Dated Oct. 24, 2012 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/049,013.
Official Action Dated Sep. 25, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/462,956.
Official Action Dated Aug. 29, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/449,539.
Official Action Dated Jan. 29, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/049,151.
Restriction Official Action Dated Oct. 5, 2012 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/049,151.
Restriction Official Action Dated Jul. 7, 2014 From the US Patent and Trademark Office Re. U.S. Appl. No. 14/049,238.
Restriction Official Action Dated Nov. 17, 2014 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/880,066.
Restriction Official Action Dated Jun. 28, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/449,539.
Restriction Official Action Dated Aug. 30, 2012 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/049,013.
Restriction Official Action Dated Oct. 30, 2014 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/880,083.
Search Report Dated Jul. 17, 2014 From the State Intellectual Property Office of the People's Republic of China Re. Application No. 201180060741.3 and Its Machine Translation in English.
Supplementary European Search Report Dated Mar. 12, 2014 From the European Patent Office Re. Application No. 11833950.6.
Ahmed et al. “Renal Sympathetic Denervation Using an Irrigated Radiofrequency Ablation Catheter for the Management of Drug-Resistant Hypertension”, Journal of the American College of Cardiology: Cardiovascular Interventions, JACC, 5(7): 758-765, 2012.
Anonymus “Indication for and Results of Sympathectomy in Patients With Peripheral Vascular Disease”, Lumbar Sympathectomy, Poster, 34 P., 2009.
Aoyama et al. “Comparison of Cryothermia and Radiofrequency Current in Safety and Efficacy of Catheter Ablation Within the Canine Coronary Sinus Close to the Left Circumflex Coronary Artery”, Journal of Cardiovascular Electrophysiology, 16: 1218-1226, Nov. 2005.
Atherton et al. “Micro-Anatomy of the Renal Sympathetic Nervous System: A Human Postmortem Histologic Study”, Clinical Anatomy, p. 1-6, Oct. 4, 2011.
Bailey et al. “Cavitation Detection During Shock-Wave Lithotripsy”, Ultrasound in Medicine and Biology, XP027605630, 31(9): 1245-1256, Sep. 1, 2005. Abstract, Fig.1, p. 1246, p. 1247, r-h Col., p. 1249, r-h Col.
Baker et al. “Operative Lumbar Sympathectomy for Severe Lower Limb Ischaemia: Still A Valuable Treatment Option”, Annals of the Royal College of Surgeons of England, 76(1): 50-53, Jan. 1994.
Bharat et al. “Monitoring Stiffness Changes in Lesions After Radiofrequency Ablation at Different Temperatures and Durations of Ablation”, Ultrasound in Medicine & Biology, 31(3): 415-422, 2005.
Blankestijn et al. “Renal Denervation: Potential Impact on Hypertension in Kidney Disease?”, Nephrology, Dialysis, Transplantation, 26(9): 2732-2734, Apr. 19, 2011.
Brandt et al. “Effects of Renal Sympathetic Denervation on Arterial Stiffness and Central Hemodynamics in Patients With Resistant Hypertension”, Journal of the American College of Cardiology, 60(19): 1956-1965, 2012.
Brandt et al. “Renal Sympathetic Denervation Reduces Left Ventricular Hypertrophy and Improves Cardiac Function in Patients With Resistant Hypertension”, Journal of the American College of Cardiology, 59(10): 901-909, 2012.
Brasselet et al. “Effect of Local Heating on Restenosis and In-Stent Neointimal Hyperplasia in the Atherosclerotic Rabbit Model: A Dose-Ranging Study”, European Heart Journal, 29: 402-412, 2008.
Brinton et al. “Externally Focused Ultrasound for Sympathetic Renal Denervation”, WAVE I First-In-Man Study, Kona Medical Inc., PowerPont Presentation, TCT 2012, 15 P., 2012.
Campese et al. “Renal Afferent Denervation Prevents the Progression of Renal Disease in the Renal Ablation Model of Chronic Renal Failure in the Rat”, American Journal of Kidney Diseases, 26(5): 861-865, Nov. 1995. Abstract.
Campese et al. “Sympathetic Renal Innervation and Resistant Hypertension”, International Journal of Hypertension, 2011(Art.ID 814354): 1-6, 2011.
Cardiosonic “Cardiosonic New Applications”, Cardiosonic, p. 1-20, Mar. 2014.
Cardiosonic “Histological Map of Swine Pulmonary Arteries”, Cardiosonic, Animal #223, Mar. 26, 2014.
Cardiosonic “Histological Map of Swine Pulmonary Arteries”, Cardiosonic, Animal #234, Mar. 18, 2014.
Cardiosonic “Histological Map of Swine Pulmonary Arteries”, Cardiosonic, Animal #234, Mar. 26, 2014.
Cardiosonic “Histopathology Report”, Cardiosonic, 2 P., Dec. 26, 2013.
Cardiosonic “PA/Trachea—Feedback Provisional”, Cardiosonic, 5 P, Jun. 9, 2014.
Cardiosonic “PAH Preliminary Development Meeting Minutes”, Cardiosonic, 2 P., Mar. 23, 2014.
Copty et al. “Localized Heating of Biological Media Using A 1-W Microwave Near-Field Probe”, IEEE Transactions on Microwave Theory and Techniques, 52(8): 1957-1963, Aug. 2004.
Copty et al. “Low-Power Near-Field Microwave Applicator for Localized Heating of Soft Matter”, Applied Physics Letters, 84(25): 5109-5111, Jun. 21, 2004.
Damianou et al. “Dependence of Ultrasonic Attenuation and Absorpteion in Dog Soft Tissues on Temperature and Thermal Dose”, Journal of the Acoustical Society of America, 102(1): 628-634, Jul. 1997.
Davies et al. “First-in-Man Safety Evaluation of Renal Denervation for Chronic Systolic Heart Failure: Primary Outcome From REACH-Pilot Study”, International Journal of Cardiology, 162: 189-192, 2013.
Deneke et al. “IIistopathology of Intraoperatively Induced Linear Radiofrequency Ablation Lesions in Patients With Chronic Atrial Fibrillation”, European Heart Journal, 26: 1797-1803, 2005.
DiBona “Neural Control of Renal Function: Cardiovascular Implications”, Hypertension, 13: 539-548, 1989.
DiBona “Neural Control of the Kidney: Past, Present, and Future”, Hypertension, 41: 621-624, Dec. 16, 2002.
DiBona “Physiology in Perspective: The Wisdom of the Body. Neural Control of the Kidney”, American Journal of Physiology, Regulatory, Integrative and Comparative Physiology, 289(3): R633-R641, Sep. 2005.
DiBona et al. “Differentiated Sympathetic Neural Control of the Kidney”, American Journal of Physiology, 271: R84-R90, 1996.
DiBona et al. “Translational Medicine: the Antihypertensive Effect of Renal Denervation”, American Journal of Physiology, Regulatory, Integrative and Comparative Physiology, 298(2): R245-R253, Feb. 2010.
Diederich et al. “Catheter-Based Ultrasound Applicators for Selective Thermal Ablation: Progress Towards MRI-Guided Applications in Prostate”, International Journal of Hyperthermia, 20(7): 739-756, Nov. 2004.
Diederich et al. “Catheter-Based Ultrasound Devices and MR Thermal Monitoring for Conformal Prostate Thermal Therapy”, 30th Annual International IEEE EMBS Conference, Vancouver, British Columbia, Canada, Aug. 20-24, 2008, p. 3664-3668, 2008.
Diederich et al. “Induction of Hyperthermia Using an Intracavitary Multielement Ultrasonic Applicator”, IEEE Transactions on Biomedical Engineering, 36(4): 432-438, Apr. 1989.
Diederich et al. “Ultrasound Technology for Hyperthermia”, Ultrasound in Medicine & Biology, 25(6): 871-887, 1999.
Donoho et al. “Stable Recovery of Sparse Overcomplete Representations in the Presence of Noise”, IEEE Transactions on Information Theory, 52(1): 1-42, Jan. 2006.
Drake et al. “Problematic Anatomical Sites Around the Pulmonary Artery”, Gray's Anatomy for Students, 9 P., 2004.
Esler “The 2009 Carl Ludwig Lecture: Pathophysiology of the Human Sympathetic Nervous System in Cardiovascular Diseases: The Transition From Mechanisms to Medical Management”, Journal of Applied Physiology, 108: 227-237, 2010.
Esler et al. “Renal Sympathetic Denervation for Treatment of Drug-Resistant Hypertension: One-Year Results From the Symplicity HTN-2 Randomized, Controlled Trial”, Circulation, 126: 2976-2982, 2012.
Failla et al. “Sympathetic Tone Restrains Arterial Distensibility of Healthy and Atherosclerotic Subjects”, Journal of Hypertension, 17: 1117-1123, 1999.
Fischell PeriVascular Renal Denervation (PVRD™), Ablative Solutions Inc., TransCatheter Therapeutics Meeting, Miami, FL, USA, Oct. 24, 2012, PowerPoint Presentation, 14 P., Oct. 2012.
Fort Wayne Metals “HHS Tube”, Fort Wayne Metals Research Products Corporation, 2 P., 2009.
Fujikura et al. “Effects of Ultrasonic Exposure Parameters on Myocardial Lesions Induced by High-Intensity Focused Ultrasound”, Journal of Ultrasound Medicine, 25: 1375-1386, 2006.
Gander et al. “Least-Squares Fitting of Circles and Ellipses”, BIT Numerical Mathematics, 34(4): 558-578, Dec. 1994.
Glazier et al. “Laser Balloon Angioplasty Combined With Local Intrcoronary Heparin Therapy: Immediate and Short-Term Follow-Up Results”, American Heart Journal, 134: 266-273, 1997.
Goswami “Renal Denervation: A Percutaneous Therapy for HTN”, Prairie Heart Institute, Synvacor, The VEINS: Venous Endovascular Interventions Strategies, Chicago, USA, 42 P., 2012.
Granada et al. “A Translational Overview for the Evaluation of Peri-Renal Denervation Technologies”, Cardiovascular Research Foundation, Columbai University Medical Center, New York, USA, Alizee Pathology, 25 P., 2011.
Grassi et al. “Sympathetic Mechanisms, Organ Damage, and Antihypertensive Treatment”, Current Hypertension Report, 13: 303-308, 2011.
Griffiths et al. “Thoraco-Lumbar Splanchnicectomy and Sympathectomy. Anaesthetic Procedure”, Anaesthesia, 3(4): 134-146, Oct. 1948.
Grimson et al. “Total Thoracic and Partial to Total Lumbar Sympathectomy, Splanchnicectomy and Celiac Ganglionectomy for Hypertension”, Annals of Surgery, 138(4): 532-547, Oct. 1953.
Heath et al. “The Structure of the Pulmonary Trunk at Different Ages and in Cases of Pulmonary Hypertension and Pulmonary Stenosis”, The Journal of Pathology and Bacteriology, 77(2): 443-456, Apr. 1959.
Hering et al. “Renal Denervation in Moderate to Severe CKD”, Journal of the American Society of Nephrology, 23: 1250-1257, 2012.
Hering et al. “Substantial Reduction in Single Sympathetic Nerve Firing After Renal Denervation in Patients With rRsistant Hypertension”, Hypertension, 61: 1-14, Nov. 19, 2012.
Holdaas et al. “Modulation of Reflex Renal Vasoconstriction by Increased Endogenous Renal Prostaglandin Synthesis”, The Journal of Pharmacology and Experimental Therapeutics, 232(3): 725-731, 1985.
Janssen et al. “Role of Afferent Renal Nerves in Spontaneous Hypertension in Rats”, Hypertension, 13: 327-333, 1989.
Joner “Histopathological Characterization of Renal Arteries After Radiofrequency Catheter Based Sympathetic Denervation in a Healthy Porcine Model”, Deutsches Herzzentrum M?nchen, Technische Universit?t M?nchen, PowerPoint Presentation, TCT 2012, 15 P., 2012.
Katholi “Renal Nerves in the Pathogenesis of Hypertension in Experimental Animals and Humans”, American Journal of Physiology, 245: F1-F14, 1983.
Katholi et al. “Intrarenal Adenosine Produces Hypertension by Activating the Sympathetic Nervous System Via the Renal Nerves in the Dog”, Journal of Hypertension, 2: 349-359, 1984.
Katholi et al. “Renal Nerves in the Maintenance of Hypertension: A Potential Therapeutic Target”, Current Hypertension Reports, 12(3): 196-204, Jun. 2010.
Kleinlogel et al. “A Gene-Fusion Strategy for Stoichiometric and Co-Localized Expression of Light-Gated Membrane Proteins”, Nature Methods, 8(12): 1083-1091, Dec. 2011.
Kline et al. “Functional Reinnervation and Development of Supersensitivity to NE After Renal Denervation in Rats”, American Journal of Physiology, 238: R353-R358, 1980.
Kolh “Carotid Denervation by Adventitial Stripping: A Promising Treatment of Carotid Sinus Syndrome?”, European Journal of Vascular and Endovascular Surgery, 39(2): 153-154, Feb. 2010.
Krum et al. “Catheter-Based Renal Sympathetic Denervation for Resistant Hypertension: A Multicentre Safety and Proof-of-Principle Cohort Study”, The Lancet, 373: 1275-1281, Apr. 11, 2009.
Krum et al. “Catheter-Based Renal Sympathetic Denervation for Resistant Hypertension: A Multicentre Safety and Proof-of-Principle Cohort Study”, The Lancet, 373: 1275-1281, Mar. 30, 2009.
Lafon “Miniature Devices for Minimally Invasive Thermal Ablation by High Intensity Ultrasound”, Cargese Workshop 2009, University of Lyon, France, INSERM U556, Presentation, 39 P., 2009.
Lambert et al. “Redo of Percutaneous Renal Denervation in a Patient With Recurrent Resistant Hypertension After Primary Treatment Success”, Catheterization and Cardiovascular Interventions, p. 1-11, 2012.
Lele “Effects of Focused Ultrasonic Radiation on Peripheral Nerve, With Observations on Local Heating”, Experimental Neurology, 8: 47-83, 1963.
Lemoine et al. “Amputations and Sympathectomy in Peripheral Vascular Disease of the Lower Extremity. Experience With 180 Patients”, Journal of the National Medical Association, 61(3): 219-221, May 1969.
Li et al. “Acoustic Proximity Ranging in the Presence of Secondary Echoes”, IEEE Transactions on Instrumentation and Measurement, XP011102759, 52(5): 1593-1605, Oct. 1, 2003. p. 1593.
Lin et al. “Utility of the PlasmaKinetic™ Bipolar Forceps® for Control of the Renal Artery in a Porcine Model”, JTUA, 14(3): 118-121, Sep. 2003.
Liu et al. “A Helical Microwave Antenna for Welding Plaque During Balloon Angioplasty”, IEEE Transactions on Microwave Theory and Techniques, 44(10): 1819-1831, Oct. 1996.
Lopez et al. “Effects of Sympathetic Nerves on Collateral Vessels in the Limb of Atherosclerosis Primates”, Atherosclerosis, 90: 183-188, 1991.
Mabin et al. “First Experience With Endovascular Ultrasound Renal Denervation for the Treatment of Resistant Hypertension”, EuroIntervention, 8: 57-61, 2012.
Mahfoud et al. “Effect of Renal Sympathetic Denervation on Glucose Metabolism in Patients With Resistant Hypertension: A Pilot Study”, Circulation, 123: 1940-1946, 2011.
Mahfoud et al. “Is There a Role for Renal Sympathetic Denervation in the Future Treatment of Resistant Hypertension?”, Future Cardiology, 7(5): 591-594, 2011.
Mahfoud et al. “Renal Hemodynamics and Renal Function After Catheter-Based Renal Sympathetic Denervation in Patients With Resistant Hypertension”, Hypertension, 60: 419-424, 2012.
Makris et al. “Resistant Hypertension Workup and Approach to Treatment”, International Journal of Hypertension, 2011(Art.ID598694): 1-10, 2011.
Manasse et at “Clinical Histopathology and Ultrstructural Analysis of Myocardium Following Microwave Energy Ablation”, European Journal of Cardio-Thoracic Surgery, 23: 573-577, 2003.
Mangoni et al. “Effect of Sympathectomy on Mechanical Properties of Common Carotid and Femoral Arteries”, Hypertension, 30: 1085-1088, 1997.
Martin et al. “Premise, Promise, and Potential Limitations of Invasive Devices to Treat Hypertension”, Current Cardiology Reports, 13(1): 86-92, Feb. 2011.
Mazor “Efficacy of Renal Denervation Is Positively Impacted by Longitudinal Treatments”, Vessix Vascular Inc., PowerPoint Presentation, TCT 2012, 20 P., 2012.
Mogil et al. “Renal Innervation and Renin Activity in Salt Metabolism and Hypertension”, American Journal of Physiology, 216(4): 693-697, Apr. 1969.
Mortensen et al. “Catheter-Based Renal Sympathetic Denervation Improves Central Hemodynamics and Arterial Stiffness: A Pilot Study”, The Journal of Clinical Hypertension, 14(12): 861-870, Dec. 2012.
Ohkubo et al. “Histological Findings After Angioplasty Using Conventional Balloon, Radiofrequency Thermal Balloon, and Stent for Experimental Aortic Coarctation”, Pediatrics International, 46: 39-47, 2004.
Olafsson et al. “Ultrasound Current Source Density Imaging”, IEEE Transactions on Biomedical Engineering, 55(7): 1840-1848, Jul. 2008.
Ong et al. “Successful Treatment of Resistant Hypertension With Percutaneous Renal Denervation Therapy”, Heart, 98(23): 1754-1755, Dec. 2012.
Ormiston “OneShot (Covidien)”, Maya Medical, Auckland, New Zealand, PowerPoint Presentation.
Ormiston et al. “First-in-Human Use of the OneShot™ Renal Denervation System From Covidien”, EuroIntervention, 8: 1090-1094, 2013.
Page et al. “The Effect of Renal Denervation on Patients Suffering From Nephritis”, The Journal of Clinical Investigation, 14(4): 443-458, Jul. 1935.
Papademetriou et al. “Renal Sympathetic Denervation for the Treatment of Difficult-to-Control or Resistant Hypertension”, International Journal of Hypertension, 2011(Art.ID196518): 1-8, Jan. 2011.
Para Tech Coating “Parylene Properties”, Para Tech Coating Inc., 1 P.
Pokushalov et al. “A Randomized Comparison of Pulmonary Vein Isolation With Versus Without Concomitant Renal Artery Denervation in Patients With Refractory Symptomatic Atrial Fibrillation and Resistant Hypertension”, Journal of the American College of Cardiology, 60(13): 1163-1170, 2012.
Prapa et al. “Histopathology of the Great Vessels in Patients With Pulmonary Arterial Hypertension in Association With Congenital Heart Disease: Large Pulmonary Arteries Matter Too”, international Journal of Cardiology, 168: 2248-2254, Available Online Feb. 28, 2013.
Prochnau et al. “Catheter-Based Renal Denervation for Drug-Resistant Hypertension by Using a Standard Electrophysiology Catheter”, EuroIntervention, 7: 1077-1080, 2012.
Prochnau et al. “Efficacy of Renal Denervation With a Standard EP Catheter in the 24-h Ambulatory Blood Pressure Monitoring—Long-Term Follow-Up”, International Journal of Cardiology, 157(3): 447-448, Jun. 14, 2012.
Quinn “Pre-Eclampsia and Partial Uterine Denervation”, Medical Hypotheses, 64(3): 449-454, 2005. Abstract.
Rappaport “Treating Cardiac Disease With Catheter-Based Tissue Heating”, IEEE Microwave Magazine, p. 57-64, Mar. 2002.
Reddy “Sound Intervention”, Mount Sinai School of Medicine, MSSM, Presentation, 19 P., 2012.
Rothman “FIM Evaluation of A New, Multi-Electrode RF System for Renal Denervation (Medtronic)”, Medtronic Inc., PowerPoint Presentation, 8 P., 2012.
Rousselle “Experimental Pathways for the Evaluation of Extrinsic Renal Nerve Distribution, Density, and Quantification (Swine Model)”, Alizee Pathology in Collaboration With Jack Skirkball Center for Cardiovascular Research, TCT, 20 P., Nov. 8, 2011.
Rousselle “Renal Artery Dervation: Experimental Pathways for the Evaluation of Extrinsic Renal Nerve Distribution, Density, and Quantification (Swine Model)”, Alizee Pathology, Cardiovascular Research Foundation, Nov. 8, 2011.
Sangiorgi et al. “Histo-Morphometric Evaluation of 2D Characteristics and 3D Sympatetic Renal Nerve Distribution in Hypertensive Vs. Normotensive Patients”, Department of Pathology, Department of Cardiology, University of Rome Tor Vergata, Department of Cardiology University of Modena and Reggio Emilia, Medtronic Cardiovascular, PowerPoint Presentation, TCT 2012, 22 P., 2012.
Sanni et al. “Is Sympathectomy of Benefit in Critical Leg Ischaemia Not Amenable to Revascularisation?”, Interactive CardioVascular and Thoracic Surgery, 4: 478-483, 2005.
Scheinert “Cardiosonic TIVUS™ Technology: An Intra-Vascular Ultrasonic Catheter for Targeted Renal Denervation”, Center for Vascular Medicine, Park Hospital Leipzig, Germany, PowerPoint Presentation, TCT 2012, 16 P., 2012.
Schelegle et al. “Vagal Afferents Contribute to Exacerbates Airway Responses Following Ozone and Allergen Challenge”, Respiratory Physiology & Neurobiology, 181(3): 277-285, May 31, 2012.
Schlaich “Long-Term Follow Up of Catheter-Based Renal Denervation for Resistant Hypertension Confirms Durable Blood Pressure Reduction”, Hypertension & Kidney Disease Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne VIC, Australia, PowerPoint Presentation, TCT 2012, 22 P., 2012.
Schlaich et al. “Renal Sympathetic-Nerve Ablation for Uncontrolled Hypertension”, New England Journal of Medicine, 361(9): 932-934, Aug. 27, 2009.
Schwartz “Strategies to Model Efficacy of Hypertension Devices”, EuroPCR 2013, The Leading Cardiovascular Course, 24 P., 2013.
Sievert et al. “Catheter-Based Technology Alternatives for Renal Denervation”, CardioVascular Center Frankfurt, Germany, TCT 2012, Miami, FL, USA, Oct. 22-26, 2012, PowerPoint Presentation, 35 P., Oct. 2012.
Souchon et al. “Monitoring the Formation of Thermal Lesions With Heat-Induced Echo-Strain Imaging: A Feasibility Study”, Ultrasound in Medicine & Biology, 31(2): 251-259, 2005.
Stefanadis “Vincristine Local Delivery for Renal Artery Denervation”, Athens, Greece, PowerPoint Presentation, TCT 2012, 21 P., 2012.
Steigerwald et al. “Morphological Assessment of Renal Arteries After Radiofrequency Catheter-Based Sympathetic Denervation in a Porcine Model”, Journal of Hypertension, 30(11): 2230-2239, Nov. 2012.
Swierblewska et al. “An Independent Relationship Between Muscle Sympathetic Nerve Activity and Pulse Wave Velocity in Normal Humans”, Journal of Hypertension, 28: 979-984, 2010.
Symplicity HTN-1 Investigators “Catheter-Based Renal Sympathetic Denervation for Resistant Hypertension: Durability of Blood Pressure Reduction Out to 24 Months”, Hypertension, 57: 911-917, Mar. 14, 2011.
Symplicity HTN-2 Investigators “Renal Sympathetic Denervation in Patients With Treatment-Resistant Hypertension (The Symplicity HTN-2 Trial): A Randomised Controlled Trial”, The Lancet, 376: 1903-1909, Dec. 4, 2010.
Szabo “Diagnostic Ultrasound Imaging: Inside Out”, Academic Press Series in Biomedical Engineering, 2004. Book: Diagnostic Ultrasound Imaging Inside Out—Bronzino ; Academic Press Series in Biomedical Engineering ,Joseph Bronzino, Series Editor ; Trinity College—Hartford, Connecticut “Diagnostic Ultrasound Imaging Inside Out”, Academic Press Series in Biomedical Engineering, 2004.
Techavipoo et al. “Temperature Dependence of Ultrasonic Propagation Speed and Attenuation in Excised Canine Liver Tissue Measured Using Transmitted and Reflected Pulses”, Journal of the Acoustical Society of America, 115(6): 2859-2865, Jun. 2004.
Tibshirani “Regression Shrinkage and Selction Via the Lasso: A Retrospective”, Journal of the Royal Statistical Society, Series B: Statistical Methodology, 73(Pt.3): 273-282, 2011.
Tibshirani “Regression Shrinkage and Selection Via the Lasso”, Journal of the Royal Statistical Society, Series B: Methodological, 58(1): 267-288, 1996.
Toorop et al. “Clinical Results of Carotid Denervation by Adventitial Stripping in Caotid Sinus Syndrome”, Europan Journal of Vascular and Endovascular Syndrome, 39: 146-152, 2010.
Tyreus et al. “Two-Dimensional Acoustic Attenuation Mapping of High-Temperature Interstitial Ultrasound Lesions”, Physics in Medicine and Biology, 49: 533-546, 2004.
Verloop et al. “The Effects of Renal Denervation on Renal Haemodynamics”, Interventions for Hypertenison & Heart Failure, Abstracts of EuroPCR & AsiaPCR/SingLIVE 2013, May 21, 2013.
Virmani “Translation Medicine and Renal Denervation: Pre-Clinical Animal Models and Histoanatomy”, CVPath Institute, Gaithersburg, MD, USA, PowerPoint Presentation.
Voskuil et al. “Percutaneous Renal Denervation for the Treatment of Resistant Essential Hypertension; The First Dutch Experience”, Netherlands Heart Journal, 19(7-8): 319-323, Aug. 2011.
Warwick et al. “Trackless Lesions in Nervous Tissues Produced by High Intensity Focused Ultrsound (High-Frequency Mechanical Waves)”, Journal of Anatomy, 102(3): 387-405, 1968.
Wikswo Jr. et al. “Magnetic Field of a Nerve Impulse: First Measurements”, Science, 208: 53-55, Apr. 4, 1980.
Wilcox “Resistant Hypertension and the Role of the Sympathetic Nervous System”, Medtronic, 30 P.
Williams et al. “Laser Energy Source in Surgical Atrial Fibrillation Ablation: Preclinical Experience”, The Annals of Thoracic Surgery, 82: 2260-2264, 2006.
Witkowski “Future Perspective in Renal Denervation: Congestive Heart Failure, Insulin Resistance and Sleep Apnea”, Innovations in Cardiovascular Interventions, ICI Meeting 2011, Tel Aviv, Israel, Dec. 4-6, 2011, 23 P., 2011.
Witkowski et al. “Effects of Renal Sympathetic Denervation on Blood Pressure, Sleep Apnea Course, and Glycemic Control in Patients With Resistant Hypertension and Sleep Apnea”, Hypertension, 58(4): 559-565, Oct. 2011.
Witkowski et al. “Effects of Renal Sympathetic Denervation on Blood Pressure, Sleep Apnea Course, and Glycemic Control in Patients With Resistant Hypertension and Sleep Apnea”, Hypertension, 58: 559-565, Aug. 15, 2011.
Witte et al. “Imaging Current Flow in Lobster Nerve Cord Using the Acoustoelectric Effect”, Applied Physics Letters, 90: 163902-1-163902-3, 2007.
Wolf-De Jonge et al. “25 Years of Laser Assisted Vascular Anastomosis (LAVA): What Have We Learned?”, European Journal of Vascular and Endovascular Surgery, 27(5): 466-476, May 2004.
Worthington et al. “Changes in Ultrasound Properties of Porcine Kidney Tissue During Heating”, Ultrasound in Medicine & Biology, 27(5): 673-682, 2001.
Worthington et al. “Ultrasound Properties of Human Prostate Tissue During Heating”, Ultrsound in Medicine & Biology, 28(10): 1311-1318, 2002.
Xu et al. “Experimental Nerve Thermal Injury”, Brain, 117: 375-384, 1994.
Zeller “Percutaneous Renal Denervation System. The New Ultrasound Solution for the Mangament of Hypertension”, Paradise Ultrasound Denervation System, ReCor Medical, 27 P., 2013.
Applicant-Initiated Interview Summary Dated Jan. 21, 2015 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/449,539.
Communication Pursuant to Article 94(3) EPC Dated Apr. 10, 2015 From the European Patent Office Re. Application No. 11782222.1.
Notice of Allowance Dated Jan. 8, 2015 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/880,061.
Notification of Office Action and Search Report Dated Dec. 1, 2014 From the State Intellectual Property Office of the People's Republic of China Re. Application No. 201180060862.8.
Official Action Dated Dec. 3, 2014 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/462,956.
Restriction Official Action Dated Apr. 14, 2015 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/880,124.
Restriction Official Action Dated Feb. 27, 2015 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/905,224.
Restriction Official Action Dated Mar. 27, 2015 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/880,095.
Translation Dated Mar. 12, 2015 of Notification of Office Action and Search Report Dated Dec. 1, 2014 From the State Intellectual Property Office of the People's Republic of China Re. Application No. 201180060862.8.
Notice of Non-Compliant Amendment Dated Sep. 23, 2015 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/880,124.
Official Action Dated Sep. 11, 2015 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/880,066.
Reason for Rejection Dated Aug. 20, 2015 From the Japanese Patent Office Re. Application No. 2013 534435.
Schnyder et al. “Common Femoral Artery Anatomy Is Influenced by Demographics and Comorbidity: Implications for Cardiac and Peripherial Invasive Studies”, Catheterization and Cardiovascular Interventions, 53(3): 289-295, Jul. 2001.
Wu et al. “A Quality Control Program for MR-Guided Focused Ultrasound Ablation Therapy”, Journal of Applied Clinical Medical Physics, 3(2): 162-167, Spring 2002.
Applicant-Initiated Interview Summary Dated Jan. 4, 2016 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/449,539.
Communication Pursuant to Article 94(3) EPC Dated Feb. 8, 2016 From the European Patent Office Re. Application No. 11833950.6.
International Preliminary Report on Patentability Dated Dec. 3, 2015 From the International Bureau of WIPO Re. Application. No. PCT/IL2014/050457.
Official Action Dated Jan. 5, 2016 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/880,124.
Official Action Dated Jul. 2, 2015 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/879,400.
Official Action Dated Aug. 5, 2015 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/905,224.
Official Action Dated Aug. 14, 2015 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/449,539.
Ali et al. “Signal Processing Overview of Ultrasound Systems for Medical Imaging”, Texas Instruments White Paper, SPRAB12: 1-27, Nov. 2008.
Bambi et al. “Real-Time Digital Processing of Doppler Ultrasound Signals”, IEEE International Conference on Acoustics, Speech, and Signal Processing, Proceedings, (ICASSP '05), (5): v/977-v/980, Mar. 23-23, 2005.
Shung “Doppler Flow Measurements”, Diagnostic Ultrasound—Imaging and Blood Flow Measurements, Chap.5:103-104, 2006.
Applicant-Initiated Interview Summary Dated Jul. 14, 2016 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/449,539.
Applicant-Initiated Interview Summary Dated Feb. 22, 2016 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/880,066.
Applicant-Initiated Interview Summary Dated Sep. 28, 2016 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/905,224.
Communication Pursuant to Article 94(3) EPC Dated Jul. 20, 2016 From the European Patent Office Re. Application No. 11782221.3.
Communication Pursuant to Article 94(3) EPC Dated Jul. 27, 2016 From the European Patent Office Re. Application No. 11782222.1.
Decision of Rejection Dated Apr. 28, 2016 From the Japanese Patent Office Re. Application No. 2013-534435 and Its Machine Translation in English.
International Search Report and the Written Opinion Dated May 2, 2016 From the International Searching Authority Re. Application No. PCT/IL2015/051145.
Invitation Pursuant to Rule 137(4) EPC Dated Mar. 21, 2016 From the European Patent Office Re. Application No. 11782222.1.
Invitation to Pay Additional Fees Dated Mar. 4, 2016 From the International Searching Authority Re. Application No. PCT/IL2015/051145.
Official Action Dated Jun. 3, 2016 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/880,066.
Official Action Dated Mar. 10, 2016 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/449,539.
Official Action Dated Jul. 26, 2016 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/880,124.
Official Action Dated Apr. 29, 2016 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/905,224.
Restriction Official Action Dated Oct. 27, 2016 From the US Patent and Trademark Office Re. U.S. Appl. No. 14/394,276.
Shelton Jr. et al. “A Nondestructive Technique to Measure Pulmonary Artery Diameter and Its Pulsatile Variations”, Journal of Applied Physiology, 33(4): 542-544, Oct. 1972.
Applicant-Initiated Interview Summary Dated Apr. 25, 2018 From the US Patent and Trademark Office Re. U.S. Appl. No. 14/394,276. (3 pages).
Communication Pursuant to Rule 164(1) EPC: Supplementary Partial European Search Report and the European Provisional Opinion Dated May 18, 2018 From the European Patent Office Re. Application No. 15862313.2. (15 Pages).
Official Action Dated Jun. 21, 2018 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/449,539. (8 pages).
Restriction Official Action Dated May 24, 2018 From the US Patent and Trademark Office Re. U.S. Appl. No. 14/889,890. (8 pages).
Patent number: 10368893
Patent Publication Number: 20140180197
Assignee: CardioSonic Ltd. (Tel-Aviv)
Inventors: Ariel Sverdlik (Tel-Aviv), Or Shabtay (Kibbutz Farod)
Application Number: 14/190,113
International Classification: A61B 17/32 (20060101); A61B 17/22 (20060101); A61N 7/02 (20060101); A61M 37/00 (20060101); A61B 90/00 (20160101); A61B 17/00 (20060101); A61N 7/00 (20060101);