1. Field of the Invention
The present invention relates to a catheter, and more particularly, to a catheter having an ultrasound assembly.
2. Description of Related Art
Many medical treatments can be performed using catheters with an ultrasound transducer. These ultrasound transducers deliver ultrasound energy to a target site within a patient. The ultrasound energy can provide a therapeutic effect by itself or can enhance the effects of other therapeutic media exposed to the ultrasound energy. Inefficient ultrasound transducer arrangements can generate excessive heat during a medical treatment.
The invention relates to a catheter system. The system comprises a catheter body having a chamber containing a low acoustic impedance medium. The catheter body includes an elongated body with an external surface and an ultrasound transducer having an external side between a first end and a second end. The ultrasound transducer is positioned over the external surface of the elongated body such that the first end of the ultrasound transducer is adjacent to the chamber.
Another embodiment of the system comprises a catheter body having an external surface. The catheter body includes an ultrasound transducer having a side between a first end and a second end. A first medium is positioned adjacent to the first end of the ultrasound transducer and a second medium is positioned adjacent to the external side of the ultrasound transducer. The second medium is harder than the first medium to encourage flexibility of the catheter body adjacent to the first end of the ultrasound transducer and efficient transmission of ultrasound energy from the external side of the ultrasound transducer.
The catheter system can also include a sheath for receiving the catheter.
The invention also relates to a method for forming a catheter. The method includes positioning an ultrasound transducer over an external surface of an elongated body and positioning a collar over the external surface of the elongated body such that at least a portion of the collar is spaced apart from the ultrasound transducer. The method also includes positioning a transducer sheath over at least a portion of the ultrasound transducer and over at least a portion of the collar to form a chamber between the ultrasound transducer and the collar.
Another embodiment of the method includes positioning a first spacer over an external surface of an elongated body and positioning a member over at least a portion of the first spacer so as to form a chamber between the member and the external surface of the elongated body. The method also includes positioning an ultrasound transducer over the member.
Yet another embodiment of the method includes providing an ultrasound transducer having a side between a first end and a second end. The ultrasound transducer is positioned over an external surface of an elongated body. The method includes forming a first medium adjacent to the first end of the ultrasound transducer and forming a second medium adjacent to the side of the ultrasound transducer. The second medium is harder than the first medium to encourage flexibility of the catheter body adjacent to the first end of the ultrasound transducer and efficient transmission of ultrasound energy from the external side of the ultrasound transducer.
The invention relates to a catheter having a chamber containing a low acoustic impedance medium. The catheter can also include an elongated body with an external surface. An ultrasound transducer having an external side between a first end and a second end can be positioned over the external surface of the elongated body such that the first side of the ultrasound transducer is adjacent to the chamber.
The low acoustic impedance material within the chamber reduces the portion of ultrasound energy which is transmitted through the chamber. This reduction causes an increased portion of ultrasound energy to be delivered from the second end of the ultrasound transducer and/or from the external side of the ultrasound transducer. As a result, the ultrasound energy produced from these sections of the ultrasound transducer is delivered with a greater efficiency.
The ultrasound transducer can be positioned distally relative to the chamber in order to increase the efficiency of the ultrasound energy transmitted in the distal direction. Alternatively, the ultrasound transducer can be positioned proximally relative to the chamber in order to increase the efficiency of the ultrasound energy transmitted in the proximal direction.
Another embodiment of the catheter includes a chamber between the elongated body and an internal side of the ultrasound transducer. The chamber can include a low acoustic impedance medium to reduce the portion of ultrasound energy transmitted into the elongated body. As a result, the ultrasound energy produced from the ends and the external side of the ultrasound transducer is delivered with a greater efficiency than could be achieved without the chamber.
A catheter according to the present invention can include various combinations of the above chambers. Each of the chambers can be independent of one another or they can be in communication with one another. The chambers can contain a low acoustic impedance medium. For instance, a catheter can include a first chamber adjacent to the first end of the ultrasound transducer, a second chamber adjacent to the second end of the ultrasound transducer and a third chamber between the internal side of the ultrasound transducer and the elongated body. As a result, the ultrasound energy produced from the external surface of the catheter is delivered at an increased efficiency. Such a catheter efficiently delivers ultrasound energy from the side of the catheter.
As another example, a catheter can include the first chamber adjacent to the first end of the ultrasound transducer and the third chamber between the internal side of the ultrasound transducer and the elongated body. Further, the ultrasound transducer can be positioned distally relative to the first chamber. The chambers can contain a low acoustic impedance medium. As a result, the ultrasound energy produced from the second end and the external surface of the catheter is delivered at an increased efficiency. Such a catheter efficiently delivers ultrasound energy both distally and from the side of the catheter.
A catheter according to the present invention can also include a plurality of ultrasound transducers. Each ultrasound transducer can be associated with one or more chambers. As a result, each ultrasound transducer can have an increased efficiency.
An embodiment of a catheter having a plurality of ultrasound transducers includes ultrasound transducers with matched resonant frequencies. For instance, the catheter can include ultrasound transducers selected such that any one has a resonant frequency within about 1% of the resonant frequency of any other ultrasound transducer in the plurality of ultrasound transducers. The matching of the ultrasound transducers allows the ultrasound transducers to be concurrently driven at a single frequency while reducing the inefficiencies associated with driving ultrasound transducers at a frequency which is significantly different than their resonant frequency.
Another embodiment of the catheter includes a first binding medium adjacent to the first end of the ultrasound transducer and a second binding medium adjacent to the external side of the ultrasound transducer. The first and second media are selected to provide the catheter with flexibility and a high level of ultrasound transmission efficiency. Since a softer media is typically more flexible and harder media typically transit ultrasound energy more efficiently, the second medium is preferably harder than the first medium. The advantages of the first and second media are emphasized in multiple ultrasound transducer catheters which tend to lose flexibility with the increased number of ultrasound transducers.
Catheters according to the present invention can also include an autotransformer in the proximal portion of the catheter. The autotransformer can serve to adjust the characteristic impedance of the catheter to match the impedance of components used to drive the one or more ultrasound transducers included on the catheter. The matched impedance serves to increase the efficiency of the catheter system.
Catheters according to the present invention can also include a catheter identification electronics. The catheter identification electronics indicate to a catheter control system the frequency that ultrasound transducers should be driven.
The ultrasound assembly 10 includes an elongated body 12 with an external surface 14. A plurality of spacers 16 are positioned over the external surface 14 of an elongated body 12 and a member 18 is positioned over at least a portion of the spacers 16. The ultrasound assembly 10 also includes an ultrasound transducer 20 with an external side 22 and an internal side 24 between a first end 26 and a second end 28. The ultrasound transducer 20 is positioned over the member 18 and can surround the member 18. Suitable materials for the member 18 include, but are not limited to, polyimide, polyester and nylon. A suitable ultrasound transducer 20 includes, but is not limited to, PZT-4D, PZT-4, PZT-8 and various piezoceramics.
The internal side 24 of the ultrasound transducer 20, the spacers 16 and the member 18 each define a portion of a chamber 30 between the internal side 24 of the ultrasound transducer 20 and the external surface 14 of the elongated body 12. The chamber 30 preferably has a height from 0.25-10 μm, more preferably from 0.50-5 μm and most preferably from 0.0-1.5 μm.
The member 18 can extend beyond the first end 26 and/or the second end 28 of the ultrasound transducer 20. Additionally, the spacers 16 can be positioned beyond the ends of the ultrasound transducer 20. As a result, the chamber 30 can extend along the longitudinal length of the ultrasound transducer 20 to increase the portion of the ultrasound transducer 20 which is adjacent to the chamber 30.
The chamber 30 can contain a low acoustic impedance medium. Suitable low acoustic impedance media include, but are not limited to, fluids such as helium, argon, air and nitrogen and/or solids such as silicone and rubber. The chamber 30 can also be evacuated. Suitable pressures for an evacuated chamber 30 include, but are not limited to, negative pressures to −760 mm Hg.
As illustrated in
A transducer sheath 34 is positioned over at least a portion of the ultrasound transducer 20 and the collar 32 to form a chamber 30 adjacent to a side of the ultrasound transducer 20. An inner side of the collar 32, the ultrasound transducer 20 and the transducer sheath 34 each partially define the chamber 30. The chamber 30 preferably has a width, W, from 12-2500 μm, more preferably from 25-250 μm and most preferably from 25-125 μm. The chamber 30 can contain a low acoustic impedance medium. Suitable materials for the transducer sheath 34 include, but are not limited to air, N2, O2, and vacuum. The transducer sheath 34 preferably has a thickness from 10-100 μm and more preferably from 25-50 μm.
The ultrasound assembly 10 can also include a chamber 30 adjacent to the second end 28 of the ultrasound transducer 20 as illustrated in
Each of the chambers can be isolated from one another. However, when the ultrasound assembly 10 includes a chamber 30 between the ultrasound transducer 20 and the elongated body 12, one or more of the spacers 16 can be formed of a porous material to provide communication between the chambers 30. This communication can permit the pressures in each of the chambers 30 to reach an equilibrium. Alternatively, one or more of the spacers 16 can include channels, lumens 38 and/or a ridged external surface to permit the communication between chambers 30.
An embodiment of the ultrasound assembly 10 does not include a chamber 30 between the elongated body 12 and the internal side 24 of the ultrasound transducer 20 as illustrated in
The ultrasound assembly 10 of
A utility lumen 38 extends through the elongated body 12. The utility lumen 38 can be sized to receive a guidewire, to deliver therapeutic media including drugs, medication, microbubbles and other compounds which provide a therapeutic effect. Although, the elongated body 12 is illustrated as having a single utility lumen 38, the elongated body 12 can include a plurality of lumens 38 or can be solid.
Each of the ultrasound assemblies 10 illustrated in
Each ultrasound assembly 10 discussed and/or suggested above can include an assembly 10 sheath.
A volume between the assembly sheath 44 and the ultrasound transducer 20 can contain a binding medium 42 as illustrated in
Each of the ultrasound assemblies 10 illustrated above show the elongated body 12 extending outward from the ultrasound assembly 10. However, the elongated body 12 can be trimmed to provide an elongated body 12 which is flush with one or more sides of the elongated body 12. Additionally, a sensor such as a temperature sensor can be positioned in the binding medium 42 associated with any of the above ultrasound assemblies 10.
The collar 32 can be integral with the spacers 16 as illustrated in
The catheter includes a catheter body 52 having an external surface 53, a distal portion 54 and a proximal portion 56. The catheter body 52 can include an extension region 58, an assembly region 60 and a terminal region 62. Lumens 38 within the extension region 58, assembly region 60 and terminal region 62 are aligned with one another to provide one or more lumens 38 extending through the entire catheter. These lumens 38 can be sized to receive a guidewire or for the delivery of a therapeutic agent such as a drug.
The extension region 58 includes an extension body 64 having one or more lumens 38. The one or more lumens 38 included in the extension body 64 have cross sectional dimensions approximating the cross section dimensions of the one or more utility lumens 38 of the elongated body 12. The extension body 64 can be used to add length to the catheter. Specifically, the extension body 64 can provide additional length beyond the length provided by the assembly region 60. Accordingly, the extension body 64 can be short or can be eliminated from the catheter body 52. Suitable materials for the extension body 64 include, but are not limited to, polyimide, silicone, and polyurethane.
The terminal region 62 is positioned at the distal tip of the catheter. The terminal region 62 includes a terminal body 66. The terminal body 66 can be solid or include one or more lumens 38 with cross sectional dimensions approximating the cross section dimensions of the one or more utility lumens 38 of the elongated body 12. Suitable materials for the terminal region 62 include, but are not limited to, polyimide, silicone, and polyurethane. The assembly region 60 is the region of the catheter body 52 including any of the ultrasound assemblies 10 discussed and/or suggested above.
A catheter sheath 68 is positioned over the extension region 58, the assembly region 60 and the terminal region 62 so as to define a portion of the external surface 53 of the catheter body 52. The catheter sheath 68 can serve to immobilize the extension region 58, the assembly region 60 and the terminal region 62 relative to one another. The catheter sheath 68 is optional and can be removed from the catheter body 52.
The volume between the ultrasound assembly 10 and the extension body 64 can contain a binding medium 42. Such binding media can serve to couple the extension region 58, the assembly region 60 and the terminal region 62 together. Suitable materials for the catheter sheath 68 include, but are not limited to polyethylene, polyurethane, and polyimide. The thickness of the catheter sheath 68 material is preferably 0.001″ to 0.020″, more preferably 0.004″ to 0.010″ and most preferably 0.006″ to 0.008″.
As illustrated in
The first binding medium 42A can also be positioned adjacent to the external side 22 of the ultrasound transducer 20 as illustrated in
As illustrated in
The first binding medium 42A and the second binding medium 42B can be the same or different. When the second binding medium 42B is different than the first binding medium 42A, the second binding medium 42B is preferably harder than the first binding medium 42A. A harder binding medium 42 typically transmits ultrasound energy more efficiently than a softer binding medium 42. As a result, the hardness of the second binding medium 42B can preserve the ultrasound transmitting efficiency of the catheter. Additionally, the softness of the first binding medium 42A provides the catheter with additional flexibility. As a result, the choices of the first and second binding media effect both the flexibility and the ultrasound transmission efficiency of the catheter.
The second binding medium 42B is preferably at least 2 times harder than the first binding medium 42A and more preferably from about 3 to about 5 times harder than the first binding medium 42A. The first binding medium 42A preferably has a hardness of at least about 10 Shore D, more preferably from about 15 to about 80 Shore D and most preferably from about 20 to about 40 Shore D. The second binding medium 42B preferably has a hardness of at least about 60 Shore D, more preferably from about 65 to about 120 Shore D and most preferably from about 80 to about 100 Shore D.
As described above, any of the ultrasound assemblies 10 described and/or suggested above can be included in a catheter according to the present invention.
The catheter of
Two or more of the first, second and third binding media can be the same or they can all be different. In a preferred embodiment, the first and second binding media are the same while the third binding medium 42C transmits is harder than the first and second binding media. Accordingly, when the first and second binding media are the same, the third binding media is preferably harder than the first binding medium 42A. Preferably, the first binding medium 42A is also more flexible than the third binding medium 42C. Further, the third binding medium 42C is preferably at least 2 times harder than the first binding medium 42A and more preferably from about 3 to about 5 times harder than the first binding medium 42A. Additionally, the first binding medium 42C preferably has a hardness of at least about 10 Shore D, more preferably from about 15 to about 80 Shore D and most preferably from about 20 to about 40 Shore D. The third binding medium 42B preferably has a hardness of at least about 60 Shore D, more preferably from about 65 to about 120 Shore D and most preferably from about 80 to about 100 Shore D. In another preferred embodiment, the second and third binding media are each harder than the first binding medium 42A. In another preferred embodiment, the second and third binding media are the same and are harder than the first binding medium 42A.
Two or more of the first, second and third binding media can be the same or they can all be different. The second binding medium 42B preferably transmits ultrasound energy more efficiently than the first binding medium 42A. Further, the first binding medium 42A is preferably more flexible than the second binding medium 42B. The first and second binding media preferably have the hardness relationships and levels described with respect to the first and second binding media of
The catheter can include two or more ultrasound assemblies 10 as illustrated in
Two or more ultrasound assemblies 10 can share a member 18 as illustrated in
As illustrated in
As illustrated in
In
In
The methods described in
As illustrated in
As illustrated in
When the quantity of binding medium 42 precursor delivered fills the volume adjacent to the external side 22 of the ultrasound transducer 20, a second binding medium 42B precursor can be delivered into the volumes adjacent to the ends of the ultrasound transducer 20 as illustrated in
Once the binding media delivered above have solidified, the catheter sheath 68 can be removed from the catheter body 52. Additionally, once a chamber 30 is formed, a fluid low acoustic impedance medium can be delivered into the chamber 30. A low acoustic impedance medium preferably has an acoustic impedance less than about 1.7 Megarayls, more preferably of about 0-0.7 Megarayls and most preferably from 0-0.4 Megarayls. As described above, suitable low acoustic impedance media include, but are not limited to, helium, argon, air and nitrogen. These media can be delivered into the chamber 30 during or after the media solidification process using an injection device such as a hypodermic needle 70. Similar techniques can be used to draw a vacuum within the chamber 30. Solid low acoustic impedance media such as silicones and rubbers can be positioned within the chamber 30 during the formation of the ultrasound assembly 10.
The methods for forming a catheter described with respect to
When the ultrasound assembly 10 or catheter includes multiple ultrasound transducers 20, the methods for forming the ultrasound assembly 10 or catheter can include matching the resonant frequencies of the ultrasound transducers 20. For instance, the ultrasound transducers 20 can be selected such that any member of the plurality of ultrasound transducers 20 has a resonant frequency within about 10% of the resonant frequency of any other ultrasound transducer 20. More preferably, the ultrasound transducers 20 are selected such that any one has a resonant frequency within about 3%, even more preferably within about 1% and most preferably within about 0.5% of any other ultrasound transducer 20 in the plurality of ultrasound transducers 20. The selected ultrasound transducers 20 are then used to form an ultrasound assembly 10 or catheter.
The matching of the ultrasound transducers 20 allows the ultrasound transducers to be concurrently driven at a single frequency while reducing the inefficiencies associated with driving ultrasound transducers 20 at a frequency which is significantly different than their resonant frequency. Since the ultrasound transducers 20 can be driven at a single frequency, the matching the resonant frequencies of the ultrasound transducers 20 is preferred when the plurality of ultrasound transducers 20 are connected in parallel or in series.
The electrical connections for driving the one or more ultrasound transducers 20 can be done at various stages during the assembly of the catheter and/or ultrasound assembly 10. For instance, electrical wires can be coupled with the ultrasound transducers 20 before the ultrasound transducers 20 are positioned over the elongated body. Additionally, the electrical wires can be coupled with the ultrasound transducers 20 after the ultrasound transducers 20 are in position over the elongated body. Further, electrical connections can be made alternating with positioning the ultrasound transducers 20 over the elongated body.
Alternatively, one or more electrical wires can be positioned along the elongated body before the ultrasound transducers 20 are positioned over the elongated body. One or more ultrasound transducers 20 can then be slid over the elongated body such that the one or more electrical wires contact the inner side of the ultrasound transducers 20. The contact between the ultrasound transducers 20 and the electrical wire can serve as the electrical connection to the one or more ultrasound transducers 20. When a catheter or ultrasound assembly 10 includes more than one ultrasound transducer 20, the ultrasound transducers 20 can be connected in parallel, in series or independently connected. Wires extending from the one or more ultrasound transducers 20 can be threaded up through one or more lumens 38 in the extension body 64.
During the formation of the catheter and/or formation of the ultrasound assemblies 10, one or more sensors can be included in any of the media described above. The sensor can be positioned within a volume before a medium is delivered into the volume. Alternatively, the sensor can be delivered into a binding medium 42 precursor while the binding medium 42 precursor is in a flowable state. Wires extending from the one or more sensors can be threaded up through one or more lumens 38 in the extension body 64. Suitable sensors for use with the catheter include, but are not limited to, a temperature sensor. When a catheter includes one or more temperature sensors, the temperature sensor is preferably positioned adjacent to the external side 22 of an ultrasound transducer 20. Specifically, the one or more temperature sensors are preferably positioned in a volume between the external side 22 of the ultrasound transducer 20 and the external surface 53 of the catheter body 52.
The solidification of the binding medium 42 precursors can occur concurrently or independently of one another. As discussed with respect to
Binding medium 42 precursors for use with the catheters and ultrasound assemblies 10 discussed above are preferably flowable to optimize delivery into a desired volume. These precursors preferably solidify to a binding medium 42 having a reduced flowability. These precursors more preferably solidify to a binding medium 42 having a reduced flowability and an increased degree of adhesiveness. This solidification can occur through mechanisms including, but not limited to, cooling, setting and curing. Suitable binding media precursors and/or binding media include, but are not limited to, adhesives, epoxies, polymers, plastics, rubbers. Examples of suitable binding media with different degrees of hardness are EPOTEK 310 having a hardness of about 22 Shore D and HYSOL 3561 and 2939 having a hardness of about 85 Shore D. The binding media to be used can be selected for its particular hardness. Alternatively, binding media, such as epoxies, cure to a different hardness based on the component ratio in the binding media. The component ratio can be adjusted to achieve the desired hardness.
The binding media adjacent to the external side 22 of the ultrasound transducer 20 and/or adjacent to the ends of the ultrasound transducer 20 preferably has an acoustic impedance of about 1-20 Megarayls, more preferably about 1.3-10 Megarayls and most preferably about 4-8 Megarayls. As described above, the low acoustic impedance medium contained within the chambers preferably has an acoustic impedance less than about 1.7 Megarayls, more preferably of about 0-0.7 Megarayls and most preferably from 0-0.4 Megarayls. Further, the ratio of the acoustic impedances for the binding medium adjacent to the external side and/or adjacent ends the of the ultrasound transducer 20 measured relative to the acoustic impedance of the low acoustic impedance medium contained within the chambers is preferably at least 1.5:1, more preferably at least 2:1 and most preferably at least 4:1. Additionally the ratio is preferably 1.5:1 to 10,000:1, more preferably about 1.5:1 to 100:1 and most preferably 1.5:1 to 4:1.
The electrical coupling 74 includes an autotransformer 76 for adjusting the characteristic impedance of the catheter to match the impedance of an amplifier included in the catheter control system. For instance, if the amplifier has an input impedance of 50 ohms and the catheter has a characteristic impedance of 40 ohms, the addition of the autotransformer can provide the catheter with a characteristic impedance of about 50 ohms. The matched impedance serves to increase the efficiency of the catheter system.
Because each catheter can have a different characteristic impedance, the windings on the autotransformer can be adjusted to match the particular catheter of interest. As a result, a method of assembling a catheter can include the step of providing an autotransformer which matches the characteristic impedance of the catheter to the characteristic impedance of a component in a catheter control system.
The electrical coupling also includes catheter identification electronics 78. The catheter identification electronics 78 indicate to the catheter control system what frequency the catheter should be driven. For instance, the catheter identification electronics 78 can be one or more resistors. The catheter control system can include logic for identifying the resistance. This resistance can be associated with a catheter of a particular frequency. The logic can identify the particular frequency of the catheter and can then cause the catheter to be driven at the indicated frequency. A computer chip is another example of suitable catheter identification electronics 78. The computer chip can produce signals indicating the frequency of the catheter to the catheter control system. In response, the catheter control system can drive the catheter at the appropriate frequency.
A catheter according to the present invention can be used by itself or can be used in conjunction with a sheath 82 as illustrated in
The catheter can be rotated or moved within the sheath 82 as illustrated by the arrow labeled A. The movement of the catheter within the sheath 82 can be caused by manipulating the proximal portion of the catheter body 52 while holding the sheath proximal end 84 stationary. Although not illustrated, the sheath distal end 86 can include on or more temperature sensors.
As illustrated in
The drug delivery ports 94 are positioned close enough to achieve a substantially even flow of drug solution around the circumference of the sheath 82. The proximity of adjacent drug delivery ports 94 can be changed by changing the density of drug delivery ports 94 along the drug delivery lumen 92 or by changing the number of windings of the drug delivery lumen 92 around the energy delivery section 90. Suitable displacement between adjacent drug delivery ports 94 includes, but is not limited to, from 0.1″ to 1.0″, preferable 0.2″ to 0.6″.
The size of the drug delivery ports 94 can be the same or change along the length of the drug delivery lumen 92. For instance, the size of the drug delivery ports 94 distally positioned on the drug delivery section can be larger than the size of the drug delivery ports 94 which are proximally positioned on the drug delivery section. The increase in sizes of the drug delivery ports 94 can be designed to produce similar flowrates of drug solution through each drug delivery port 94. This similar flowrate increases the uniformity of drug solution flowrate along the length of the sheath 82. When the drug delivery ports 94 have similar sizes along the length of the drug delivery lumen 92, a suitable size for a drug delivery port includes, but is not limited to 0.0005″ to 0.0050″. When the size of the drug delivery ports 94 changes along the length of the drug delivery lumen 92, suitable sizes for proximally positioned drug delivery ports 94 includes, but is not limited to from 0.0001″ to 0.005″ and suitable sizes for distally positioned drug delivery ports 94 includes, but is not limited to, 0.0005″ to 0.0020″. The increase in size between adjacent drug delivery ports 94 can be substantially uniform between or along the drug delivery lumen 92. The dimensional increase of the drug delivery ports 94 is dependent upon material and diameter of the drug delivery lumen 92. The drug delivery ports 94 can be formed by burnt into the sheath 82 with a laser.
Uniformity of the drug solution flow along the length of the sheath 82 can also be increased by increasing the density of the drug delivery ports 94 toward the distal end of the drug delivery lumen 92.
The drug delivery ports 94 can optionally be closed slits in the sheath 82. The slits can have a straight or arcuate shape. When the dug delivery lumen 92 contains drug solution, the slits remain closed until the pressure within the drug delivery lumen 92 exceeds a threshold pressure. As the pressure within the drug delivery lumen 92 builds the pressure on each of the slits will be approximately uniform. Once, the threshold pressure is reached, the uniform pressure will result in the slits opening almost simultaneously and cause a nearly uniform flow of drug solution out of all the slits. When the pressure within the drug delivery lumen 92 falls below the threshold pressure, the slits close and prevent delivery of additional drug solution. The stiffer the material used to construct the drug deliver lumen 38, the higher the threshold pressure required to open the slit shaped drug delivery ports 94. The slit shape can also prevent the drug delivery ports 94 from opening when exposed to low pressures from outside the sheath 82. As a result, slit shaped drug delivery ports 94 can maximize control of drug delivery.
In
In
In
In operation, the ultrasound elements 112 and drug delivery ports 114 can be positioned adjacent a large lesion 118 in a vessel 120 as illustrated in
The average power required to activate an ultrasound element 112 is proportional to the activated area of the ultrasound element 112. Hence, a 2-cm long element requires approximately twice as much power as a 1-cm long element of similar shape and diameter. As the power increases, the diameter of the electrical wires that bring electrical energy to the ultrasound elements 112 must also increase. This requires an increase in catheter diameter that in turn reduces flexibility and restricts use of the catheter 110 in larger vessels.
These difficulties are solved by the present invention that creates a distribution of smaller ultrasound elements 112. The ultrasound elements 112 are sized small enough so that they in combination with the catheter 110 provide a flexible structure that can be moved down a tortuous vein tree to the site of the lesion 118 or to any vessel in which there is a lengthy lesion 118 to be treated. Additionally, the ultrasound elements 112 are small enough that each individual ultrasound element 112, if excited individually, does not take an inordinate amount of power through the wires which supply power to the catheter 110. The ultrasound elements 112 are positioned to reduce dead space between the ultrasound elements 112. This provides some overlap in the radiation patterns that emit from each of the ultrasound elements 112 to maximize the enhancement effect. There is also a proximity between the ultrasound element 112 and the drug delivery ports 114 so that the drug emitted proximal or next to the catheter 110 is then affected by a nearby source of ultrasound energy. However, the drug delivery ports 114 do not need to be correlated with a particular ultrasound element 112 and there need be no relationship between the number of drug delivery ports 114 and the number of ultrasound elements 112.
The ultrasound energy can be generated at an ultrasound energy source located external to the body and transmitted via wire to the ultrasound elements. Ultrasound can also be internally generated from electrical power delivered to the ultrasound elements from an electrical energy source. A suitable example of an ultrasound element for internal generation of ultrasound energy includes, but is not limited to, a piezoelectric ceramic oscillators. The ultrasound elements can be shaped as a cylinder, a hollow cylinder and a disk which are concentric with the catheter. The ultrasound elements can also be an array of smaller ultrasound elements or a thin plate positioned within the body of the catheter. Similarly, a single ultrasound element can be composed of several smaller ultrasound elements.
The individual ultrasound elements 112 can each be individually powered. When the catheter includes N ultrasound elements, the catheter body must include 2N wires to individually power N ultrasound elements 112. The individual ultrasound elements 112 can also be electrically coupled in serial or in parallel as illustrated in
As illustrated in
As illustrated in
The temperature sensors 113 can be electrically connected as illustrated in
Each temperature sensor 113 can also be independently wired. A catheter 110 including N temperature sensors 113 which are independently wired will require 2N wires to pass the length of the catheter.
The catheter flexibility can also be improved by using fiber optic based temperature sensors. The flexibility can be improved because only N fiber optics need to be included in the catheter to sense the temperature at N temperature sensors.
The temperature sensors 113 do not need to be correlated with the ultrasound elements 112. For instance, the catheter 110 can include a temperature sensor 113 which is positioned to provide a signal indicating the temperature of the portion of the lumen being treated. For instance, the temperature sensor 113 can be positioned between the central two ultrasound elements. The ultrasound output from the ultrasound elements 112 can be manually or automatically adjusted in response to the signal from the temperature sensor 113.
The drug delivery ports 114 can be coupled with a common lumen 125 as illustrated in
The catheter 110 can be used in various body structures and body lumens including, but not limited to, the pancreas, sinuses, esophagus, rectum, gastrointestinal vessels and urological vessels. The catheter 110 is selected from a variety of different sizes, diameter and length, depending on the type and location of the lesion 118. An active length of catheter 110 is defined by the number and spacing of the ultrasound elements 112 and drug delivery ports 114 at the distal end. The number of ultrasound elements 112 depends on the length of the vessel being treated. Suitable numbers of ultrasound elements include, but are not limited to 2-10, 2-8 and 4-6. Each of the ultrasound elements 112 can be from one millimeter in length to up to a half centimeter in length. Other dimensions can also be used. The spacing between ultrasound elements 112 can be approximately equal to the length of each ultrasound element 112. If one ultrasound element 112 has a length L, a second ultrasound element 112 can be spaced up to three L lengths away from the first ultrasound element 112. Suitable L include, bur are not limited to 0.2-2 cm, 0.2-1.2 cm and 0.3-0.7 cm.
The catheter 110 can be constructed to overcome the reduced flexibility which results from the multiple ultrasound elements 112. As illustrated in
The ultrasound elements 112 can be positioned internally or externally to catheter 110, and can have any number of different geometric designs. Suitable, geometric designs include, but are not limited to a band which lies flush with the circumference of the catheter. Additionally, ultrasound elements 112 can be designed provide any desired directionality of ultrasound.
The catheter 110 can be coupled with an open or closed loop feedback system. Referring now to
With the use of the temperature sensors 113 and the feedback control system, the tissue adjacent to the ultrasound elements 112 can be maintained at a desired temperature for a selected period of time. Each ultrasound element 112 is connected to resources which generate an independent output. The output maintains a selected energy at each ultrasound element 112 for a selected length of time.
Power delivered to the ultrasound elements 112 is measured by the power calculation device 144. The power can then be displayed at user interface and display 146. Signals representative of power and impedance values are received by the processing unit 142.
A control signal is generated by the processing unit 142 that is proportional to the difference between an actual measured value, and a desired value. The control signal is used by power circuits 147 to adjust the power output in an appropriate amount in order to maintain the temperature at each ultrasound element 112 within a desired range.
The temperatures detected at the temperature sensors 113 provide feedback for maintaining the desired temperature range. The temperature at each temperature sensor 112 can be used as safety devices to interrupt the delivery of energy when maximum pre-set temperatures are exceeded. The temperature at each ultrasound sensor 112 is measured at temperature measurement device 148, and can be displayed at user interface and display 146. A temperature control signal is generated by the processing unit 142 that is proportional to the difference between an actual measured temperature and a desired temperature. The temperature control signal is used to determine the desired power. For instance, when the control signal exceeds a pre-determined level, the desired power supplied to a particular ultrasound element can be reduced or turned off. Similarly, when the control signal falls below a pre-determined level, the desired power supplied to a particular ultrasound element 112 can be increased or turned on.
The processing unit 142 can be a digital or analog controller, or a computer with software. When the processing unit 142 is a computer it can include a CPU coupled through a system bus. On this system can be a keyboard, a disk drive, or other non-volatile memory systems, a display, and other peripherals, as are known in the art. Also coupled to the bus is a program memory and a data memory.
User interface and display 146 includes operator controls and a display.
The output of the temperature sensors 113 is used by the processing unit 142 to maintain a selected temperature range at each temperature sensor 113. A profile of the power delivered to each ultrasound element 112 can be incorporated in the processing unit 142 and a preset amount of energy to be delivered may also be profiled.
Circuitry, software and feedback to the processing unit 142 result in process control, and the maintenance of the selected power setting that is independent of changes in voltage or current, and used to change, (i) the selected power setting, (ii) the duty cycle (on-off time), (iii) bipolar or monopolar energy delivery and (iv) fluid delivery, including flow rate and pressure. These process variables are controlled and varied, while maintaining the desired delivery of power independent of changes in voltage or current, based on temperatures monitored at the temperature sensor 113.
The catheter 110 is guided along the artery or vein to the lesion site by fluoroscopy. Radio opaque markers may be used with the catheter 110 next to each of the ultrasound elements 112, or in the case of certain piezoelectric elements 112, the ultrasound elements 112 themselves are radio opaque and readily identified and also readily identify the site of the adjacent drug port 114. The catheter 110 is advanced through the vessel with the assistance of a guidewire. The catheter can be advanced until each of the ultrasound elements are adjacent the lesion or until only a portion of the ultrasound elements are adjacent the lesion. The drug is hydraulically delivered through the lumen to the drug delivery ports 114. The ultrasound elements 112 are then all turned on together, sequenced or multiplexed according to the preferred treatment by the physician. The feedback control system is then engaged to control the temperature of within the vessel. The catheter 110 remains in place for the treatment period and the drug can be continually infused with the ultrasound elements 112 on, off, partially on, or partially off. After a section of the vessel is treated, the catheter can be advanced to treat additional untreated portions of the vessel. The ultrasound elements which are used to treat the additional untreated portion can be different from the ultrasound elements used during the initial treatment(s). When the desired clinical result is obtain, as verified by fluoroscopy, the catheter 110 is removed.
Segmentation of ultrasound elements 112 greatly reduces the required amount of a lumen of the catheter 110 that is used for segment wiring, increases the flexibility of the catheter 110, and permits radiation of a long lesion 118. When a single continuous length ultrasound element is used the power requirements necessitate the use of thick wires. This is eliminated with the use of ultrasound elements 112 in segment form. Replacement of one large wire by multiple wires of equivalent cross-sectional area or a cumulated cross-section area is more flexible and also avoids having to excite entirely a long ultrasound element, smaller ultrasound elements 112 that are segmented are used. Therefore, a fraction of the power at any one time is needed, depending on the number of ultrasound elements 112 activated.
While the present invention is disclosed by reference to the preferred embodiments and examples detailed above, it is to be understood that these examples are intended in an illustrative rather than limiting sense, as it is contemplated that modifications and combinations will readily occur to those skilled in the art, which modifications and combinations will be within the spirit of the invention and the scope of the appended claims.
This application is a continuation of U.S. patent application Ser. No. 10/383,292, filed Mar. 6, 2003, now abandoned, which is a continuation of U.S. patent application Ser. No. 09/375,162, filed Aug. 16, 1999, now U.S. Pat. No. 6,582,392, which is a continuation-in-part of U.S. patent application Ser. No. 09/129,980, filed Aug. 5, 1998, now U.S. Pat. No. 6,210,356, a continuation-in-part of U.S. patent application Ser. No. 09/107,078, filed Jun. 29, 1998, now 6,723,063, and a continuation-in-part of U.S. patent application Ser. No. 09/071,285, filed May 1, 1998, now U.S. Pat. No. 6,001,069, which claims priority to U.S. Provisional Application No. 60/045,268, filed May 1, 1997. The entire disclosure of these priority applications is hereby incorporated by reference herein in its entirety.
Number | Name | Date | Kind |
---|---|---|---|
2961382 | Singher et al. | Nov 1960 | A |
3430625 | McLeod, Jr. | Mar 1969 | A |
3433226 | Boyd | Mar 1969 | A |
3565062 | Kuris | Feb 1971 | A |
3827115 | Bom | Aug 1974 | A |
3941122 | Jones | Mar 1976 | A |
4027659 | Slingluff | Jun 1977 | A |
4040414 | Suroff | Aug 1977 | A |
4192294 | Gekhman et al. | Mar 1980 | A |
4309989 | Fahim | Jan 1982 | A |
4319580 | Colley et al. | Mar 1982 | A |
4354502 | Colley et al. | Oct 1982 | A |
4466442 | Hilmann et al. | Aug 1984 | A |
4512762 | Spears | Apr 1985 | A |
4531943 | Van Tassel et al. | Jul 1985 | A |
4549533 | Cain et al. | Oct 1985 | A |
4573470 | Samson et al. | Mar 1986 | A |
4582067 | Silverstein et al. | Apr 1986 | A |
4657543 | Langer et al. | Apr 1987 | A |
4657756 | Rasor et al. | Apr 1987 | A |
4692139 | Stiles | Sep 1987 | A |
4697595 | Breyer et al. | Oct 1987 | A |
4698058 | Greenfeld et al. | Oct 1987 | A |
4699150 | Kawabuchi et al. | Oct 1987 | A |
4710192 | Liotta et al. | Dec 1987 | A |
4717379 | Ekholmer | Jan 1988 | A |
4729384 | Bazenet | Mar 1988 | A |
4750902 | Wuchinich et al. | Jun 1988 | A |
4762915 | Kung et al. | Aug 1988 | A |
4767402 | Kost et al. | Aug 1988 | A |
4769017 | Fath et al. | Sep 1988 | A |
4772594 | Hashimoto et al. | Sep 1988 | A |
4774958 | Feinstein | Oct 1988 | A |
4780212 | Kost et al. | Oct 1988 | A |
4781677 | Wilcox | Nov 1988 | A |
4795439 | Guest | Jan 1989 | A |
4797285 | Barenholz et al. | Jan 1989 | A |
4808153 | Parisi | Feb 1989 | A |
4821740 | Tachibana et al. | Apr 1989 | A |
4844882 | Widder et al. | Jul 1989 | A |
4870953 | DonMicheal et al. | Oct 1989 | A |
4877031 | Conway et al. | Oct 1989 | A |
4900540 | Ryan et al. | Feb 1990 | A |
4917088 | Crittenden | Apr 1990 | A |
4917102 | Miller et al. | Apr 1990 | A |
4920954 | Alliger et al. | May 1990 | A |
4924863 | Sterzer | May 1990 | A |
4936281 | Stasz | Jun 1990 | A |
4947852 | Nassi et al. | Aug 1990 | A |
4948587 | Kost et al. | Aug 1990 | A |
4953565 | Tachibana et al. | Sep 1990 | A |
4955863 | Walker et al. | Sep 1990 | A |
4969470 | Mohl et al. | Nov 1990 | A |
4971991 | Umemura et al. | Nov 1990 | A |
4992257 | Bonnett et al. | Feb 1991 | A |
4995865 | Gahara et al. | Feb 1991 | A |
5007898 | Rosenbluth et al. | Apr 1991 | A |
5021044 | Sharkawy | Jun 1991 | A |
5040537 | Katakura | Aug 1991 | A |
5053044 | Mueller et al. | Oct 1991 | A |
5069664 | Guess et al. | Dec 1991 | A |
5081993 | Kitney et al. | Jan 1992 | A |
5085662 | Willard | Feb 1992 | A |
5088499 | Unger | Feb 1992 | A |
5117831 | Jang et al. | Jun 1992 | A |
5121749 | Nassi et al. | Jun 1992 | A |
5125410 | Misono et al. | Jun 1992 | A |
5149319 | Unger | Sep 1992 | A |
5156050 | Schmid et al. | Oct 1992 | A |
5158071 | Umemura et al. | Oct 1992 | A |
5163421 | Bernstein et al. | Nov 1992 | A |
5163436 | Hashimoto et al. | Nov 1992 | A |
5181920 | Mueller et al. | Jan 1993 | A |
5190766 | Ishihara | Mar 1993 | A |
5197946 | Tachibana | Mar 1993 | A |
5207214 | Romano | May 1993 | A |
5209720 | Unger | May 1993 | A |
5215680 | D'Arrigo | Jun 1993 | A |
5216130 | Line et al. | Jun 1993 | A |
5250034 | Appling et al. | Oct 1993 | A |
5267954 | Nita | Dec 1993 | A |
5267985 | Shimada et al. | Dec 1993 | A |
5269291 | Carter | Dec 1993 | A |
5269297 | Weng et al. | Dec 1993 | A |
5277913 | Thompson et al. | Jan 1994 | A |
5279546 | Mische et al. | Jan 1994 | A |
5282785 | Shapland et al. | Feb 1994 | A |
5286254 | Shapland et al. | Feb 1994 | A |
5295484 | Marcus et al. | Mar 1994 | A |
5295958 | Shturman | Mar 1994 | A |
5304115 | Pflueger et al. | Apr 1994 | A |
5307816 | Hashimoto et al. | May 1994 | A |
5315998 | Tachibana et al. | May 1994 | A |
5318014 | Carter | Jun 1994 | A |
5323769 | Bommannan et al. | Jun 1994 | A |
5324225 | Passafaro et al. | Jun 1994 | A |
5327891 | Rammler | Jul 1994 | A |
5328470 | Nabel et al. | Jul 1994 | A |
5342292 | Nita et al. | Aug 1994 | A |
5344395 | Whalen et al. | Sep 1994 | A |
5344435 | Tumer et al. | Sep 1994 | A |
5345940 | Seward et al. | Sep 1994 | A |
5353798 | Sieben | Oct 1994 | A |
5354279 | Hofling | Oct 1994 | A |
5362309 | Carter | Nov 1994 | A |
5363853 | Lieber et al. | Nov 1994 | A |
5364344 | Beattie et al. | Nov 1994 | A |
5368036 | Tanaka et al. | Nov 1994 | A |
5368557 | Nita et al. | Nov 1994 | A |
5368558 | Nita | Nov 1994 | A |
5378230 | Mahurkar | Jan 1995 | A |
5380273 | Dubrul et al. | Jan 1995 | A |
5385148 | Lesh et al. | Jan 1995 | A |
5390678 | Gesswein et al. | Feb 1995 | A |
5399158 | Lauer et al. | Mar 1995 | A |
5401237 | Tachibana et al. | Mar 1995 | A |
5409458 | Khairkhahan et al. | Apr 1995 | A |
5415636 | Forman | May 1995 | A |
5419763 | Hildebrand | May 1995 | A |
5421338 | Crowley et al. | Jun 1995 | A |
5423797 | Adrian et al. | Jun 1995 | A |
5431663 | Carter | Jul 1995 | A |
5440914 | Tachibana et al. | Aug 1995 | A |
5445155 | Sieben | Aug 1995 | A |
5447509 | Mills et al. | Sep 1995 | A |
5447510 | Jensen | Sep 1995 | A |
5456259 | Barlow et al. | Oct 1995 | A |
5458568 | Racchini et al. | Oct 1995 | A |
5462523 | Samson et al. | Oct 1995 | A |
5465726 | Dickinson et al. | Nov 1995 | A |
5474530 | Passafaro et al. | Dec 1995 | A |
5474531 | Carter | Dec 1995 | A |
5489279 | Meserol | Feb 1996 | A |
5498238 | Shapland et al. | Mar 1996 | A |
5509896 | Carter | Apr 1996 | A |
5514092 | Forman et al. | May 1996 | A |
5520189 | Malinowski et al. | May 1996 | A |
5533986 | Mottola et al. | Jul 1996 | A |
5542917 | Nita et al. | Aug 1996 | A |
5542935 | Unger et al. | Aug 1996 | A |
5558092 | Unger et al. | Sep 1996 | A |
5558642 | Schweich, Jr. et al. | Sep 1996 | A |
5567687 | Magda et al. | Oct 1996 | A |
5569197 | Helmus et al. | Oct 1996 | A |
5569198 | Racchini | Oct 1996 | A |
5580575 | Unger et al. | Dec 1996 | A |
5582586 | Tachibana et al. | Dec 1996 | A |
5585112 | Unger et al. | Dec 1996 | A |
5586982 | Abela | Dec 1996 | A |
5588432 | Crowley | Dec 1996 | A |
5588962 | Nicholas et al. | Dec 1996 | A |
5594136 | Sessler et al. | Jan 1997 | A |
5599923 | Sessler et al. | Feb 1997 | A |
5603327 | Eberle et al. | Feb 1997 | A |
5603694 | Brown et al. | Feb 1997 | A |
5606974 | Castellano et al. | Mar 1997 | A |
5609574 | Kaplan et al. | Mar 1997 | A |
5616342 | Lyons | Apr 1997 | A |
5617851 | Lipkovker | Apr 1997 | A |
5618275 | Bock | Apr 1997 | A |
5620409 | Gans et al. | Apr 1997 | A |
5620479 | Diederich | Apr 1997 | A |
5624382 | Oppelt | Apr 1997 | A |
5628728 | Tachibana et al. | May 1997 | A |
5628730 | Shapland | May 1997 | A |
5630837 | Crowley | May 1997 | A |
5632970 | Malinowski et al. | May 1997 | A |
5648098 | Porter | Jul 1997 | A |
5656016 | Ogden | Aug 1997 | A |
5660180 | Malinowski et al. | Aug 1997 | A |
5660909 | Tachibana et al. | Aug 1997 | A |
5663327 | Tarabo et al. | Sep 1997 | A |
5665076 | Roth et al. | Sep 1997 | A |
5681296 | Toshinobu | Oct 1997 | A |
5695460 | Siegel et al. | Dec 1997 | A |
5697897 | Buchholtz et al. | Dec 1997 | A |
5707608 | Liu | Jan 1998 | A |
5713848 | Dubrul et al. | Feb 1998 | A |
5715825 | Crowley | Feb 1998 | A |
5718921 | Mathiowitz et al. | Feb 1998 | A |
5720710 | Tachibana et al. | Feb 1998 | A |
5724976 | Hirama et al. | Mar 1998 | A |
5725494 | Brisken | Mar 1998 | A |
5728062 | Brisken | Mar 1998 | A |
5733572 | Unger et al. | Mar 1998 | A |
5735811 | Brisken | Apr 1998 | A |
5752930 | Baudino et al. | May 1998 | A |
5766902 | Craig et al. | Jun 1998 | A |
5770222 | Unger et al. | Jun 1998 | A |
5772632 | Forman | Jun 1998 | A |
5776429 | Unger et al. | Jul 1998 | A |
5779673 | Roth et al. | Jul 1998 | A |
5817048 | Lawandy | Oct 1998 | A |
5823962 | Lerch et al. | Oct 1998 | A |
5827203 | Nita | Oct 1998 | A |
5834880 | Lewandowski et al. | Nov 1998 | A |
5836896 | Rosenschein | Nov 1998 | A |
5840031 | Crowley | Nov 1998 | A |
5843109 | Mehta et al. | Dec 1998 | A |
5846218 | Brisken et al. | Dec 1998 | A |
5849727 | Porter et al. | Dec 1998 | A |
5876345 | Eaton et al. | Mar 1999 | A |
5876989 | Berg et al. | Mar 1999 | A |
5895356 | Andrus | Apr 1999 | A |
5895358 | Becker et al. | Apr 1999 | A |
5895398 | Wensel et al. | Apr 1999 | A |
5897503 | Lyon et al. | Apr 1999 | A |
5916192 | Nita et al. | Jun 1999 | A |
5922687 | Mann et al. | Jul 1999 | A |
5925016 | Chornenky et al. | Jul 1999 | A |
5928186 | Homsma et al. | Jul 1999 | A |
5938595 | Glass et al. | Aug 1999 | A |
5941868 | Kaplan et al. | Aug 1999 | A |
5957851 | Hossack | Sep 1999 | A |
5957882 | Nita et al. | Sep 1999 | A |
5971949 | Levin et al. | Oct 1999 | A |
5976120 | Chow et al. | Nov 1999 | A |
5997497 | Nita et al. | Dec 1999 | A |
6001069 | Tachibana et al. | Dec 1999 | A |
6024718 | Chen et al. | Feb 2000 | A |
6030374 | McDaniel | Feb 2000 | A |
6059731 | Seward et al. | May 2000 | A |
6063069 | Cragg et al. | May 2000 | A |
6066123 | Bednarski et al. | May 2000 | A |
6068857 | Weitschies et al. | May 2000 | A |
6088613 | Unger | Jul 2000 | A |
6089573 | Udagawa | Jul 2000 | A |
6096000 | Tachibana et al. | Aug 2000 | A |
6096070 | Ragheb et al. | Aug 2000 | A |
6113558 | Rosenschein et al. | Sep 2000 | A |
6113570 | Siegel et al. | Sep 2000 | A |
6117101 | Diederich et al. | Sep 2000 | A |
6117858 | Porter et al. | Sep 2000 | A |
6120454 | Suorsa et al. | Sep 2000 | A |
6135976 | Tachibana et al. | Oct 2000 | A |
6149596 | Bancroft | Nov 2000 | A |
6149599 | Schlesinger et al. | Nov 2000 | A |
6176842 | Tachibana et al. | Jan 2001 | B1 |
6206831 | Suorsa et al. | Mar 2001 | B1 |
6210356 | Anderson et al. | Apr 2001 | B1 |
6210393 | Brisken | Apr 2001 | B1 |
6221038 | Brisken | Apr 2001 | B1 |
6228046 | Brisken | May 2001 | B1 |
6235024 | Tu | May 2001 | B1 |
6238347 | Nix et al. | May 2001 | B1 |
6245747 | Porter et al. | Jun 2001 | B1 |
6270460 | McCartan et al. | Aug 2001 | B1 |
6277077 | Briskem et al. | Aug 2001 | B1 |
6283920 | Eberie et al. | Sep 2001 | B1 |
6287271 | Dubrul et al. | Sep 2001 | B1 |
6295990 | Lewis et al. | Oct 2001 | B1 |
6296619 | Brisken et al. | Oct 2001 | B1 |
6309370 | Haim et al. | Oct 2001 | B1 |
6312402 | Hansmann | Nov 2001 | B1 |
6346098 | Yock et al. | Feb 2002 | B1 |
6361554 | Brisken | Mar 2002 | B1 |
6372498 | Newman et al. | Apr 2002 | B2 |
6391042 | Cimino | May 2002 | B1 |
6398772 | Bond et al. | Jun 2002 | B1 |
6416740 | Unger | Jul 2002 | B1 |
6425853 | Edwards | Jul 2002 | B1 |
6433464 | Jones | Aug 2002 | B2 |
6461296 | Desai | Oct 2002 | B1 |
6461383 | Gesswein et al. | Oct 2002 | B1 |
6464680 | Briskem et al. | Oct 2002 | B1 |
6471683 | Drasier et al. | Oct 2002 | B2 |
6478765 | Siegel et al. | Nov 2002 | B2 |
6506584 | Chandler et al. | Jan 2003 | B1 |
6508816 | Shadduck | Jan 2003 | B2 |
6524251 | Rabiner et al. | Feb 2003 | B2 |
6524271 | Brisken et al. | Feb 2003 | B2 |
6527761 | Soltesz et al. | Mar 2003 | B1 |
6548047 | Unger | Apr 2003 | B1 |
6551337 | Rabiner et al. | Apr 2003 | B1 |
6558366 | Drasler et al. | May 2003 | B1 |
6562021 | Derbin et al. | May 2003 | B1 |
6565552 | Barbut | May 2003 | B1 |
6575956 | Brisken et al. | Jun 2003 | B1 |
6579277 | Rabiner et al. | Jun 2003 | B1 |
6582392 | Bennett et al. | Jun 2003 | B1 |
6605084 | Acker et al. | Aug 2003 | B2 |
6607502 | Maguire et al. | Aug 2003 | B1 |
6635046 | Barbut | Oct 2003 | B1 |
6645150 | Angelsen et al. | Nov 2003 | B2 |
6647755 | Rabiner et al. | Nov 2003 | B2 |
6652547 | Rabiner et al. | Nov 2003 | B2 |
6652581 | Ding | Nov 2003 | B1 |
6660013 | Rabiner | Dec 2003 | B2 |
6663613 | Evans et al. | Dec 2003 | B1 |
6676626 | Bennett et al. | Jan 2004 | B1 |
6680301 | Berg et al. | Jan 2004 | B2 |
6682502 | Bond et al. | Jan 2004 | B2 |
6689086 | Nita et al. | Feb 2004 | B1 |
6695781 | Rabiner et al. | Feb 2004 | B2 |
6695782 | Ranucci et al. | Feb 2004 | B2 |
6695785 | Brisken et al. | Feb 2004 | B2 |
6723063 | Zhang et al. | Apr 2004 | B1 |
6726698 | Cimino | Apr 2004 | B2 |
6730048 | Hare et al. | May 2004 | B1 |
6733451 | Rabiner et al. | May 2004 | B2 |
6740040 | Mandrusov et al. | May 2004 | B1 |
6767345 | St. Germain et al. | Jul 2004 | B2 |
6794369 | Newman et al. | Sep 2004 | B2 |
6824575 | Otomo et al. | Nov 2004 | B1 |
6830577 | Nash et al. | Dec 2004 | B2 |
6849062 | Kantor | Feb 2005 | B2 |
6855123 | Nita | Feb 2005 | B2 |
6866670 | Rabiner et al. | Mar 2005 | B2 |
6905505 | Dodson, Jr. et al. | Jun 2005 | B2 |
6921371 | Wilson | Jul 2005 | B2 |
6929633 | Evans et al. | Aug 2005 | B2 |
6942620 | Nita et al. | Sep 2005 | B2 |
6945937 | Culp et al. | Sep 2005 | B2 |
6958040 | Oliver et al. | Oct 2005 | B2 |
6958059 | Zadno-Azizi | Oct 2005 | B2 |
6979293 | Hansmann et al. | Dec 2005 | B2 |
6985771 | Fischell et al. | Jan 2006 | B2 |
7137963 | Nita et al. | Nov 2006 | B2 |
7141044 | Gentsler | Nov 2006 | B2 |
7166098 | Steward et al. | Jan 2007 | B1 |
7186246 | Bennett et al. | Mar 2007 | B2 |
7220233 | Nita et al. | May 2007 | B2 |
7309334 | von Hoffmann | Dec 2007 | B2 |
7335180 | Nita et al. | Feb 2008 | B2 |
7341569 | Soltani et al. | Mar 2008 | B2 |
7503895 | Rabiner et al. | Mar 2009 | B2 |
7540852 | Nita et al. | Jun 2009 | B2 |
7567016 | Lu et al. | Jul 2009 | B2 |
7604608 | Nita et al. | Oct 2009 | B2 |
7621902 | Nita et al. | Nov 2009 | B2 |
7758509 | Angelsen et al. | Jul 2010 | B2 |
7771372 | Wilson | Aug 2010 | B2 |
7789830 | Fujita et al. | Sep 2010 | B2 |
7828754 | Abe et al. | Nov 2010 | B2 |
7901359 | Mandrusov et al. | Mar 2011 | B2 |
7914509 | Bennett et al. | Mar 2011 | B2 |
8012092 | Powers et al. | Sep 2011 | B2 |
8062566 | Nita et al. | Nov 2011 | B2 |
8123789 | Khanna | Feb 2012 | B2 |
8152753 | Nita et al. | Apr 2012 | B2 |
20010000791 | Suorsa et al. | May 2001 | A1 |
20010003790 | Ben-Haim et al. | Jun 2001 | A1 |
20010007666 | Hoffman et al. | Jul 2001 | A1 |
20010014775 | Koger et al. | Aug 2001 | A1 |
20010041842 | Eberle et al. | Nov 2001 | A1 |
20010041880 | Brisken et al. | Nov 2001 | A1 |
20010053384 | Greenleaf et al. | Dec 2001 | A1 |
20020032394 | Brisken et al. | Mar 2002 | A1 |
20020045890 | Celliers et al. | Apr 2002 | A1 |
20020052620 | Barbut | May 2002 | A1 |
20020068717 | Borrelli | Jun 2002 | A1 |
20020068869 | Brisken et al. | Jun 2002 | A1 |
20020077550 | Rabiner et al. | Jun 2002 | A1 |
20020082238 | Newman et al. | Jun 2002 | A1 |
20020123787 | Weiss | Sep 2002 | A1 |
20020151792 | Conston et al. | Oct 2002 | A1 |
20020193708 | Thompson et al. | Dec 2002 | A1 |
20030036705 | Hare et al. | Feb 2003 | A1 |
20030040501 | Newman et al. | Feb 2003 | A1 |
20030050662 | Don Michael | Mar 2003 | A1 |
20030065263 | Hare et al. | Apr 2003 | A1 |
20030069525 | Brisken et al. | Apr 2003 | A1 |
20030163147 | Hare et al. | Aug 2003 | A1 |
20030220568 | Hansmann et al. | Nov 2003 | A1 |
20030236539 | Rabiner et al. | Dec 2003 | A1 |
20040001809 | Brisken et al. | Jan 2004 | A1 |
20040019318 | Wilson et al. | Jan 2004 | A1 |
20040024347 | Wilson et al. | Feb 2004 | A1 |
20040039311 | Nita et al. | Feb 2004 | A1 |
20040039329 | Ueberle | Feb 2004 | A1 |
20040049148 | Rodriguez et al. | Mar 2004 | A1 |
20040059313 | Anderson et al. | Mar 2004 | A1 |
20040068189 | Wilson et al. | Apr 2004 | A1 |
20040097996 | Hare et al. | May 2004 | A1 |
20040106847 | Shaw et al. | Jun 2004 | A1 |
20040138570 | Nita et al. | Jul 2004 | A1 |
20040162571 | Rabiner et al. | Aug 2004 | A1 |
20040171981 | Buffen et al. | Sep 2004 | A1 |
20040220514 | Cafferata | Nov 2004 | A1 |
20040236350 | Bolduc et al. | Nov 2004 | A1 |
20040255957 | Cafferata | Dec 2004 | A1 |
20040265393 | Unger et al. | Dec 2004 | A1 |
20050021063 | Hall et al. | Jan 2005 | A1 |
20050027247 | Carrison et al. | Feb 2005 | A1 |
20050043629 | Rabiner et al. | Feb 2005 | A1 |
20050043753 | Rabiner et al. | Feb 2005 | A1 |
20050096669 | Rabiner et al. | May 2005 | A1 |
20050113688 | Nita et al. | May 2005 | A1 |
20050119679 | Rabiner et al. | Jun 2005 | A1 |
20050124877 | Nita et al. | Jun 2005 | A1 |
20050137520 | Rule et al. | Jun 2005 | A1 |
20050187513 | Rabiner et al. | Aug 2005 | A1 |
20050187514 | Rabiner et al. | Aug 2005 | A1 |
20050197619 | Rule et al. | Sep 2005 | A1 |
20050209578 | Evans et al. | Sep 2005 | A1 |
20050215942 | Abrahamson et al. | Sep 2005 | A1 |
20050215946 | Hansmann et al. | Sep 2005 | A1 |
20050216044 | Hong | Sep 2005 | A1 |
20050256410 | Rabiner et al. | Nov 2005 | A1 |
20060069303 | Couvillon | Mar 2006 | A1 |
20060106308 | Hansmann et al. | May 2006 | A1 |
20060173387 | Hansmann et al. | Aug 2006 | A1 |
20060184070 | Hansmann et al. | Aug 2006 | A1 |
20070037119 | Pal et al. | Feb 2007 | A1 |
20070066978 | Schafer et al. | Mar 2007 | A1 |
20070225619 | Rabiner et al. | Sep 2007 | A1 |
20070239027 | Nita | Oct 2007 | A1 |
20070265560 | Soltani et al. | Nov 2007 | A1 |
20080045865 | Kislev | Feb 2008 | A1 |
20080065014 | McCrystle et al. | Mar 2008 | A1 |
20080154181 | Khanna | Jun 2008 | A1 |
20080167602 | Nita et al. | Jul 2008 | A1 |
20080171965 | Soltani et al. | Jul 2008 | A1 |
20080172067 | Nita et al. | Jul 2008 | A1 |
20080194954 | Matsunaga et al. | Aug 2008 | A1 |
20080221506 | Rodriguez et al. | Sep 2008 | A1 |
20080262350 | Abrahamson et al. | Oct 2008 | A1 |
20080306499 | Katoh et al. | Dec 2008 | A1 |
20080319355 | Nita | Dec 2008 | A1 |
20080319376 | Wilcox et al. | Dec 2008 | A1 |
20090018472 | Soltani et al. | Jan 2009 | A1 |
20090112150 | Unger et al. | Apr 2009 | A1 |
20090216246 | Nita et al. | Aug 2009 | A1 |
20100010393 | Duffy et al. | Jan 2010 | A1 |
20100063413 | Volz | Mar 2010 | A1 |
20100063414 | Volz | Mar 2010 | A1 |
20100081934 | Hansmann et al. | Apr 2010 | A1 |
20100204582 | Lu | Aug 2010 | A1 |
20100210940 | Bradley et al. | Aug 2010 | A1 |
20100222715 | Nita | Sep 2010 | A1 |
20100256616 | Katoh et al. | Oct 2010 | A1 |
20100262215 | Gertner | Oct 2010 | A1 |
20100292685 | Katoh et al. | Nov 2010 | A1 |
20110160621 | Nita | Jun 2011 | A1 |
20110201974 | Hansmann et al. | Aug 2011 | A1 |
20110288449 | Schenkengel | Nov 2011 | A1 |
20110313328 | Nita | Dec 2011 | A1 |
20110319927 | Nita | Dec 2011 | A1 |
20120016272 | Nita et al. | Jan 2012 | A1 |
20120041307 | Patel et al. | Feb 2012 | A1 |
20120059285 | Soltani et al. | Mar 2012 | A1 |
20120078140 | Nita | Mar 2012 | A1 |
20120123273 | Okuno et al. | May 2012 | A1 |
20120179073 | Nita | Jul 2012 | A1 |
20120197277 | Stinis | Aug 2012 | A1 |
Number | Date | Country |
---|---|---|
3919592 | Feb 1990 | DE |
40 05 743 | Aug 1991 | DE |
0189329 | Jul 1986 | EP |
0 529 675 | Aug 1992 | EP |
0 629 382 | Nov 1993 | EP |
668052 | Feb 1995 | EP |
0 744189 | Nov 1996 | EP |
0788774 | Aug 1997 | EP |
1090658 | Apr 2001 | EP |
1 252885 | Oct 2002 | EP |
0 746 245 | Nov 2002 | EP |
H 02-180275 | Jul 1990 | JP |
WO 8904142 | May 1989 | WO |
WO 8905160 | Jun 1989 | WO |
WO 9109629 | Jul 1991 | WO |
WO 9200113 | Jan 1992 | WO |
WO 9207622 | May 1992 | WO |
WO 9308738 | May 1993 | WO |
WO 9405361 | Mar 1994 | WO |
WO 9501751 | Jan 1995 | WO |
WO 9505866 | Mar 1995 | WO |
WO 9510233 | Apr 1995 | WO |
WO 9515118 | Jun 1995 | WO |
WO 9526777 | Oct 1995 | WO |
WO 9604955 | Feb 1996 | WO |
WO 9607432 | Mar 1996 | WO |
WO 9615815 | May 1996 | WO |
WO 9627341 | Sep 1996 | WO |
WO 9629935 | Oct 1996 | WO |
WO 9635469 | Nov 1996 | WO |
WO 9636286 | Nov 1996 | WO |
WO 9639935 | Dec 1996 | WO |
WO 9719645 | Jun 1997 | WO |
WO 9721462 | Jun 1997 | WO |
WO 9811826 | Mar 1998 | WO |
WO 9818391 | May 1998 | WO |
WO 9848711 | Nov 1998 | WO |
WO 9858699 | Dec 1998 | WO |
WO 9925385 | May 1999 | WO |
WO 9933500 | Jul 1999 | WO |
WO 9933550 | Jul 1999 | WO |
WO 9934858 | Jul 1999 | WO |
WO 9939647 | Aug 1999 | WO |
WO 9939738 | Aug 1999 | WO |
WO 9944512 | Sep 1999 | WO |
WO 0000095 | Jan 2000 | WO |
WO 0000095 | Jan 2000 | WO |
WO 0038580 | Jul 2000 | WO |
WO 0038580 | Jul 2000 | WO |
WO 0213678 | Feb 2002 | WO |
WO 0215803 | Feb 2002 | WO |
WO 0215804 | Feb 2002 | WO |
WO 03051208 | Jun 2003 | WO |
WO 05027756 | Mar 2005 | WO |
WO 05084552 | Sep 2005 | WO |
WO 2005084553 | Sep 2005 | WO |
Entry |
---|
B.D. Butler, J. clin. Ultrasound 14(5): 408-12 (Jun. 1986) Production of Microbubbles for Use as Echo Contrast Agents*. |
Bao, et al. “Transfection of a Reporter Plasmid into Cultured Cells by Sonoporation In Vitro,” Ultrasound in Med. and Biol., vol. 23, No. 6, pp. 953-. |
Bleeker et al., J. Ultrasound, Med. 9(8): 461-71 (Aug. 1990) On the Application of Ultrsonic Contrast Agents for Blood Flowmetry and Assessment of Cardiac Perfusion*. |
Cancer Letters, vol. 78 (1-3), 1994, pp. 177-181. |
Feldman, et al. “Optimal Techniques for Arterial Gene Transfer,” Cardiovascular Research, 35 (1997) pp. 391-404. |
G. Maywald et al., “Experience With Atraumatic Vascular Diagnosis With the Aid of the Ultrasonic Doppler Technique”, Electromedica, vol. 2 pp. 43-48 (1976). |
Greenleaf, William J. et al.; Artifical Cavitation Nuclei Significantly Enhance Accoustically Induced Cell Transfection. vol. 24, No. 4 pp. 587-595, 1998. |
Ho and Parkinson, Antisense Oigonucleoties and Therapeutics for Malignant Diseases, (Seminars in Drug Discovery 24(2): 187-202, 1997). |
Holland, C.K. and R.E. Apfel, J. Acoust. Soc. Am. 88(5): 2059-2069 (Nov. 1990) Thresholds for Transient Caviation Produced by Pulsed Ultrsound in a Controlled Nuclei Environment*. |
Hynynen et al.; “Small Cylindrical Ultrasound Sources for Induction of Hyperthermia Via Body Cavities or Interstitial Implants”; Arizona Cancer Center and DEuropeartment of Radiation Oncology, University of Arizona Health Sciences Center; vol. 9, No. 2; pp. 263-274; 1993. |
Japanese Journal of Cancer Research, vol. 81, No. 3, Mar. 1990, pp. 304-308. |
Jeffers, R.J. et al.; Evaluation of the Effect of Cavitation Activity on Drug-Ultrsound Synergisms, 1993. |
Jeffers, Russel et al; Dimethylformamide as an Enhancer of Cavitation-Induced Cell Lysis In Vitro, vol. 97, No. 1, Jan. 1995. |
Keller et al., J. Ultrasound Med. 5(9): 493-498 (Sep. 1986) Automated Production and Analysis of Echo Contrast Agents*. |
Kim, et al. “Ultra-sound Mediated Transfection of Mammalian Cells,” Human Gene Therapy, 7: 1339-1346 (Jul. 10, 1996). |
Kim, T. F. Medical news & Perspectives, JAMA261(11): 1542 (Mar. 17, 1989) Microbubbles Show Promise for Enhancing Ultrasound Signal, Image, Other Applications*. |
Kotnis, et al. “Optimisation of Gene Transfer into Vascular Endothelial Cells Using Electroporation,” Eur J. Vasc Surg, 9, 71-79 (1995). |
Lang et al., Circulation 75(1): 229-234 (Jan. 1987) Contrast Ultrasonography of the Kidney: a New Method for Evaluation of Renal Perfusion in Vivo*. |
Lee et al.; “Arrays of Multielement Ultrasound Applicators for Interstitial Hyperthermia”; IEEE Transactions on Biomedical Engineering; vol. 46, No. 7; Jul. 1999. |
Leong et al., Biomaterials, vol. 7: 364-371 (Sep. 1986) Polyanhydrides for Controlled Release of Bioactive Agents*. |
Meltzer et al., J. Clin. Ultrasound 8(2): 121-127 (Apr. 1980) The Source of Ultrsound Contrast Effect*. |
Miller, Douglas L. et al.; Sonoporation of Cultured Cells in the Rotation Tube Exposure System, vol. 25, No. 1, 1999. |
Somia and Verma, Gene Therapy: Trials and Tribulations, (Nature Reviews Genetics 1 :91-99,2000). |
Tsurumi, et al. “Direct Intramuscular Gene Transfer of Naked DNA Encoding Vascular Endothelial Growth Factor Augments Collateral Development and Tissue Perfusion,” Circulation, 1996; 94: 3281-3290. |
Orkin and Motulsky, Report and Recommendations of the Panel to Assess the NIH Investment in Research on Gene Therapy, (p. 1-38, Dec. 7, 1995). |
Porter, et al “Interaction of Diagnostic Ultrasound with Synthetic Olionucleotide-Labeled Perfluorcarbon-Exposed Sonicated Dextrose Albumin Microbubbles,” J Ultrasound Med, 15:557-584, 1996. |
Porter, T.R. et al., Thrombolytic Enhancement With Perfluorocarbom-Exposed Sonicated Dextrose Albumin Microbubbles, Nov. 1996. |
Prat, F. et al.; In Vivo Effects of Cavitation Alone or in Combination Wity Chemotherapy in a Peritoneal Carinomatosis in the Rat. vol. 68, pp. 13-17. |
Price, Richard et al.; Delivery of Colloidal Particles and Red Blood Cells to Tissue Through Microvessel Ruptures Created by Targeted Microbubble Destruction With Ultrasound, Sep. 29, 1998. |
Romano et al., Latest Developments in Gene Transfer Technology: Achievements, Perspectives, and Controversies over Therapeutice Applications, (Stem Cells 18: 19-39, 2000). |
Rosenschein, U. et al., Experimental Ultrasonic Angioplasty: Disruption of Atherosclerotic Plaques and Thrombi in Vitro and Arterial Recanalization in. |
Somia and Verma, Gene Therapy: Trials and Tribulations, (Nature Reviews Genetics 1 :91-99, 2000). |
Tachibana K.; Albumin Microbubble Echo-Contrast Materials as an Enhancer for Ultrasound Accelerated Thrombolysis, Sep. 1, 1995. |
Tachibana, K. “Enhancement of Fibrinolysis with Ultrasound Energy”, JVIR, vol. 3, No. 2, May 1992, pp. 299-303. |
Tsurumi, et al. “Direct Intramuscular Gene Transfer of Naked DnNA Encoding Vascular Endothelial Growth Factor Augments Collateral Development and Tissue Perfusion,” Circulation, 1996; 94: 3281-3290. |
Unger, et al. “Ultrasound Enhances Gene Expression of Liposomal Transfection,” Investigative Radiology, vol. 32, No. 12, pp. 723-727, 1997. |
Unger, Evan C. et al.; Acoustically Active Liposheres Containing Paclitaxel, vol. 11, No. 12, 1992. |
Vandenburg et al., Am. Heart J., 115(4), 733-739 (Apr. 1988) Myocardial Risk Area and Peak Gray Level Measurement by Contrast Echocardiography: Effecct of Microbubble Size and Concentration, Injection Rate, and Coronary Vasodilation*. |
Verma et al., Gene Therapy—promises, problems and prospects, (Nature 389: 239-242, 1997). |
Wheatl Yet al., Biomaterials 11 (19): 713-717 (Nov. 1990) Contrast Agents for Diagnostic Ultrsound: Development and Evaluation of Polymer-Coated Microbubbles. |
Wu, Yunqiu et al., Binding as Lysing of Blood Clots Using MRX-408, May 1998. |
Wyber, et al. “The Use of Sonication for the Efficient Delivery of Plasmid DNA into Cells,” Pharmaceutical Research, vol. 14, No. 6, pp. 750-756. |
Akhtar, Anti-HIV therapy with antisense oligonucleotides and ribozymes: realistic approaches or expensive myths (J. Antimicrob Chemother. 38(2): 159-165, 1996). |
Anderson, Human gene therapy. (Nature 392:25-30, 1998). |
B.D. Butler, J. clin. Ultrasound 14(5): 408-412 (Jun. 1986) Production of Microbubbles for Use as Echo Contrast Agents*. |
Bao, et al “Transfection of a Reporter Plasmid into Cultured Cells by Sonoporation in Vitro,” Ultrasound in Med. and Biol., vol. 23, No. 6, pp. 953-. |
Bleeker et al., J. Ultrasound, Med. 9(8): 461-471 (Aug. 1990) on the Application of Ultrsonic Contrast Agents for Blood Flowmetry and Assessment of Cardiac Perfusion*. |
Branch, A Good Antisense Molecule is Hard to Find, (Trends in Biochem Sci 23: 45-50, 1998). |
Cancer Letters, vol. 72, 1993, pp. 195-199. |
Cancer Letters, vol. 78 (1-3),1994, pp. 177-181. |
Crooke, Basic Principles of Antisense Therapeutics (Springer-Verlag, Eds, New York, 1998, pp. 1 and 4). |
Fechmeier, et al. “Transfection of Mammalian Cells with Plasid DNA by Scrape Loading and Sonication Loading,” Proc. Natl. Acad. Sci. USA, vol. 84, pp. 8463-8467, Dec. 1987. |
Feinstein et al., J. Am. Coil. Cardiol. 3(1): 14-20 (Jan. 1984) Two-dimensional Contrast Echocardiography I. In Vitrro Development and Quantitative Analysis of Echo Contrast Agents*. |
Number | Date | Country | |
---|---|---|---|
20120095389 A1 | Apr 2012 | US |
Number | Date | Country | |
---|---|---|---|
60045268 | May 1997 | US |
Number | Date | Country | |
---|---|---|---|
Parent | 10383292 | Mar 2003 | US |
Child | 13333922 | US | |
Parent | 09375162 | Aug 1999 | US |
Child | 10383292 | US |
Number | Date | Country | |
---|---|---|---|
Parent | 09129980 | Aug 1998 | US |
Child | 09375162 | US | |
Parent | 09107078 | Jun 1998 | US |
Child | 09129980 | US | |
Parent | 09071285 | May 1998 | US |
Child | 09107078 | US |