Medical device with CMUT array and solid state cooling, and associated methods and systems

A medical device includes a capacitive micromachined ultrasonic transducer (CMUT) array configured to emit ultrasound to target tissue, and at least one thermoelectric cooler mechanically coupled with the CMUT array and configured to cool non-target tissue heated by the ultrasound. The medical device may be implemented in a catheter together with a solid thermal conductor coupled to the thermoelectric cooler and extending along the catheter, to conduct heat away from the thermoelectric cooler. A catheter or catheter sleeve includes a tubular wall for insertion into a body channel, and at least one thermoelectric cooler coupled to the tubular wall for cooling the body channel wall. A catheter sleeve includes tubular casing for insertion into a body channel and capable of encasing a catheter, and at least one sensor coupled to the tubular casing for sensing one or more properties of the body channel wall, such as temperature and pressure.

BACKGROUND

The normal male urethra passes through the prostate gland. The portion of the urethra located within the prostate is referenced herein as the prostatic urethra.

Benign prostate hyperplasia (BPH), an overgrowth of cells within the prostate often causing enlargement of the prostate, is quite common. According to Wikipedia, 50% of men show BPH histology by age 50 and 75% by age 80; of these as many as half may develop symptoms. The most common symptoms of BPH include interference with urine flow caused by an enlarged prostate applying pressure to the urethra, interference with urine flow leads to incomplete voiding, urine retention, frequent urination, and urinary tract infections which can lead to bladder and kidney damage.

Roughly 80% of men develop prostate cancer by age 80. Although most of these prostate cancers are slow growing, prostate cancer killed approximately 250,000 men worldwide in 2010. Even slow-growing prostate tumors can compromise the urethra by mass effect and tumor invasion and obstruct urine flow, similarly to obstruction in BPH.

BPH and prostate cancer can coexist in a prostate; the combination also can enlarge the prostate sufficiently to interfere with urine flow. High pressure in the prostate, whether from mass effect of a tumor or from BPH, causes the urethra to partially or fully collapse, thus constricting urine flow.

Interference with urine flow caused by prostate glands enlarged by BPH often needs treatment to improve urine flow. This interference has been treated in several ways, including medications that interfere with testosterone, or surgical procedures such as open prostatectomy, transurethral resection of the prostate (TURP), and transurethral laser ablation of the prostate. Transurethral procedures are favored because infection risk, pain, and healing times are typically reduced compared to open surgical procedures.

Transurethral microwave therapy (TUMT), where the prostate is heated using a microwave antenna placed within the prostatic urethra, is among known treatments. TUMT side effects can include urethral damage due to excess heating of the urethra. Laser ablation suffers from similar side effects.

Ultrasonic treatment of the prostate intended to heat portions of the gland sufficient to ablate some of the excess tissue of BPH has been proposed in, for example “Prostate cancer ablation with transrectal high-intensity focused ultrasound: assessment of tissue destruction with contrast-enhanced US”, Rouviere et al., Radiology. 2011 May, volume 259, issue 2, pp 583-91, and “Transurethral Ultrasound Array for Prostate Thermal Therapy: Initial Studies”, Chris J. Diederich, and Everette C. Burdette, IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control. Vol. 43. No. 6. November 1996 (Diederich). Diederich proposes a catheter having two lumens; coolant water flows into the catheter through one lumen and exits over 7 MHz piezoceramic transducers through a second lumen. Diederich, experimenting in pig muscle, reported significant temperature increases in tissue one and a half centimeters from the transducers; these temperature increases are believed sufficient to kill prostate tissue.

High intensity ultrasound for heating tissue of localized prostate cancer, using piezoceramic transducers is proposed by SonaCare Medical, Alpinion Medical Systems, and Profound Medical (as seen at http://www.profoundmedical.com/new-tulsa/). As reported in Magnetic Resonance Imaging—Guided Transurethral Ultrasound Ablation of Prostate Tissue in Patients with Localized Prostate Cancer: A Prospective Phase 1 Clinical Trial, Joseph Chin et al., European Urology vol. 70, pp 447-455 (2016), the Profound Medical device, named MRI-TULSA, relies on external nuclear magnetic resonance imaging (MRI) for precise location of the array for treatment, uses a rigid urethral catheter having ten directional piezoelectric transducers, and employs water cooling by a rectal catheter to avoid destruction of the prostatic urethra. A clinical trial of MRI-TULSA reached internal prostate temperatures of 55 C, sufficient to damage or ablate tissue.

Capacitive micromachined ultrasonic transducers (CMUTs) operate on principles different from those of piezoelectric transducers. Piezoelectric transducers are based on piezoelectric crystals that bend or contract/expand in response to applied electric fields. A CMUT has a cavity formed in a silicon-based substrate. A thin membrane equipped with an electrode is suspended atop of the cavity. Another electrode is positioned below the cavity, fixed on a substrate. Then, when a voltage is applied between the two electrodes, electrostatic attractive forces pull the membrane downwards, shrinking the cavity. When the voltage drop is removed, the membrane rebounds. If the applied voltage is a sinusoid at sufficiently high frequency, the membrane vibrates at the same frequency and sends acoustic energy into the medium with which it is in contact. As opposed to piezoelectric transducers, CMUTs have no significant internal loss mechanism and essentially lack self-heating.

SUMMARY

In an embodiment, a medical device includes a capacitive micromachined ultrasonic transducer (CMUT) array configured to emit ultrasound to target tissue, and at least one thermoelectric cooler mechanically coupled with the CMUT array and configured to cool non-target tissue heated by the ultrasound.

In an embodiment, a catheter for ultrasound treatment with solid state cooling includes (a) a CMUT array configured to emit ultrasound to target tissue, (b) a thermoelectric cooler configured to cool non-target tissue heated by the ultrasound, the ultrasound transducer being disposed at a distal end of the catheter, and (c) a solid thermal conductor coupled to the thermoelectric cooler and extending along the catheter away from the distal end toward a proximal end of the catheter, to conduct heat away from the thermoelectric cooler.

In an embodiment, a system for enhanced ultrasound treatment with solid state cooling includes the catheter, mentioned in the preceding paragraph, and two acoustic mirrors. Each of the two acoustic mirrors is configured to cooperate with the CMUT array to form a respective acoustic cavity, to increase intensity of the ultrasound within the acoustic cavity.

In an embodiment, a medical device includes a catheter for exposing target tissue to ultrasound. The catheter includes (a) a CMUT array disposed at a distal end of the catheter and configured to emit the ultrasound to the target tissue, (b) a thermoelectric cooler configured to cool non-target tissue heated by the ultrasound, and (c) a solid thermal conductor coupled to the thermoelectric cooler and extending along the catheter away from the distal end toward a proximal end of the catheter, to conduct heat away from the thermoelectric cooler. The medical device further includes a catheter handle mechanically coupled to a proximal end of the catheter and configured to be positioned outside a body channel into which the catheter is inserted, to at least partly control the catheter.

In an embodiment, a system for enhanced ultrasound treatment includes a catheter including an ultrasound transducer array and configured to position the ultrasound transducer array in a channel of a body to expose target tissue of the body to ultrasound, and at least one acoustic mirror. Each acoustic mirror is configured for positioning externally to the channel on a side of the target tissue that is opposite the ultrasound transducer array, to form an acoustic cavity that enhances intensity of the ultrasound at the target tissue by creating a standing acoustic wave between the ultrasound transducer array and the acoustic mirror.

In an embodiment, a system for enhanced ultrasound treatment includes a first ultrasound transducer array, and a second ultrasound transducer array cooperatively configured with the first ultrasound transducer array to form an acoustic cavity that enhances intensity of ultrasound, generated by the first ultrasound transducer array and the second ultrasound transducer array, at the target tissue by creating a standing acoustic wave within the acoustic cavity.

In an embodiment, a catheter or catheter sleeve with solid state cooling includes a tubular wall for insertion into a channel of a body, and at least one thermoelectric cooler coupled to the tubular wall for cooling tissue of the channel.

In an embodiment, a catheter sleeve with integrated sensing includes tubular casing for insertion into a channel of a body and capable of encasing a catheter, and at least one sensor coupled to the tubular casing and configured to sense one or more properties of tissue of the channel Each of the one or more properties is selected from the group consisting of temperature and pressure.

In an embodiment, a system for ultrasound treatment with solid state cooling includes ultrasound driving circuitry configured to generate drive signals to drive a CMUT array, so as to expose target tissue to ultrasound. The system further includes Peltier driving circuitry configured to drive at least one thermoelectric cooler, to cool non-target tissue heated by the ultrasound.

In an embodiment, a method for ultrasound treatment with solid state cooling includes (a) exposing target tissue to ultrasound generated by a CMUT array, (b) cooling non-target tissue using one or more thermoelectric coolers to prevent damage to the non-target tissue, and (c) removing heat from the one or more thermoelectric coolers and away from the non-target tissue.

In an embodiment, a method for ultrasound treatment with ultrasound imaging feedback includes (a) obtaining an image of target tissue from an ultrasound transducer array to determine a spatially resolved clutter signal for the target tissue, and (b) based upon the clutter signal and a predetermined correspondence between the clutter signal and treatment efficacy, determining one or more properties of subsequent generation of ultrasound by the ultrasound transducer array to treat the target tissue.

In an embodiment, a product for controlling ultrasound treatment using ultrasound imaging feedback includes machine-readable instructions encoded in non-transitory memory. The machine-readable instructions include (a) a correspondence between an ultrasound clutter signal and efficacy of the ultrasound treatment, and (b) treatment control instructions that, when executed by a processor, evaluate spatially resolved clutter signals obtained from ultrasound imaging of target tissue and utilize the correspondence to determine one or more properties of subsequent ultrasound exposure of the target tissue.

In an embodiment, a method for manufacturing a CMUT array with solid state cooling includes fabricating the CMUT array on a first thermal conductor of a thermoelectric cooler. The thermoelectric cooler includes (a) the first thermal conductor, (b) a second thermal conductor, and (c) disposed between the first thermal conductor and the second thermal conductor, a plurality of n-type semiconductors and a plurality of p-type semiconductors electrically coupled in series such that the series alternates between the n-type semiconductors and the p-type semiconductors.

DETAILED DESCRIPTION OF THE EMBODIMENTS

FIG. 1illustrates one medical device100with a capacitive micromachined ultrasonic transducer (CMUT) array and solid state cooling. Device100is configured to treat body tissue from a body cavity, duct, or vessel; herein collectively referred to as a “body channel”.

In the embodiment ofFIG. 1, medical device100includes a catheter110configured for insertion into a body channel, such as a urethra194. Medical device100further includes a handle120mechanically coupled to a proximal end102of catheter110and configured to be positioned outside the body channel to at least partly control catheter110. Catheter110includes, at or near a distal end104thereof, a CMUT-thermoelectric cooler device116having a CMUT array112and at least one thermoelectric cooler (TEC)114providing solid state cooling). By wielding catheter110, CMUT-TEC device116may be positioned within working distance of target tissue of a subject190to be treated by ultrasound.

In operation, CMUT array112emits ultrasound to target tissue, such as a prostate192, for example to induce necrosis of the target tissue, and thermoelectric cooler114cools non-target tissue that is heated by the ultrasound, to prevent heat-induced damage to the non-target tissue. The non-target tissue may be heated by direct exposure to the ultrasound and/or by heat propagating to the non-target tissue from the target tissue or other tissue exposed to the ultrasound.

FIG. 1shows medical device100in one exemplary scenario, to expose a prostate, or a portion thereof, to ultrasound from the urethra. In this exemplary scenario, medical device100may treat benign prostate hyperplasia (BPH), for example to improve flow of urine from bladder196; or device100may treat prostate cancer. Certain embodiments of medical device100may treat a combination of BPH and prostate cancer. Regardless of which of these conditions is being treated, CMUT array112may operate to emit ultrasound to tissue of the prostate, while thermoelectric cooler114cools at least a portion of the urethral wall to prevent heat-induced damage to the urethra. However, without departing from the scope hereof, medical device100may be used in other scenarios to treat other types of body tissue from a different body channel than the urethra.

CMUT array112includes an array of CMUT cells150. In one embodiment, CMUT cells150are organized in an array of CMUT elements. Each CMUT element includes a plurality of CMUT cells150configured to be driven in unison to cooperatively function as a single larger CMUT cell.FIG. 1schematically illustrates one exemplary embodiment of a CMUT cell150. In this embodiment, each CMUT cell150includes a substrate180, an electrically insulating layer170having a cavity172formed therein, a membrane160with an electrode162disposed thereon, and, optionally, a protective/electrically insulating layer164disposed over electrode162and membrane160. Together, layer170and membrane160may contain a vacuum in cavity172; or layer170and membrane160may contain a gas at less than atmospheric pressure in cavity172. When a time-varying voltage drop of an appropriate frequency is applied between electrode162and substrate180, functioning as a bottom electrode, the resulting electric field between electrode162and substrate180will cause membrane160to vibrate and generate ultrasound. In certain embodiments, substrate180is a silicon substrate, and each of electrically insulating layer170and membrane160is silicon-based. Alternatively, membrane160may be a nanotube-based membrane. Without departing from the scope hereof, CMUT cell150may be of a different configuration. For example, CMUT cell150may include additional layers, and/or cavity172may be formed in a glass substrate with an electrode disposed on the bottom of cavity172.

CMUT cell150generates very little heat, if any at all. In contrast, about 40% of the electrical energy delivered to a typical piezoelectric transducer is lost to friction in the piezoelectric material (as dictated by the imaginary part of the dielectric constant of the piezoelectric transducer), thus generating a substantial amount of heat at the piezoelectric transducer itself. Consequently, when using piezoelectric transducers to heat target tissue a distance away from the piezoelectric transducers (e.g., prostate tissue), the heat generated at the piezoelectric transducers is generally as great as, if not greater than, the heat induced by the ultrasound in the target tissue. Therefore, if the tissue near the piezoelectric transducers is not part of the target tissue, and undesirable damage would result from heating of this tissue, substantial cooling must be applied at the site of the piezoelectric transducers to cool the piezoelectric transducers and/or the adjacent tissue. In the case of a urethral catheter intended for ultrasound treatment of the prostate using piezoelectric transducers, liquid cooling of the piezoelectric transducers and/or the urethral wall near the piezoelectric transducers must accompany the ultrasound treatment to prevent damage to the urethral wall. As a result, such a catheter must be equipped with a cooling fluid circuit carrying cold liquid through the urethral catheter to the site of the piezoelectric transducers, where the cold liquid may absorb some of the heat before being transported back out of the urethra through the catheter. Such a cooling fluid circuit adds complexity and bulkiness to the catheter, and is further associated with safety regulatory requirements relating to introducing a foreign liquid to a patient. Advantageously, the presently disclosed ultrasound transducer116, by virtue of the negligible heat generation of CMUT cells150, may operate safely with much lower cooling capacity. Solid state cooling, as provided by thermoelectric cooler114, is sufficient. Solid state cooling offers a high degree of temperature control. Since the cooling provided by thermoelectric coolers is governed by the Peltier effect, thermoelectric coolers may be turned on and off instantaneously and the degree of cooling is easily adjustable. In contrast, cooling based upon passive heat exchange with a thermal reservoir, e.g., water-cooling or other liquid cooling, is associated with slower on/off transitions due to the thermal mass of the coolant. Thus, the operation of thermoelectric cooler114may be easily and rapidly adjusted as needed during ultrasound treatment by CMUT array112. It is even possible to run thermoelectric cooler114in reverse to heat the non-target tissue if necessary, for example to prevent or compensate for over-cooling.

In the embodiment ofFIG. 1, medical device100is communicatively coupled with a control module140in an ultrasound treatment system130, and handle120includes electronic circuitry associated with operation of CMUT array112and thermoelectric cooler114. Control module140controls the electronic circuitry of handle120to operate CMUT array112and thermoelectric cooler114according to a treatment procedure. Without departing from the scope hereof, the electronic circuitry of handle120may instead be integrated in or with control module140externally to handle120, or control module140may be implemented in handle120together with the electronic circuitry of handle120.

In addition to generating ultrasound to treat the target tissue (e.g., prostate192), CMUT array112may perform ultrasound imaging of the target tissue (or other tissue in the field of view of CMUT array112). In one example, control module140utilizes ultrasound images of the target tissue recorded by CMUT array112to evaluate the progress of ultrasound treatment of the target tissue and adjust ultrasound exposure of target tissue by CMUT array112according to this evaluation. In one treatment protocol example, control module140commands CMUT array112to alternate between (a) emitting ultrasound at a high energy level to heat the target tissue and (b) imaging the target tissue (and/or other tissue in the field of view of CMUT array112) by emitting ultrasound at a lower energy level and detecting ultrasound reflected back to CMUT array112by the tissue.

FIG. 2illustrates one CMUT-TEC device200having a CMUT array210and at least one thermoelectric cooler220. CMUT-TEC device200is, for example, an embodiment of ultrasound transducer116,FIG. 1. Alternatively, CMUT-TEC device200may be deployed in a different catheter. Or, CMUT-TEC device200may be configured for operation without a catheter, for example for placement on the skin or a surgically exposed surface of a patient.

CMUT array210includes an array of CMUTs150configured to emit ultrasound270from an ultrasound emission face212to target tissue280. Thermoelectric coolers220are configured to cool, by the Peltier effect, non-target tissue290heated directly or indirectly by ultrasound270.

In certain embodiments, CMUT-TEC device200includes one or more sensors230that sense one or more properties of non-target tissue290and/or target tissue280. Sensor(s)230may, for example, sense temperature, pressure, or both. Each sensor230is for example a solid state sensor, such as a solid state temperature sensor or a solid state pressure sensor.

Accordingly, sensor(s)230may sense one or more properties indicative of the direct or indirect effect of ultrasound270on non-target tissue290. For example, an operator or an automatic controller may at least temporarily cease, reduce, or redirect emission of ultrasound270by CMUT array210when sensor(s)230sense that a property of non-target tissue290is outside an acceptable range, such as a temperature that exceeds a threshold temperature or a pressure that exceeds a threshold pressure. In one use scenario associated with ultrasound treatment of prostate192from urethra194, the threshold temperature is in the range between 41 and 45 degrees Celsius (C), such as 42 degrees C., to prevent damage to urethra194. Heating of target tissue280, and potentially also non-target tissue290, may cause swelling of the tissue. An operator or automatic controller may at least temporarily cease, reduce, or redirect emission of ultrasound270by CMUT array210when sensor(s)230sense a pressure that exceeds a threshold pressure, so as to keep the degree of swelling below a certain level. An operator or automatic controller may also adjust the operation of thermoelectric cooler114based upon temperature measurements provided by sensor(s)230.

In other embodiments, sensor(s)230sense one or more properties indicative of the progress of treatment of target tissue280by ultrasound270. For example, sensor(s)230may sense the temperature of target tissue280to facilitate evaluation of the difference between a target temperature and the measured temperature of target tissue280; sensor(s)230may sense the temperature of non-target tissue290to facilitate deduction of an at least approximate temperature of target tissue280from this measured temperature together with backpropagation to target tissue280using a thermal model; and/or sensor(s)230may sense the pressure of target tissue280and/or non-target tissue290to facilitate evaluation of heating of target tissue280from the measured pressure together with known characteristics of heat-induced swelling of tissue. In one use scenario, information obtained based upon measurements performed by sensor(s)230is combined with information obtained from ultrasound images to determine a property of target tissue280, such as a necrosis, temperature, and/or volume of target tissue280. The ultrasound images may be obtained using CMUT array210.

Although not shown inFIG. 2, it should be understood that CMUT-TEC device200may be equipped with electrical connections that connect CMUT array210and each thermoelectric cooler220(and optionally also each sensor230) to external electronic circuitry located outside CMUT-TEC device200. When CMUT-TEC device200is implemented in catheter110, electrical connections between CMUT-TEC device200and the external electronic circuitry may run through catheter110to handle120. In one example, the external electronic circuitry drives CMUT array210and each thermoelectric cooler220(and optionally each sensor230), and may also receive ultrasound imaging signals from CMUT array210and/or sensor signals from sensor(s)230. Alternatively, a portion of the electronic circuitry is located onboard CMUT-TEC device200.

FIG. 3illustrates CMUT-TEC device200in an exemplary use scenario, wherein CMUT-TEC device200is positioned in a body channel392to treat target tissue380. Body channel392has a wall390. CMUT array210emits ultrasound270to target tissue380. Ultrasound270is at least partly converted to heat370in target tissue380. A portion of heat370may diffuse to adjacent non-target tissue. In addition, non-target tissue between CMUT-TEC device200and target tissue380, such as wall390, is directly exposed to ultrasound270resulting in direct generation of some amount of heat370in this non-target tissue. Thermoelectric cooler(s)220cool at least a portion of wall390to prevent heat-induced damage to wall390.

In operation, a voltage drop is applied to thermoelectric cooler(s)220to generate a hot side424and a cold side422through the Peltier effect. The direction of the voltage drop is such that cold side422of each thermoelectric cooler220is in thermal coupling480with CMUT array210, which is in thermal coupling470with non-target tissue290.

FIG. 5illustrates another CMUT-TEC device500configured to thermally couple thermoelectric cooler(s)220to non-target tissue290via CMUT array210, such that thermoelectric cooler(s)220may cool non-target tissue290via a thermal pathway passing through CMUT array210. CMUT-TEC device500is an embodiment of CMUT-TEC device400,FIG. 4. CMUT-TEC device500includes a lens510coupled to ultrasound emission face212of CMUT array210. Lens510focuses ultrasound270, for example on target tissue280. In one embodiment, CMUT-TEC device500is elongated and configured for implemention in a catheter, such as catheter110,FIG. 1, with the elongated dimension (see elongated dimension340inFIG. 3) being aligned with the longitudinal axis of the catheter. In this embodiment, lens510focuses ultrasound270to a certain distance in the elevation direction (see elevation direction350inFIG. 3); that is, lens510manipulates emission of ultrasound270along the direction perpendicular to the elongated dimension340of CMUT-TEC device500. In operation, lens510is in physical contact with non-target tissue290, optionally via fixture260, and therefore provides thermal coupling between CMUT array210and non-target tissue290. Lens510forms part of the thermal pathway between thermoelectric cooler(s)220and non-target tissue290. In the embodiment shown inFIG. 5, thermoelectric cooler(s)220are mounted to, or co-fabricated with, a side of CMUT array210that is opposite ultrasound emission face212. However, without departing from the scope hereof, thermoelectric cooler(s)220may be mounted to or co-fabricated with (a) another side of CMUT array210, (b) fixture260, or (c) tubing of a catheter in which CMUT-TEC device500is implemented.

In an embodiment, thermoelectric cooler(s)220are bonded to CMUT array210by a thermal adhesive. In another embodiment, thermoelectric cooler(s)220are contact bonded to CMUT array210. In yet another embodiment, fixture260holds thermoelectric cooler(s)220in physical contact with CMUT array210. Without departing from the scope hereof, an intermediate substrate (for example containing electrical connections for one or both of CMUT array210and thermoelectric cooler(s)220) may be positioned between CMUT array210and thermoelectric cooler(s)220. In a further embodiment, CMUT array210is fabricated directly on thermoelectric cooler(s)220.

Lens510may be substantially composed of silicone rubber, such as polydimethylsiloxane (for example Sylgard, e.g., Sylgard 160) or another silicone rubber having a lower ultrasound attenuation coefficient than polydimethylsiloxane (for example a room-temperature-vulcanizing silicone, e.g., Momentive RTV-615). A lens material characterized by a low ultrasound attenuation coefficient reduces the amount of ultrasound absorbed by lens510, thus (a) maximizing ultrasound delivery to target tissue280and (b) minimizing heating of non-target tissue290from ultrasound-induced heating of lens510. When CMUT-TEC device500is configured for implementation in a urethral catheter for ultrasound treatment of prostate192from urethra194, the focal length of lens510may be in the range between 10 and 20 millimeters, such as 15 millimeters.

FIG. 7illustrates one medical device700that includes CMUT-TEC device200(having CMUT array210and thermoelectric coolers220) and a solid thermal conductor710that conducts heat away from CMUT-TEC device200. Medical device700is an embodiment of CMUT-TEC device400,FIG. 4. Solid thermal conductor710is thermally coupled to hot side424of each thermoelectric cooler220. As thermoelectric cooler220cools non-target tissue290, heat is transported to hot side424, to be conducted away from thermoelectric cooler220by solid thermal conductor710.

In one embodiment, solid thermal conductor710includes or is substantially composed of metal, such as copper, silver, and/or aluminum. In one example, solid thermal conductor710is a metal rod, such as a copper rod. In another example, solid thermal conductor710includes a plurality of braided metal wires, such as a plurality of braided copper wires. The braided metal wires may be configured to allow solid metal conductor710to flex, for example if the path available to solid metal conductor710is not straight. Such flexibility may advantageously improve patient comfort when solid thermal conductor710is positioned along a catheter passing through body channel392, particularly in situations where solid metal conductor710is placed in body channel392for an extended period of time or if repositioning/reorientation of the catheter is required. In another embodiment, solid thermal conductor710includes or is substantially composed of a non-metallic thermal conductor, for example a thermally conductive nanomaterial such as thermally conductive nanofibers. In yet another embodiment, solid thermal conductor710includes or is substantially composed of a thermally conductive nanocomposite. In a further embodiment, solid thermal conductor710includes or is substantially composed of a metamaterial.

Solid thermal conductor710may extend beyond medical device700to conduct heat780further away from medical device700. For example, when implemented in catheter110, solid thermal conductor710may extend at least partway toward proximal end102to remove heat780from thermoelectric cooler(s)220and from non-target tissue290. Heat780is then distributed along a portion of the length of catheter110, and/or conducted by solid thermal conductor710to a heat exchanger (not shown) positioned outside catheter110, for example in handle120.

FIG. 8illustrates one one-dimensional (1D) CMUT array800.FIG. 8shows a top plan view of an ultrasound emission face812of 1D CMUT array800. 1D CMUT array800is an embodiment of CMUT array210and of CMUT array112. 1D CMUT array800includes a substrate810(e.g., a silicon substrate) having a 1D array of CMUT elements820arranged along an axis890. For clarity of illustration, not all CMUT elements820are labeled inFIG. 8. Axis890refers to a direction that, when an associated device is implemented in catheter110, is substantially parallel to the longitudinal axis of catheter110. Herein, the longitudinal axis of catheter110refers to the general path described by catheter110from proximal end102to distal end104. This path may or may not be a straight line, and the direction of the longitudinal axis of catheter110may therefore vary along the path between proximal end102and distal end104.

1D CMUT array800has extent880along axis890and extent882in the direction perpendicular to axis890. In one embodiment, extent880is greater than extent882, such that 1D CMUT array800is elongated along axis890. For embodiments of CMUT array800intended for insertion into body channel392with axis890generally oriented along the length of body channel392(see, for example,FIG. 3), extent882may be limited by the width of body channel392, whereas extent880may be configured based upon a typical extent of target tissue380in the direction along the length of body channel392. In one embodiment adapted for implementation in a urethral catheter, extent882is in the range between 2.5 and 3.5 millimeters or in the range between 3.0 and 3.2 millimeters, and extent880is in the range between 10 and 50 millimeters. For example, an embodiment with 128 CMUT elements820having a center-to-center spacing of 0.2 millimeters, extent880is approximately one inch. In another embodiment adapted for implementation in a urethral catheter, extent882is 5 millimeters or less.

The number of CMUT elements820may be different from that shown inFIG. 8, without departing from the scope hereof. For example, 1D CMUT array800may include 128 or 256 CMUT elements820. Each CMUT element820may have the shape of an elongated rectangle, as shown inFIG. 8, or have a different shape such as square, circular, or oval.

Each CMUT element820includes one or more CMUT cells150. In each CMUT cell150of CMUT element820, membrane160has electrode162on a side822of CMUT element820facing in the same direction as ultrasound emission face812. The electrical connection to electrode162of each CMUT cell150(for clarity not shown inFIG. 8) may be located on ultrasound emission face812, or be passed through substrate810to a side of substrate810opposite ultrasound emission face812. In each CMUT cell150of CMUT element820, substrate180(seeFIG. 1) may be a layer of substrate810that is shared between all CMUT cells150of 1D CMUT array800and has a single electrical connection. This layer may be interrupted by through-wafer electrical connections to electrodes162of CMUT elements820from the side of substrate810opposite ultrasound emission face812. When 1D CMUT array800is implemented in catheter110, a flex cable may connect electrical connections of 1D CMUT array800to electronic circuitry configured to drive CMUT elements820. This electronic circuitry is, for example, located in handle120or integrated in CMUT-TEC device116in the form of an application-specific integrated circuit (ASIC).

1D CMUT array800is compatible with beamforming of ultrasound270, wherein some of CMUT elements820receive an electrical drive signal that is phase shifted compared to that received by other CMUT elements820. In one beamforming scenario, CMUT elements820are divided into eight different groups. All CMUT elements820belonging to the same group receives the same electrical drive signal, but different groups of CMUT elements820may receive different electrical drive signals. Although CMUT elements820may be divided into more or fewer groups, it is found that eight different groups provide sufficient spatial resolution of the beamformed ultrasound generated by 1D CMUT array800.

In one use scenario, some of CMUT elements820are dedicated to generate ultrasound270to treat target tissue280, while other CMUT elements820perform ultrasound imaging of target tissue280. In another use scenario, at least some of CMUT elements820may, during some periods, generate ultrasound for treatment of target tissue280and, during other periods, perform ultrasound imaging of target tissue280.

In certain embodiments, 1D CMUT array800further includes one or more sensors830/832disposed on ultrasound emission face812or formed in substrate810at or near ultrasound emission face812. For clarity of illustration, not all sensors830/832are labeled inFIG. 8. Each sensor830/832is an embodiment of sensor230and senses a property of tissue near 1D CMUT array800. In one embodiment, 1D CMUT array800includes one or more temperature sensors830and/or one or more pressure sensors832. Sensors830/832may, as shown inFIG. 8, be positioned within the portion of ultrasound emission face812occupied by CMUT elements820or, alternatively, be positioned outside this portion of ultrasound emission face812. In the embodiment shown inFIG. 2, the presence of sensors830/832shrinks the active area of some of CMUT elements820. Without departing from the scope hereof, all CMUT elements820may be identically sized, and sensors830/832positioned on ultrasound emission face812without spatially restricting the size of some CMUT elements820compared to other CMUT elements820.

1D CMUT array820may be implemented in CMUT-TEC device500such that lens510manipulates the extent of ultrasound270emitted by CMUT array800in the dimension perpendicular to axis890. In this implementation, beamforming of ultrasound270may be combined with the action of lens510to achieve two-dimensional focusing of ultrasound270.

FIG. 9illustrates a 1.5D CMUT array900.FIG. 9shows a top plan view of ultrasound emission face812of 1.5D CMUT array900. 1.5D CMUT array900is an embodiment of CMUT array210and of CMUT array112. “1.5D” is a term of art in the field of beamforming. A 1.5D transducer array is a two-dimensional transducer array that (a) has high spatial resolution in first dimension and much more limited spatial resolution in an orthogonal second dimension, and (b) is operated in a manner that is symmetrical about a line parallel to the first dimension and centered in the second dimension. For example, a 1.5D transducer array may have three rows, with 128 or 256 transducers in each row, to form an array with 3×128 or 3×256 transducers.

1.5D CMUT array900is similar to 1D CMUT array800except for the one-dimensional array of CMUT elements820being replaced by three rows of CMUT elements: a central row930of CMUT elements920, and two outer rows932of CMUT elements922. Each of rows930and932has N CMUT elements920/922(wherein N is an integer significantly greater than 3, such as 128 or 256) to form a 3×N array of CMUT elements920/922. CMUT element922is similar to CMUT element820, but may have smaller extent in the direction perpendicular to axis890. CMUT element920is similar to CMUT element920except for having smaller extent than CMUT element920in the direction perpendicular to axis890. Without departing from the scope hereof, 1.5D CMUT array900may include more rows of CMUT elements, such as a total of five rows. 1.5D CMUT array900allows for some degree of beamforming of ultrasound in the dimension perpendicular to axis890, although the spatial resolution of beamforming in the dimension perpendicular to axis890is less than the spatial resolution of beamforming in the dimension parallel to axis890. This beamforming may serve to electronically focus the ultrasound emitted by 1.5D CMUT array900, in the dimension orthogonal to axis890, to achieve focus at a desired distance away from the emission face of 1.5D CMUT array900. 1.5D CMUT array900may be implemented with a lens, such as lens510, for focusing of ultrasound in conjunction with electronic beamforming, or 1.5D CMUT array900may be implemented without lens510and rely on beamforming for focusing.

FIG. 10illustrates a 1.75D CMUT array1000.FIG. 10shows a top plan view of ultrasound emission face812of 1.75D CMUT array1000. 1.75D CMUT array1000is an embodiment of CMUT array210and of CMUT array112. “1.75D” is a term of art in the field of beamforming. A 1.75D transducer array is a two-dimensional transducer array that (a) has high spatial resolution in first dimension and much more limited spatial resolution in an orthogonal second dimension, and (b) is operated in a manner that is asymmetrical about a line parallel to the first dimension and centered in the second dimension. For example, a 1.75D transducer array may have five rows, with 128 or 256 transducers in each row, to form an array with 5×128 or 5×256 transducers.

1.75D CMUT array1000is similar to 1.5D CMUT array900except for including additional rows of CMUT elements. 1.75D CMUT array1000includes five rows of CMUT elements: a central row1030of CMUT elements1020, two rows1032of CMUT elements1022flanking row1030, and two outer rows1034of CMUT elements1024. Each of rows1030,1032and1034has N CMUT elements1020/1022/1024(wherein N is an integer significantly greater than 5, such as 128 or 256) to form a 5×N array of CMUT elements1020/1022/1024. CMUT element1030is similar to CMUT element820, but may have smaller extent in the direction perpendicular to axis890. CMUT element1022is similar to CMUT element1020except for having smaller extent than CMUT element1020in the direction perpendicular to axis890, and CMUT element1024is similar to CMUT element1022except for having smaller extent than CMUT element1022in the direction perpendicular to axis890. Without departing from the scope hereof, 1.75D CMUT array1000may include more rows of CMUT elements. 1.75D CMUT array1000allows for some degree of beamforming of ultrasound in the dimension perpendicular to axis890, although the spatial resolution of beamforming in the dimension perpendicular to axis890is less than the spatial resolution of beamforming in the dimension parallel to axis890. This beamforming may serve to electronically focus the ultrasound emitted by 1.75D CMUT array1000, in the dimension orthogonal to axis890, to achieve focus at a desired distance away from the emission face of 1.75D CMUT array1000as well as at a desired location along the dimension orthogonal to axis890. 1.75D CMUT array1000may be implemented with a lens, such as lens510, for focusing of ultrasound in conjunction with electronic beamforming, or 1.75D CMUT array1000may be implemented without lens510and rely on beamforming for focusing.

2D CMUT array1100may include sensors1130and/or sensors1132. Sensor1130is similar to sensor830, and sensor1132is similar to sensor832. Each of sensors1130/1132may occupy one site in the array formed by CMUT elements1120, such that this particular site has a sensor1130/1132instead of a CMUT element1120. Alternatively, sensors1130/1132are positioned in locations that do not interfere with the 2D array of CMUT elements1120. Without departing from the scope hereof, the shape of CMUT elements1120may be different from that shown inFIG. 11. For example, each CMUT element1120may be square, rectangular, or oval.

FIGS. 12A and 12Billustrate one CMUT-TEC device1200. CMUT-TEC device1200is an embodiment of CMUT-TEC device200. CMUT-TEC device1200includes a thermoelectric cooler1210with CMUT array210disposed or formed directly on thermoelectric cooler1210. Thermoelectric cooler1210is an embodiment of thermoelectric cooler220or114.FIG. 12Ais a cross sectional view of CMUT-TEC device1200, with the cross section taken in a plane perpendicular to ultrasound emission face212of CMUT array210.FIG. 12Bis a top plan view of the semiconductors of thermoelectric cooler1210, with the view being in a direction from ultrasound emission face212toward the semiconductors of thermoelectric cooler1210.FIGS. 12A and 12Bare best viewed together in the following description.

Thermoelectric cooler1210includes a plurality of n-type semiconductors1220and a plurality of p-type semiconductors1222electrically coupled in series by electrodes1230such that the series alternates between the n-type semiconductors and the p-type semiconductors, as indicated by line1290inFIG. 12B. Without departing from the scope hereof, electrodes1230may be arranged differently from what is shown inFIGS. 12A and 12B, and line1290may take a different path. In addition, it should be understood that the number of n-type semiconductors1220and a plurality of p-type semiconductors1222may be different from what is shown inFIG. 12B. In operation, a voltage drop is applied across the series of n-type semiconductors1220and the plurality of p-type semiconductors1222to form a cold side1252of thermoelectric cooler1210facing CMUT array210and a hot side1250of thermoelectric cooler1210facing away from CMUT array210. Thermoelectric cooler1210further includes a thermal conductor1240that thermally couples n-type semiconductors1220and p-type semiconductors1222on hot side1250. Optionally, thermoelectric cooler1210also includes a thermal conductor1242that thermally couples n-type semiconductors1220and p-type semiconductors1222on cold side1252. Alternatively, a portion of CMUT array210forms thermal conductor1242. Each of thermal conductors1240and1242are electrical insulators. In one example, each of thermal conductors1240and1242are formed from a thin film of silicon dioxide, silicon nitride, or another thermally conductive dielectric.

In certain embodiments, CMUT-TEC device1200includes a solid thermal conductor1260that is thermally coupled to hot side1250and configured to conduct heat away from hot side1250. Solid thermal conductor1260is an embodiment of solid thermal conductor710.

FIG. 13illustrates one CMUT-TEC device1300with two planar CMUT subarrays1310(1) and1310(2) having an adjustable angle therebetween. CMUT-TEC device1300is an embodiment of CMUT-TEC device200. CMUT subarrays1310(1) and1310(2) are thermally coupled to respective thermoelectric coolers1320(1) and1320(2). Each instance of CMUT subarray1310paired with the respective thermoelectric cooler1320may be similar to CMUT-TEC device1200. CMUT-TEC device1300may further include solid thermal conductors1330(1) and1330(2) that are thermally coupled to the hot sides of thermoelectric coolers1320(1) and1320(2), respectively.

CMUT-TEC device1300includes a hinge1340that enables pivoting of (a) CMUT subarray1310(2) and associated thermoelectric cooler1320(2) (and optionally solid thermal conductor1330(2)) relative to (b) CMUT subarray1310(1) and associated thermoelectric cooler1320(1) (and optionally solid thermal conductor1330(1)), as indicated by arrows1350. This pivoting action may serve to direct ultrasound270generated by CMUT subarrays1310to target tissue280and/or improve the ability of CMUT-TEC device1300to conform to curvature of body channel392.

CMUT-TEC device1300has extent1380in the direction along axis890. Extent1380is, for example, in the range between 10 millimeters and 50 millimeters.

FIG. 14is a pictorial view of one CMUT-TEC device1400with two planar CMUT subarrays1410(1) and1410(2) having an adjustable angle therebetween. CMUT-TEC device1400is an embodiment of CMUT-TEC device1300that allows pivoting of CMUT subarray1410(2) by an angle1420away from being coplanar with CMUT subarray1410(1). Angle1420is for example in the range up to 30 degrees, such as between 10 and 30 degrees.

FIG. 15illustrates one CMUT-TEC device1500with two planar CMUT subarrays1510(1) and1510(2) angled away from each other. CMUT-TEC device1500is an embodiment of CMUT-TEC device200. CMUT subarrays1510(1) and1310(2) are thermally coupled to respective thermoelectric coolers1520(1) and1520(2). Each instance of CMUT subarray1510paired with the respective thermoelectric cooler1520may be similar to CMUT-TEC device1200. CMUT-TEC device1500may further include solid thermal conductors1530(1) and1530(2) that are thermally coupled to the hot sides of thermoelectric coolers1520(1) and1520(2), respectively. Without departing from the scope hereof, thermoelectric coolers1520(1) and1520(2) may be implemented as a single thermoelectric cooler that is thermally coupled to both CMUT subarray1510(1) and1510(2).

CMUT-TEC device1500includes a mechanical coupler1540that positions (a) CMUT subarray1510(2) and associated thermoelectric cooler1520(2) (and optionally solid thermal conductor1530(2)) at an angle to (b) CMUT subarray1510(1) and associated thermoelectric cooler1520(1) (and optionally solid thermal conductor1530(1)), in such a manner that ultrasound emission faces1512of CMUT subarrays1510face away from each other to a certain extent. CMUT-TEC device1500thereby has greater angular range than that achievable by a single planar CMUT-TEC device. Each ultrasound emission face1512is substantially parallel to axis890such that, when implemented in catheter110, CMUT-TEC device1500is oriented with each ultrasound emission face1512substantially parallel to the longitudinal axis of catheter110. In implementations intended for ultrasound treatment of prostate192from urethra194, the two ultrasound emission faces1512of CMUT-TEC device1500may facilitate simultaneous ultrasound exposure of a greater portion of prostate192, for example such that less or no rotation of CMUT-TEC device1500is needed during ultrasound treatment of prostate192.

In an embodiment, the angle between normal vectors1514of ultrasound emission faces1512is between 45 and 90 degrees, such as in the range between 60 and 65 degrees. Each CMUT subarray1510may be elongated in the dimension parallel to axis890.

CMUT-TEC device1500has extent1582in a dimension orthogonal to axis890. Extent1582is, for example, in the range between 2.5 millimeters and 3.5 millimeters or in the range between 2 and 5 millimeters, in an embodiment compatible with implementation in a urethral catheter.

FIG. 16is a pictorial view of one CMUT-TEC device1600with two planar CMUT subarrays1610(1) and1610(2) angled away from each other. CMUT-TEC device1600is an embodiment of CMUT-TEC device1500, wherein each CMUT subarray1610is elongated in the dimension parallel to axis890.

FIG. 17illustrates one catheter1700with a CMUT-TEC transducer device.FIG. 17is a cross sectional view of catheter1700with the cross section being parallel to a longitudinal axis1790of catheter1700. In one embodiment, catheter1700is rigid and straight such that the direction of longitudinal axis1790is always constant along the length of catheter1700. In another embodiment, catheter1700is pliable and may be bent such that the direction of longitudinal axis1790may vary along the length of catheter1700. In relation to this embodiment, the cross sectional view ofFIG. 17corresponds to a view of catheter1700in its straight configuration. Without departing from the scope hereof, catheter1700may be configured to always be bent, either in a rigid manner or a pliable manner. In this case, the cross sectional view ofFIG. 17corresponds to a straightened version of catheter1700.

In one embodiment, solid thermal conductor1720includes or is substantially composed of metal, such as copper, silver, and/or aluminum. In one example, solid thermal conductor1720is a metal rod, such as a copper rod. In another example, solid thermal conductor1720includes a plurality of braided metal wires, such as a plurality of braided copper wires. The braided metal wires may be configured to allow solid thermal conductor1720to flex, for example if the path available to solid thermal conductor1720is not straight. As discussed above in reference toFIG. 7and solid thermal conductor710, such flexibility may improve patient comfort when catheter1700is placed in body channel392, in particular if catheter1700is left in body channel392for an extended period of time or if repositioning/reorientation of catheter1700is required. In another embodiment, solid thermal conductor1720includes or is substantially composed of a non-metallic thermal conductor, for example a thermally conductive nanomaterial such as thermally conductive nanofibers. In yet another embodiment, solid thermal conductor1720includes or is substantially composed of a thermally conductive nanocomposite. In a further embodiment, solid thermal conductor1720includes or is substantially composed of a metamaterial.

In the embodiment depicted inFIG. 17, solid thermal conductor1720extends all the way to the extreme of proximal end102to conduct at least a portion of the heat removed from CMUT-TEC device200out of catheter1700. This embodiment of catheter1700may be implemented in a device1750together with a heat exchanger1730coupled to solid thermal conductor1720at or beyond proximal end102. Heat exchanger1730cools solid thermal conductor1720outside the body channel into which catheter1700is inserted. Heat exchanger1730may employ liquid cooling or gas cooling. In one example, heat exchanger1730includes cooling fins for cooling of solid thermal conductor1720. In another example, heat exchanger1730circulates liquid or gas by solid thermal conductor1720to cool solid thermal conductor1720, at least during operation of CMUT-TEC device200. Device1750may implement heat exchanger1730in a handle1740. Handle1740is an embodiment of handle120.

In an alternate embodiment, not shown inFIG. 17, solid thermal conductor1720extends only partway to proximal end102. In this embodiment, solid thermal conductor1720may redistribute, along a portion of the length of catheter, heat removed from CMUT-TEC device200, while taking advantage of the catheter to ensure that the temperature of the catheter wall in contact with non-target tissue does not exceed a set threshold. In one such example, solid thermal conductor1720uniformly redistributes the heat along at least part of catheter1700in the longitudinal direction (associated with longitudinal axis1790). This embodiment of catheter1700may also be coupled with handle1740to form an alternate embodiment of device1750that includes handle1740but not heat exchanger1730.

Catheter1700has extent1780along longitudinal axis1790and extent1782in dimension orthogonal to longitudinal axis1790. The cross section of catheter1700, orthogonal to axis1790may be circular, such that extent1782is a diameter. In one embodiment, extent1780is sufficiently long that distal end104can be positioned in body channel392at or near target tissue380while the proximate end102is at the exit of body channel392or outside body channel392. In certain embodiments, extent1782is in the range from 2 to 10 millimeters. In one such embodiment, catheter1700is configured as a urethral catheter, and extent1782may be in the range from 3 to 7 millimeters, such as around 5 millimeters.

FIG. 18illustrates another catheter1800with a CMUT-TEC device, in a cross sectional view similar to that used inFIG. 17. Catheter1800is an embodiment of catheter1700, which further includes electrical connections1820from CMUT-TEC device200to proximal end102. Electrical connections1820are configured to connect CMUT-TEC device200to external electronic circuitry1830. Electronic circuitry1830includes (a) ultrasound driving circuitry generating drive signals that are transmitted to CMUT array210of CMUT-TEC device200via some of electrical connections1820, and (b) Peltier driving circuitry that powers thermoelectric cooler(s)220of CMUT-TEC device200via other ones of electrical connections1820. Electronic circuitry1830may further include circuitry that receives and processes ultrasound imaging signals received from CMUT array210via some of electrical connections1820.

Catheter1800and electronic circuitry1830may be implemented together in a device1850. In an embodiment, device1850includes a handle1840that contains electronic circuitry1830. Handle1840may further include heat exchanger1730.

Without departing from the scope hereof, at least some of electrical connections1820may serve to both (a) couple electronic circuitry1830to CMUT-TEC device200and (b) conduct heat away from thermoelectric cooler(s)220of CMUT-TEC device200. In this case, electrical connections1820may replace solid thermal conductor1720, or reduce the requirements to the heat conduction capacity of solid thermal conductor1720. In one such example, some of electrical connections1820are coaxial cables and the outer conductors of the coaxial cables are thermally coupled to the hot side of thermoelectric cooler(s)220to remove heat from thermoelectric cooler(s)220. Also without departing from the scope hereof, electronic circuitry1830may be implemented externally to device1850, for example in or integrated with control module140externally to device1850.

FIGS. 19-21illustrate yet another catheter1900with a CMUT-TEC device.FIG. 19shows catheter1900in a cross sectional view similar to that used inFIG. 17.FIG. 20shows catheter1900in a cross sectional view indicated by line A-A′ inFIG. 19.FIG. 21shows a catheter tip1910of catheter1900in a cross sectional view indicated by line B-B′ inFIG. 19.FIGS. 19-21are best viewed together in the following description.

Catheter1900is an embodiment of catheter1700. Catheter1900may further include electrical connections1820, in which case catheter1900is an embodiment of catheter1800. Catheter1900further includes a tubular catheter jacket1920defining the wall of catheter1900. Tubular catheter jacket1920has a window1922positioned above ultrasound emission face212of CMUT-TEC device200. Window1922may accommodate lens510or another material capable of transmitting ultrasound. Tubular catheter jacket1920has outer diameter2010and inner diameter2012. In an embodiment configured for use as a urethral catheter, outer diameter2010is in the range from 3 to 7 millimeters, such as around 5 millimeters, and inner diameter2012is in the range from 2.5 to 6.5 millimeters, such as around 4 millimeters. Tubular catheter jacket may be rigid or pliable. In one embodiment, tubular catheter jacket includes or is substantially composed of a metal, such as stainless steel. This embodiment of tubular catheter jacket1920is rigid. In another embodiment, tubular catheter jacket1920includes or is substantially composed of a polymer. This embodiment of tubular catheter jacket1920may be rigid or pliable. Tubular catheter jacket1920contains solid thermal conductor1720and, when included, electrical connections1820(seeFIG. 20). The positioning of solid thermal conductor1720and optional electrical connections1820may be different from that shown inFIG. 20, without departing from the scope hereof. For example, solid thermal conductor1720may be located closer to the wall defined by tubular catheter jacket1920.

In certain embodiments, tubular catheter jacket1920is thermally insulating to prevent or reduce transport of heat, conducted by solid thermal conductor1720(and/or electrical connections1820), through the wall of tubular catheter jacket1920. When catheter1900is positioned in a body channel392(seeFIG. 3orFIG. 6), such thermal insulation of tubular catheter jacket1920helps prevent heat-induced damage to wall390due to heat escaping catheter1900. In one scenario, thermal insulation of tubular catheter jacket1920prevents solid thermal conductor1720from burning wall390. In one thermally insulating embodiment, tubular catheter jacket1920includes or is substantially composed of a solid material that is a poor thermal conductor, such as a polymer or rubber. In another thermally insulating embodiment, tubular catheter jacket1920includes or is substantially composed of a porous material with the pores resulting in a low thermal conductivity of the porous material. In yet another thermally insulating embodiment, tubular catheter jacket1920includes a vacuum layer.

In an alternative embodiment, insulating outer sheaths of electrical connections1820at least partly thermally insulates solid thermal conductor1720from tubular catheter jacket1920, such that tubular catheter jacket1920may be thermally conductive or at least be a less effective thermal insulator. In such embodiments, solid thermal conductor1720may advantageously be surrounded by electrical connections1820.

Although depicted inFIG. 21as having sharp edges and gaps in the regions2190near sides of CMUT array210(and optional lens510), catheter tip1910may be configured with a smooth outer surface to improve patient comfort and prevent damage to the body channel into which catheter1900is inserted, without departing from the scope hereof. In one example, the contour of catheter tip1910in regions2190, and optionally also at lens510, is a continuation of the contour of tubular catheter jacket1920.

FIG. 22illustrates one catheter sleeve2200configured to encase catheter1900in a removable fashion.FIG. 22shows catheter sleeve2200and catheter1900in a cross sectional view similar to that used inFIG. 19. In one use scenario, catheter sleeve2200is placed over catheter1900prior to insertion of catheter1900into body channel392to treat target tissue380with ultrasound. After ultrasound treatment, catheter1900is extracted from catheter sleeve2200and from body channel392along direction2290, while catheter sleeve2200stays in body channel392. In a modification to this use scenario, catheter sleeve2200is first inserted into body channel392without catheter1900, whereafter catheter1900is inserted into catheter sleeve2200to position catheter1900in body channel392. Catheter sleeve2200may remain in body channel392(e.g., urethra194) for some time after ultrasound treatment of target tissue380(e.g., prostate192) by catheter1900, so as to monitor temperature and/or pressure of wall390(e.g., the wall of urethra194near prostate192). In addition, catheter sleeve2200may serve to keep body channel392open after ultrasound treatment, for example until a treatment induced swelling has subsided. In embodiments, where catheter sleeve2200is configured for use in urethra194to aid ultrasound treatment of prostate192, catheter sleeve2200may be left in urethra194after ultrasound treatment to prevent complete blockage of urethra, otherwise potentially resulting from treatment induced swelling, and allow passage of urine from bladder196through catheter sleeve2200.

Catheter sleeve2200has a window2222. When catheter1900is fully inserted into catheter sleeve2200, window2222is positioned over ultrasound emission face212of CMUT-TEC device200. Window2222may be an actual opening, or window2222may be covered by a material that is capable of transmitting ultrasound. In an alternative embodiment, catheter sleeve2200has no window2222. In this alternative embodiment, all of catheter sleeve2200or the portion of catheter sleeve2200is made of an ultrasound transmitting material, such as plastic. In one implementation, the ultrasound transmitting material encircles the region occupied by CMUT-TEC device200during treatment, to enable ultrasound exposure in 360 degrees. This implementation of catheter sleeve2200may provide access to all of prostate192from urethra194with no need for rotating catheter sleeve2200relative to urethra194.

Catheter sleeve2200may be rigid or pliable, or a combination thereof. For example, a distal portion of catheter sleeve2200configured to accommodate catheter tip1910may be rigid, while a more proximal portion is pliable. A fully or partly pliable embodiment of catheter sleeve2200may be compatible with a rigid or pliable embodiment of catheter1900.

Catheter sleeve2200may include a thermally insulating layer, or be substantially composed of a thermally insulating material, such that catheter sleeve2200is capable of protecting wall390from heat conducted by solid thermal conductor1720.

FIG. 23illustrates one catheter2350with CMUT-TEC device200, employing a tubular catheter jacket2300permitting removal of CMUT-TEC device200and associated electrical and thermal connections therefrom. Catheter2350is an embodiment of catheter1900that implements tubular catheter jacket1920as a removable tubular catheter jacket2300, thus allowing for extraction of CMUT-TEC device200, solid thermal conductor1720, and optional electrical connections1820from tubular catheter jacket2300along direction2390. The function of removable tubular catheter jacket2300may be similar to that of catheter sleeve2200discussed above in reference toFIG. 22.

Tubular catheter jacket2300has a window2312. When CMUT-TEC device200is fully inserted into tubular catheter jacket2300, window2312is positioned over ultrasound emission face212of CMUT-TEC device200. Window2312may be an actual opening, or window2312may be a material that is capable of transmitting ultrasound.

FIG. 24illustrates one catheter or catheter sleeve2400with solid state cooling. Catheter/catheter sleeve2400includes a tubular wall2410and at least one thermoelectric cooler2420coupled to tubular wall2410. Tubular wall2410is configured to be inserted into body channel392, and thermoelectric cooler(s)2420are configured to cool at least a portion of wall390of body channel392. Thermoelectric cooler(s)2420may cool wall390through direct physical contact between thermoelectric cooler(s)2420and wall390, or thermoelectric cooler(s)2420may cool wall390through thermal coupling via tubular wall2410. Tubular wall2410is, for example, a tubular catheter jacket or a tubular wall of a catheter sleeve. In the latter case, the catheter sleeve may encase other parts of catheter/catheter sleeve2400, such as thermoelectric cooler2420, in a removable manner similar to that discussed for catheter sleeve2200. In addition to thermoelectric cooler(s)2420, catheter/catheter sleeve2400may contain other functionality that serves one or more other purposes than cooling of wall390.

Tubular wall2410may be rigid or pliable. In one embodiment, tubular wall2410includes or is substantially composed of a metal, such as stainless steel. This embodiment of tubular wall2410is rigid. In another embodiment, tubular wall2410includes or is substantially composed of a polymer. This embodiment of tubular wall2410may be rigid or pliable, or a combination thereof.

FIG. 25illustrates one catheter or catheter sleeve2500having at least one thermoelectric cooler2520coupled to its tubular wall2510. Catheter/catheter sleeve2500is an embodiment of catheter/catheter sleeve2400, wherein the thermoelectric cooling is implemented in or on tubular wall2410to be thermally coupled to wall390of body channel392. Catheter/catheter sleeve2500may also form an embodiment of tubular catheter jacket1920. In the embodiment shown inFIG. 25, each thermoelectric cooler2520is on the outside of tubular wall2510. In this embodiment, each thermoelectric cooler2520may be in direct physical contact with wall390to cool wall390. In another embodiment, each thermoelectric cooler2520is on the inside of tubular wall2510or formed within the material of tubular wall2510, such that each thermoelectric cooler2520is thermally coupled to wall390when an associated portion of tubular wall2510is thermally coupled to wall390. In one use scenario, thermoelectric cooler(s)2520cool a portion of wall390prior to or after ultrasound treatment of target tissue280through this portion of wall390. In this scenario, catheter/catheter sleeve2500may be rotated in body channel392between cooling and ultrasound treatment such that a thermoelectric cooler(s)2520are placed in contact with a portion of wall390before and/or after CMUT array112is positioned to expose target tissue280to ultrasound through this portion of wall390.

In certain embodiments, catheter/catheter sleeve2500is configured to accommodate CMUT array112and associated electrical connections1820inside tubular wall2510, and thus form a catheter2550for ultrasound treatment of target tissue280with solid state cooling of non-target tissue290. In such embodiments of catheter2550, tubular wall2510may form or include a window2512that permits ultrasound emission from CMUT array112to target tissue280. Window2512may be similar to window2312. Catheter2550is an embodiment of catheter110implementing an embodiment of CMUT-TEC device200that has (a) an embodiment of thermoelectric cooler(s)114coupled to the catheter wall and (b) CMUT array112within the space contained by the catheter wall. Together, CMUT array112and thermoelectric cooler(s)114form an embodiment of CMUT-TEC device200.

In one embodiment of catheter2550, tubular wall2510permits extraction of CMUT array112and associated electrical connections1820from tubular wall2510along direction2590. This embodiment of tubular wall2510cooperates with thermoelectric cooler(s)2520to form an embodiment of tubular catheter jacket2300that further includes thermoelectric cooler(s)2520. The associated embodiment of catheter2550is similar to catheter2350, except that thermoelectric cooler(s)2520of catheter2550are coupled to tubular wall2510.

FIG. 26illustrates another catheter or catheter sleeve2600that has at least one thermoelectric cooler2520and a solid thermal conductor2620mechanically coupled to its tubular wall2610. Catheter/catheter sleeve2600is an embodiment of catheter/catheter sleeve2500, tubular wall2610is an embodiment of tubular wall2510, and solid thermal conductor2620is an embodiment of solid thermal conductor1720. Solid thermal conductor2620is thermally coupled to thermoelectric cooler(s)2520to conduct heat away from the hot side of thermoelectric cooler(s)2520during operation of thermoelectric cooler(s)2520.

To avoid direct physical contact between solid thermal conductor2620and wall390, solid thermal conductor2620is located on the inside of tubular wall2610, at least over the portion2680of tubular wall2610that is away from thermoelectric cooler(s)2520. Tubular wall2610may be thermally insulating to further prevent transport of heat from solid thermal conductor2620through tubular wall2610, and thus protect portions of wall390in contact with tubular wall2610from heat induced damage. Thermally insulated embodiments of tubular wall2610may be composed of materials similar to those discussed above in reference toFIG. 19for tubular catheter jacket1920. Alternatively, if tubular wall2610is a thermal conductor, solid thermal conductor2620may be thermally isolated from tubular wall2610.

Although shown inFIG. 26as extending all the way to the proximal end2602of tubular wall2610, solid thermal conductor2620may extend only partway from thermoelectric cooler(s)2520toward proximal end2602, as discussed above in reference toFIG. 17and solid thermal conductor1720.

In certain embodiments, catheter/catheter sleeve2600is configured to accommodate CMUT array112and associated electrical connections1820inside tubular wall2610, in a manner similar to that discussed above in reference toFIG. 25and catheter/catheter sleeve2500, and thus form a catheter2650for ultrasound treatment of target tissue280with solid state cooling of non-target tissue290. In such embodiments of catheter2650, tubular wall2610may include window2512to permit ultrasound emission from CMUT array112to target tissue280. Catheter2650is an embodiment of catheter1800or1900.

In one embodiment of catheter2650, tubular wall2610permits extraction of CMUT array112and associated electrical connections1820from tubular wall2610along direction2690. This embodiment of tubular wall2610cooperates with thermoelectric cooler(s)2520and solid thermal conductor2620to form an embodiment of tubular catheter jacket2300that further includes thermoelectric cooler(s)2520and solid thermal conductor2620. The associated embodiment of catheter2650is similar to catheter2350, except that thermoelectric cooler(s)2520and solid thermal conductor2620of catheter2650are coupled to tubular wall2610.

FIGS. 27A and 27Billustrate one catheter or catheter sleeve2700with thermoelectric cooling. Catheter/catheter sleeve2700is an embodiment of catheter/catheter sleeve2500.FIGS. 27A and 27Bare orthogonal cross sectional views of catheter/catheter sleeve2700and are best viewed together in the following description. Catheter/catheter sleeve2700includes a tubular wall2710and one or more thermoelectric coolers2720on the outside of tubular wall2710. Thermoelectric cooler(s)2720may span around the circumference of tubular wall2710, or cover only one or more sections along the circumference of tubular wall2710. Thermoelectric cooler2720is an embodiment of thermoelectric cooler2520and may be implemented in either one of catheter/catheter sleeve2500and catheter/catheter sleeve2600.

Each thermoelectric cooler2720includes (a) a thermal conductor2730disposed on tubular wall2710, (b) a thermal conductor2732a distance away from tubular wall2710, and (c) a plurality of n-type semiconductors2740and a plurality of p-type semiconductors2742electrically coupled in series by metal electrodes2750and2752such that the series alternates between n-type semiconductors2740and p-type semiconductors2742. Thermal conductors2730and2732are electrical insulators. In operation, a voltage drop is applied across the series of n-type semiconductors2740and p-type semiconductors2742to form a cold side at thermal conductor2732, which is capable of cooling wall390of body channel392.

In one embodiment, at least the portion of tubular wall2710supporting thermoelectric cooler(s)2720is rigid, and n-type semiconductors2740and p-type semiconductors2742are rigidly coupled in a configuration that matches the curvature of tubular wall2710. In another embodiment, at least the portion of tubular wall2710supporting thermoelectric cooler(s)2720is pliable, and metal electrodes2750and2752and thermal conductors2730and2732are flexible, such that thermoelectric cooler(s)2720are capable of conforming to bending of the associated portion of tubular wall2710.

Although not shown inFIG. 27B, the outer surface of catheter/catheter sleeve2700may be smooth. Also without departing from the scope hereof, thermoelectric coolers2720may replace a portion of tubular wall2710. Additionally, thermoelectric coolers2720may be implemented on the inside of tubular wall2710and thermally coupled to tubular wall2710, without departing from the scope hereof. In this implementation, at least a section of tubular wall2710, to which tubular wall2710is thermally coupled, is thermally conducting to allow thermoelectric coolers2720to cool of wall390of body channel392through tubular wall2710. One such implementation is discussed below in reference toFIGS. 28A-D.

FIGS. 28A-Dillustrate another catheter or catheter sleeve2800with thermoelectric cooling. Catheter/catheter sleeve2800is an embodiment of catheter/catheter sleeve2500.FIG. 28Ais a perspective view of catheter/catheter sleeve2800.FIG. 28Bis a cross sectional view of catheter/catheter sleeve2800taken near distal end104of catheter/catheter sleeve2800in a plane orthogonal to longitudinal axis1790(see arrow28B-28B′ ofFIG. 28A).FIG. 28Cis a cross sectional view of catheter/catheter sleeve2800taken further toward proximal end102of catheter/catheter sleeve2800in a plane orthogonal to longitudinal axis1790(see arrow28C-28C′ ofFIG. 28A).FIGS. 28A-Care best viewed together in the following description.

Catheter/catheter sleeve2800includes (a) a tubular wall2810, (b) one or more thermoelectric coolers2820that is thermally and mechanically coupled to a thermally conductive pad2812of tubular wall2810, and (c) a solid thermal conductor2830thermally coupled to the thermoelectric cooler(s)2820. In operation, the cold side of each thermoelectric cooler is in thermal connection with tubular wall2810, and the hot side of each thermoelectric cooler is in thermal connection with solid thermal conductor2830. Thermoelectric cooler2820is an embodiment of thermoelectric cooler2520and may be implemented in either one of catheter/catheter sleeve2500and catheter/catheter sleeve2600. Each thermoelectric cooler2820may be of a construction similar to that of thermoelectric cooler2720. Tubular wall2810is an embodiment of tubular wall2510of catheter/catheter sleeve2500and of tubular wall2610of catheter/catheter sleeve2600. In tubular wall2810, thermally conductive pad2812is surrounded by a thermal insulator2814that thermally isolates thermally conductive pad2812from a thermally conductive portion2816of tubular wall2810. Thermally conductive portion2816is, for example, all of tubular wall2810except thermally conductive pad2812and thermal insulator2814. In one implementation, thermally conductive portion2816is metal, such as stainless steel. Thermally conductive pad2812may be a metal as well.

The thermal isolation of thermally conductive pad2812from other portions of tubular wall2810limits the area of tubular wall2810(and thus adjacent tissue in contact with tubular wall2810) that is cooled by thermoelectric cooler(s)2820. This area limitation may facilitate more effective cooling by thermoelectric cooler(s)2820, compared to the cooling achievable if thermoelectric cooler(s)2820was in thermal connection with a significantly greater portion of tubular wall2810or all of tubular wall2810(which could result in overloading of thermoelectric cooler(s)2820).

Solid thermal conductor2830is disposed inside tubular wall2810and extends from thermoelectric cooler(s)2820toward proximate end102. Solid thermal conductor2830may extend all the way the proximate end102, or only partway to proximate end102. Solid thermal conductor2830is an embodiment of solid thermal conductor1720. In an embodiment, catheter/catheter sleeve2800is configured to redistribute heat, conducted by solid thermal conductor2830, to tubular wall2810, while taking advantage of the thermal mass of tubular wall2810to accommodate the heat while keeping the temperature at an acceptable level. In this embodiment, solid thermal conductor2830is in thermal connection with thermally conductive portion2816over an extended portion of tubular wall2810, for example via one or more thermal connectors2840, such that heat from thermally conductive pad2812is redistributed to a significantly greater portion of tubular wall2810. Even though the temperature of this greater portion of tubular wall2810increases during this process and potentially heats adjacent tissue, the area of the greater portion of tubular wall2810, over which the heat is redistributed, may be sufficiently large that the temperature increase is within an acceptable range. In another embodiment, solid thermal conductor2830is mechanically supported by non-thermally conductive bridges so as to prevent solid thermal conductor2830from forming a thermal short with tubular wall2810.

In any cross section along the length of catheter/catheter sleeve2800that is occupied by solid thermal conductor2810, the number of thermal connectors2840may be smaller or greater than the four thermal connectors2840depicted inFIG. 28C, without departing from the scope hereof. Furthermore, one or more thermal connectors2840may be slab-shaped and bridge between solid thermal conductor2830and tubular wall2810along an extended segment of longitudinal axis1790. Alternatively, several rod-shaped thermal connectors2840, each connecting to a respective local portion of tubular wall2810, may cooperate to redistribute the heat to a larger portion of tubular wall2810. In one implementation, thermal connector(s)2840are arranged to uniformly, or at least approximately uniformly, redistribute the heat over a segment of tubular wall2810. The shape and thickness of thermal connector(s)2840may be a function of position along longitudinal axis1790to achieve this uniform, or approximately uniform, heat redistribution.

Without departing from the scope hereof, thermally conductive pad2812may function as the cold-side thermal conductor of thermoelectric cooler(s)2820.

FIG. 28Dillustrates an alternate embodiment2800′ of catheter/catheter sleeve2800.FIG. 28is a cross sectional view of catheter/catheter sleeve2800′, with the cross section taken in the same manner as forFIG. 28C. Catheter/catheter sleeve2800′ is similar to catheter/catheter sleeve2800except that (a) thermally conductive portion2816of tubular wall2810is replaced by a thermally insulating portion2816′ and (b) solid thermal conductor2830and optional thermal connectors2840are replaced by solid thermal conductor2830′. Solid thermal conductor2830′ is a hollow cylindrical conductor disposed inside tubular wall2810, for example adjacent to or even directly on the inner surface of thermally insulating portion2816′. In one implementation, solid thermal conductor2830′ extends all the way to proximate end102and is configured to conduct at least a portion of the heat out of tubular wall2810, for example to a heat exchanger. In another implementation, the thermal mass of solid thermal conductor2830′ is sufficient to accommodate the heat captured by thermoelectric cooler(s)2820while still allowing for effective cooling by thermoelectric cooler(s)2820. The thickness of solid thermal conductor2830′ may be a function of position along longitudinal axis1790to achieve optimal heat redistribution and heat removal away from thermoelectric cooler(s)2820.

In an embodiment, thermally insulating portion2816′ is flexible (e.g., a flexible polymer) and solid thermal conductor2830′ is a braided wire connector, such that catheter/catheter sleeve2810is flexible along at least a part of its length. This flexibility may increase patient comfort.

FIG. 29illustrates one catheter sleeve2900configured to encase a catheter for ultrasound treatment of target tissue280from inside body channel392while being secured to a wider portion of body channel392. In one use scenario, catheter sleeve2900encases catheter1700or catheter2400. Catheter sleeve2900may form an embodiment of catheter sleeve2200. Alternatively, catheter sleeve2900is configured to permanently encase the catheter.

Catheter sleeve2900includes a tubular casing2910having a window2912capable of transmitting ultrasound emitted by an ultrasound transducer array of a catheter, such as CMUT array210or CMUT array112. Window2912may be an opening or a material that is capable of transmitting ultrasound. Catheter sleeve2900further includes an inflatable balloon2920mounted on distal end104of catheter sleeve2900, and a conduit2922that leads a fluid to inflatable balloon2920for inflation thereof, so as to secure inflatable balloon to a wider portion of body channel392. Optionally, catheter sleeve2900further includes a rotation joint2940that permits rotation of tubular casing2910relative to inflatable balloon2920. Rotation joint2940may facilitate rotation of CMUT array210about longitudinal axis1790when CMUT array210is coupled with catheter sleeve2900. In one example, rotation joint2940allows for rotation of CMUT array210within a range from −135 degrees to +135 degrees. In one embodiment, rotation joint2940is configured to permit a discrete plurality of orientations of CMUT array210about longitudinal axis1790, for example at every 5 or 10 degrees.

Catheter sleeve2900may further include a fluid port2930at distal end104and a conduit2932that passes a fluid received from a part of body channel392via fluid port2930, through catheter sleeve2900, to proximate end102, and out of catheter sleeve2900.

Catheter sleeve2900may be coupled with an external fluid handling system that supplies a fluid for inflating inflatable balloon2920via conduit2922and, optionally, accepts a fluid from body channel392via conduit2932.

Tubular casing2910may be rigid or pliable, or a combination thereof.

FIG. 30illustrates one urethral catheter sleeve3000configured to encase a urethral catheter3090for ultrasound treatment of prostate192from inside urethra194while being secured to bladder196. Urethral catheter3090is, for example, an embodiment of catheter1700or catheter2400. Catheter sleeve3000is an embodiment of catheter sleeve2900specifically adapted for ultrasound treatment of prostate192from urethra194. Catheter sleeve3000may form an embodiment of catheter sleeve2200. Alternatively, catheter sleeve3000is configured to permanently encase the urethral catheter. For clarity of illustration,FIG. 30does not show fluid conduit(s) of catheter sleeve3000and optional rotation joint2940.

In operation, catheter sleeve3000is inserted into urethra194, together with urethral catheter3090or prior to insertion of urethral catheter3090into catheter sleeve3000. Next, an inflatable balloon3020of catheter sleeve3000is inflated to secure catheter sleeve3000to bladder196. Catheter sleeve3000facilitates positioning of a tip of urethral catheter3090at prostate192, to expose prostate192to ultrasound emitted by the tip of urethral catheter3090, for example using CMUT array210or CMUT array112. In one example of use, urethral catheter3090is extracted from catheter sleeve3000after ultrasound treatment of prostate192by urethral catheter3090, while catheter sleeve3000is left in place for a longer period of time. In another example of use, catheter sleeve3000and urethral catheter3090are removed from urethra194together. Removal of catheter sleeve3000from urethra194takes place after deflation of inflatable balloon3020.

Although not shown inFIG. 30, it should be understood that catheter sleeve3000may include conduit2932to pass urine from bladder196through catheter sleeve3000and out of urethra192.

Tubular casing3010may be rigid or pliable, or a combination thereof. In one example, a portion of tubular casing3010spanning from bladder196and through the region near prostate192is rigid to prevent collapse of urethra194due to prostate pressure and allow passage of urine from bladder196through catheter sleeve3000and out of urethra194, while the remaining more proximal portion of tubular casing3010is pliable for patient comfort.

FIG. 31illustrates one catheter sleeve3100with one or more integrated sensors for sensing at least one property of wall390when catheter sleeve3100is within body channel392. Catheter sleeve3100includes a tubular casing3110and one or more sensors3120that are coupled to tubular casing3110. Sensor3120is similar to sensor230. Tubular casing3110is configured to encase a catheter3190. Catheter3190is, for example, an embodiment of catheter110. In one embodiment, each sensor3120is a temperature sensor. In another embodiment, each sensor3120is a pressure sensor. In yet another embodiment, catheter sleeve3100includes both pressure and temperature sensors3120.

In an exemplary use scenario, catheter sleeve3100remains in body channel392for some time after extraction of catheter3190therefrom. For example, catheter sleeve3100may remain in body channel392(e.g., urethra194) for some time after ultrasound treatment of target tissue380(e.g., prostate192) by catheter110, so as to monitor temperature and/or pressure of wall390(e.g., the wall of urethra194near prostate192). In addition, catheter sleeve3100may serve to keep body channel392open after ultrasound treatment, for example until a treatment induced swelling has subsided. In embodiments, where catheter sleeve3100is configured for use in urethra194to aid ultrasound treatment of prostate192, catheter sleeve3100may be left in urethra194after ultrasound treatment to prevent complete blockage of urethra, otherwise potentially resulting from treatment induced swelling, and allow passage of urine from bladder196through catheter sleeve3100.

Embodiments of catheter sleeve3100including a plurality of sensors3120may determine one or more properties of wall390(such as temperature and/or pressure) as a function of position, so as to obtain spatially resolved information about the one or more properties.

Tubular casing3110may be rigid or pliable. In one embodiment, tubular casing3110includes or is substantially composed of a metal, such as stainless steel. This embodiment of tubular casing3110is rigid. In another embodiment, tubular casing3110includes or is substantially composed of a polymer. This embodiment of tubular casing3110may be rigid or pliable, or a combination thereof.

Each of catheter sleeves2200,2900, and3000may include one or more sensors3120and thus forms an embodiment of catheter sleeve3100. Furthermore, each of tubular catheter jackets1920and2300, and each of tubular walls2410,2510,2610, and2710may have one or more sensors3120coupled thereto.

FIG. 32illustrates one catheter sleeve3200having one or more hardwired sensors3220on its tubular casing3210. Each sensor3220is configured to sense a property of wall390when catheter sleeve3200is positioned in body channel392. Sensor3220is an embodiment of sensor3120. Catheter sleeve3200is an embodiment of catheter sleeve3100that includes electrical connections3230from sensor(s)3220to external electronic circuitry (not shown inFIG. 32) located outside body channel392, so as to facilitate readout of sensor signals from sensor(s)3220via hardwired electrical connections in catheter sleeve3200. In an embodiment, each sensor3220is an active sensor that requires power, and electrical connections3230further serve to provide such power to each sensor3220.

In an embodiment, at least a portion of catheter sleeve3100is formed of a pliable polymer having at least a portion of electrical connections3230embedded therein or disposed thereon while maintaining the flexibility of the pliable polymer.

FIG. 33illustrates one catheter sleeve3300having one or more wireless-communication based sensors3320on its tubular casing3310, wherein each sensor3320is read out by a catheter3390inserted into catheter sleeve3300. Catheter3390may be inserted into catheter sleeve3300when readout of sensor(s)3320is required and does not need to remain in catheter sleeve3300at other times. Each sensor3320is capable of sensing a property of wall390when catheter sleeve3300is positioned in body channel392. Sensor3320is an embodiment of sensor3120. Catheter sleeve3300is an embodiment of catheter sleeve3100configured for readout of sensor signals from sensor(s)3320via catheter3390. Catheter3390may be dedicated to readout of sensor(s)3320, or be a ultrasound treatment catheter, such as catheter110, with additional sensor readout capability. Catheter3390includes at least one reader3392that communicates with sensor3320via a radio-frequency signal and receives a sensor signal from sensor3320in the form of a radio-frequency signal. Reader3392may further emit a radio-frequency signal to sensor3320to activate sensor3320.

Each sensor3320may be a passive sensor that does not require power. Alternatively, each sensor3320is an active sensor that is activated by a radio-frequency signal emitted by reader3392.

In one embodiment, catheter3390includes a single reader3392, catheter sleeve3300includes several sensors3320, and catheter3390is moved to sequentially position reader3392to read out different ones of sensors3320. In another embodiment, catheter sleeve3300includes several sensors3320, and catheter3390includes a single reader3392that has wireless range sufficient to read each of sensors3320without moving reader3392. In yet another embodiment, catheter sleeve3300includes several sensors3320, and catheter3390includes a corresponding set of readers3392positioned to match the positions of sensor3320, such that each reader3392reads out a respective sensor3320with no need to move catheter3390between readings of different sensors3320.

Catheter3390includes one or more electrical connections3394that couple each reader3392to electronic readout circuitry outside body channel392.

In an embodiment, a portion of catheter3390includes a ruler or markings. The ruler/markings are located on a portion of catheter3390that is external to and/or located at the exit of body channel392when catheter3390is positioned in catheter sleeve3300to read out sensors3320. The ruler/markings guides an operator to position electrical contact(s)3392in locations that match sensor(s)3320. In one implementation, the ruler/markings provide visual feedback to the operator. In another embodiment, catheter sleeve3300and catheter3390are cooperatively configured to define a preferred seating position of catheter3390inside catheter sleeve3300for each sensor3320. To read out a given sensor3320, the operator “clicks” catheter3390into the preferred seating position associated with this sensor3320. In this embodiment, catheter3390may further have one or more markings located on a portion of catheter3390that is external to and/or located at the exit of body channel392when catheter3390is positioned in catheter sleeve3300to read out sensors3320, wherein each marking visually indicates an associated seating position of catheter3390to the operator.

In an alternative embodiment, each sensor3320is configured for wireless readout from outside body channel392. In this embodiment, sensor(s)3320may be configured to cooperate with a wireless readout circuit (for example similar to reader3392) positioned near subject190and sensor(s)3320.

FIG. 34illustrates one catheter sleeve3400having one or more sensors3420on its tubular casing3410, wherein each sensor3420is configured to be read out by a catheter3490inserted into catheter sleeve3400and placed in electrical contact with sensor3420. Each sensor3420is configured to sense a property of wall390when catheter sleeve3400is positioned in body channel392. Sensor3420is an embodiment of sensor3120. Catheter sleeve3400is an embodiment of catheter sleeve3100configured for readout of sensor signals from sensor(s)3420via catheter3490having one or more electrical contacts3492. Catheter sleeve3400is similar to catheter sleeve3300and catheter3490is similar to catheter3390, except that each sensor3420is read out electrically when brought into physical contact with an electrical contact3492. Catheter3490includes one or more electrical connections3494that couples each electrical contact3492to electronic readout circuitry outside body channel392. Electrical contact3492may further provide power to sensor3420.

FIG. 35illustrates one system3500for ultrasound treatment with solid state cooling. System3500includes electronic circuitry3510having ultrasound driving circuitry3512and Peltier driving circuitry3514. Ultrasound driving circuitry3512generates drive signals to drive CMUT array210or112, so as to expose target tissue280to ultrasound270. Peltier driving circuitry3514powers at least one thermoelectric cooler220or114, to cool non-target tissue290heated by ultrasound270.

System3500may include a handle3560containing electronic circuitry3510, wherein handle3560is configured to be coupled to a catheter3570containing CMUT array210/112and thermoelectric cooler(s)220/114. Handle3560and catheter3570are embodiments of handle120and catheter110, respectively. Optionally, system3500includes both handle3560and catheter3570and thus forms an embodiment of medical device100. Without departing from the scope hereof, electronic circuitry3510may be implemented externally to handle3510, for example in or integrated with control module140externally to handle3510.

In an embodiment, system3500further includes measurement circuitry3516that processes sensor signals from one or more sensors230to determine a property of non-target tissue290(and/or target tissue280). The property may be temperature, pressure, or a combination thereof. Alternatively, the property may be a parameter or electrical signal that is related to temperature, pressure, or a combination thereof. Sensor(s)230may be implemented in catheter3570. In an alternate embodiment, measurement circuitry3516processes sensor signals from one or more sensors3120of catheter sleeve3100to determine a property of non-target tissue290.

In certain embodiments, system3500is further configured for ultrasound imaging on target tissue280. In these embodiments, electronic circuitry3510further includes ultrasound imaging circuitry3518that (a) generates a plurality of signals to drive CMUT array210/112to image target tissue280and (b) produces an ultrasound image of target tissue280from resulting electrical transducer signals received from CMUT array210/112.

Electronic circuitry3510may be configured to be at least partly controlled by a control module3520(an embodiment of control module140). In one embodiment, system3500further includes control module3520. Handle3560, catheter3570, and control module3520together form an embodiment of ultrasound treatment system130. Without departing from the scope hereof, control module3520may be a standalone product configured to control electronic circuitry3510that is provided by a third party. In one implementation, control module3520is a computer system having (a) a processor and (b) non-transitory memory storing machine-readable instructions that, when executed by the processor, commands electronic circuitry3510to perform certain steps. Also without departing from the scope hereof, such machine-readable instructions may be a standalone software product configured for implementation on a third party computer system.

In an embodiment, control module3520includes a treatment controller3540that commands electronic circuitry3510to treat target tissue280according to a treatment protocol and/or based upon one or both of (a) properties of non-target tissue280and/or target tissue290determined by measurement circuitry3516in cooperation with sensor(s)230or sensor(s)3120and (b) ultrasound imagery of target tissue280generated by ultrasound imaging circuitry3518in cooperation with CMUT array210/112. Treatment controller3540may command ultrasound driving circuitry3512to drive CMUT array210/112to expose target tissue280to ultrasound270. Treatment controller3540may command Peltier driving circuitry3514to drive thermoelectric cooler(s)220/114to cool non-target tissue290. Alternatively, Peltier driving circuitry3514may operate without being directly controlled by treatment controller3540. For example, Peltier driving circuitry3514may be configured to always drive thermoelectric cooler(s)220/114when ultrasound driving circuitry3512drives CMUT array210/112to generate ultrasound270, and optionally for a set duration thereafter.

Control module3520may further include one or both of measurement unit3532and ultrasound imaging controller3550. Measurement unit3532cooperates with measurement circuitry3516to determine one or more properties (e.g., temperature, pressure, or both) of non-target tissue290and/or target tissue280based upon sensor signals received from sensor(s)230or sensor(s)3120. Treatment controller3540may utilize the determination of such properties in the management of electronic circuitry3510and/or peltier driving circuitry3514.

Ultrasound imaging controller3550cooperates with ultrasound imaging circuitry3518to generate ultrasound imagery of target tissue280using CMUT array210/112. Ultrasound imaging controller3550may command ultrasound imaging circuitry3518to generate ultrasound imagery of target tissue280according to requests received from treatment controller3540. Ultrasound imaging controller3550may further be configured to process ultrasound images of target tissue280, for example to inform treatment control performed by treatment controller3540. Ultrasound imaging controller3550may include one, two, or all of a clutter signal unit3552, a Doppler imaging unit3554, and a brightness imaging unit3556. Clutter signal unit3552(a) commands ultrasound imaging circuitry3518to obtain ultrasound imagery of target tissue280, which contains a spatially resolved clutter signal, and (b) processes the spatially resolved clutter signal, for example for the purpose of evaluating the instantaneous efficacy of ultrasound treatment of target tissue280by CMUT array210/112. Doppler imaging unit3554commands ultrasound imaging circuitry3518to obtain Doppler imagery of target tissue280, for example for the purpose of evaluating the degree of blood perfusion in target tissue280. Brightness imaging unit3556commands ultrasound imaging circuitry3518to obtain one or more brightness images of target tissue280and/or other tissue near CMUT array210/112. Such brightness images may be used to evaluate the positioning of CMUT array210/112relative to target tissue280.

In an embodiment, treatment controller3540includes a beamforming unit3542that commands ultrasound driving circuitry3512to beamform ultrasound270generated by CMUT array210/112. Beamforming unit3542may command ultrasound driving circuitry3512to generate a plurality of drive signals to drive CMUT array210/112in a manner that focuses ultrasound270on one or more localized regions of target tissue280. Treatment controller3540may utilize data received from ultrasound imaging controller3550to determine desired beamforming to be effected by beamforming unit3542.

Without departing from the scope hereof, some or all of the functionality of control module3520may be contained in handle3560.

In an embodiment, handle3560includes one or more actuators3620capable of adjusting the position of catheter tip3670or a portion thereof. In operation, actuator(s)3620may be used to position catheter tip3670relative to a reference position. The reference position may be associated with target tissue280. In one example, handle3560includes an actuator3620that positions catheter tip3670in a desired manner relative to prostate192. Alternatively, the reference position may be associated with a catheter sleeve (not shown inFIG. 36), such as catheter sleeve2200. In one implementation, handle3560includes an actuator3620that is capable of rotating catheter tip3670or all of catheter3570about longitudinal axis1790of catheter3570. In this implementation, catheter3570may include a rotation joint, such as rotation joint2940. In another implementation, handle3560includes an actuator3620that is capable of translating catheter tip3670or all of catheter3570along longitudinal axis1790. In yet another implementation, handle3560includes actuators3620cooperatively capable of translating catheter tip3670or all of catheter3570along longitudinal axis1790and also rotating catheter tip3670or all of catheter3570about longitudinal axis1790. Embodiments of handle3560including one or more actuators3620may further include one or more indicators3622, respectively, that indicate an respective position or orientation of catheter tip3670.

Medical device3600may further include control module3520to form an ultrasound treatment system3602that is an embodiment of system3500.

FIG. 37illustrates one medical device3700with a CMUT array, solid state cooling, and associated solid state heat removal. Medical device3700is an embodiment of medical device3600, wherein catheter3570includes an embodiment of solid thermal heat conductor1720extending all the way to proximal end102or beyond. In this embodiment, handle3560may further include heat exchanger1730to cool solid thermal conductor1720.

Medical device3700may further include control module3520to form an ultrasound treatment system3702that is an embodiment of system3500.

FIG. 38illustrates one medical system3800with a CMUT array and solid state cooling, which further includes catheter sleeve2900configured to be secured to body channel392. In one implementation, medical system3800is adapted for ultrasound treatment of prostate192from urethra194, and catheter sleeve2900is configured to be secured to bladder196. Medical system3800is an extension of device3600or device3700that further includes catheter sleeve2900. In medical system3800, catheter sleeve2900encases catheter3570. Medical system3800includes a handle3860which is an embodiment of handle3560. Handle3860includes an inflation control3810connected to conduit2922and is configured to inflate (or deflate) inflatable balloon2920to secure catheter sleeve to body channel392(such as to bladder196). Handle3860may further include a fluid handler3820that receives and handles fluid passed through conduit2932from fluid port2930.

Optionally, medical system3800implements catheter sleeve2900with one or more sensors3120. Medical system3800may further include control module3520to form an embodiment of system3500.

FIG. 39illustrates one system3900for controlling ultrasound treatment. System3900includes a processor3910, a memory3920communicatively coupled with processor3910, and an interface3990communicatively coupled with processor3910and also configured to communicatively couple system3900with electronic circuitry3510. System3900is an embodiment of control module3520.

Memory3920is a non-transitory memory that includes machine-readable instructions3930and a data storage3960that stores sensor measurements3970and, optionally, ultrasound images3980. Machine-readable instructions3930include treatment control instructions3940that, upon execution by processor3910, commands electronic circuitry3510to perform ultrasound treatment of target tissue280. Together, treatment control instructions3940and processor3910form an embodiment of treatment controller3540. Treatment control instructions3940may include beamforming instructions3942that, upon execution by processor3910, command ultrasound driving circuitry3512to beamform ultrasound270generated by CMUT array210/112. Beamforming instructions3942cooperate with processor3910to form an embodiment of beamforming unit3542.

Machine-readable instructions3930further include measurement instructions3932that, upon execution by processor3910, (a) command measurement circuitry3516to obtain one or more tissue property measurements from sensor(s)230or sensor(s)3120, (b) store the tissue property measurements to sensor measurements3970, and optionally (c) further process the tissue property measurement(s).

Together, measurement instructions3932and processor3910form an embodiment of measurement unit3532. Machine-readable instructions3930may also include one or both of a threshold temperature3934and a threshold pressure3936. Treatment control instructions3942, or measurement instructions3932, may, upon execution by processor3910, (a) retrieve a measured temperature3972or a measured pressure3974from sensor measurements3970, (b) compare measured temperature3972or measured pressure3974to respective threshold temperature3934and a threshold pressure3936, and (c) adjust ultrasound treatment accordingly.

In an embodiment, machine-readable instructions3930further include ultrasound imaging instructions3950that, upon execution by processor3910, command ultrasound imaging circuitry3518to obtain ultrasound imagery of target tissue280using CMUT array210/112. Ultrasound imaging instructions3950and processor3910cooperate to form an embodiment of ultrasound imaging controller3550. Ultrasound imaging instructions3950may include one, two, or all of clutter signal instructions3952, Doppler imaging instructions3954, and brightness imaging instructions3956. Each of clutter signal instructions3952, Doppler imaging instructions3954, and brightness imaging instructions3956is executable by processor3910to perform the functionality of respective clutter signal unit3552, Doppler imaging unit3554, and brightness imaging unit3556. Ultrasound imaging instructions3950may be configured to store ultrasound images3980to data storage3960. Clutter signal instructions3952, Doppler imaging instructions3954, and brightness imaging instructions3956may, upon execution by processor3910, obtain from and store in data storage3960, respective clutter signal images3982, Doppler images3984, and brightness images3986.

Without departing from the scope hereof, machine-readable instructions3930may be a standalone software product configured for implementation in a third party computer system.

FIG. 40illustrates a system4000for enhanced ultrasound treatment. System4000includes an ultrasound transducer array4010and an acoustic mirror4020. In operation, ultrasound transducer array4010and acoustic mirror4020and are positioned on opposite sides of target tissue280to form an acoustic cavity4040that contains target tissue280. Ultrasound generated by ultrasound transducer array4010and coupled to acoustic cavity4040(in the form of a standing acoustic wave between ultrasound transducer array4010and acoustic mirror4020) is amplified by acoustic cavity4040. This amplification results in increased ultrasound intensity at target tissue280, as compared to that achievable in the absence of acoustic cavity4040. In operation, ultrasound transducer array4010may emit ultrasound at a frequency that meets the resonance condition of acoustic cavity4040to establish a standing wave. As the properties of tissue within acoustic cavity4040change in response to the ultrasound, the resonance condition may change, in which case ultrasound transducer array4010may adjust the ultrasound frequency to maintain or reestablish the standing wave.

Ultrasound transducer array4010has an ultrasound emission face4016. Emission face4016may be oriented orthogonal to the length axis of acoustic cavity4040to efficiently couple ultrasound, emitted by ultrasound transducer4010, to acoustic cavity4040. In some use scenarios, it may be necessary or beneficial to orient emission face4016away from being orthogonal to the length axis of acoustic cavity4040. In such scenarios, ultrasound transducer array4010may be operated to beamform the ultrasound to be directed in a direction substantially parallel to the length axis of acoustic cavity4040.

System4000may implement CMUT array112as ultrasound transducer array4010. Alternatively, ultrasound transducer array4010may be of a different type, such as a piezoelectric transducer array.

In an embodiment, system4000includes a catheter4012that contains transducer array4010, to enable placement of transducer array4010in body channel392. In this embodiment, acoustic mirror4020may be placed in body channel392, outside the body, or in a different body channel, depending on the location of target tissue280. Catheter4012may implement CMUT array112as ultrasound transducer array4010, and further implement thermoelectric cooler114, to form an embodiment of catheter110.

System4000may include one or more additional acoustic mirrors4030. Each acoustic mirror4030may cooperate with ultrasound transducer array4010to form a respective acoustic cavity4050. Each acoustic mirror4030allows for treatment of different target tissue portion4080. In one use scenario, ultrasound transducer array4010first couples ultrasound to acoustic cavity4040to treat target tissue280located within acoustic cavity4040; ultrasound transducer array4010is then reoriented to couple ultrasound to acoustic cavity4050to treat target tissue portion4080located within acoustic cavity4050but outside acoustic cavity4040.

Certain embodiments of ultrasound transducer4010have two opposite facing emission faces4016and4018. In such embodiments, ultrasound transducer device4010may be positioned between acoustic mirror4020and an acoustic mirror4030that faces acoustic mirror4020. Efficient coupling of the emitted ultrasound to acoustic cavities4040and4050may then be ensured by orienting emission faces4016and4018orthogonal to the length axis of acoustic cavities4040and4050and/or by beamforming the ultrasound emitted by ultrasound transducer array4010.

FIG. 41illustrates a system4100for enhanced ultrasound treatment of prostate192with solid state cooling of urethra194. System4100is an embodiment of system4000. System4100includes (a) catheter110, adapted for insertion into urethra194to position CMUT array112at prostate192, (b) an acoustic mirror4120configured to be positioned anterior to prostate192outside the body of subject190, and (c) a rectal catheter4142including acoustic mirror4130and configured for insertion into rectum4190of subject190to position acoustic mirror4130posteriorly to prostate192. Ultrasound transducer may thereby form an acoustic cavity with either one of acoustic mirrors4120and4130, thereby forming an acoustic cavity that contains a portion of prostate192. This acoustic cavity increases the intensity at prostate192of ultrasound generated by CMUT array112.

System4100may further include handle120and, optionally, control module140. In addition, rectal catheter4142may be equipped with a handle4144.

In one implementation, acoustic mirror4120is coupled with a buffer4122that transmits ultrasound between the skin of subject190and acoustic mirror4120. Buffer4122is, for example, a fluid-filled bag, a gel-filled bag, or a solid plastic object. Buffer4122eliminates, or at least reduces, air gaps between acoustic mirror4120and the skin of patient190, so as to prevent ultrasound emitted by CMUT array112from being reflected/scattered by an air-tissue interface at the skin of subject190. Buffer4122may be pushed against the skin of subject190to eliminate air gaps. Alternatively, acoustic mirror4120may be pushed directly against the skin of subject190, or with a gel therebetween, to eliminate air gaps between acoustic mirror4120and the skin of subject190without using buffer4122. Likewise, acoustic mirror4130may be (a) coupled with a buffer4132(similar to buffer4122) or (b) pushed directly against the wall of rectum4190, optionally with gel between acoustic mirror4130and the wall of rectum4190.

In one example scenario, ultrasound emission from CMUT array112is beamformed to be directed along the acoustic cavity formed by ultrasound transducer4110and acoustic mirror4120or4130, so as to efficiently couple the ultrasound emission from CMUT array112to the acoustic cavity. In another example scenario, CMUT array112and acoustic mirror4120or4130are positioned such that an emission face of CMUT array112is orthogonal to the length axis of the acoustic cavity formed by ultrasound transducer4110and acoustic mirror4120or4130.

Without departing from the scope hereof, CMUT array112of system4100may be replaced by another type of ultrasound transducer array, such as a piezoelectric transducer array. In this case, system4100may also, instead of catheter110having solid state cooling, implement a catheter with liquid cooling. Also without departing from the scope hereof, system4100may be provided with only one of acoustic mirrors4120and rectal catheter4142. For example, if the target tissue is exclusively in the anterior portion of prostate192, rectal catheter4142is not needed.

FIG. 42illustrates another system4200for enhanced ultrasound treatment. System4200includes two ultrasound transducer arrays4210and4220having respective ultrasound emission faces4212and4222. In operation, ultrasound transducer arrays4210and4220are positioned on opposite sides of target tissue280, with ultrasound emission faces4212and4222substantially facing each other, to form an acoustic cavity4240that contains target tissue280. Ultrasound that is generated by ultrasound transducer arrays4210and4220and coupled to acoustic cavity4240(in the form of a standing acoustic wave between acoustic mirrors4020and4030) is amplified by acoustic cavity4240. This amplification results in increased ultrasound intensity at target tissue280, as compared to that achievable by a single ultrasound transducer array not coupled to or incorporated in an acoustic cavity.

Furthermore, system4200enables tuning of the standing wave pattern inside acoustic cavity4240to sweep the location of one or more antinodes. In operation, ultrasound transducer arrays4210and4220may be driven at the same frequency but with an adjustable phase shift relative to each other. The phase shift between ultrasound generated by ultrasound transducer array4210and ultrasound generated by ultrasound transducer array4220determines the position of antinodes within acoustic cavity4240. In one use scenario, this phase shift is adjusted to accurately position an antinode at the position of localized target tissue, to deliver a relatively large amount of energy to this localized target tissue. In another use scenario, the phase shift is varied to sweep the position of one or more antinodes across more extended target tissue so as to deliver energy to the target tissue in a more uniform manner than that associated with a fixed standing wave pattern.

System4200may implement one or both of ultrasound transducer arrays4210and4220as CMUT array112. However, one or both of ultrasound transducer arrays4210and4220may be of a different type, such as a piezoelectric transducer array.

In an embodiment, system4200includes a catheter4212that contains transducer array4210, to enable placement of transducer array4210in body channel392. In this embodiment, ultrasound transducer array4220may be placed outside the body or in a different body channel, depending on the location of target tissue280. Catheter4212may implement CMUT array112as ultrasound transducer array4210, and further implement thermoelectric cooler114, to form an embodiment of catheter110. In embodiments where ultrasound transducer array4220is configured for positioning inside a body channel, system4200may include a catheter4222that contains transducer array4210. Catheter4220may further include thermoelectric cooler114.

Either one or both of ultrasound transducer arrays4210and4220may perform ultrasound imaging, for example to confirm the positioning of the other one of ultrasound transducer arrays4210and4220relative to target tissue280, and/or to provide ultrasound images to assess treatment efficacy. Furthermore, ultrasound transducer arrays4210and4220may cooperate to generate ultrasound transmission images of target tissue280, wherein one of ultrasound transducer arrays4210and4220images ultrasound emitted by the other one of ultrasound transducer arrays4210and4220. Such ultrasound images may provide a clutter signal to be used in the assessment of treatment efficacy.

Certain embodiments of system4200further include a control module4240that controls ultrasound generation, and optionally also ultrasound imaging, by each of ultrasound transducer arrays4210and4220. Control module4240may be configured to adjust a phase shift between ultrasound emitted by ultrasound transducer array4210and ultrasound transducer array4220, so as to tune the position of antinode(s) of a standing wave within acoustic cavity4240. One such embodiment of control module4240is capable of sweeping this phase shift to substantially uniformly expose target tissue280. Control module may include machine-readable instructions, encoded in non-transitory memory, and a processor that executes the machine-readable instructions to adjust or sweep the phase shift.

FIG. 43illustrates another system4300for enhanced ultrasound treatment of prostate192with solid state cooling of urethra194. System4300is an embodiment of system4200. System4300includes (a) catheter110, adapted for insertion into urethra194to position CMUT array112at prostate192, and (b) ultrasound transducer array4220configured to cooperate with CMUT112to form an embodiment of acoustic cavity4240that contains a portion of prostate192. In system4300, CMUT array112is an embodiment of ultrasound transducer array4210.

In one embodiment, system4300includes a rectal catheter4342that includes ultrasound transducer array4220(shown as ultrasound transducer array4220(1) inFIG. 43) and is configured for insertion into rectum4190of subject190to position ultrasound transducer array4220posterior to prostate192. This embodiment of system4300facilitates enhanced ultrasound treatment of the posterior portion of prostate192. In another embodiment, system4300includes an embodiment of ultrasound transducer array4220(shown as ultrasound transducer array4220(2) inFIG. 43) configured to be positioned anterior to prostate192outside the body of subject190. This embodiment of system4300facilitates enhanced ultrasound treatment of the anterior portion of prostate192. In yet another embodiment, system4300includes both rectal catheter4342and ultrasound transducer array4220(2), to facilitate sequential or alternating treatment of the anterior and posterior portions of prostate192. It should be understood that CMUT array112may be oriented to face in an anterior direction or a posterior direction, as needed to treat the anterior and posterior portions of prostate192.

System4300may further include handle120and, optionally, a control module4340. In addition, rectal catheter4342may be equipped with a handle4344. Control module4340is an embodiment of control module140and also an embodiment of control module4240. Control module4240is configured to control ultrasound generation by (a) CMUT array112and (b) ultrasound transducer4220(1) and/or ultrasound transducer array4220(2). In an embodiment, control module4340is capable of adjusting a phase shift between ultrasound generated by CMUT array112and ultrasound transducer array4220(1)/4220(2), in a manner similar to that discussed above in reference toFIG. 42.

In one implementation, ultrasound transducer array4220(2) is coupled with buffer4122to eliminate, or at least reduce, air gaps between ultrasound transducer array4220(2) and the skin of patient190, so as to prevent ultrasound emitted by ultrasound transducer array4220(2) or CMUT array112from being reflected/scattered by an air-tissue interface at the skin of subject190. Alternatively, ultrasound transducer array4220(2) may be pushed directly against the skin of subject190, or with a gel therebetween, to eliminate air gaps between ultrasound transducer array4220(2) and the skin of subject190without using buffer4122. Likewise, ultrasound transducer array4220(1) may be (a) coupled with a buffer4132or (b) pushed directly against the wall of rectum4190, optionally with gel between ultrasound transducer array4220(1) and the wall of rectum4190.

Any one of CMUT array112, ultrasound transducer array4220(1) and ultrasound transducer array4220(2) may perform ultrasound imaging, for example to confirm the positioning of another one of CMUT array112, ultrasound transducer array4220(1) and ultrasound transducer array4220(2).

Without departing from the scope hereof, CMUT array112of system4300may be replaced by another type of ultrasound transducer array, such as a piezoelectric transducer array. In this case, system4300may also, instead of catheter110having solid state cooling, implement a catheter with liquid cooling.

FIG. 44illustrates one method4400for ultrasound treatment with solid state cooling. Method4400is performed by catheter110, for example. The performance of method4400may be commanded by treatment controller3540utilizing electronic circuitry3510. Certain embodiments of method4400may be encoded in machine-readable instructions3930as treatment control instructions3940. Other embodiments of method4400may be encoded in machine-readable instructions3930as treatment control instructions3940in combination with one or both of measurement instructions3932and ultrasound imaging instructions3950.

Method4400includes steps4410,4420, and4430. Step4410exposes target tissue, such as target tissue280, to ultrasound generated by a CMUT array. The CMUT array may be advanced to the target tissue on a catheter through a body channel Step4420uses one or more thermoelectric coolers to cool non-target tissue, such as non-target tissue290, to prevent damage to the non-target tissue. In embodiments where the CMUT array is advanced to the target tissue on a catheter through a body channel, the non-target tissue may be or include at least a portion of the wall of the body channel, and each thermoelectric cooler is coupled to the CMUT array and/or the catheter. Step4430removes heat from the thermoelectric cooler(s) and away from the non-target tissue, e.g., the wall of a body channel. In one example of method4400, CMUT array210exposes target tissue380to ultrasound270from body channel392in step4410, thermoelectric cooler(s)220cools wall390in step4420, and solid thermal conductor710removes heat from thermoelectric cooler(s)230and wall390in step4430. In this example of method4400, CMUT array210and thermoelectric cooler(s)230may be advanced to target tissue380on catheter110.

Although shown inFIG. 44as being sequential, it should be understood that steps4410,4420, and4430may be performed in parallel.

In an embodiment, step4430includes a step4432of conducting heat away from the thermoelectric cooler(s) through a solid thermal conductor coupled to the thermoelectric cooler(s). In embodiments where the CMUT array is advanced to the target tissue on a catheter through a body channel, the solid thermal conductor extends through the catheter toward an exit of the body channel. The solid thermal conductor may extend all the way to the exit of the body channel, or extend only partway toward the exit of the body channel. In the case where the solid thermal conductor extends only partway toward the exit of the body channel, the solid thermal conductor may be configured to redistribute (e.g., uniformly) the heat removed from the thermoelectric cooler(s) along a portion of the catheter, while keeping the temperature of the catheter wall, in contact with body tissue, below a threshold value. In one example of step4430, solid thermal conductor1720or2620conducts heat away from thermoelectric cooler(s)220and2520, respectively. Step4432may include a step4434of cooling the solid thermal conductor outside the body channel. In one example of step4434, heat exchanger1730cools solid thermal conductor1720outside body channel392, or a similar heat exchanger cools solid thermal conductor2620outside body channel392.

In certain embodiments, step4410includes a step4412of adjusting the ultrasound exposure according to a temperature measurement, a pressure measurement, and/or a treatment effect indicated by an ultrasound image. For example, the ultrasound exposure in step4410may be at least temporarily stopped if the temperature of wall390exceeds a threshold temperature, if the pressure of wall390exceeds a threshold pressure; the ultrasound exposure in step4410may be stopped or reduced if the temperature or pressure of wall390indicates that target tissue380is at or near a target temperature; or the ultrasound exposure in step4410may be adjusted according to an evaluation of temperature, elasticity, echogenicity, necrosis, or treatment efficacy in target tissue380based upon ultrasound imagery of target tissue380. In one use scenario associated with ultrasound treatment of prostate192from urethra194, the threshold temperature is in the range between 41 and 45 degrees C., such as 42 degrees C., to prevent damage to urethra194. Heating of target tissue380, and potentially also wall390, may cause swelling of the tissue. Implementation of a threshold pressure in step4412may help keep the degree of swelling in an acceptable range.

In one such embodiment, method4400further includes a step4440of monitoring temperature and/or pressure of the non-target tissue, e.g., the wall of a body channel. In one example of this embodiment, sensor(s)230or sensor(s)3120monitor the temperature and/or pressure of wall390in step4440, and the ultrasound exposure by CMUT array210is adjusted according to this temperature and/or pressure in step4412. Method4400may perform steps4440in parallel with step4410.

In another such embodiment, method4400further includes a step4450of using the CMUT array to image the target tissue to obtain an ultrasound image that indicates an effect of the ultrasound treatment on the target tissue. In one example of this embodiment, CMUT array210images target tissue380, and the ultrasound exposure by CMUT array210is adjusted, in step4412, according to a treatment effect indicated by the ultrasound image obtained from CMUT array210. Method4400may perform steps4410and4450simultaneously or alternate between steps4410and4450.

Method4400may utilize step4440to guide the performance of step4420. In one such example, cooling of non-target tissue290by thermoelectric cooler(s)220, in step4420, is adjusted according to measurements performed by sensor(s)230in step4440. Without departing from the scope hereof, step4420may include running the thermoelectric cooler(s) in reverse to heat the non-target tissue, for example to prevent or compensate for over-cooling.

Step4410may include a step4414of beamforming the ultrasound to target localized tissue or target one or more local portions of the target tissue. In one example of step4414, the drive signals for different transducers of CMUT array210are phase shifted relative to each other to beamform ultrasound270, for example as discussed above in reference toFIG. 8-10. Step4410may perform the beamforming in step4414according to a treatment effect indicated by an ultrasound image obtained in step4450. For example, if an ultrasound image obtained in step4450indicates that a particular portion of target tissue380is in need of more ultrasound exposure, step4414may beamform ultrasound270to target this particular portion of target tissue380.

In an embodiment, step4410includes a step4416of sequentially targeting different portions of the target tissue. Step4416may systematically scan across the target tissue according to a predefined scan pattern, or step4416may sequentially target different portions of the target tissue according to a treatment effect indicated by an ultrasound image obtained in step4450. Step4416may include one or both of steps4417and4418. Step4417moves the CMUT array to a different position. In one example of step4417actuator3620translates CMUT array along the length of body channel392to sequentially direct ultrasound270to different portions of target tissue380. In another example of step4417, actuator3620rotates CMUT array to sequentially direct ultrasound270to different portions of target tissue380located on different sides of body channel392. Step4418beamforms the ultrasound to sequentially target different portions of target tissue380. Step4416may perform steps4417and4418in conjunction. Additionally, step4416may, optionally in conjunction with steps4417and/or4418, sequentially activate different CMUT cells or CMUT elements of the CMUT array to sequentially target different portions of target tissue380.

Furthermore, step4410may include a step4419of exposing the target tissue to multifrequency ultrasound to target localized regions. Multifrequency ultrasound has the capability of very accurately focusing ultrasound to a localized region, and step4419may therefore be particularly useful in scenarios where the target tissue is a cancerous tumor and it is particularly important to induce necrosis in all the cancerous tissue without damaging significant amounts of neighboring healthy tissue. In one example of step4410, different transducers of CMUT array210are driven at different frequencies.

Optionally, method4400includes a step4460of heating a greater tissue region, containing the target tissue, to a temperature that is below a target temperature for the target tissue in step4410. Inclusion of step4460in method4400may reduce the amount of ultrasound energy that must be delivered to the target tissue in step4410to reach the target temperature of the target tissue. Step4460may thus shorten the duration of step4410and, in some scenarios, reduce the risk of heat-induced damage to non-target tissue. In one example of step4460, an external heat source is positioned on the skin of a subject near the target tissue. The external heat source may advantageously be positioned to heat the greater tissue region from a direction that is significantly different from the direction of ultrasound exposure in step4410, to avoid the external heat source delivering a relatively large amount of heat to locations close to the CMUT array of step4410. In a scenario where the target tissue is in prostate192, an external heater may be positioned on the skin of subject190anterior to prostate192, so as to heat the greater tissue region from a direction that is substantially opposite to the direction of ultrasound exposure in step4410. In another example of step4460, the body temperature of the subject is raised using medicine. In yet another example, step4460applies the CMUT array of step4410in a less targeted fashion to raise the temperature of a larger region around and including the target tissue. In one embodiment, step4460is performed prior to step4410, to raise the temperature of the greater tissue region prior to method4400commencing step4410. In another embodiment, step4460delivers heat to the greater tissue region during at least some of the ultrasound treatment of step4410.

FIG. 45illustrates one method4500for ultrasound treatment of prostate192with solid state cooling of the urethra194. Method4400is performed by catheter110, for example. Method4500is an embodiment of method4400specifically adapted for ultrasound treatment of prostate192, for example to treat BPH or prostate cancer.

Method4500includes steps4510,4520, and4530, which are embodiments of steps4410,4420, and4430, respectively. Step4510exposes prostate192to ultrasound generated by a CMUT array that is advanced to the prostate192on a catheter through urethra194. Step4520uses one or more thermoelectric coolers to cool the wall of urethra194to prevent heat-induced damage to urethra194(and, optionally, heat the wall of urethra194to prevent or compensate for over-cooling of urethra194). Each thermoelectric cooler is coupled to the CMUT array and/or the catheter. Step4530removes heat from the thermoelectric cooler(s) and away from the wall of urethra194.

Method4500may further include steps4540,4550, and/or4560. Step4540is an embodiment of step4440that monitors the temperature, pressure, or both temperature and pressure of the wall of urethra194. Step4550is an embodiment of step4450that obtains an ultrasound image of prostate192. Step4560is an embodiment of step4460that heats a greater tissue region around prostate192.

Step4510may include steps4512,4412,4514,4516, and4519. Step4512induces necrosis of tissue or prostate192to treat BPH or prostate cancer. Step4514is an embodiment of step4414that uses beamforming to target localized regions within prostate192. Step4516is an embodiment of step4416that sequentially targets different portions of prostate192. Step4516may include one or both of steps4417and4418. Step4510is an embodiment of step4419that exposes tissue of prostate192to multifrequency ultrasound to target a localized region of a cancerous tumor.

Step4530may include step4532. Step4532is an embodiment of step4434that conducts heat away from the thermoelectric cooler(s) through a solid thermal conductor coupled to the thermoelectric cooler(s) and extending through a urethral catheter toward the exit of urethra194. Step4532may include step4534. Step4534is an embodiment of step4434that cools the solid thermal conductor outside urethra194.

FIG. 46illustrates one method4600for ultrasound treatment with ultrasound imaging feedback. Method4600may be performed by treatment controller3540. Method4600may be encoded in machine-readable instructions3930as at least a portion of treatment control instructions3940. Each of methods4400and4500may implement method4600in step4412. The feedback used in method4600utilizes a predetermined correspondence between an ultrasound clutter signal for the target tissue and an ultrasound treatment efficacy. Thus, method4600uses ultrasound images, recorded by the same ultrasound device used for actual treatment, to guide subsequent ultrasound treatment. Advantageously, method4600does not require magnetic resonance imaging to monitor treatment progress.

The predetermined correspondence between the clutter signal and the treatment efficacy may be obtained from clinical trials preceding the performance of method4600. In these trials, a patient cohort is subjected to ultrasound treatment of target tissue, e.g., prostate tissue. Ultrasound imaging is performed, at least at the end of the ultrasound treatment of each patient, to obtain spatially resolved clutter signals for the target tissue. In one implementation, the trials ultrasound treatment utilizes alternating ultrasound imaging and ultrasound treatment. In the trials, the treatment efficacy is determined using conventional methods, such as through biopsy or magnetic resonance imaging. The treatment efficacy may be determined at a later point in time after all tissue changes induced by the ultrasound treatment have taken place. Each of the degree of necrosis of the tissue and the degree to which cancerous tissue has been destroyed may serve as a parameter indicative of treatment efficacy. The treatment efficacy may be determined in a spatially resolved fashion. A comparison of clutter signals and the treatment efficacy results in a correspondence between clutter signal and treatment efficacy. This correspondence may depend on the type of tissue being treated. For example, the correspondence associated with prostate tissue may be different from the correspondence associated with breast tissue. In addition, the correspondence may depend on the degree of blood perfusion in the target tissue. Thus, in certain implementations, the predetermined correspondence applied in step4620may be specific to the tissue type and, optionally, the degree of blood perfusion.

Method4600includes steps4610and4620. Step4610obtains an ultrasound image of target tissue from an ultrasound transducer array to determine a spatially resolved clutter signal for the target tissue, that is, a clutter signal as a function of position within the target tissue. Step4620determines, based upon a predetermined correspondence between the clutter signal and a treatment efficacy, one or more properties of subsequent generation of ultrasound by the ultrasound transducer array to treat the target tissue. In one example of step4610, treatment controller3540receives an ultrasound image of target tissue (e.g., prostate tissue) that includes a spatially resolved clutter signal or may be processed by treatment controller3540to determine a spatially resolved clutter signal for the target tissue. In one example of step4620, treatment controller3540uses a predetermined correspondence between the clutter signal and a treatment efficacy to determine one or more properties of subsequent generation of ultrasound, by the same ultrasound transducer array used to record the ultrasound image in step4610, to treat the target tissue. The ultrasound transducer array may be CMUT array112. However, without departing from the scope hereof, the ultrasound transducer array may be a different type of transducer array, such as a piezoelectric ultrasound transducer array.

Method4600may be performed several times during an ultrasound treatment procedure. In one implementation, method4600provided real-time feedback.

Step4620may include a step4622of deducing the instantaneous efficacy of ultrasound treatment, based upon an instantaneous clutter signal and the predetermined correspondence between clutter signal and treatment efficacy.

In certain embodiments, step4620includes a step4626of determining a spatially resolved intensity of ultrasound to be generated in a subsequent stage of ultrasound treatment by the ultrasound transducer array. In one example, step4626applies the predetermined correspondence between clutter signal and treatment efficacy to the spatially resolved clutter signal obtained in step4610to identify which local regions need more ultrasound exposure than others.

Step4620may include a step4628of utilizing a tissue-type specific correspondence between clutter signal and treatment efficacy. In one example, the target tissue is prostate tissue and step4628utilizes a prostate-specific correspondence between clutter signal and treatment efficacy. In one embodiment, step4628includes a step4629and method4600further includes steps4650and4652. Step4629selects the tissue-type specific correspondence between clutter signal and treatment efficacy from a selection of blood-perfusion specific correspondences. Step4629is preceded by steps4650and4652. Step4650receives a Doppler image of the target tissue obtained using the ultrasound transducer array. Step4652processes the Doppler image to evaluate the degree of blood perfusion in the target tissue, and step4629selects a blood-perfusion specific correspondence that most closely relates to the degree of blood-perfusion in the target tissue.

In an embodiment, step4620includes a step4624and method4600further includes a step4612. Step4612receives a measurement of temperature and/or pressure of non-target tissue heated by the ultrasound, for example obtained using sensor(s)230or sensor(s)3120. Step4624further takes into account the measured temperature and/or pressure of the non-target tissue to determine the one or more properties of subsequent ultrasound exposure. In this embodiment, method4600may further include a step4640of at least temporarily ceasing ultrasound exposure if either temperature or pressure exceeds a corresponding threshold value.

Optionally, method4600further includes a step4630of commanding the ultrasound transducer array to generate the ultrasound with the one or more properties determined in step4620. In one example of step4630, treatment controller3540commands ultrasound driving circuitry3512to drive CMUT array112/210in a manner that generates ultrasound having the one or more properties determined in step4620. In embodiments of method4600including both step4626and4630, step4630may include a step4632of commanding the ultrasound transducer array to beamform the ultrasound with the spatially resolved intensity determined in step4626. Step4632may be performed by beamforming unit3542.

Without departing from the scope hereof, the predetermined correspondence between treatment efficacy and clutter signal may be replaced by a similarly predetermined correspondence between treatment efficacy and Doppler signal. For example, a reduced Doppler signal may be associated with reduced vascularization, which in turn may indicate complete treatment. Also without departing from the scope hereof, the predetermined correspondence between treatment efficacy and clutter signal may be replaced by a predetermined correspondence between treatment efficacy and a combination of clutter signal and Doppler signal. Furthermore, the predetermined correspondence between (a) treatment efficacy and (b) clutter signal and/or Doppler signal may be used in conjunction with predetermined correlation between treatment efficacy and other measurable parameters such as one or more of temperature at the body channel wall, pressure at the body channel wall, frequency of the ultrasound emission, and thermal dose delivered by the CMUT array (optionally corrected for known energy losses). Clinical trials may consider and evaluate such parameters together with evaluation of treatment efficacy, for use in method4600.

FIG. 47illustrates one system4700for controlling ultrasound treatment with ultrasound imaging feedback. System4700is similar to system3900but specifically adapted for ultrasound imaging feedback based on clutter signals. System4700includes processor3910, a memory4720communicatively coupled with processor3910, and interface3990communicatively coupled with processor3910and also configured to communicatively couple computer4700with electronic circuitry3510. System4700is an embodiment of control module3520that is configured to perform method4600.

Memory4720is a non-transitory memory that includes machine-readable instructions4730and a data storage4760that stores ultrasound images3980including clutter signal images3982received by system4700via interface3990when system4700performs step4610of method4600. Data storage4760also stores ultrasound exposure properties4770determined by system4700when performing step4620of method4600. Ultrasound exposure properties4770may include a spatially resolved ultrasound intensity4772determined by system4700when performing step4626. In certain embodiments, data storage4760stores sensor measurements3970, such as temperature3972and/or pressure3974received by system4700via interface3990when system4700performs step4612. Data storage4760may further store one or both of Doppler images3984(received by system4700via interface3990when system4700performs step4650) and brightness images3986.

Machine-readable instructions4730include treatment control instructions4740and one or more clutter-signal-to-treatment-efficacy correspondences4750. Treatment control instructions4740are an embodiment of treatment control instructions3940. When executed by processor3910, treatment control instructions4740perform method4600, utilizing at least one clutter-signal to treatment-efficacy correspondence4750. Treatment control instructions4740include clutter signal evaluation instructions4742that, upon execution by processor3910, evaluates a clutter signal image3982and utilizes at least one clutter-signal to treatment-efficacy correspondence4750to determine at least one ultrasound exposure property4770. Treatment control instructions4740may further include temperature/pressure evaluation instructions4744and/or correspondence selection instructions4746. Upon execution by processor3910, temperature/pressure evaluation instructions4744perform step4624and, optionally, step4640. Machine-readable instructions4730may include measurement instructions3932, and optionally one or both of threshold temperature3934and threshold pressure3936, and further utilize these when executing temperature/pressure evaluation instructions to perform step4624and, optionally, step4640. Upon execution by processor3910, correspondence selection instructions4746perform step4628.

In an embodiment, clutter-signal to treatment-efficacy correspondences4750include a plurality of blood-perfusion specific correspondences4752, and machine-readable instructions4730include blood perfusion evaluation instructions4748. In this embodiment, processor3910may execute blood perfusion evaluation instructions4748, retrieve a Doppler image3984from data storage4760, and select a corresponding one of blood-perfusion specific correspondences4752to perform step4629.

In an embodiment, machine-readable instructions4730include ultrasound imaging instructions3950. Processor3910may execute ultrasound imaging instructions3950to perform step4630. Treatment control instructions4740may further include beamforming instructions3942that, upon execution by processor3910, perform step4632.

Without departing from the scope hereof, system4700may be configured to be communicatively coupled with a modified version of electronic circuitry3510that drives an ultrasound transducer array of a different type than CMUT, such as a piezoelectric transducer array.

In a step4810, protocol4800initiates alternating (a) ultrasound treatment of target tissue and (b) ultrasound imaging of tissue associated with the ultrasound treatment including the target tissue but optionally also including non-target tissue. The ultrasound treatment and the ultrasound imaging are performed from within a body channel by a CMUT array positioned in the body channel. In one example of step4810, control module140of system3900initiates alternating (a) ultrasound treatment of target tissue280and (b) ultrasound imaging of target tissue280(and optionally also other tissue such as non-target tissue290), wherein CMUT array210performs both the ultrasound treatment and the ultrasound imaging from within body channel392. In one scenario, protocol4800is applied to treatment of target tissue that may be addressed from a single position and orientation of the CMUT array. In another scenario, protocol4800is applied to a treatment of target tissue of such extent that several different positions and/or orientations of CMUT array must be used to treat all of the target tissue. In this scenario, the ultrasound treatment initiated by step4810treats a portion of the target tissue. However, it should be understood that the ultrasound imaging initiated by step4810may image a larger portion of the target tissue than that being treated.

Protocol4800also includes step4820. Step4820uses one or more thermoelectric coolers to cool a wall of the body channel, and further removes heat from the thermoelectric cooler(s) using a solid thermal conductor. Step4820is an embodiment of steps4420and4430. In one example of step4820, thermoelectric cooler(s)220cool wall390and solid thermal conductor710removes heat from thermoelectric cooler(s)220. In certain embodiments, protocol4800further includes a step4830of monitoring the temperature and/or pressure of the wall of the body channel at or near the CMUT array. In one example of step4830, sensor(s)230measure temperature and/or pressure of wall390. Step4830is an embodiment of step4440. Steps4820and4830are performed in parallel with the ultrasound treatment and imaging initiated by step4810. Step4820may be performed based, at least in part, upon measurements obtained in step4830. Without departing from the scope hereof, step4820may run the thermoelectric cooler(s) in reverse to heat the body channel wall, so as to prevent or compensate for over-cooling of the body channel wall.

Method4820performs a step4840while the ultrasound treatment and imaging, initiated by step4810, is active. Step4840evaluates (a) ultrasound images obtained from the ultrasound imaging initiated by step4810and optionally, in embodiments including step4830, (b) wall temperature/pressure measurements obtained in step4830. Based upon this evaluation, step4840determines if the ultrasound treatment initiated by step4810should continue or be stopped.

In a decision step4842, step4840determines if the ultrasound treatment of the target tissue, currently being treated by the CMUT array, is complete. If so, protocol4800proceeds to a step4850that ceases the ultrasound treatment (and optionally also the ultrasound imaging) initiated by step4810and marks the ultrasound treatment complete. In one scenario, step4842determines that the ultrasound treatment of the target tissue currently being treated is complete, based upon information (e.g., a clutter signal as discussed above in reference toFIGS. 46 and 47) obtained from one or more ultrasound images. In another scenario, step4842determines that the ultrasound treatment of the target tissue currently being treated is complete, based upon one or more temperature and/or pressure measurements obtained from step4830. In this latter scenario, step4840back-projects the temperature/pressure value(s) to the target tissue, using a thermal model, to determine the temperature of the target tissue. In yet another example, step4842utilizes a combination of ultrasound images and temperature/pressure measurements to determine if the ultrasound treatment is complete.

Embodiments of protocol4800that include step4830, step4840may further include a decision step4844that determines if a temperature or pressure of the body channel wall has reached a threshold value, above which damage to the body channel wall is likely to occur. If such a threshold value has been reached, protocol4800proceeds to a step4860that ceases the ultrasound treatment (and optionally also the ultrasound imaging) initiated by step4810. If the treatment is not yet complete (as determined by step4842), step4860may mark the treatment as being incomplete, and protocol4800may continue the ultrasound treatment of this target tissue later. In one implementation, protocol4800relies on step4842in the initial phase of treatment before further utilizing step4844in later phases of treatment.

Protocol4800may include a step4802, preceding step4810, of positioning the CMUT array to expose the target tissue or a certain portion of the target tissue. Step4802may include adjusting the orientation of the CMUT array within the body channel and/or adjusting how far into the body channel the CMUT array is inserted.

In scenarios, wherein the extent of the target tissue is such that not all of the target tissue can be reached from a single fixed position/orientation of the CMUT array, step4810initiates treatment of a portion of the target tissue. In such scenarios, steps4850and4860may be followed by a step4870that repositions the CMUT array to target another portion of the target tissue, prior to protocol4800returning to step4810to initiate ultrasound treatment of this other portion of the target tissue. Protocol4800may perform several such iterations to treat all of the target tissue. In one example of such a scenario, protocol4800is applied to ultrasound treatment of prostate192, for example treatment of BPH. In this example, protocol4800includes several repetitions of steps4810,4840,4850,4860, and4870, wherein each repetition is associated with a different orientation of the CMUT array in urethra194to effect ultrasound treatment in essentially 360 degrees about urethra194.

In one implementation of protocol4800, steps4802and4870are performed manually by an operator. The operator may utilize an embodiment of handle120or catheter110that defines discrete positions/orientations of CMUT array112(or210). In another implementation of protocol4800, steps4802and4870are performed automatically using control module140or system3900and a motorized embodiment of handle120or catheter110.

Certain embodiments of protocol4800may be encoded in either one of treatment control instructions3940and4740.

FIG. 49illustrates one graphical user interface4900that may be utilized in conjunction with protocol4800to manage treatment of target tissue of an extent that requires several different positions/orientations of the CMUT array. User interface4900may be implemented in control module140, or cooperatively implemented in system3900and a display communicatively coupled with system3900.

User interface4900includes a treatment progress indicator4910that visually indicates treatment status of each portion of the target tissue. Each portion of the target tissue is represented by a segment4912of treatment progress indicator4910. Color, shading, text, or another visual marker, is applied to each segment4912to indicate the treatment status of this segment4912. Possible status types include currently being treated, treatment complete, treatment incomplete, and not yet exposed to treatment. In the example depicted inFIG. 49, one segment4912is in active status (label4922), indicating that this segment4912is currently being exposed to ultrasound treatment initiated by step4810of protocol4800. Several other segments4912have been treated and the treatment is complete (labels4924). One segment4912has been treated but the treatment is not yet complete (label4926). The remaining segments4912have not yet been exposed to treatment (labels4928and all segments4912with no shading inFIG. 49). For clarity of illustration, not all segments4912,4924,4926, and4928are labeled inFIG. 49.

The particular example of treatment progress indicator4910shown inFIG. 49is associated with a scenario wherein the CMUT array must be placed in several different orientations, for example to perform 360 degrees of treatment of prostate192, while treating from the outside toward the inside. In certain scenarios, treatment may be most effective when, at any given orientation of the CMUT array, the ultrasound is first focused on the most distant segment before working inwards. This ensures that the ultrasound does not need to pass through tissue with significant necrosis before reaching the target segment; necrosis may adversely affect the ultrasound propagation properties. In the example shown inFIG. 49, each segment4912corresponds to a respective orientation of the CMUT array and radial distance at which the ultrasound is focused. Without departing from the scope hereof, treatment progress indicator4910may be tailored to display translation of the CMUT array rather than, or in combination with, rotation of the CMUT array. Also without departing from the scope hereof, treatment progress indicator4910may include more or fewer segments4912than shown inFIG. 49, for example only segmentation according to orientation and not radial distance. User interface4900may be used together with (a) an embodiment of handle120or catheter110that senses the position/orientation of the CMUT array and (b) a computer (such as control module140or system3900) that processes the sensed position/orientation together with the radial focus distance of the ultrasound. When an operator manually controls the orientation/position of the CMUT array, user interface4900provides the operator with information about which segments4912that need treatment or further treatment and which segments4912should not receive further treatment. When the repositioning/refocusing of the CMUT array is performed automatically, for example controlled by control module140or system3900, user interface4900shows progress of the treatment. Software associated with user interface4900may be configured to prevent treatment of a radially more inward segment4912prior to treatment of a radially more outward segment4912.

In certain embodiments, user interface4900includes a warning indicator4930that displays a warning to an operator if, e.g., it is time to manually reposition/refocus the CMUT array or if the CMUT array has been positioned incorrectly.

FIG. 50illustrates one method5000for manufacturing a CMUT array with solid state cooling, wherein the CMUT array is manufactured directly on a thermoelectric cooler. Method5000may be used to manufacture CMUT-TEC device1200. Method5000may also be used to manufacture an embodiment of CMUT-TEC device200having CMUT array210in direct physical contact with thermoelectric cooler220, for example as in CMUT-TEC device500.

Method5000includes steps5010and5020. Step5010receives a thermoelectric cooler that includes two thermal conductors and, disposed between the two thermal conductors, a plurality of n-type semiconductors and a plurality of p-type semiconductors electrically coupled in series such that the series alternates between the n-type semiconductors and the p-type semiconductors. Step5020fabricates a CMUT array on one of the thermal conductors of the thermoelectric cooler. In one example of method5000, step5010receives thermoelectric cooler1210, and step5020fabricates CMUT array210on thermal conductor1242of thermoelectric cooler1210.

Method5000may further include a step5002, preceding step5010, of producing the thermoelectric cooler from a substrate using micromachining processes. Additionally, step5020may implement a step5022of fabricating the CMUT array using micromachining processes.

In an embodiment, step5020includes steps5030,5032,5034, and5036. Step5030deposits a plurality of first electrodes of the CMUT array (yet to be completed) on a first one of the two thermal conductors of the thermoelectric cooler. Step5032forms an electrically insulating layer on the first thermal conductor. The electrically insulating layer covers the first electrodes and has a plurality of vacuum cavities. Each of the vacuum cavities corresponds to a respective transducer of the CMUT array and is positioned above a respective one of the first electrodes. Step5034deposits a plurality of second electrodes of the CMUT array on the electrically insulating layer. Each of the second electrodes is positioned above a respective one of the vacuum cavities. Step5036deposits a protective layer over the second electrodes. The protective layer may be electrically insulating.

Without departing from the scope hereof, steps5010and5020(and, optionally, step5002) may be performed with a thermoelectric cooler not yet equipped with the second thermal conductor. This second thermal conductor may be formed at a later stage, or the ultrasound transducer array may be mounted on a thermal conductor that serves as the second thermal conductor. Also without departing from the scope hereof, electrodes between the p-type and n-type semiconductors on the side of the thermoelectric cooler facing away from the CMUT array may be formed after step5020.

It is understood that the thermoelectric coolers of the present disclosure, such as thermoelectric cooler114or220, may be extended to use with non-CMUT type ultrasound transducers such as piezoelectric ultrasound transducers and ultrasound transducers known in the art. The presently disclosed thermoelectric coolers may be thermally coupled to such ultrasound transducers to cool the ultrasound transducers, and the heat harvested by the thermoelectric cooler(s) may be removed by a thermal conductor, such as solid thermal conductor710. Piezoelectric ultrasound transducers are frequently operated below their full capacity to avoid overheating of the piezoelectric transducers. One or more of the presently disclosed thermoelectric coolers may be thermally coupled to a piezoelectric transducer, or a piezoelectric transducer array, and provide sufficient cooling to allow ultrasound generation closer to the full capacity of the piezoelectric transducer(s).

FIG. 51illustrates one medical CMUT device5100with passive cooling. CMUT device5100includes CMUT array210and solid thermal conductor1720. CMUT device5100is a modification of device700that, instead of utilizing thermoelectric cooler(s)220to actively cool non-target tissue290via CMUT array210, utilizes solid thermal conductor1720to passively cool non-target tissue290via CMUT array210. Solid thermal conductor1720is in thermal coupling480with CMUT array210. CMUT device5100is configured to cooperate with heat exchanger1730. In operation, when cooling of non-target tissue290is needed, heat exchanger1730cools solid thermal conductor1720, thereby removing heat from non-target tissue290via CMUT array210. For example, when CMUT device5100is implemented in a catheter5160, solid thermal conductor1720extends to a handle that is coupled to the proximate end of catheter5160(outside the body channel) and includes heat exchanger1730. CMUT device5100may be provided together with heat exchanger1730, for example, incorporated in catheter5160and a handle, respectively. Alternatively, CMUT device5100or catheter5160may be provided as a standalone device configured for coupling with a heat exchanger1730provided by a third party.

In certain embodiments, catheter5160includes a heater5130. Heater5130is, for example, a resistive heater. In certain treatment scenarios, passive cooling of non-target tissue290by solid thermal conductor1720requires cooling solid thermal conductor1720to a temperature that is uncomfortable or damaging to the patient when CMUT array210is turned off and therefore does not heat non-target tissue290. Since solid thermal conductor1720is always in thermal coupling480with CMUT array210and the thermal mass of thermal conductor1720prevents instantaneous heating of solid thermal conductor1720, it may not be possible to turn off cooling by solid thermal conductor as quickly as the ultrasound induced heating of non-target tissue290dissipates. Thus, when CMUT array210is turned off, non-target tissue290may be over-cooled by solid thermal conductor1720. Similarly, it may be necessary to at least begin cooling down solid thermal conductor1720some time prior to turning on CMUT array210to ensure that solid thermal conductor1720can sufficiently cool non-target tissue290when CMUT array210is turned on. During this pre-cooling phase, solid thermal conductor1720may over-cool non-target tissue290. Heater5130is configured with low thermal mass and, hence, provides temperature control on a faster time scale than that of solid thermal conductor1720.

Although CMUT device5100does not benefit from certain advantages of thermoelectric cooling, such as easy and rapid temperature control, CMUT device5100does provide cooling directly at the treatment location (as opposed to in another nearby body channel). CMUT device5100also has benefits over a liquid-cooled catheter tip. In particular, CMUT device5100performs passive cooling without having to introduce a liquid coolant into the body channel Thus, there is no risk of liquid coolant leaking out of catheter5160to directly expose the patient, and catheter CMUT device5100/catheter5160does not require regulatory approval of introduction of a liquid coolant into the patient.

In an embodiment, CMUT device5100includes lens510, as discussed above in reference toFIG. 5. CMUT device5100may also include one or more sensor(s)230as discussed above in reference toFIG. 2.

Without departing from the scope hereof, CMUT device5100may be implemented in catheters1700,1800, and1900, in tubular catheter jacket2300, in catheters2550, and2650, and in devices3700and3800, in place of CMUT-TEC device200and solid thermal conductor1720. Also without departing from the scope hereof, CMUT device5100may be implemented in systems4000,4100,4200, and4300.

FIG. 52is an exploded view of one configuration5200of CMUT device5100that includes a heater. Configuration5200implements solid thermal conductor1720as a solid thermal conductor5220having a rod section5218and a flattened section5212. In one embodiment, rod section5218and flattened section5212are parts of an integrally formed, solid piece. Flattened section5212has a top surface5214and a bottom surface5216. CMUT array210and lens510are disposed on top surface5214, and a resistive heater5230is coupled to bottom surface5216. Resistive heater5230is an embodiment of heater5130.

FIG. 53is an exploded view of another configuration5300of CMUT device5100that includes a heater. Configuration5300implements solid thermal conductor1720as a solid thermal conductor5320having rod section5218and an at least partly flattened section5312. In one embodiment, rod section5218and flattened section5312are parts of an integrally formed, solid piece. Flattened section5312has a top surface5314. CMUT array210and lens510are disposed on top surface5314, and a resistive heater5330is wound around rod section5218near flattened section5312. Resistive heater5330is an embodiment of heater5130.

FIG. 54is an exploded view of yet another configuration5400of CMUT device5100that includes a heater. Configuration5400implements solid thermal conductor1720as solid thermal conductor5320. CMUT array210and lens510are disposed on top surface5314, with a resistive heater5430on flattened section5312at the interface between top surface5314and CMUT array210. In one implementation, resistive heater5430is wire that is embedded in a thermal adhesive between top surface5314and CMUT array210. Resistive heater5430is an embodiment of heater5130.

FIG. 55illustrates one system5500for ultrasound treatment with passive cooling. System5500is similar to system3500apart from being configured for passive cooling by solid thermal conductor1720instead of active cooling by thermoelectric cooler220. System5500includes electronic circuitry5510(in place of electronic circuitry3510) and heat exchanger1730, optionally mounted together in handle3560. Electronic circuitry5510and heat exchanger1730are configured to cooperate with catheter5160. Electronic circuitry5510is an adaptation of electronic circuitry3510that does not include Peltier driving circuitry3514. Electronic circuitry5510may include heating circuitry5530to drive heater5130, when electronic circuitry5510is coupled with an embodiment of catheter5160that includes heater5130. In an embodiment of system5500, treatment controller3540is adapted to control heating circuitry5530(when included) and/or at least partly control heat exchanger1730. In this embodiment, treatment controller3540may cooperate with measurement unit3532to control heating circuitry5530(when included) and/or heat exchanger1730based upon measurements obtained from sensor(s)230(when included).

FIG. 56illustrates one method5600for ultrasound treatment with passive cooling. Method5600is performed by catheter5160and heat exchanger1730, for example. The performance of method5600may be commanded by treatment controller3540utilizing electronic circuitry5510. Certain embodiments of method5600may be encoded in machine-readable instructions3930as treatment control instructions3940. Other embodiments of method5600may be encoded in machine-readable instructions3930as treatment control instructions3940in combination with one or both of measurement instructions3932and ultrasound imaging instructions3950.

Method5600is similar to method4400apart from steps4420and4430being replaced by a step5620. Step5620removes heat from the non-target tissue. Step5620includes a step5622that conducts the heat from the non-target tissue via a solid thermal conductor to a heat exchanger outside the body channel. In one example of steps5620and5622, heat exchanger1730cools solid thermal conductor1720of catheter5160, such that solid thermal conductor1720removes heat from non-target tissue290via CMUT array210. Heat exchanger1730may utilize liquid cooling of solid thermal conductor1720, for example by liquid nitrogen, antifreeze cooled to −30 degrees Celsius, chilled water at near-zero degrees Celsius, or room temperature water. Step5620may include a step5624of heating the catheter tip, and thus the non-target tissue, as needed to prevent excessive cooling. In one example of step5624, heater5130heats at least a portion of the tip of catheter5160to heat non-target tissue290, so as to prevent or compensate for over-cooling of non-target tissue290by solid thermal conductor1720.

FIG. 57illustrates one method5700for ultrasound treatment of prostate192with passive cooling of the urethra194. Method5700is performed by catheter5160and heat exchanger1730, for example Method5700is an embodiment of method5600specifically adapted for ultrasound treatment of prostate192, for example to treat BPH or prostate cancer.

Method5700includes steps4510and5720, which are embodiments of steps4410and5620, respectively. Step4510is discussed above in reference toFIG. 45. Step5720removes heat from the wall of urethra194. Step5720includes a step5722that conducts the heat from the wall of urethra194via a solid thermal conductor to a heat exchanger outside urethra194. Step5720may include a step5724of heating the catheter tip, and thus the wall of urethra194, as needed to prevent excessive cooling. Steps5722and5724are embodiments of steps5622and5624, respectively.

Method5700may further include steps4540,4550, and/or4560, as discussed above in reference toFIG. 46.

Without departing from the scope hereof, each of methods5600and5700may implement method4600in step4412. Also without departing from the scope hereof, each of methods5600and5700may be performed according to protocol4800.

EXAMPLE I

Modeling of Cooling Performance of CMUT-TEC Device

The thermal properties of an embodiment of device700and adjacent tissue have been evaluated using an electrical circuit model and the software SPICE (Simulation Program with Integrated Circuit Emphasis). The model takes advantage of the fact that thermal conduction and electrical conduction are governed by analogous physical laws. The model assumes that (a) device700includes lens510, (b) solid thermal conductor710is coupled to a heat exchanger, such as heat exchanger1730, and (c) solid thermal conductor710is housed in a stainless steel catheter jacket. The model takes into account ultrasound heating of both the adjacent tissue and lens510, and further takes into account heat generated by the thermoelectric coolers. The model accounts for thermal couplings between the solid thermal conductor, the heat exchanger, the stainless steel catheter jacket, the thermoelectric coolers, the CMUT, the lens, and the tissue.

In this example, solid thermal conductor710is a copper rod shaped in a manner similar to solid thermal conductor5320, wherein rod section5218is 20 cm long and has a diameter of 3.2 mm, and wherein flattened section5312is 2.5 cm long. (Heater5330is not included in the model.) Six thermoelectric coolers (Marlow, NL1020T) are attached side-by-side to top surface5314with thermal epoxy and run in parallel, and a CMUT is attached to the side of the thermoelectric coolers facing away from top surface5314. The CMUT active area is 3.4 mm by 25.6 mm. Each thermoelectric cooler covers an area of approximately 3.4 mm by 3.4 mm and has a thickness of 1.6 mm. The stainless steel catheter jacket has an inner diameter of 4 mm, an outer diameter of 5 mm, and a length of 20 cm. The stainless steel catheter jacket houses rod section5218. The CMUT generates 10 Watts of ultrasound when turned on. When turned on, each thermoelectric cooler is driven with a current of 0.3 Amperes, which has been found to provide optimal cooling performance

The temperature at the lens-tissue interface is modeled as a function of time after turning on the CMUT and thermoelectric coolers. The calculations are performed for different temperatures of the cooling reservoir of the heat exchanger and for two different materials of lens510(Sylgard 160 and RTV-615. Table 1 lists steady state temperatures, in degrees Celsius, at the lens-tissue interface when heating and cooling have reached equilibrium. Table 2 lists rise times (in seconds) from a steady-state temperature, with no heating or cooling engaged, to a temperature of 41 degrees at the lens-tissue interface, with and without thermal insulation between the solid thermal conductor and the stainless steel catheter jacket.

The results listed in Table 1 and Table 2 demonstrate that cooling is most effective when the cooling reservoir temperature is low, and that the reduced ultrasound attenuation of RTV-615, as compared to Sylgard 160, results in a lower steady-state temperature at the lens-tissue interface as well as a longer rise-time to 41° C. In one treatment scenario, the on-time of the CMUT is limited to the corresponding rise-time listed in Table 2, to prevent the temperature at the lens-tissue interface from exceeding 42° C. Treatment may be resumed when the temperature at the lens-tissue interface has dropped by a desired amount. The thermoelectric coolers may be left on to accelerate this cooling.

The heating of the target tissue has been simulated using a bio-heat transfer equation. This simulation shows that the volume of necrosed tissue is a highly non-linear function of ultrasound exposure time. In one example, two seconds of exposure causes necrosis of a tissue volume of about 2.5 mm3, but an additional two-second exposure causes necrosis of an additional tissue volume of almost 10 mm3. Thus, ultrasound treatment may be significantly more effective when the cooling provides for a long rise-time (see Table 2) to a maximum upper temperature.

EXAMPLE II

Modeling of Cooling Performance of Passively Cooled CMUT Device

The thermal properties of an embodiment of CMUT device5100and adjacent tissue has been evaluated using an electrical circuit model and the software SPICE (Simulation Program with Integrated Circuit Emphasis), in a manner similar to that discussed above in Example I, except without thermoelectric coolers. Table 3 lists steady state temperatures, in degrees Celsius, at the lens-tissue interface when heating and cooling have reached equilibrium, with and without thermal insulation between the solid thermal conductor and the stainless steel catheter jacket. Table 4 lists rise times (in seconds) from a steady-state temperature, with no heating or cooling engaged, to a temperature of 41 degrees at the lens-tissue interface, with and without thermal insulation between the solid thermal conductor and the stainless steel catheter jacket.

The results listed in Table 3 and Table 4 demonstrate that cooling is most effective when the cooling reservoir temperature is low, and that the reduced ultrasound attenuation of RTV-615, as compared to Sylgard 160, results in a lower steady-state temperature at the lens-tissue interface as well as a longer rise-time to 41° C. At the lowest cooling reservoir temperatures, the rise-times with passive cooling are as long as or longer than the rise-times with thermoelectric cooling (see Table 2). However, in these scenarios, to prevent over-cooling of the patient's tissue, heater5130may need to be engaged when the ultrasound emission is off. For higher cooling reservoir temperatures, the rise-times achieved with passive cooling are shorter than those achieved with thermoelectric cooling.

Combinations of Features

Features described above as well as those claimed below may be combined in various ways without departing from the scope hereof. For example, it will be appreciated that aspects of one medical device, system or method, described herein may incorporate or swap features of another medical device, system, or method, described herein. The following examples illustrate possible, non-limiting combinations of embodiments described above. It should be clear that many other changes and modifications may be made to the methods and device herein without departing from the spirit and scope of this invention:

(A1) A medical device may include a capacitive micromachined ultrasonic transducer (CMUT) array configured to emit ultrasound to target tissue, and at least one thermoelectric cooler mechanically coupled with the CMUT array and configured to cool non-target tissue heated by the ultrasound.

(A2) In the device denoted as (A1), the CMUT array may be configured to project the ultrasound from a first side of the CMUT array, and each thermoelectric cooler may be thermally coupled to a second side of the CMUT array.

(A3) In the device denoted as (A2), the first side of the CMUT array may be configured to be thermally coupled with the non-target tissue, to facilitate cooling of the non-target tissue by the at least one thermoelectric cooler through the CMUT array.

(A4) Either of the devices denoted as (A2) and (A3) may further include an acoustic lens disposed on the first side of the CMUT array, wherein the acoustic lens is configured to be thermally coupled with the non-target tissue to provide a thermal pathway between the non-target tissue and the at least one thermoelectric cooler through the CMUT array and the acoustic lens.

(A5) In the device denoted as (A4), the acoustic lens may be configured to be in physical contact with the non-target tissue.

(A6) Any of the devices denoted as (A1) through (A5) may further include a solid thermal conductor thermally coupled to each thermoelectric cooler to remove heat from the thermoelectric cooler.

(A7) In the device denoted as (A6), each thermoelectric cooler may be implemented in a layer having (a) a first side thermally coupled to the second side of the CMUT array and (b) a second side facing away from the first side of the layer and thermally coupled to the solid thermal conductor.

(A8) In either of the devices denoted as (A6) and (A7), the solid thermal conductor may include metal.

(A9) Any of the devices denoted as (A1) through (A8) may include a silicon substrate with the CMUT array, wherein each thermoelectric cooler is bonded to the silicon substrate via a thermally conductive adhesive.

(A10) Any of the devices denoted as (A1) through (A9) may further include one or more sensors for sensing a property of the non-target tissue, wherein the property may be selected from the group consisting of temperature, pressure, and a combination of temperature and pressure.

(A11) In the device denoted as (A10), each of the sensors may be a solid state sensor.

(A12) In the device denoted as (A11), the one or more solid state sensors may include a strain gauge configured to sense pressure of the non-target tissue.

(A13) In any of the devices denoted as (A1) through (A12), the CMUT array may be planar.

(A14) In any of the devices denoted as (A1) through (A12), the CMUT array may include two planar CMUT subarrays positioned at an angle to each other.

(A15) In the device denoted as (A14), respective ultrasound emission faces of the two planar CMUT subarrays may be angled away from each other to increase angular range of the CMUT array.

(A16) In the device denoted as (A15), each of the planar CMUT subarrays may be elongated in a first dimension, wherein an angle between the respective ultrasound emission faces of the two planar CMUT subarrays is in a plane orthogonal to the first dimension.

(A17) In either of the devices denoted as (A15) and (A16), the angle between respective normal vectors of the ultrasound emission faces may be in the range between 45 and 90 degrees.

(B1) A catheter for ultrasound treatment with solid state cooling may include (a) a capacitive micromachined ultrasonic transducer (CMUT) array configured to emit ultrasound to target tissue, (b) a thermoelectric cooler configured to cool non-target tissue heated by the ultrasound, wherein the ultrasound transducer is disposed at a distal end of the catheter, and (c) a solid thermal conductor coupled to the thermoelectric cooler and extending along the catheter away from the distal end toward a proximal end of the catheter, to conduct heat away from the thermoelectric cooler.

(B2) In the catheter denoted as (B1), the thermoelectric cooler may be mechanically coupled with the CMUT array.

(B3) In either of the catheters denoted as (B1) and (B2), the solid thermal conductor may include a metal conductor.

(B4) In the catheter denoted as (B3), the metal conductor may be a flexible braided-wire metal conductor.

(B5) Any of the catheters denoted as (B1) through (B4) may further include first electrical conductors configured to electrically couple the CMUT array to ultrasound driving circuitry external to the catheter, and second electrical conductors configured to electrically couple the thermoelectric cooler to Peltier driving circuitry, external to the catheter, for driving the thermoelectric cooler.

(B6) Any of the catheters denoted as (B1) through (B5) may further include a temperature sensor for sensing temperature of the non-target tissue.

(B7) Any of the catheters denoted as (B1) through (B6) may further include a pressure sensor for sensing pressure of the non-target tissue.

(B8) Any of the catheters denoted as (B1) through (B7) may be configured for insertion into a urethra, wherein the target tissue is a prostate and the non-target tissue is at least a portion of wall of the urethra.

(B9) The catheter denoted as (B8) may implement the CMUT array and the thermoelectric cooler in a catheter tip, and further include a catheter jacket coupled to the catheter tip and having length to reach from the prostate to exit of the urethra.

(B10) In the catheter denoted as (B9), the catheter jacket may include a thermally insulating layer for preventing heat conducted by the solid thermal conductor from damaging the wall of the urethra.

(B11) Either of the catheters denoted as (B9) and (B10) may further include a removable sleeve disposed about the catheter tip and the catheter jacket, wherein the removable sleeve includes an inflatable balloon for securing the removable sleeve to a bladder and having length to at least reach from the bladder to the exit of the urethra and being configured to remain in the urethra for a duration after extraction of the catheter tip from the urethra.

(B12) In the catheter denoted as (B11), the removable sleeve may further include a thermally insulating layer for preventing heat conducted by the solid thermal conductor from damaging the wall of the urethra.

(B13) Either of the catheters denoted as (B11) and (B12) may further include a rotation joint permitting rotation of the catheter tip relative to the inflatable balloon about a longitudinal axis of the catheter.

(B14) In the catheter denoted as (B13), the rotation joint may define a discrete plurality of orientations of the catheter tip about the longitudinal axis.

(B15) In any of the catheters denoted as (B11) through (B14), the removable sleeve may form a conduit for passing urine from the bladder to the exit of the urethra.

(B16) In any of the catheters denoted as (B11) through (B15), the removable sleeve may be rigid.

(B17) In any of the catheters denoted as (B11) through (B16), the removable sleeve may be pliable.

(C1) A system for enhanced ultrasound treatment with solid state cooling may include any one of the catheters denoted as (B1) through (B17), and two acoustic mirrors, each configured to cooperate with the CMUT array to form a respective acoustic cavity, to increase intensity of the ultrasound within the acoustic cavity.

(C2) The system denoted as (C1) may be configured for ultrasound treatment of a prostate, wherein the catheter is configured to position the CMUT array in a urethra at the prostate, and the two acoustic mirrors are respectively configured for (a) internal positioning in a rectum and (b) external positioning anterior to the prostate.

(D1) A medical device may include a catheter for exposing target tissue to ultrasound and a catheter handle mechanically coupled to a proximal end of the catheter and configured to be positioned outside a body channel into which the catheter is inserted, to at least partly control the catheter, wherein the catheter includes (a) a capacitive micromachined ultrasonic transducer (CMUT) array disposed at a distal end of the catheter and configured to emit the ultrasound to the target tissue, (b) a thermoelectric cooler configured to cool non-target tissue heated by the ultrasound, and (c) a solid thermal conductor coupled to the thermoelectric cooler and extending along the catheter away from the distal end toward a proximal end of the catheter, to conduct heat away from the thermoelectric cooler.

(D2) In the device denoted as (D1), the solid thermal conductor may extend to the catheter handle, and the catheter handle may include a heat exchanger for cooling the solid thermal conductor.

(D3) In either of the devices denoted as (D1) and (D2), the catheter handle may include electronic circuitry for driving the CMUT array and driving the thermoelectric cooler, and the catheter may include electrical connections coupling the electronic circuitry to the CMUT array and the thermoelectric cooler.

(D4) Any of the devices denoted as (D1) through (D3) may further include (i) one or more sensors positioned in the catheter and configured to sense a property of the non-target tissue, wherein the property is selected from the group consisting of temperature, pressure, and a combination thereof, and (ii) measurement circuitry positioned in the handle and electrically coupled to the one or more sensors, the measurement circuitry being configured to process sensor signals from the one or more sensors to determine the property.

(D5) Any of the devices denoted as (D1) through (D4) may further include a catheter sleeve for encasing the catheter, wherein the catheter sleeve and the catheter are removably coupled to enable leaving the catheter sleeve in the body channel after extraction of the catheter from the body channel, and the catheter sleeve may include at least one of (a) one or more tissue property sensors and (b) a conduit for passing fluid through the catheter sleeve.

(D6) In any of the devices denoted as (D1) through (D5), the catheter may be a urethral catheter configured for insertion into a urethra to position the CMUT array and the thermoelectric cooler at the prostate to apply the ultrasound treatment to the prostate.

(D7) In the device denoted as (D6), the catheter may include a catheter tip containing the CMUT array and the thermoelectric cooler, wherein the handle includes an actuator for changing a position of the catheter tip relative to a reference position associated with the prostate.

(D8) In the device denoted as (D7), the handle may further include an indicator for indicating the position of the catheter tip relative to the reference position.

(D9) In the device denoted as (D8), the catheter may include a rotation joint permitting rotation of the catheter tip about longitudinal axis of the catheter, wherein the actuator is capable of rotating the catheter tip about the longitudinal axis.

(D10) In either of the devices denoted as (D8) and (D9), the actuator may be capable of adjusting position of the catheter tip in direction along longitudinal axis of the catheter.

(E1) A system for enhanced ultrasound treatment may include (a) a catheter including an ultrasound transducer array and configured to position the ultrasound transducer array in a channel of a body to expose target tissue of the body to ultrasound, and (b) at least one acoustic mirror, each configured for positioning externally to the channel on a side of the target tissue that is opposite the ultrasound transducer array, to form an acoustic cavity that enhances intensity of the ultrasound at the target tissue by creating a standing acoustic wave between the ultrasound transducer array and the acoustic mirror.

(E2) In the system denoted as (E1), the catheter may be a urethral catheter configured to position the ultrasound transducer array at a prostate to treat the prostate with the ultrasound.

(E3) In the system denoted as (E2), the at least one acoustic mirror may include a first acoustic mirror configured for positioning externally to the body and anterior to the prostate, and a second acoustic mirror configured for positioning in rectum of the body.

(E4) In any of the systems denoted as (E1) through (E3), the ultrasound transducer array may be a capacitive micromachined ultrasonic transducer array.

(E5) In any of the systems denoted as (E1) through (E3), the ultrasound transducer array being a piezoelectric ultrasonic transducer array.

(F1) A system for enhanced ultrasound treatment may include a first ultrasound transducer array, and a second ultrasound transducer array cooperatively configured with the first ultrasound transducer array to form an acoustic cavity that enhances intensity of ultrasound, generated by the first ultrasound transducer array and the second ultrasound transducer array, at the target tissue by creating a standing acoustic wave within the acoustic cavity.

(F2) The system denoted as (F1) may further include a control module configured to adjust a phase shift between ultrasound emission of the first ultrasound transducer array and ultrasound emission of the second ultrasound transducer array, to adjust position of each antinode of the standing acoustic wave.

(F3) In the system denoted as (F2), the control module may be configured to sweep the phase shift so as to sweep the position of each antinode.

(F4) Any of the systems denoted as (F1) through (F3) may include a urethral catheter that contains the first ultrasound transducer array, wherein the urethral catheter is configured to position the first ultrasound transducer array in a urethra of a subject at a prostate, such that a portion of the prostate is contained by the acoustic cavity.

(F5) In the system denoted as (F4), the first ultrasound transducer array may be a capacitive micromachined ultrasonic transducer (CMUT) array, and the urethral catheter may further include at least one thermoelectric cooler mechanically coupled with the CMUT array and configured to cool a portion of a wall of the urethra heated by the ultrasound.

(F6) In the system denoted as (F5), the first ultrasound transducer device may be implemented at a distal end of the urethral catheter, and the urethral catheter may further include a solid thermal conductor coupled to the at least one thermoelectric cooler and extending along the urethral catheter away from the distal end toward a proximal end of the catheter, to conduct heat away from the thermoelectric cooler.

(F7) Any of the systems denoted as (F4) through (F6) may include a rectal catheter that contains the second ultrasound transducer array, wherein the rectal catheter is configured to position the second ultrasound transducer array in a rectum, such that the acoustic cavity contains a posterior portion of the prostate.

(F8) In any of the systems denoted as (F4) through (F6), the second ultrasound transducer may be configured for positioning outside body of the subject anterior to prostate, such that the acoustic cavity contains an anterior portion of the prostate.

(F9) In any of the systems denoted as (F1) through (F8), each of the first ultrasound transducer array and the second ultrasound transducer array may be a capacitive micromachined ultrasonic transducer array.

(F10) In any of the systems denoted as (F1) through (F8), each of the first ultrasound transducer array and the second ultrasound transducer array being a piezoelectric ultrasonic transducer array.

(G1) A catheter or catheter sleeve with solid state cooling may include a tubular wall for insertion into a channel of a body, and at least one thermoelectric cooler coupled to the tubular wall for cooling tissue of the channel.

(G2) In the catheter or catheter sleeve denoted as (G1), each thermoelectric cooler may be mounted to outside of the tubular wall and configured for operation with a cold side of the thermoelectric cooler facing away from the tubular wall and a hot side of the thermoelectric cooler facing the tubular wall.

(G3) The catheter or catheter sleeve denoted as (G2) may further include a solid thermal conductor positioned within space bounded by the tubular wall and thermally coupled to the hot side of each thermoelectric cooler to remove heat from the hot side.

(G4) In the catheter or catheter sleeve denoted as (G3), at least a portion of the tubular wall away from the at least one thermoelectric cooler may include a thermally insulating layer to prevent heat conducted by the solid thermal conductor from damaging tissue in thermal contact with the at least a portion of the tubular wall.

(G5) The catheter or catheter sleeve denoted as (G2) may further include (a) a solid thermal conductor disposed on outside of the tubular wall or integrated in the tubular wall, wherein the solid thermal conductor is thermally coupled to the hot side of each thermoelectric cooler to remove heat from the hot side of each thermoelectric cooler, and (b) a thermally insulating layer disposed on outside of the solid thermal conductor to prevent heat conducted by the solid thermal conductor from damaging tissue adjacent the solid thermal conductor.

(G6) In the catheter or catheter sleeve denoted as (G2), the tubular wall may have a proximal end configured to be external to the channel, each thermoelectric cooler may be at a section of the tubular wall a distance away from the proximal end, and the catheter may further include a solid thermal conductor thermally coupled to hot side of each thermoelectric cooler and extending to the proximal end of the tubular wall to conduct heat from the hot side of each thermoelectric cooler out of the channel.

(G7) In any of the catheters or catheter sleeves denoted as (G2) through (G6), each thermoelectric cooler may include (i) a plurality of n-type semiconductors and a plurality of p-type semiconductors electrically coupled in series such that the series alternates between the n-type semiconductors and the p-type semiconductors, (ii) a first thermal conductor thermally coupling the n-type semiconductors and the p-type semiconductors on the cold side, and (iii) a second thermal conductor mounted to the outside of the tubular wall and thermally coupling the n-type semiconductors and the p-type semiconductors on the hot side.

(G8) In the catheter or catheter sleeve denoted as (G7), a portion of the tubular wall supporting the thermoelectric cooler may be rigid, and the n-type semiconductors and the p-type semiconductors may be arranged in a rigid configuration conformed to curvature of the tubular wall.

(G9) In the catheter or catheter sleeve denoted as (G7), a portion of the tubular wall supporting the thermoelectric cooler may be pliable, and electrical connections between the n-type semiconductors and the p-type semiconductors may be flexible to conform to bending of the portion of the tubular wall.

(H1) A catheter sleeve with integrated sensing may include tubular casing for insertion into a channel of a body and capable of encasing a catheter, and at least one sensor coupled to the tubular casing and configured to sense one or more properties of tissue of the channel, wherein each of the one or more properties is selected from the group consisting of temperature and pressure.

(H2) The catheter sleeve denoted as (H1) may be configured to encase a urethral catheter.

(H3) The catheter sleeve denoted as (H2) may further include a conduit for passing urine from the bladder out of the urethra.

(H4) In the catheter sleeve denoted as (H3), the conduit may be formed in the tubular casing.

(H5) Any of the catheter sleeves denoted as (H1) through (H4) may further include an inflatable balloon for securing the catheter sleeve to a bladder, and a conduit for passing a fluid to the inflatable balloon to inflate the inflatable balloon.

(H6) In the catheter sleeve denoted as (H5), the conduit may be formed in the tubular casing.

(H7) In any of the catheter sleeves denoted as (H1) through (H6), the at least one sensor may include a plurality of sensors to sense the at least one property in a plurality of locations.

(H8) In any of the catheter sleeves denoted as (H1) through (H7), the tubular casing may include one or more electrical connections coupled to the at least one sensor and extending toward proximal end of the tubular casing to communicate, to electronic circuitry outside the channel, at least one sensor signal indicative of the one or more properties of the tissue.

(H9) In any of the catheter sleeves denoted as (H1) through (H8), the at least one sensor may include an active sensor, and the electrical connections may include a power connection to the active sensor from a power supply external to the channel.

(H10) In the catheter sleeve denoted as (H9), the tubular casing may include a pliable polymer casing, and the electrical connections may be formed in the pliable polymer casing.

(H11) In any of the catheter sleeves denoted as (H1) through (H8), each sensor may be a passive sensor.

(H12) In the catheter sleeve denoted as (H11), each sensor may be configured to wirelessly couple to a catheter placed in the sleeve, for readout of a respective sensor signal by the catheter.

(H13) In the catheter sleeve denoted as (H11), each sensor may include an electrical connection configured to electrically couple with an electrical connection of a catheter placed in the sleeve, for readout of a respective sensor signal by the catheter.

(I1) A system for ultrasound treatment with solid state cooling may include (1) ultrasound driving circuitry configured to generate drive signals to drive a capacitive micromachined ultrasonic transducer (CMUT) array, so as to expose target tissue to ultrasound, and (2) Peltier driving circuitry configured to drive at least one thermoelectric cooler, to cool non-target tissue heated by the ultrasound.

(I2) The system denoted as (I1) may further include ultrasound imaging circuitry configured to (a) generate a plurality of second signals to drive the CMUT array to image the target tissue and (b) produce an ultrasound image of the target tissue from electrical transducer signals received from the CMUT array.

(I3) The system denoted as (I2) may further include a control module configured to control generation of the drive signals by the ultrasound driving circuitry at least in part based upon the ultrasound image.

(I4) In the system denoted as (I3), the control module may be configured to control generation of the drive signals by the ultrasound driving circuitry at least in part based upon clutter signals and a predetermined correspondence between the clutter signals and efficacy of the ultrasound treatment.

(I5) In either of the systems denoted as (I3) through (I4), the ultrasound imaging circuitry may be configured to produce a Doppler image of the target tissue from the electrical transducer signals to evaluate degree of blood perfusion of the target tissue.

(I6) In any of the systems denoted as (I3) through (I5), the ultrasound imaging circuitry may be configured to produce a brightness image of the target tissue from the electrical transducer signals.

(I7) Any of the systems denoted as (I3) through (I6) may further include measurement circuitry configured to process signals from one or more sensors to determine a property of the non-target tissue, wherein the property being selected from the group consisting of temperature, pressure, and a combination thereof, and wherein the control module is configured to control generation of the drive signals by the ultrasound driving circuitry based upon the ultrasound image and the property.

(I8) Any of the systems denoted as (I1) through (I7) may further include temperature measurement circuitry configured to process signals from one or more temperature sensors to determine one or more respective temperatures of at least a portion of the non-target tissue.

(I9) Any of the systems denoted as (I1) through (I8) may further include pressure measurement circuitry configured to process signals from one or more pressure sensors to determine one or more respective pressures of the non-target tissue.

(I10) Any of the systems denoted as (I1) through (I9) may further include (i) measurement circuitry configured to process signals from one or more sensors to determine a property of the non-target tissue, the property being selected from the group consisting of temperature, pressure, and a combination thereof, and (ii) a control module configured to control generation of the drive signals by the ultrasound driving circuitry at least in part based upon the property.

(I11) Any of the systems denoted as (I1) through (I10) may further include (i) a catheter including the CMUT array and the at least one thermoelectric cooler, wherein the catheter is configured for insertion into a body channel, and (ii) a handle mechanically coupled with the catheter and containing the ultrasound driving circuitry and the Peltier driving circuitry, wherein the handle is configured for positioning outside the body channel.

(I12) In the system denoted as (I11), the catheter may include first electrical connections between the CMUT array and the ultrasound driving circuitry, and second electrical connections between the at least one thermoelectric cooler and the Peltier driving circuitry.

(I13) In the system denoted as (I12), the catheter may further include a solid thermal conductor thermally coupled to the at least one thermoelectric cooler and extending to the handle, for conducting heat from the at least one thermoelectric cooler out of the body channel.

(I14) In the system denoted as (I13), the handle may further include a heat exchanger for removing heat from the solid thermal conductor.

(I15) Any of the systems denoted as (I11) through (I14) may further include (I) one or more sensors positioned in the catheter and configured to sense a property of the non-target tissue, the property being selected from the group consisting of temperature, pressure, and a combination thereof, (II) measurement circuitry positioned in the handle and configured to process sensor signals from one or more sensors to determine the property from one or more sensor signals received from the one or more sensor, and (III) third electrical connections passing through the catheter and connecting the one or more sensors to the measurement circuitry to communicate the sensor signals.

(I16) In any of the systems denoted as (I11) through (I15), the catheter may be a urethral catheter configured for insertion into a urethra to position the CMUT array and the at least one thermoelectric cooler at the prostate to apply the ultrasound treatment to the prostate.

(J1) A method for ultrasound treatment with solid state cooling may include exposing target tissue to ultrasound generated by a capacitive micromachined ultrasonic transducer (CMUT) array, cooling non-target tissue using one or more thermoelectric coolers to prevent damage to the non-target tissue, and removing heat from the one or more thermoelectric coolers and away from the non-target tissue.

(J2) The method denoted as (J1) may include (a) in the step of exposing, generating the ultrasound from within a body channel, wherein the CMUT array has been advanced to the target tissue on a catheter through the body channel, (b) in the step of cooling, using the one or more thermoelectric coolers to cool wall of the body channel, wherein the one or more thermoelectric coolers are coupled to at least one of the CMUT array and the catheter, and (c) in the step of removing, removing the heat from the wall.

(J3) The method denoted as (J2) may include, in the step of exposing, exposing a prostate to the ultrasound from a urethra, and, in the step of cooling, cooling the wall of the urethra.

(J4) In either of the methods denoted as (J2) and (J3), the target tissue may be at least part of a prostrate, and the step of exposing may include inducing necrosis of the target tissue to treat benign prostatic hyperplasia.

(J5) In either of the methods denoted as (J2) and (J3), the target tissue may be a cancerous tumor of a prostrate, and the step of exposing may include inducing necrosis of the tissue of the cancerous tumor.

(J6) In any of the methods denoted as (J2) through (J5), the step of removing may include conducting the heat away from the one or more thermoelectric coolers through a solid thermal conductor coupled to the one or more thermoelectric coolers and extending through the catheter toward exit of the body channel.

(J7) In the method denoted as (J6), the step of removing may include conducting at least a portion of the heat through the solid thermal conductor to outside the exit.

(J8) The method denoted as (J7) may further include cooling the solid thermal conductor outside the exit.

(J9) In the method denoted as (J6), the step of removing may include redistributing the heat across at least a portion of the catheter.

(J10) Any of the methods denoted as (J1) through (J9) may further include monitoring temperature of the non-target tissue, and, in the step of exposing, adjusting exposure of the target tissue to the ultrasound according to the temperature.

(J11) In the method denoted as (J10), the step of adjusting may include at least temporarily ceasing said exposing when the temperature exceeds a threshold temperature.

(J12) Any of the methods denoted as (J1) through (J10) may further include monitoring pressure of the non-target tissue, and in the step of exposing, adjusting exposure of the target tissue to the ultrasound according to the pressure.

(J13) In the method denoted as (J12), the non-target tissue may be a wall of a body channel through which the CMUT array has been advanced to the target tissue.

(J14) Any of the methods denoted as (J1) through (J13) may further include imaging the target tissue using the CMUT array to obtain an ultrasound image indicating effect on the target tissue of the step of exposing, and, in the step of exposing, adjusting exposure of the target tissue to the ultrasound according to the effect.

(J15) The method denoted as (J14) may include alternatingly performing the steps of exposing and imaging.

(J16) Either of the methods denoted as (J14) and (J15) may further include, based upon the ultrasound image, comparing the effect as a function of position to a goal of the ultrasound treatment to identify a first portion of the target tissue in need of further ultrasound exposure, and, in the step of adjusting, redirecting ultrasound emission of the CMUT array to increase ultrasound exposure to the first portion.

(J17) In the method denoted as (J16), the step of redirecting may include applying beamforming to the CMUT array to focus at least a portion of the ultrasound on the first portion of the target tissue.

(J18) In either of the methods denoted as (J16) and (J17), the step of exposing may include generating the ultrasound from within a body channel, wherein the CMUT array has been advanced to the target tissue on a catheter through the body channel, and the step of redirecting may include rotating the CMUT array in the body channel to direct at least a portion of the ultrasound to the first portion of the target tissue.

(J19) Any of the methods denoted as (J14) through (J18) may include recording a spatially resolved clutter signal in the step of imaging, deducing instantaneous efficacy of the ultrasound treatment from the clutter signal, and, in the step of adjusting, adjusting the exposure according to the instantaneous efficacy.

(J20) In any of the methods denoted as (J1) through (J19), the step of exposing may include sequentially targeting different portions of the target tissue with the ultrasound.

(J21) In the method denoted as (J20), the step of sequentially targeting may include sequentially positioning the CMUT array in a plurality of positions along longitudinal axis of the catheter.

(J22) In either of the methods denoted as (J20) and (J21), the step of sequentially targeting may include rotating the CMUT array about longitudinal axis of the catheter.

(J23) In any of the methods denoted as (J20) through (J22), the step of sequentially targeting may include applying beamforming to the CMUT array to sequentially focus at least a portion of the ultrasound on the different portions.

(J24) Any of the methods denoted as (J1) through (J23) may further include heating a greater tissue region around and including the target tissue.

(J25) In any of the methods denoted as (J1) through (J23), the step of exposing may include exposing the target tissue to multifrequency ultrasound to focus the ultrasound on a localized region of the target tissue.

(J26) In the method denoted as (J25), the target tissue may be a cancerous prostate tumor.

(K1) A method for ultrasound treatment with ultrasound imaging feedback may include obtaining an image of target tissue from an ultrasound transducer array to determine a spatially resolved clutter signal for the target tissue, and, based upon the clutter signal and a predetermined correspondence between the clutter signal and treatment efficacy, determining one or more properties of subsequent generation of ultrasound by the ultrasound transducer array to treat the target tissue.

(K2) The method denoted as (K1) may include repeatedly performing the step of obtaining to update the spatially resolved clutter signal, and repeatedly revising the step of determining in accordance with the spatially resolved clutter signal as updated, to update the one or more properties.

(K3) Either of the methods denoted as (K1) and (K2) may further include commanding the ultrasound transducer array to generate the ultrasound having the one or more properties.

(K4) The method denoted as (K3) may include alternatingly performing the steps of obtaining and commanding.

(K5) In any of the methods denoted as (K1) through (K4), the step of determining may further include taking into account a measurement of temperature of non-target tissue heated by the ultrasound, to determine the one or more properties.

(K6) In the method denoted as (K5), the target tissue may be prostate tissue, the non-target tissue being a portion of a urethral wall.

(K7) Either of the methods denoted as (K5) and (K6) may include at least temporarily ceasing the generation of ultrasound when the temperature as measured exceeds a threshold temperature.

(K8) In any of the methods denoted as (K1) through (K4), the step of determining may further include taking into account measurement of one or both of temperature and pressure of non-target tissue heated by the ultrasound, to determine the one or more properties.

(K9) In the method denoted as (K8), the target tissue may be prostate tissue, and the non-target tissue may be a portion of a urethral wall.

(K10) In any of the methods denoted as (K1) through (K9), the step of determining may include determining intensity of the ultrasound to be subsequently generated by the ultrasound transducer array as a function of position within the target tissue.

(K11) The method denoted as (K10) may include commanding the ultrasound transducer array to beamform the ultrasound according to the intensity as a function of position as determined in the step of determining.

(K12) In the method denoted as (K11), the step of commanding may include commanding the ultrasound transducer array to focus the ultrasound on one or more localized regions of the target tissue.

(K13) Any of the methods denoted as (K1) through (K12) may include in the step of obtaining, obtaining an image of a prostate, and, in the step of determining, utilizing a prostate-tissue specific, predetermined correspondence between the clutter signal and treatment efficacy to determine the one or more properties applicable to prostate tissue, to enable ultrasound treatment of a prostate.

(K14) In any of the methods denoted as (K1) through (K13), the step of determining may include selecting the predetermined correspondence from a selection of blood-perfusion specific correspondences.

(K15) The method denoted as (K14) may further include evaluating degree of blood perfusion of the target tissue from a Doppler image of the target tissue generated by the ultrasound transducer array, and, in the step of determining, selecting the predetermined correspondence from the selection of blood-perfusion specific correspondences according to the degree of blood perfusion.

(L1) A product for controlling ultrasound treatment using ultrasound imaging feedback may include machine-readable instructions encoded in non-transitory memory, wherein the machine-readable instructions include (a) a correspondence between an ultrasound clutter signal and efficacy of the ultrasound treatment, and (b) treatment control instructions that, when executed by a processor, evaluate spatially resolved clutter signals obtained from ultrasound imaging of target tissue and utilize the correspondence to determine one or more properties of subsequent ultrasound exposure of the target tissue.

(L2) In the product denoted as (L1), the treatment control instructions may be configured to repeatedly determine the one or more properties, to adjust the ultrasound exposure according to updated spatially resolved clutter signals from repetitions of the ultrasound imaging.

(L3) In either of the products denoted as (L1) and (L2), the treatment control instructions may be configured to, when determining the one or more properties, further take into account a measurement of temperature of non-target tissue heated by the ultrasound exposure.

(L4) In the product denoted as (L3), the machine-readable instructions may further include a threshold temperature, and the treatment control instructions may be configured to at least temporarily cease the ultrasound exposure when the temperature, as measured, exceeds the threshold temperature.

(L5) In any of the products denoted as (L1) through (L4), at least one of the properties may be spatially resolved such that the ultrasound exposure is position sensitive.

(L6) In the product denoted as (L5), the treatment control instructions may include beamforming instructions that, when executed by the processor, generate a plurality of drive signals configured to drive an ultrasound transducer array to focus the ultrasound exposure on one or more localized regions of the target tissue, based upon the spatially resolved clutter signals and the correspondence.

(L7) In any of the products denoted as (L1) through (L6), the correspondence may be applicable to prostate tissue to enable ultrasound treatment of a prostate.

(L8) In any of the products denoted as (L1) through (L7), the correspondence may be sensitive to degree of blood perfusion in the target tissue.

(L9) In the product denoted as (L8), the machine-readable instructions may further include correspondence selection instructions that, when executed by the processor, select the correspondence from a plurality of blood-perfusion specific correspondences between the ultrasound clutter signal and the efficacy.

(L10) In the product denoted as (L9), the machine-readable instructions may further include perfusion evaluation instructions that, when executed by a processor, determine the degree of blood perfusion from an ultrasound Doppler image of the prostate tissue.

(L11) In any of the products denoted as (L1) through (L10), the efficacy may be characterized by one or more properties selected from the group consisting of elasticity and echogenicity of the target tissue.

(L12) In any of the products denoted as (L1) through (L10), the efficacy may be characterized by one or more properties selected from the group consisting of elasticity, necrosis, and temperature of the target tissue.

(M1) A method for manufacturing a capacitive micromachined ultrasonic transducer (CMUT) array with solid state cooling may include fabricating the CMUT array on a first thermal conductor of a thermoelectric cooler, wherein the thermoelectric cooler includes the first thermal conductor, a second thermal conductor, and, disposed between the first thermal conductor and the second thermal conductor, a plurality of n-type semiconductors and a plurality of p-type semiconductors electrically coupled in series such that the series alternates between the n-type semiconductors and the p-type semiconductors.

(M2) In the method denoted as (M1), each of the first thermal conductor and the second thermal conductor may be an electric insulator.

(M3) In either of the methods denoted as (M1) and (M2), the step of fabricating may include (a) depositing a plurality of first electrodes of the CMUT array on the first thermal conductor, (b) forming an electrically insulating layer on the first thermal conductor and covering the first electrodes, wherein the electrically insulating layer has a plurality of vacuum cavities therein, and wherein each of the vacuum cavities corresponds to a respective transducer of the CMUT array and is positioned above a respective one of the first electrodes, and (c) depositing a plurality of second electrodes of the CMUT array on the electrically insulating layer, each of the second electrodes being positioned above a respective one of the vacuum cavities.

(M4) The method denoted as (M3) may further include depositing a protective layer over the second electrodes.