WO1999000061A1 - Ensemble transducteur et procede permettant de coupler de l'energie ultrasonore a un corps dans le but de realiser une thrombolyse de thrombus vasculaires - Google Patents

Ensemble transducteur et procede permettant de coupler de l'energie ultrasonore a un corps dans le but de realiser une thrombolyse de thrombus vasculaires Download PDF

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Publication number
WO1999000061A1
WO1999000061A1 PCT/US1998/013450 US9813450W WO9900061A1 WO 1999000061 A1 WO1999000061 A1 WO 1999000061A1 US 9813450 W US9813450 W US 9813450W WO 9900061 A1 WO9900061 A1 WO 9900061A1
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WO
WIPO (PCT)
Prior art keywords
reservoir
conductive medium
transducer
fluid conductive
ultrasonic
Prior art date
Application number
PCT/US1998/013450
Other languages
English (en)
Inventor
Thomas P. Peterson
Pal Dharmendra
Eugene Decastro
Original Assignee
Cybersonics, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US08/922,188 external-priority patent/US5879314A/en
Application filed by Cybersonics, Inc. filed Critical Cybersonics, Inc.
Priority to EP98931690A priority Critical patent/EP1006896A4/fr
Priority to AU81741/98A priority patent/AU8174198A/en
Priority to JP50583499A priority patent/JP2002507138A/ja
Priority to CA002301145A priority patent/CA2301145A1/fr
Publication of WO1999000061A1 publication Critical patent/WO1999000061A1/fr

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Classifications

    • G—PHYSICS
    • G10—MUSICAL INSTRUMENTS; ACOUSTICS
    • G10K—SOUND-PRODUCING DEVICES; METHODS OR DEVICES FOR PROTECTING AGAINST, OR FOR DAMPING, NOISE OR OTHER ACOUSTIC WAVES IN GENERAL; ACOUSTICS NOT OTHERWISE PROVIDED FOR
    • G10K11/00—Methods or devices for transmitting, conducting or directing sound in general; Methods or devices for protecting against, or for damping, noise or other acoustic waves in general
    • G10K11/02—Mechanical acoustic impedances; Impedance matching, e.g. by horns; Acoustic resonators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B17/225—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for for extracorporeal shock wave lithotripsy [ESWL], e.g. by using ultrasonic waves
    • A61B17/2251—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for for extracorporeal shock wave lithotripsy [ESWL], e.g. by using ultrasonic waves characterised by coupling elements between the apparatus, e.g. shock wave apparatus or locating means, and the patient, e.g. details of bags, pressure control of bag on patient
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B2017/22082—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for after introduction of a substance
    • A61B2017/22084—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for after introduction of a substance stone- or thrombus-dissolving

Definitions

  • the present invention relates to noninvasive medical treatment of vascular thrombi using ultrasound in conjunction with therapeutic agents.
  • Reperfusion of an occluded coronary artery in a patient having acute myocardial infarction has been conventionally achieved by either intravenous administration of thrombolytic therapy agents, such as streptokinase, or by percutaneous transcatheter mechanical devices, such as balloon angioplasty devices.
  • thrombolytic therapy agents such as streptokinase
  • percutaneous transcatheter mechanical devices such as balloon angioplasty devices.
  • thrombolytic agents While administration of thrombolytic agents is currently the most widely used reperfusion therapy, the use of thrombolytic agents presents several unresolved problems. Such agents provide inadequate treatment in many cases. For example, it has been found that typically, the initial reperfusion rate is only about 70%, and TIMI grade III flow is achieved in less than 60% of patients. Furthermore, intermittent reperfusion and reocclusion of the infarct related artery is frequent, and substantial time is necessary to achieve successful recanalization. In addition, about 30%) of patients presenting with acute myocardial infarction are excluded from thrombolytic agent therapy due to the risk of bleeding complications. In spite of this, thrombolytic agent therapy is still associated with significant hemorrhage complications in five to six percent of patients.
  • Destruction of thrombosis and other medical targets, including cancerous growths and calcifications, in a living being may be obtained through the use of ultrasound by induced hyperthermia, or thermal heating of the target tissues, or by the effects of cavitation, or both.
  • Hyperthermia is due to acoustic absorption of the tissue which converts mechanical energy of the acoustic wave into thermal energy.
  • Living cells, including cells of cancerous tumors, are destroyed by the heating effect of ultrasound.
  • ultrasound has the effect of accelerating activity of thrombolytic agents injected near the site of an occlusion in an artery.
  • ultrasound has a synergistic effect on such medicinal agents and consequently, a lower dosage of medicinal agent coupled with ultrasound therapy can be used as a substitute for conventional therapies which rely primarily on the use of drugs alone. Consequently, it is possible to minimize the administrative amount of medicinal agent, and thus reduce undesirable side effects that may be attributable to the agent.
  • transcutaneous and endocavity ultrasound probes have been designed for transmitting ultrasound through a body surface of a patient in order to treat a medical target beneath the body surface.
  • transcutaneous ultrasound in conjunction with low dose medicinal agents for example, streptokinase
  • enhances thrombolysis in animals in vivo however skin and soft tissue damage induced by ultrasound energy passing through skin and soft tissues has been a major limitation.
  • Hashimoto discloses a thrombus resolving treatment apparatus which may be useful for treating a thrombus, or blood clot with noninvasive, external radiation of therapeutic ultrasound in conjunction with administration of a thrombus resolving agent.
  • a water bag or jelly pad positioned between the ultrasonic radiator and a body surface of a patient.
  • deaerated water is a satisfactory coupling medium which can be circulated in order to provide protection to healthy tissues.
  • circulation of the water as well as the vibration of the ultrasonic probe causes increased expulsion of gasses from the water. Gasses expelled from the water, or other coupling fluid, while the fluid is in the ultrasonic field may significantly impair conductivity, and cause attenuation of the ultrasonic wave.
  • the present invention provides an improved ultrasonic transducer assembly and method which addresses this problem, and other problems encountered with the use of conventional devices which will later become apparent.
  • the apparatus and method of the present invention is designed to remove expelled gasses in a cooling medium while the medium is within the ultrasonic transducer probe and circulated through the ultrasonic field.
  • the apparatus may comprise an assembly of components, including an ultrasonic transducer, hereinafter sometimes referred to as a "catalytic transducer", as it may be used as a catalyst for accelerating the activity of medicinal agents.
  • an ultrasonic transducer hereinafter sometimes referred to as a "catalytic transducer”
  • a catalyst for accelerating the activity of medicinal agents.
  • the catalytic transducer includes a housing, and means, such as a piezoelectric element, for generating ultrasonic waves in response to, for example, a electrical signal supplied by an external power source.
  • the transducer comprises a front mass disposed in the housing and a radiator for directing the ultrasonic waves into a medical target in a patient.
  • a reservoir is provided in the housing for containing a fluid conductive medium, i.e. a coupling medium, between the front mass and the a body surface of a patient.
  • the medium provides means for coupling the ultrasonic waves with the body surface.
  • the reservoir may comprise a flexible membrane or bladder.
  • the fluid conductive medium is circulated into the transducer reservoir from an external tank which contains a replenishing supply of the medium and may include means for degassing the medium, for example by vacuum sonification.
  • the assembly is designed to manage a flow of the conductive medium into and out of the reservoir in a manner which provides optimal transmission of ultrasonic energy. More specifically, means are provided for accumulating and removing expelled gasses from the reservoir.
  • the flow management means is defined by a front mass surface area which is preferably an arcuate, concave surface area.
  • the concave surface area includes an apex for enabling gasses expelled as the medium flows into the reservoir, to accumulate at the apex.
  • An outlet in fluid communication with the reservoir means and disposed generally at the apex, provides means for passing fluid conductive medium and accumulated gasses out of the reservoir, which may be circulated back to the tank.
  • the flow management means additionally includes inlet means for directing fluid conductive medium into the reservoir. Preferably, coupling fluid being circulated into the transducer will pass between the front mass and the transducer housing and into the reservoir generally along a perimeter of the concave surface area.
  • the flow management means may include an irrigation manifold in fluid communication with the reservoir and having means for directing flow of circulating fluid conductive medium into and out of the reservoir.
  • the irrigation manifold manages the flow of fluid in such a way as to reduce the amount of expelled gasses present in the ultrasonic field and additionally provide sufficient dwell time of conductive fluid in the field.
  • the irrigation manifold includes an outlet disposed at the concavity apex such that gasses accumulated at the concavity apex will pass into an outlet conduit provided by the irrigation manifold and rise toward the back end of the transducer, i.e. upward from the reservoir.
  • the irrigation manifold may have an inlet for directing the fluid conductive medium into the reservoir at the perimeter of the concave surface area.
  • the catalytic transducer may be precisely positioned on a body surface of a patient by means of a flexible, articulating arm connected to a back end of the transducer housing.
  • the flexible arm may contain cannulas or the like for providing fluid communication between the supply tank and the transducer.
  • electrical wiring for providing electrical connection between the transducer and the external power source may be contained within the flexible arm. This design keeps an operator's work area free of irrigation cannulas and electrical wiring .
  • Means for cooling the fluid conductive medium is preferably provided, which includes means for circulating the medium between the reservoir and a cooling source, such as a refrigerated tank.
  • a cooling source such as a refrigerated tank.
  • FIG. 1 shows an ultrasonic medical transducer assembly, including a catalytic transducer, suitable for performing a method for coupling ultrasonic energy to a body for destruction of blood clots, or other medical targets, in accordance with the present invention
  • FIG 2 shows a cross-sectional view of the catalytic transducer shown in Figure 1 , said catalytic transducer including means for accumulating and removing gasses from a fluid conductive medium in the ultrasonic field;
  • Figure 3 shows a diagrammatical view of the medical transducer assembly including cooling means for maintaining a comfortable temperature at a body surface of the patient;
  • Figure 4 shows a block diagram of a transducer assembly in accordance with the present invention.
  • the assembly 10 generally comprises a catalytic transducer 14 and may also comprise a generator unit 16, including a generator 17 for driving the catalytic transducer 14.
  • the generator unit 16 powering the transducer 14 may be operable by standard 1 lOv AC 50/60hz, but may be modified to accommodate any line voltage, as the AC is converted to DC by the generator.
  • An articulating arm 18 may be provided as means for positioning the transducer 14 on the body 12.
  • the catalytic transducer 14 is shown in greater detail in Figure 2. Importantly, the transducer 14 may be used as a catalyst for, and as an adjunct to, injected chemical agents for dissolving arterial thrombi.
  • the dosage of a chemical agent may be introduced at a level below its threshold of performance and then the agent is acted upon by the ultrasonic energy in the thrombus area to increase the effectiveness of the agent and shorten the time required to dissolve the thrombus.
  • the transducer 14 generally comprises a housing 24, and a piezoelectric element 26 or other suitable means for generating ultrasonic waves.
  • the transducer 14 includes a front mass 28 and a back mass 29 which may be comprised of, for example, aluminum, stainless steel or titanium or another suitable material.
  • the front mass 28 provides means 30 for radiating the ultrasonic energy generated by the piezoelectric elements 26 into the body 12.
  • the ultrasonic energy is preferably applied within the frequency range of about 20 kHz to about 130 kHz.
  • the generator 17 preferably produces a frequency range of about 18 kHz to about 100 kHz and provides a pulse for a given frequency of about 30 Hz to about 480 Hz and a frequency sweep of plus or minus 4 kHz.
  • Wattage output from the generator is variable from 5 to 200 watts.
  • Wattage output from the transducer 14 may be from about one watt per square centimeter to about 30 watts per square centimeter.
  • the front mass 28 includes structure which optimizes the transmission of ultrasonic energy, as will be discussed hereinafter.
  • the front mass 28 may have a diameter from between about 1.75 inches to about six inches.
  • a reservoir 32 is provided for containing a fluid conductive medium 34 between the front mass 28 and a body surface 36 of the patient 12 and for coupling ultrasonic energy therewith.
  • the transducer 14 is designed to be placed directly on the body surface 36 such that the reservoir 32 provides an interface between the front mass 28 and the body surface 36.
  • the reservoir 32 may be comprised of a flexible membrane 38 in the form of a pocket or bladder connected at an open end 40 thereof to the front mass 28 by a fluid tight seal 44.
  • the medium 34 may comprise water or another suitable fluid conductive medium.
  • the assembly 10 may include a tank 46 which holds a replenishing supply of the fluid conductive medium 34.
  • the tank 46 may include a port 50 for providing access to the tank 46 for filling thereof.
  • the tank 46 preferably includes means for degassing the fluid conductive medium 34 within the tank 46.
  • Figure 3 shows the tank 46 and means for degassing which may comprise for example, a ultrasonic vacuum reservoir portion 56 of the tank 46 including a degassing transducer 58 which functions to remove gasses from the medium 34 by vacuum sonification as will be readily understood by those in the art.
  • a vacuum pump 60 for supplying vacuum required for the degassing, as well as a vent valve 62 for releasing expelled gasses into the atmosphere.
  • a circulating pump 66 may be provided for circulating the fluid conductive medium 34 from the tank 46 to the catalytic transducer 14 and for maintaining fluid pressure in the reservoir 32.
  • the present invention is designed such that a flow of the circulating medium 34 may be managed in such a way as to provide optimal transmission of ultrasonic energy thorough the medium 34 in the reservoir 32.
  • the catalytic transducer 14 includes means for accumulating and removing expelled gasses 68 from the transducer reservoir 32.
  • gasses are also removed from the medium while in the transducer 14, and more particularly, while in the ultrasonic field.
  • the flow management means is defined by a surface area 72 of the front mass 28 which is preferably arcuate in cross-section and includes concavity means, comprising a concavity apex 78, for accumulating the gasses expelled from the fluid conductive medium 34.
  • the arcuate surface area enables gasses 68 within the reservoir 32 to coarse freely upward toward the apex as they are expelled from the medium 34.
  • the surface area 72 includes outlet means 74 for removing fluid conductive medium from the reservoir and the gasses expelled therefrom.
  • the reservoir outlet 74 is disposed generally at the apex 78 of the surface area 72.
  • the outlet 74 enables gasses accumulated at the apex to pass through the surface area 72 and out of the reservoir 32.
  • the flow management means also includes inlet means 86 for directing fluid conductive medium into the reservoir 32, generally along a perimeter 80 of the arcuate surface area 72.
  • the flexible membrane 38 will maintain a wide breadth as a result of the inward flow of medium 34 along the membrane 38, i.e. the reservoir boundary 82, providing optimal contact thereof with the body surface 36.
  • the transducer 14 includes an irrigation manifold 88 for directing flow of the medium 34.
  • the irrigation manifold 88 may be disposed generally through a center 90 of the front mass 28 as shown. More particularly, the irrigation manifold 88 includes an inlet conduit 94, in fluid communication with the inlet means 86, for directing the medium 34 supplied by the tank into the reservoir 32 and an outlet conduit 96, in fluid communication with the outlet 74, for removing the medium and gasses from the reservoir.
  • the front mass 28 may include one or more bores 98 therethrough for directing the inward flow of medium 34 into the reservoir boundary 82 as shown.
  • the medium 34 will flow into the reservoir 32 in a flow path represented by arrows 99, and the medium 34 as well as expelled gasses 68 will pass from the reservoir 32 in flow path represented by arrows 102 in Figure 2.
  • the fluid medium 34 is degassed prior to being circulated to the transducer 14 as discussed hereinabove, the circulation of the medium 34 through constrictions within the transducer 14 as well as vibrations of the transducer 14 tends to promote further expulsion of gasses.
  • the present invention manages the flow of the medium 34 in a way which reduces the impact of the expelled gasses within the reservoir 32 by allowing the gasses 68 to accumulate at the apex 78 and be rapidly removed therefrom.
  • Figure 1 shows the arm 18 of the transducer assembly 10.
  • the arm 18 may be articulated, or jointed and preferably includes a flexible portion 110 connected to a back end 1 12 of the transducer 14 which provides means for precise positioning of the transducer 14 on the body surface 36 of the patient 12.
  • the flexible portion 110 of the arm 18 may be designed to contain cannulas or conduits 114 which provide for the circulation of the fluid medium 34 into and out of the transducer 14.
  • Insulated electrical wiring 116 for providing electrical communication between the generator unit 16 and the transducer 14 may also be disposed through the flexible arm 1 10.
  • Means for circulating the medium between the reservoir and a cooling source may be provided in order to maintain a cool temperature at the body surface in contact with the transducer 14.
  • the replenishing tank 46 may be refrigerated in a conventional manner.
  • a heat exchange unit 120 may be provided for cooling the medium 34 as it is circulated out of the tank 46 after the medium has been degassed by vacuum sonification.
  • the fluid conductive medium is water
  • the medium is cooled to a temperature of between about 32 ° F and about 40° F to enable a range of between about 60° F and about 70° F to be maintained at the irrigation manifold and front mass. This temperature range is comfortable to the patient and also prevents overheating of the transducer 14.
  • the irrigation manifold and front mass have structure which optimizes heat absorption during inward flow of the cooling medium 34 and provides sufficient dwell time of the medium within the ultrasonic field.
  • heat generated in the transducer 14 will be rapidly conducted into the flowing cooled medium 34, warming the medium and cooling the transducer 14.
  • the medium 34 is initially cooled to between about 32° F and about 40° F, the heat absorbed by the transducer elements cause the medium 34 in the reservoir 32 to be maintained at a comfortable range of between about 60° F and about 70° F.
  • the outlet conduit 96 promotes rapid removal of the warmed conductive media 34 by providing a relatively brief flow path out of the reservoir 32, and eventually back to the tank 46 for degassing and cooling.
  • a shroud 130 is adjustably engaged to a base portion 132 forward of the piezoelectric element 26 as shown in Figure 2.
  • Figure 4 shows a block diagram of an embodiment of the present invention in order to illustrate potential connections between components of the transducer assembly.
  • transcutaneous ultrasonic transducer has been hereinabove described, with appropriate modification thereof, the present invention may encompass an endocavity probe incorporating the novel features hereinabove described.
  • a method for coupling ultrasonic energy to a body for dissolution or treatment of a medical target, such as vascular thrombi or the like, in accordance with the present invention generally comprises the steps of positioning the ultrasonic transducer 14 described hereinabove onto a body surface 12 over a medical target, radiating ultrasound waves from the ultrasonic transducer 14 into a medical target beneath the body surface in order to treat the medical target, and accumulating and removing gasses 68 expelled from the circulating fluid conductive medium as described in detail hereinabove.
  • the method further comprising the step of disposing a medicinal agent adjacent the medical target prior to the step of radiating ultrasound waves.
  • Thrombus preparation-induction of thrombolytic occlusion Briefly, a 0.014 inch coronary guide wire was advanced into the proximal part of the iliofermoral artery with 1 centimeter beyond a tip of the Tracker catheter. A positive electrode of a 3 volt battery was connected to the guidewire and a negative electrode to the rabbits skin. Electrical interference on a electrocardiographic monitor indicated that an electric shock was established. Occlusion was induced in both iliofemoral arteries in random order. Thrombotic occlusion of the artery was confirmed by selective angiography.
  • Controls Two control groups were studied to assess the potential of ultrasound mediated damage to skin, soft tissue and artery as detected by gross inspection, histology, and biochemical measurements.
  • Group 1 consisted of five rabbits in which transcutaneous ultrasound was applied to the left carotoid artery after 30 minutes prior to the iliofemoral thrombus induction.
  • a second control group consisting of four rabbits, there was no attempt at thrombus induction, however, ultrasound was applied for one hour above the area of the left or right iliofemoral arteries.
  • Plasma levels of creatine kinase (CK), lactate dehydrogenase (LDH) and a total red blood cell counts (RBC) were checked at baseline, after 3 minutes and after 60 minutes of ultrasound application, and 60 minutes thereafter.
  • a transducer assembly in accordance with the present invention was used that operates at approximately 37 kHz, and utilizes both pulse and sweep frequencies, 91 kHz and ⁇ 2 kHz, respectively.
  • the power can range to 160 watts and to prevent tissue damage from both such high outputs a transducer designed in accordance with the present invention was utilized, including the irrigation manifold and the reservoir to provide for efficient cooling and coupling to the skin.
  • the overall dimension of the transducer apparatus is about 7.0 cm in length and about 4.0 cm in diameter which can be easily positioned over the selected site.
  • the ultrasound was applied trascutaneously over the area of he thrombolytically occluded artery.
  • the arterial occlusion site was marked on the skin, using a metallic marker placed over the skin placed just above the occlusion site at the time of the last angiograohy.
  • Angiographic protocol for iliofemoral arteries Manual injection of 1 to 2 ml of Omnipaque (Sanofi Withrop Pharmaceuticals, New York, NY) was used for each angiogram. All studies were recorded with both 35-mm cine film at 30 frames/s and digital acquisition (Advantex, DXC, GE Medical System, Wakeshaw, WI) with a posterior-anterior projection.
  • Each angiograohy was performed just after an intraarterial injection of lOO ⁇ g of nitroglycerin to exclude possible arterial spasm.
  • the angiograms were analyzed by the consensus of four investigators for the presence or absence of an occlusion, vessels spasm, and distal or side branch embolization.
  • Biochemical and hematologic measurements To assess the potential tissue damage after electrical induction as well as after ultrasound treatment and in controls with ultrasound exposure alone, serum CK, LDH levels, and RBC counts were checked at baseline, after thrombosis induction and after ultrasound treatment.
  • Temperature was measured with a subcutaneous needle thermistor in the ultrasound treated area and was recorded every one minute during ultrasound therapy.
  • the preparations were examined macroscopically and microscopically for presence of thermal injury, and for the potency of iliofemoral arteries.
  • the preparations were examined in random order, with the examiner blinded to whether the artery was treated or not with ultrasound.
  • Statistical analysis Data are given as mean values ⁇ SD. Repeated measurements were performed to assess serum CK, LDH levels and RBC counts at three different time courses. Ap value ⁇ 0.05 was considered statistically significant.
  • heparin was administered intravenously and the arterial patency was assessed by repeated angiography every fifteen minutes for a total of one hour.
  • One of the ultrasound treated arteries (6.7%) reoccluded fifteen minutes after initial recanalization, whereas one of the control arteries recanalized fifteen minutes after heparin administration and another one at 30 minutes after heparin administration.
  • None of the ultrasound treated or control arteries has distal embolization or occlusion of distal branches on repeated angiography.
  • the skin temperature ranged from 25 to 33 ° C during the application of transcutaneous ultrasound.
  • Table 1 A Comparison of serum CK, LDH levels and RBC 1
  • Table IB Comparison of serum CK, LDH levels and RBC counts in control group 2
  • Histopathology revealed that arteries that were patent by angioplasty were also patent by microscopy with only focal residual mural thrombosis, whereas arteries which remained occluded until the end of protocol showed occlusive thrombi. Small microscopic areas of focal necrosis were found in the arterial walls in all vessels. The magnitude of vessel injury was the same in the ultrasound treated arteries as in the control arteries. There was no evidence of damage or inflamation in the skin or soft tissues overlying the ultrasound treated iliofemoral arteries.
  • control group 1 there was no evidence of thermal injury or inflamation in the arteries and overlying skin and soft tissues, after continuous exposure for thirty minutes to ultrasound treatment four to five hours before sacrifice; nor was there evidence of tissue damage in any of the four rabbits in control group 2 which had sixty minutes of ultrasound exposure to a non-thrombosed iliofemoral artery.
  • transcutaneous ultrasound has a synergistic effect on thrombus disruption when combined with streptokinase or a media containing microbubbles is known
  • use of the present invention prevents significant thermal damage to skin and soft tissues and no necrosis of the vessel wall was found histologically after ultrasound application with the present invention.
  • Serum CK activity is a particularly rapid and sensitive marker for muscle damage and LDH is present in large concentration in erythrocytes as well as tissues. Muscle damage and hemolysis may result in an increase in the serum CK and LDH levels respectively, as well as a decrease in RBC counts.
  • the data given in the Tables above show that there is no increase in LDH levels and no decrease in RBC counts after ultrasound treatment compared to the baseline, which indicates that there is no hemolysis after electrical induction and ultrasound treatment.
  • the CK level was increased to 18% compared to baseline after electrical induction of thrombus and then rose slightly after ultrasound treatment, focally microscopic necrosis was found in the vessel wall by histology. This indicates that electricity and/or ultrasound might induce vascular muscle damage.

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Abstract

L'invention se rapporte à un ensemble transducteur (10) et à un procédé permettant de coupler de l'énergie ultrasonore à un corps (12) dans le but de réaliser la thrombolyse de thrombus vasculaires. Cet ensemble comporte un transducteur catalytique (14) destiné à émettre des ultrasons dans une cible médicale par la voie transcutanée. Ce transducteur catalytique comporte une masse avant (28) dont la structure permet d'optimiser l'émission d'ultrasons dans le corps. Un réservoir (32) destiné à contenir un milieu conducteur refroidissant (34) est disposé entre la masse avant (28) et la surface du corps, et se situe à l'intérieur du boîtier. La masse avant (28) comporte une voussure (78) destinée à accumuler les gaz expulsés.
PCT/US1998/013450 1997-06-30 1998-06-29 Ensemble transducteur et procede permettant de coupler de l'energie ultrasonore a un corps dans le but de realiser une thrombolyse de thrombus vasculaires WO1999000061A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP98931690A EP1006896A4 (fr) 1997-06-30 1998-06-29 Ensemble transducteur et procede permettant de coupler de l'energie ultrasonore a un corps dans le but de realiser une thrombolyse de thrombus vasculaires
AU81741/98A AU8174198A (en) 1997-06-30 1998-06-29 Transducer assembly and method for coupling ultrasonic energy to a body for thrombolysis of vascular thrombi
JP50583499A JP2002507138A (ja) 1997-06-30 1998-06-29 血栓崩壊のために超音波エネルギを身体に結合する変換器集合体および方法
CA002301145A CA2301145A1 (fr) 1997-06-30 1998-06-29 Ensemble transducteur et procede permettant de coupler de l'energie ultrasonore a un corps dans le but de realiser une thrombolyse de thrombus vasculaires

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US88533897A 1997-06-30 1997-06-30
US08/885,338 1997-06-30
US08/922,188 1997-09-02
US08/922,188 US5879314A (en) 1997-06-30 1997-09-02 Transducer assembly and method for coupling ultrasonic energy to a body for thrombolysis of vascular thrombi

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WO1999000061A1 true WO1999000061A1 (fr) 1999-01-07

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AU (1) AU8174198A (fr)
CA (1) CA2301145A1 (fr)
WO (1) WO1999000061A1 (fr)

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US5269291A (en) 1990-12-10 1993-12-14 Coraje, Inc. Miniature ultrasonic transducer for plaque ablation
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US5601526A (en) 1991-12-20 1997-02-11 Technomed Medical Systems Ultrasound therapy apparatus delivering ultrasound waves having thermal and cavitation effects

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EP1006896A4 (fr) 2002-11-13
AU8174198A (en) 1999-01-19
CA2301145A1 (fr) 1999-01-07
EP1006896A1 (fr) 2000-06-14

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