Ultrasound systems and methods for treating ischemic limbs or tissue affected by peripheral arterial disease

A method of treating tissue within a body includes aiming an ultrasound transducer towards target tissue, and delivering ultrasound energy towards the target tissue to thereby reduce pain at the target tissue. A method of treating tissue within a body includes aiming an ultrasound transducer towards target tissue, and delivering ultrasound energy towards the target tissue to increase nitric oxide at the target tissue. An ultrasound system includes a first ultrasound transducer for emitting ultrasound energy from outside a patient, and drive circuitry coupled to the first ultrasound transducer, wherein the drive circuitry is configured to generate a drive signal at a frequency that is between 20 kHz and 100 kHz for the first ultrasound transducer.

FIELD

The present invention relates generally to apparatus and methods for treating tissue, and more particularly to apparatus and methods for treating ischemic limbs or tissue affected by peripheral arterial disease.

BACKGROUND

Peripheral arterial disease is the most common form of atherosclerosis that affects many people worldwide. As a result of such disease, many people experience pain during walking. Such condition may be treated medically with exercise and drugs, such as Cilostazol, which modestly improves walking ability by inhibition of platelet aggregation. However, in many cases, patients do not follow the prescribed exercise therapy because of pain associated with the disease. Other types of drugs have also been used to treat ischemia, but many of these drugs have side effects.

Medical interventions such as balloon angioplasty, stenting, and surgery are options to treat patients who are suffering from peripheral arterial diseases and critical limb ischemia. However, many of such procedures may fail. Consequences of graft failure include continued ischemia, poor wound healing, gangrene, or amputation of a patient's limb.

Ultrasound devices have been used to diagnose patients. For example, ultrasonic energy may be employed to obtain images of a part of a patient during a diagnostic procedure. In addition, ultrasound systems have been used for treating tissue, e.g., by directing acoustic energy towards a target tissue region within a patient, such as a cancerous or benign tumor, to heat the tissue region. For example, an ultrasound transducers may be disposed adjacent a patient's body and operated (generally at a frequency that is in the megahertz range) to deliver high intensity acoustic waves, such as ultrasonic waves, at an internal tissue region of a patient to heat the tissue region, thereby injuring target tissue at the tissue region.

SUMMARY

In accordance with some embodiments, a method of treating tissue within a body includes aiming an ultrasound transducer towards target tissue, and delivering ultrasound energy towards the target tissue to thereby reduce pain at the target tissue.

In accordance with other embodiments, a method of treating tissue within a body includes aiming an ultrasound transducer towards target tissue, and delivering ultrasound energy towards the target tissue to increase nitric oxide at the target tissue.

In accordance with other embodiments, an ultrasound system includes a first ultrasound transducer for emitting ultrasound energy from outside a patient, and drive circuitry coupled to the first ultrasound transducer, wherein the drive circuitry is configured to generate a drive signal at a frequency that is between 20 kHz and 100 kHz for the first ultrasound transducer.

Other aspects and features will be evident from reading the following detailed description of the embodiments.

DETAILED DESCRIPTION OF THE EMBODIMENTS

FIG. 1illustrates an ultrasound system5in accordance with some embodiments. The ultrasound system5includes an ultrasound transducer10, a drive circuitry16coupled to the transducer10, and a controller18coupled to the drive circuitry16. The ultrasound system5also includes a structure22for carrying the transducer10, the drive circuitry16, and the controller18, and a securing device24for securing the transducer10relative to a patient during use. The transducer10is configured to deliver acoustic energy to target tissue located inside the patient. The acoustic energy may be used to increase the level of nitric oxide within the tissue, thereby relieving, or at least reducing, pain in the tissue.

The structure22is not limited to the rectangular shape shown, and can be any shapes, forms, and/or configurations in other embodiments, so long as it is capable of providing a platform or area to which the transducer10can be secured. The structure22may be substantially rigid, semi-rigid, or substantially flexible, and can be made from a variety of materials, such as plastics, polymers, metals, and alloys. Electrodes and conducting wires (not shown) may also be provided in a known manner for coupling the transducer10to the driver16. In the illustrated embodiments, the driver16and the controller18are secured directly to the structure22. Alternatively, the driver16and/or the controller18can be coupled to the structure22via a cable. In such cases, the electrodes for the transducer10are housed within the structure22, and exit from the structure22for coupling to the driver16and/or the controller18.

In the illustrated embodiments, the transducer10includes one or more transducer elements12(one is shown). Each of the transducer element(s)12may be a one-piece piezoceramic part, or alternatively, be composed of a mosaic arrangement of a plurality of small piezoceramic elements (e.g., phased array). The piezoceramic parts or the piezoceramic elements may have a variety of geometric shapes, such as hexagons, triangles, squares, and the like. The material used to construct the transducer element(s)12could be a composite material, a piezoceramic, or any other material that could transform electrical signal into acoustic wave. The transducer element(s)12are coupled to the driver16and/or controller18for generating and/or controlling the acoustic energy emitted by the transducer element(s)12. For example, the driver16may generate one or more electronic drive signals, which may be controlled by the controller18. The transducer element(s)12convert the drive signals into acoustic energy. The controller18and/or driver16may be separate or integral components. It will be appreciated by one skilled in the art that the operations performed by the controller18and/or driver16may be performed by one or more controllers, processors, and/or other electronic components, including software and/or hardware components. The terms controller and control circuitry may be used herein interchangeably, and the terms driver and drive circuitry may be used herein interchangeably.

The driver16, which may be an electrical oscillator, may generate drive signals in the ultrasound frequency spectrum, e.g., as low as ten kilohertz (10 KHz), or as high as five hundred kilohertz (500 kHz). In some embodiments, the driver16provides drive signals to the transducer10at a frequency that is between about twenty kilohertz to one hundred kilohertz (20-100 kHz). However, in other embodiments, the driver16can also be configured to operate in other ranges of frequencies. When the drive signals are provided to the transducer10, the transducer10emits acoustic energy from its surface, as is well known to those skilled in the art.

The controller18may control the amplitude, and therefore the intensity or power, of the acoustic wave transmitted by the transducer10. In other embodiments, if the transducer10includes more than one transducer elements12, the controller18may also control a phase component of the drive signals to respective transducer elements12of the transducer device10, e.g., to control a shape or size of a focal zone generated by the transducer elements12and/or to move the focal zone to a desired location. For example, the controller18may control the phase shift of the drive signals to adjust a focal distance (i.e., the distance from the face of the transducer10to the center of the focal zone). In further embodiments, the controller18can be configured to operate the transducer10for a prescribed duration, such as at least 15 minutes. Alternatively, or additionally, the controller18can be configured to automatically turn off the transducer10when a usage of the transducer10exceeds a prescribed time, such as 60 minutes.

In other embodiments, the system5further includes a coupling membrane30, such as an inflatable body or a balloon, for providing or improving an acoustic coupling between the transducer10and a skin of the patient, while ultrasound energy is being delivered (FIG. 2). The coupling membrane30can be filled with a fluid, such as degassed water.

FIG. 3illustrates a method of using the system5to treat target tissue6within a patient7in accordance with some embodiments. In the illustrated embodiments, the target tissue6is one that has been affected by a peripheral arterial disease, and is located within a leg of the patient7. In other embodiments, the target tissue6can be associated with other diseases or medical conditions (such as pain due to exercising), and can be located at other parts of the patient7.

First, the securing device24is used to secure the ultrasound transducer10relative to the patient7. As shown inFIG. 1, the securing device24includes a strap26, a plurality of openings27on the strap26, and a pin28secured to the structure22, wherein the pin28is sized to mate with a selected one of the openings27. When using the securing device24, the strap26is tightly wrapped around the leg of the patient7, and one of the openings27is mated with the pin28, thereby securing the ultrasound transducer10directly against a skin on the patient's leg. If the system5includes the coupling membrane30ofFIG. 2, the securing device24is used to secure the coupling membrane30against the skin on the patient's leg. The coupling membrane30functions as an acoustic coupler and provides good contact with the curved leg surface.

Next, the transducer10delivers ultrasound energy to the target tissue6. Particularly, the driver16and/or the controller18are used to generate and/or to control the acoustic energy emitted by the transducer10. The transducer10may emit acoustic energy in a continuous manner, or alternatively, in pulses. In some embodiments, the driver16and/or the controller18may also control a phase, an operating frequency, and/or an operating amplitude of the transducer10.

In the illustrated embodiments, the transducer10is operated at a frequency that is between 10 kHz and 500 kHz, and more preferably, at a frequency that is between 20 kHz and 100 kHz. Such frequency range produces low attenuation in the tissue6and may allow resonance to occur within the patient's limb (e.g., the leg). The effect of resonance allows the required input energy for the transducer10to be decreased. In other embodiments, the transducer10can be operated at other frequency ranges.

The delivered acoustic energy by the transducer10is at least partially absorbed by the tissue6within the patient's leg, and causes mechanical stimulation of endothelial cells by compression and wall shear stress in blood vessels, thereby stimulating production of endothelial nitric oxide syntheses (eNOs). In the illustrated embodiments, the transducer10is used for a duration of at least 10 minutes, and more preferably, at least 15 minutes, thereby causing production of eNOs that translates into nitric oxide up-regulation. The heightened level of nitric oxide is believed to have a number of effects on the tissue6, including inhibition of leukocyte and platelet adhesion, control of vascular tone and maintenance of a thromboresistant interface between the bloodstream and the vessel wall, increase in capillary circumference (vasodilation), and/or increase in blood flow (perfusion). Such effect(s) in turn helps relieve pain at the tissue6, and allows the patient7to rehabilitate through exercise. In other embodiments, the transducer10can be operated for other durations that are different from those mentioned previously.

In some embodiments, during a treatment session, the energy intensity or dosage delivered by the transducer10at the tissue6is kept below a prescribed threshold (e.g., by using appropriate driving scheme and/or by selecting appropriate operation parameters, such as an operating frequency, an operating amplitudes, etc.), thereby protecting the tissue6from being injured by the acoustic energy.

After a desired treatment effect is achieved, the transducer10is then removed from the patient7, or vice versa.

In the above embodiments, the securing device24is described as having the strap26. However, it should be noted that the securing device24is not limited to the example discussed previously, and that the securing device24can have other shapes and configurations, as long as it is capable of securing the transducer10relative to the patient7during use. For example, in other embodiments, the structure22includes a first frame60and a second frame62that is rotatably coupled to the first frame60via a shaft64(FIG. 4A). In such cases, the securing device24includes a spring66secured to the first and second frames60,62, thereby biasing the frames60,62to have a closed configuration. During use, the frames60,62are pulled apart from each other to provide an opened configuration for the structure22, and the frames60,62are placed on opposite sides of the patient's leg (FIG. 4B). The spring64undergoes tension to pull the frames60,62towards each other, thereby pressing the transducer10(or the coupling membrane30if one is provided) towards a patient's skin.

In other embodiments, the system5does not include the securing device24. For example, in other embodiments, the structure22includes a surface80for supporting at least a portion of the patient, such as a limb (e.g., an arm or a leg) (FIG. 5A). The surface80can have a curvilinear profile or a flat profile. During use, the patient's leg is placed on top of the surface80. In such cases, the gravitational force pulls the patient's leg towards the structure22, thereby effecting coupling between the patient's skin and the transducer10(or the coupling membrane30if one is provided) (FIG. 5B). The structure22can be supported by a support stand82, or alternatively, be placed on a bed during use.

In other embodiments, the structure22includes a container100having a lumen102sized to accommodate a least a portion of a limb of a patient (FIG. 6A). The ultrasound transducer10can be secured to an exterior surface or an interior surface of the container100. During use, the container100is placed on a floor, and is filled with fluid. The patient's leg is then placed in the container100(FIG. 6B). Ultrasound is emitted from the transducer10and is transmitted through the fluid in the container100to reach the patient's leg.

In any of the embodiments described herein, the system5can further include one or more additional ultrasound transducer(s)10secured to the structure22. The transducers10can be positioned in a side-by-side configuration to form a line. For example, in some embodiments, the system5includes two transducers10, the center lines of which are spaced approximately two wavelengths (of the delivered acoustic wave) apart. Alternatively, the respective center lines of the transducers10can be spaced at other distances. For example, in some embodiments, the spaced distance can be selected such that the transducers10can provide a substantially uniform acoustic field at target tissue. In other embodiments, the transducers10can be positioned relative to each other to form other desired configurations. For example, in other embodiments, the system5includes two ultrasound transducers10that are positioned opposite from each other. For example, in the embodiments ofFIG. 4A, in addition to the first transducer10that is secured to the second frame62, the system5can further include a second transducer10secured to the first frame60. As another example, in the embodiments ofFIG. 6A, the system5can further include a second transducer10secured to the container100opposite from the first transducer10. Providing a plurality of transducers10allows treatment of multiple target regions simultaneously. For example, in some embodiments, the system5includes three transducers10that are positioned relative to each other to form a line. Such configuration allows a substantial portion of a patient's calf to be treated by the system5.

In some cases, the driver16and/or the controller18can be configured to control the transducers10such that acoustic waves emitted by the respective transducers10interact in a desired manner. For example, in some embodiments, a relative phase between transducers10may be varied. In one implementation, adjacent transducers10are alternately driven in phase and 180° out of phase. Because the acoustic fields from adjacent transducers10may overlap and because of resonance, the intensity distribution within a patient's body may form a series of interference maxima and mina. By altering the phase relation between the transducers10, the locations of these pecks and nulls may be reversed, thereby providing overall uniform (or substantially uniform) insonification at target tissue6. In other embodiments, the operating frequency of one or more transducers10may be varied to move an interference pattern of the acoustic field.

In other embodiments, the transducer10can be moveable relative to the patient7. For example, in some embodiments, the system5further includes a handle110secured to the structure22(FIG. 7). During use, the handle110can be hold by a user and be used to press the transducer10(or the coupling membrane30if one is provided) towards a patient's skin.

In other embodiments, The transducer10(or the structure22) is secured to a mechanical linkage120, such as a positioner, for adjusting a position of the transducer10relative to a patient support122(FIG. 8). During use, the mechanical linkage120positions the transducer10to aim the transducer10towards different regions of the patient7, thereby allowing the transducer10to treat different portions of the patient7. For example, the mechanical linkage120can translate and/or rotate the transducer10to thereby adjusting an aiming of the transducer10. In some embodiments, the driver16and/or the controller18can be used to control positions of the transducer10in accordance with a prescribed treatment plan to thereby adjust the position, shape, and/or size of a focal zone.

In other embodiments, the structure22includes a first portion130that can be secured relative to the patient7via the securing device24, and a second portion132that is translatable relative to the first portion130(FIG. 9). In such cases, the system5includes one or more ultrasound transducer(s)10secured to the second portion132. During use, the first portion130of the structure22is secured to the patient7via the securing device24, and the second portion132is translated relative to the first portion130to thereby allow the transducer(s)10to treat different portions along the patient's leg. In some cases, such configuration allows an entire leg segment of the patient7to be treated. The positioning of the second portion132relative to the first portion130can be accomplished using a positioner, such as a motor. In some embodiments, the system5can further include a coupling membrane secured to the transducer(s)10, as similarly discussed previously.

In any of the embodiments described herein, the system5further includes one or more hydrophones (not shown) mounted either between the transducer(s)10and a patient's skin, or adjacent to the transducer(s)10, for sampling acoustic field(s). This helps ensure proper electrical operation of the system5and coupling of the transducer10.

In any of the embodiments described herein, the system5can further include a Doppler ultrasound device for measuring a degree of perfusion, which provides a qualitative measure of the increase in blood flow resulting from the ultrasound treatment provided by the system5.

In any of the embodiments described herein, the system5can include a plesthysmography device, which is configured to restrict upper leg venous flow temporarily, and measure a rate of swelling of the lower leg, either by volume displacement or by circumferential increase in leg size. The measurement can then be used to determine an effect of the performed treatment.

Although particular embodiments have been shown and described, it should be understood that the above discussion is not intended to limit the present invention to these embodiments. It will be obvious to those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the present invention. For example, in other embodiments, instead of using the system5to treat a patient's leg, any of the embodiments of the system5described herein can be configured (e.g., shaped and/or sized) to treat other parts of a patient, such as an arm, a forearm, a thigh, a neck, or a chest, of a patient. Also, in other embodiments, instead of using the system5to treat ischemic limbs or tissue affected by peripheral arterial disease, any of the embodiments of the system5described herein can be used to treat other medical conditions in other embodiments. Further, in other embodiments, instead of placing the transducer10external to a patient, the transducer10can be placed inside a patient. For example, in some embodiments, the transducer10can be secured to a distal end of a probe, which is at least partially inserted inside a patient during use. In such cases, the transducer10delivers acoustic energy from within the patient. Thus, the present invention is intended to cover alternatives, modifications, and equivalents that may fall within the spirit and scope of the present invention as defined by the claims.