CN203724652U

CN203724652U - System for curing peripheral nerves of blood vessel leading to kidney

Info

Publication number: CN203724652U
Application number: CN201320589618.7U
Authority: CN
Inventors: 迈克尔·格特纳; 戴维·佩罗泽克; 张吉民; 阿拉希·萨比特
Original assignee: Kona Medical Inc
Current assignee: Otsuka Medical Devices Co Ltd; Kona Medical Inc
Priority date: 2011-03-15
Filing date: 2011-11-21
Publication date: 2014-07-23
Anticipated expiration: 2021-11-21

Abstract

The utility model relates to a system for curing the peripheral nerves of a blood vessel leading to a kidney, and the system comprises: an ultrasonic imaging energy converter; a curing energy converter which is coupled to the ultrasonic imaging energy converter according to a well-defined relation; and a moving mechanism which is suitable for controlling the curing energy converter to aim at a zone surrounding the blood vessel of the kidney. Through the system provided by the utility model, a patient has less pain and fewer complications, and the cost of operation is lower. The visualization is improved, thereby improving the capability of executing tasks related to the visualization.

Description

Be used for the treatment of and lead to the perineural system of renal blood vessels

The application is the divisional application of the Chinese patent application No.201120473542.2 of application on November 21st, 2011.

Related application data

The application is the U.S. Patent application No.13/048 submitting on March 15th, 2011, 830 part continuation application, this patent application No.13/048, the 830th, the U.S. Patent application No.12/902 submitting on October 11st, 2010, 133 part continuation application, this patent application No.12/902, 133 require on August 27th, 2010 submit to U.S. Patent application 61/377908(unsettled at present) and on May 21st, 2010 submit to U.S. Provisional Patent Application 61/347375(unsettled at present) priority and rights and interests, and be on March 16th, 2010 submit to U.S. Patent application 12/725450(unsettled at present) part continuation application, this patent application 12/725450 is the U.S. Patent application No.12/685 submitting on January 11st, 2010, 655(is unsettled at present) part continuation application, this patent application No.12/685, the U.S. Provisional Patent Application No.61/256983(that 655 requirements were submitted on October 31st, 2009 is unsettled at present), the U.S. Provisional Patent Application No.61/250857(submitting on October 12nd, 2009 lost efficacy at present), unsettled at present at the U.S. Provisional Patent Application No.61/261741(that on November 16th, 2009 submits to) and the U.S. Provisional Patent Application No.61/291359(submitting to for 30th at December in 2009 unsettled at present) priority and rights and interests.

U.S. Patent application No.12/725450 also requires at the U.S. Provisional Patent Application No.61/303307(of submission on February 10th, 2010 unsettled at present), the U.S. Provisional Patent Application No.61/256983(that on October 31st, 2009 submits to is unsettled at present), the U.S. Provisional Patent Application No.61/250857(that on October 12nd, 2009 submits to lost efficacy at present), the U.S. Provisional Patent Application No.61/261741(that on November 16th, 2009 submits to is unsettled at present) and the U.S. Provisional Patent Application No.61/291359(submitting to for 30th at December in 2009 unsettled at present) priority and rights and interests.

The disclosure of all applications cited above is all clearly to mention that mode is incorporated to herein.

The application relates to the U.S. Patent application No.13/048 all submitting on March 15th, 2011,837,13/048,842 and 13/048,844.

Following patent application is incorporated to herein to mention mode at this equally.

U.S. Patent application No.11/583569,12/762938,11/583656,12/247969,10/633726,09/721526,10/780405,09/747310,12/202195,11/619996,09/696076,11/016701,12/887,178,12/390975,12/887178,12/887211,12/887232,11/583,656.

The theme that it should be pointed out that any other application above application and that quote at this is clearly incorporated to the application, as they are clearly narrated in this application.Thereby being incorporated in the application be not denoted as especially " to mention that mode is incorporated to " in the situation that, in fact they be considered to be described in the application.

Technical field

This utility model relates to and a kind of focused ultrasound energy is put on to patient's tremulous pulse neural system around, for the system of the circumvascular neurotransmission energy in patient, and for apply the system of focused ultrasound energy to patient.

Background technology

Hypertension be internal and international on very important disease.Singly just have 8,000 ten thousand to there is hypertensive patient and exceed 200,000,000 in global developed country in the U.S..In the U.S., have 6,000 ten thousand to suffer from uncontrollable hypertensive patient, mean they be not non-comply with can not adopt Drug therapy because of side effect feature exactly.May have up to 1,000 ten thousand people and have complete intractable hypertension, wherein they adopt any pharmacotherapy not reach target level.The sickness rate relevant to uncontrollable hypertension is far-reaching, comprises apoplexy, heart attack, renal failure, peripheral arterial disease etc.Be used for the treatment of minimum this disease treatment aspect that operates in of easily hypertensive and direct aggressive and will be the progress being popular.

Congestive heart failure (" CHF ") is at heart damage and a kind of situation of occurring while having reduced the blood flow to organ.If blood flow fully reduces, renal function changes, and this causes the vasoconstriction of fluid retention, abnormal hormone secretion and increase.These results have increased the workload of heart and have reduced heart the ability of carrying out pumping blood by kidney and blood circulation.

It is believed that, the renal perfusion reducing is gradually the main non-heart reason that the vicious cycle of CHF is continued.For example, because heart is made great efforts pumping blood, thereby cardiac output is kept or is reduced and kidney being kept in existence body fluid and electrolyte to maintain the often amount of fighting of heart.Caused blood pressure increase also makes myocardium overload, thereby cardiac muscle must be worked more hardy to resist higher blood pressure and carried out pumping blood.Then impaired cardiac muscle is subject to larger pressure and infringement because blood pressure increases.And the body fluid overload being caused by these physiological changies and relevant clinical symptoms cause other being in hospital, inferior quality of life and separately added the cost of medical health system.Except the heart failure increasing the weight of, renal failure also may cause vicious cycle and renal function is further worsened.For example, in the heart failure (systolic heart failure) of forward blood flow described above, kidney becomes ischemia.In backward heart-failu (diastolic heart failure), it is congested that kidney becomes with respect to renal veins high pressure.Therefore, kidney can cause the deterioration exhaustion of himself.

The function of kidney can be summarized as following three major types: the refuse that filtering blood and discharge are generated by the metabolism of health; Regulate salinity, moisture, electrolyte and acid-base balance; And secreting hormone is to maintain the blood flow of vitals.There is no function completely kidney in the situation that, patient will suffer from the accumulation in blood and health of water retention, hypourocrinia and waste toxins.These situations are produced by the renal function reducing or renal failure (renal failure) and are considered to will increase the workload of heart.In CHF patient, renal failure will cause heart further to worsen because body fluid is retained and blood toxicity because the kidney of dysfunction is accumulated.Caused hypertension also has great impact to the progress of cerebrovascular disease and apoplexy.

Autonomic nervous system is to affect in varying degrees the almost neutral net of each organ and physiological system.Conventionally, this system comprises sympathetic and parasympathetic nervous.For example, cross sympathetic chain to the sympathetic nerve of kidney along spinal column and the synapse in the neuroganglion of nerve chain or in ganglia coeliaca, then via the postganglionic fibers in " kidney nerve ", kidney is stimulated.Intranueral at kidney is sympathetic nerve and from the nervus centripetalis of kidney after joint, and this kidney nerve is along the hilus renalis advance (tremulous pulse and be vein to a certain extent).The nervus centripetalis of kidney is advanced (if they are pain fibers) and if they are sensory fibers in Dorsal root, enters front, then enters the specific regions of spinal cord and Zhongdao brain.Nervus centripetalis, pressure receptor and chemoreceptor, get back to sympathetic nervous system by information from kidney transmission via brain; They melt or suppress be kidney nerve melt or denervation or part fracture after at least part of reason of improveing of viewed blood pressure.Equally show and Partial Proof experimentally, response at the pressure receptor of carotid sinus aspect is mediated by renal artery nervus centripetalis, it is slow for to change arteriotony (American J.Physioogy and Renal Physiology 279:F491-F501,2000) that thereby the loss of renal artery nervus centripetalis response latens the response of carotid baroreceptor.

In animal model, determine, heart failure situation can cause the abnormal high sympathetic activity of kidney.The increase of the orthosympathetic activity of kidney causes the water of health and the removal of sodium to reduce, and stimulates the renin secretion of adrenal Aldosterone Secretion to increase.The renin secretion increasing can cause the rising of Angiotensin II level, and the rising of this Angiotensin II level causes the vasoconstriction of the blood vessel of supplying with kidney and the vasoconstriction of whole body, and all these will cause renal blood flow to reduce and hypertension.For example reduce can reverse these processes and in fact being shown clinically of kidney sympathetic activity via denervation.Similarly, in obese patient, sympathetic nerve drives inherence to be very high and to be considered to one of hypertensive reason in obese patient.

Nearest clinical position shows, kidney sympathetic chain and can cause far-reaching whole body effect in the patient (Mus, Canis familiaris L., pig, sheep, people) who suffers from hypertension, heart failure and other tract disease by other neural denervation that the hilus renalis enters kidney.This treatment can cause the improving of long-term minimizing to blood pressure class Drug therapy needs and blood pressure (O ' Breien Lancet 2,009 373; 9681).The equipment using in this test is radio frequency (RF) ablation that melts the altitude location of renal artery adventitia be suppressed equally in the thermal treatment zone around arteriorenal nerve in the situation that for inferring.Operation is carried out in invisible mode substantially because plexus nervorum be accurately positioned at operation before, after operating period or operation, be not know.In addition, renal artery wall is subject to the constant infringement of RF probe and blood vessel and has a large amount of atherosclerotic patients and cannot treat safely.In addition, depend on the neural distance from blood vessel wall, energy may not can cause melting or blocking consistently.Finally, if there is more selection, in kidney or may not consider to use inner conduit in endaortic treatment.In many cases, need to create along length and at endovascular helical to avoid that blood vessel is caused to hoop damage.

Can use cross section imaging so that patient's internal anatomy is visual via radiation (CT) or magnetic field (MRI).The ultrasonic cross section that can be used for obtaining equally specific region, but only under high frequency; Therefore, the imaging of the ultrasonic body region that is conventionally defined to effects on surface.CT and MRI are more suitable for conventionally in cross section imaging, because radiation can be penetrated in tissue well.In addition, the scale of body region is maintained the dissection making in coordinate reference and remains unchanged relative to each other; Namely, can measure the distance between structure.

By ultrasonic, convergent-divergent may be more difficult due to inhomogeneous penetrating, because ultrasound wave obtains darker through organizational communication.CT scan and MRI even ultrasonic device can be used to create patient's three dimensional representation and the cross-sectional image of reconstruct; Dissection can be used three dimensional representation and be arranged in coordinate reference system.Once in referential, energy device (transducer) just can arrange in place and energy transmitter is directed, thereby the specific region of targeting health.Once recognize that the position of the target in the relative patient body in the position of transducer is known, energy just can be passed to this target.

Ultrasonic is the acoustic pressure wave with the periodicity generation of the frequency that is greater than the human auditory upper limit-20 kilo hertz (kHz).In medical science, ultrasonic because it can be widely used by penetrate tissue.Sound wave reflection disclose basic organization feature and thereby, ultrasonic in medical domain, can be used in widely equally diagnosis and potential treatment.As treatment, ultrasonicly can either also can focus on to cause zone of ablation by penetrate tissue.Since the ability of its synchronous imaging, the damage in the enough next accurate targeting healths of ultrasonic energy.Ultrasound intensity is with the every cm of power ²(for example,, at the W/cm of therapy area ²) measure.Usually, high strength refers at 0.1-5kW/cm ²above intensity.Low intensity ultrasound comprises from about 1 or 10W/cm ²until 0.01-0.10kW/cm ²scope.

Ultrasonic energy is enough in its propagated forward ripple, and caused echo or in-house energy deposition local and be desired to heating or the light damage of tissue.For example, not to rely on reflection to carry out imaging, but the ultrasonic beam that can make lower frequency (for example, <1MHz) focus on the in-house a certain degree of depth, produce the thermal treatment zone or wherein produce the delimited area of the coelosis of microvesicle, cell membrane is opened to allow bioactive molecule to enter, or has caused in addition destruction in tissue.General 0.25 megahertz (MHz) that uses of these ultrasonic features arrives the frequency within the scope of 10MHz, depends on the degree of depth that effect is required.Needing maybe may need to focus on, and makes the surface of tissue not by simple beam excessive damage or heating.In other words, many simple beams can pass through tissue to reduce the energy deposition along any single path with different angular spread, but allow beam to converge at the focal spot of depths in tissue.In addition, can use the reflecting bundle of multiple angles, to create the three dimensional representation in region to be treated in coordinate space.

This is important in the time that ultrasonic therapeutic clearly demarcated, discontinuous interface has wherein been avoided in plan.For example, intestinal, lung, the skeleton that contains air and/or bone interface formed the obvious border with soft tissue.These interfaces make plan and treat more difficult.For example, but if interface can be avoided, treatment overcomes (, the HIFU(MR-guided HIFU of MR guiding) that must do brain of very high skull decay with wherein needing complicated simulation) compare and can be simplified widely.Following provided data have disclosed about the discovery that how to obtain this treatment simplicity that is used for the treatment of ad hoc structure (for example,, at circumvascular nerve) by a large amount of experiments.

Ultrasonic flight time measurement can be used to measurement range or measure the distance between in-house object.This type of measurement can be used for by the object such as blood vessel such as blood vessel in three-dimensional coordinate referential, make energy can be used for target tissue.Sonar (SONAR) is the acronym of sound navigation and range finding and is the method for a kind of acoustics location.Sound wave be launched by medium and sound reflection get back to emitter persond eixis the position of interested object.Doppler (Doppler) signal is generated by mobile object.The change of forward-wave and echo has caused the speed of object.

The concept of speckle tracking is to define and follow the tracks of in time the reflection of particular organization (IEEE Transactions on Ultrasonics, Ferroelectrics, AND Frequency Control, Vol.57, no.4, April 2010).With the point being defined in space, can set up three-dimensional coordinate reference, the region that energy can be put on specifically and well defines by this three-dimensional coordinate reference.Follow the tracks of speckle, ultrasonoscopy obtains by organizing.Speck and skin dark stain are defined in image, and these specks and skin dark stain represent in-house inhomogeneities.Inhomogeneities is relatively constant, is the fundamental property of tissue.With labelling relatively constant in organizing, realtime imaging that can usage flag completes tracking.With more than one plane of ultrasound, labelling is with respect to ultrasonic transducer and to be delivered to the treatment energy that defines position in three dimensional field can be three-dimensional relevant.

One or more in these formation methods are used to determine the position of target in three dimensions at present, then can and apply treatment to the specific region plan in three-D volumes.

Just introduced in early days lithotrity in the eighties in 20th century.Lithotrity is treated the calculus in kidney with shock wave.Road Neil (Dornier) lithotrity system is the first systematic of producing for this purpose.This lithotrity system send ultrasound wave through patient's health to kidney, optionally to heat and to vibrate renal calculus; Namely, optionally on contiguous tissue.At present, rubble system is not used direct targeting and the imaging to renal calculus district.The huge advance made of technology is the specific region at imaging calculus district and targeting calculus place, to minimize for example, infringement to surrounding structure (, kidney).In the situation of renal calculus, kidney is actually speckle, allow three-dimensional target to follow the tracks of its image, smash calculus with after-applied ultrasound wave.In following embodiment, described many technology and imaging results can both be applied to clinical lithotrity.For example, the tracking in the imaging in calculus district and calculus district can cause improved targeted system, for smashing renal calculus.Do not wasting energy and destroying healthy kidney containing on the region of calculus with it, can be by concentration of energy in the kidney part that contains calculus.

Histotripsy is the term that makes to organize the technology of vaporization (the non-hot type mechanicalness of percutaneous separate tissue) substantially to provide with coelosis instead of heating for wherein.These small-sized blasts do not need high temperature and can within a second, occur.The pressure wave producing for the scope of number MPas (MPa) and even up to or exceed 100MPa.Will treat soon little tissue regions, this technology can be effectively.The border of survival and non-viable tissue normally clearly and shown that this mechanism of action is cytoclasis.

Long-range energy delivery relates to the transmission of the energy wave for affecting target at a distance.It allows more efficient energy delivery to target and in the larger cost efficiency of Generation Side and technology motility.For example, mobile phone receive from target and the tower long haul communication each other of the approaching tower of user; Like this, mobile phone can be lower powered and communicate by letter in relatively little scope, but network can communication rapidly in the whole world.Similarly, the distributing electric power from large electric station to user is than more effective percentage of the own seeking solution of user.

Aspect treatment patient, long-range transferring energy provides the large advantage aspect targeting precision, technology motility, and importantly, has limited the aggressive to patient.In the simple form of one, laparoscopic surgery has been substituted to be opened abdomen surgical operation and causes new operation and equipment and for the generation of the more efficient operating process of disease treatment in the past in a large number.Laparoscopic tool is by surgical energy by the improved image normalization that is delivered to patient's tissue and generation at a distance and is treated region, and many surgeon make this region visual ability simultaneously.

May most important aspect be the following fact: patient has pain still less, complication still less, and the total cost of operation be lower.Visual being improved, thus the ability of carrying out with visual relevant task improved.

The continuous progress of calculating, miniaturization and the economization aspect of energy delivery technology, and the imaging of improvement will cause the larger chance that energy is applied in patient body from afar and treats disease.

Utility model content

In certain embodiments, one is used for the treatment of leads to the perineural system of renal blood vessels, and this system comprises: ultra sonic imaging transducer; Treatment transducer, wherein said treatment transducer is coupled to imaging transducer according to defining good relationship; Travel mechanism, its be suitable for control treatment transducer with aiming circle the region around renal blood vessels.In certain embodiments, the operation and the equipment that improve the medical care precess field that relates to the transmission of power that is used for the treatment of disease are provided.Operation and equipment defer to following route: 1) from afar transmission of power to exert an influence in patient; 2) allow improved imaging or the targeting to therapentic part; 3) with surgeon, that attempting of getting involved that cardiologist or radiologist may do directly contacts the situation of target is contrary, carrys out generation efficiency by the position from patient body or in patient body with larger and more powerful equipment.In many cases, also used advanced visual and orientation tool.

In the present invention, from patient body by focus ultrasonic in the region of renal artery and/or vein; Ultrasonicly be delivered to target by multiple angles, proposing for melting around many defects of the orthosympathetic previous methods of arteriorenal kidney and equipment thereby overcome.

Particularly, a kind of embodiment allows the visual accurately of zone of ablation, makes operator can be sure of that correct region is melted and incorrect region is not melted.Because some embodiment need to not puncture on skin, so they are that aggressive is quite little, this is happier with safer In the view of patient.And abnormal dissection and atherosclerotic blood vessel can treat to have influence on respectively kidney sympathetic nerve and the nervus centripetalis from kidney with the external energy of triangularity on renal artery.

According to some embodiment, a kind ofly comprise for high-intensity ultrasonic energy being put on to patient's tremulous pulse neural system around the piezoelectric-array that comprises multiple ultrasonic components, be arranged to the controller of the phasing of controlling individually each ultrasonic element, ultrasonic element is coupled to the platform on it, wherein this platform is arranged at least a portion that supports patient, be configured to the generator able to programme that at least one ultrasonic element generates defeated turnout, and be arranged to the programmable processor of processing by the transmitting of ultrasonic element and the signal that reflected by tissue, and determine the characteristic of tissue based on reflected signal.

In any embodiment described herein, first ultrasonic element is arranged to generation signal, and second ultrasonic element is arranged at signal by this signal of sensing after organizing reflection.

In any embodiment described herein, a ultrasonic element is arranged to generation signal, and reflects this signal of sensing afterwards at signal by organizing.

In any embodiment described herein, platform can be compatible with in magnetic field.

In any embodiment described herein, magnetic field is the permanent magnetic field that magnetic field intensity is less than 1.0 teslas (Tesla).

In any embodiment described herein, ultrasonic element is optimized for the signal of the degree of depth receiving from being greater than 8cm.

In any embodiment described herein, controller is arranged to the phasing of controlling at least partly each ultrasonic component based on determined tissue characteristics.

In any embodiment described herein, ultrasonic generating device is programmable, so that treatment ultrasonic energy focuses on the target in patient, is greater than 7cm apart from patient's skin.

In any embodiment described herein, system also comprises the processor coupling with piezoelectric-array, and wherein processor is arranged to the direction of speed, the blood flow of determining blood or both.

In any embodiment described herein, system also comprises and is arranged to the mechanical movement actuator that makes the target Mechanical Moving in the relative patient of piezoelectric-array.

In any embodiment described herein, mechanical movement actuator comprises the ball that overlaps connection mechanism.

In any embodiment described herein, mechanical movement actuator also comprises locking mechanism.

In any embodiment described herein, at least one ultrasonic component is arranged to the ultrasonic signal receiving from endovascular piezoelectric element.

In any embodiment described herein, system also comprises and is arranged to the processor of determining at least partly parameters,acoustic based on ultrasonic signal.

According to other embodiment, a kind of comprise being arranged to for ablation vessels neural system around apply the treatment energy that strides across blood vessel with the first neural ultrasonic transducer of heating blood vessel both sides, be arranged to second ultrasonic transducer of reception by the reflected energy of the energy pulse of the first ultrasonic transducer generating, and processor, be arranged to: receive the first reflected energy data in the very first time o'clock from the second ultrasonic transducer, receive the second reflected energy data at the second time point from the second ultrasonic transducer, the first reflected energy data and the second reflected energy data are compared, and be provided for the output signal of the position of controlling the first ultrasonic transducer to mover.

In any embodiment described herein, system also comprises mover, wherein this mover within workbench (table), and workbench be arranged to support patient, allow the first ultrasonic transducer to be coupled to patient simultaneously.

In any embodiment described herein, system also comprises mover, and wherein this mover comprises ball and cover connection mechanism.

In any embodiment described herein, ball and cover connection mechanism are lockable.

In any embodiment described herein, ball and cover connection mechanism comprise vacuum lock mechanism.

In any embodiment described herein, ball and cover connection mechanism can be along planar movements.

In any embodiment described herein, ball and cover connection mechanism vacuum available mechanism lock along plane.

In other embodiments, one is used for the treatment of blood vessel and perineural method comprises that the circumvascular region of identification is to limit target area, make the focus of focused ultrasound system aim at target area, wherein aim at about three-dimensional system of coordinate and carry out, move relative to focused ultrasound system detection target area, and determine to target area relative to the relevant quality factor of the relative extent moving of the focus of focused ultrasound system.

In any embodiment described herein, quality factor by focus the percentage of time within target area determine.

In any embodiment described herein, method is also included as focused ultrasound system and determines dosage scheme.

In any embodiment described herein, method also comprises at least partly revises dosage scheme based on quality factor.

In any embodiment described herein, dosage scheme defines at circumvascular treatment cloud.

In any embodiment described herein, treatment cloud is substantially uniform about blood vessel.

In any embodiment described herein, target area is detected by detecting doppler blood flow signal.

In any embodiment described herein, quality factor is about 90%.

In any embodiment described herein, quality factor is about 50%.

In any embodiment described herein, quality factor is any value of from 50% to 90%.

According to some embodiment, a kind of system being used for the treatment of comprises the focused ultrasound energy source being arranged in outside patient body, wherein this focused ultrasound energy source is arranged to ultrasonic energy is delivered to and has neural blood vessel around, described nerve is the part of the central nervous system in patient body, and wherein focused ultrasound energy source is arranged to and ultrasonic energy is delivered to the nerve that is positioned at patient body from patient body, to treat this nerve.

In any embodiment described herein, focused ultrasound energy source comprises transducer, and the angle in this focused ultrasound energy source about the line that downwards lead to transducer center relative with the line that connects transducer and blood vessel in 30 degree between 80 degree.

In any embodiment described herein, focused ultrasound energy source is arranged to provides ultrasonic energy to melt to realize neural part.

In any embodiment described herein, focused ultrasound energy source is arranged to outside patient body ultrasonic energy is delivered to nerve from multiple directions, and the relative patient in focused ultrasound energy source is static.

In any embodiment described herein, system also comprises the imaging processor for determining vessel position.

In any embodiment described herein, imaging processor comprises CT equipment, MRI equipment, thermal imaging apparatus, infrared imaging device, optical-coherence tomography equipment, photoacoustic imaging device, PET imaging device, SPECT imaging device or ultrasonic device.

In any embodiment described herein, processor is arranged to operation focused ultrasound energy source makes it during ultrasonic energy transmission, carry out the nerve of targeting around blood vessel based on determined position.

In any embodiment described herein, processor is configured to determine position by Doppler's triangulation technique.

In any embodiment described herein, focused ultrasound energy source is arranged to transmission ultrasonic energy, this ultrasonic energy has enough sympathetic stimulations to kidney with minimizing, reduces from kidney to autonomic input signal or both energy levels.

In any embodiment described herein, focused ultrasound energy source has orientation, and focused ultrasound energy source is concentrated one's gaze on and the direction that is close to neural blood vessel and aims at.

In any embodiment described herein, focused ultrasound energy source is arranged to follows the tracks of neural movement.

In any embodiment described herein, focused ultrasound energy source is arranged to the movement that is close to neural blood vessel by tracking and follows the tracks of neural movement.

In any embodiment described herein, focused ultrasound energy source be arranged to by concentrate one's gaze on neural around blood vessel concentrate one's gaze on nerve.

In any embodiment described herein, system also comprises the equipment being arranged in patient body, and for determine the processor of position with this equipment, wherein focused ultrasound energy source is arranged at least in part and transmits ultrasonic energy based on determined position.

In any embodiment described herein, equipment be resized in case insert neural around blood vessel within.

In any embodiment described herein, focused ultrasound energy source is arranged to the horizontal line with respect to the transverse process that connects spinal column and becomes the angle between-10 degree are spent to-48 that ultrasonic energy is delivered to blood vessel, and this angle is pointed to trunk from patient's lower trunk.

According to some embodiment, a kind of being used for the treatment of around the neural system of the blood vessel that leads to kidney comprises the focused ultrasound energy source being arranged in outside patient body, wherein this focused ultrasound energy source comprises ultrasound transducer array, and programmable interface, being arranged to by switching on to control source of ultrasonic energy according to one or more phase places to one or more elements of array ultrasonic energy is delivered to around the region of blood vessel of leading to kidney with skew at an angle with the central shaft of phase pair array, is the tissue of any value of 6cm～15cm to the degree of depth.

In any embodiment described herein, focused ultrasound energy source comprises transducer, and the angle that the focused ultrasound source line that leads to transducer center is downwards connected to transducer the line of blood vessel is relatively 30 degree～80 degree.

In any embodiment described herein, focused ultrasound energy source comprises being arranged to provides ultrasonic energy to melt to realize neural part.

In any embodiment described herein, processor is arranged to determines position by Doppler's triangulation technique.

According to some embodiment, a kind of patient's of being used for the treatment of autonomic system comprises the focused ultrasound energy source being arranged in outside patient body, and this focused ultrasound energy source is arranged to ultrasonic energy is delivered to the neural blood vessel that has the part of the central nervous system in patient body around, and ultrasonic energy is transmitted in the position that wherein this focused ultrasound energy source is arranged to based on the endovascular conduit of indwelling.

According to some embodiment, a kind of system being used for the treatment of comprises the focused ultrasound energy source being arranged in outside patient body, wherein this focused ultrasound energy source is arranged to ultrasonic energy is delivered to the neural blood vessel that has the part of the central nervous system in patient body around, and wherein this focused ultrasound energy source is arranged to the horizontal line with respect to the transverse process that connects spinal column and becomes the angle between-10 degree are spent to-48 that ultrasonic energy is delivered to blood vessel, and this angle is pointed to trunk from patient's lower trunk.

According to some embodiment, a kind ofly comprise formulation therapeutic scheme for applying the method that suppresses cloud around the nerve of blood vessel, wherein this Therapeutic Method specifies that nerve is suppressed to cloud puts at least major part of the circumference of blood vessel wall, and nerve is suppressed to the major part that cloud puts on the circumference of blood vessel wall reaches enough to suppress around the duration of the neural function of blood vessel wall.

In any embodiment described herein, the neural cloud that suppresses comprises Shekinah (a cloud of light).

In any embodiment described herein, the neural cloud that suppresses comprises gaseous clouds.

In any embodiment described herein, the neural cloud that suppresses comprises hot cloud.

In any embodiment described herein, the neural cloud that suppresses applies with percutaneous energy source.

In any embodiment described herein, the neural cloud percutaneous energy source that is arranged to transmission focus supersonic that suppresses applies.

In any embodiment described herein, the neural cloud that suppresses applies with ionizing radiation.

In any embodiment described herein, the neural cloud that suppresses applies by transmitting focus supersonic, and imaging device comprises MRI equipment.

In any embodiment described herein, method also comprises the image that obtains blood vessel with imaging device, and wherein therapeutic scheme is formulated with this image.

According to some embodiment, a kind ofly be delivered to around the system in the region of blood vessel and comprise and comprise the conduit that is arranged to the multiple electrodes that apply hot cloud for nerve being suppressed to cloud, store predetermined by hot cloud put on neural institute around the processor of therapeutic scheme of major part of circumference of at least blood vessel wall, and be arranged to the external detector of the measurement temperature associated with applying of hot cloud.

In any embodiment described herein, external detector comprises ultrasonic device.

In any embodiment described herein, external detector comprises MRI equipment.

In any embodiment described herein, conduit is arranged to and is arranged in intravenous.

In any embodiment described herein, conduit is arranged to and is arranged in Visceral artery.

According to some embodiment, a kind ofly comprise comprising around the system of the Neural Area of blood vessel and be arranged to the electromagnetic field that applies in response to outside and the conduit of heated part for neural suppression therapy is delivered to, and be arranged to and apply electromagnetic field and make its skin that passes patient carry out the equipment of the part of heating duct, the part that wherein heated is provided hot cloud around the Neural Area of blood vessel.

In any embodiment described herein, conduit comprises expandable element, to prop up blood vessel wall in the time that this inflatable element expands.

In any embodiment described herein, equipment is also arranged to measures temperature with electromagnetic field.

In any embodiment described herein, equipment comprises MR imaging apparatus.

In any embodiment described herein, equipment comprises ultrasonic detection equipment.

According to some embodiment, a kind of for by focused ultrasound energy, the position outside patient skin is delivered to around the neural method of blood vessel and comprises with substantially flat position patient is placed in to workbench, transducer is moved into rib is following, crista iliaca above and in the position of the horizontal side of patient's spinal column, make transducer be maintained at the position relative with patient, and by focused ultrasound energy transmission the skin (not running through skeleton) through patient, wherein the direction of this focus supersonic is pointed to upper trunk by patient's lower trunk.

In any embodiment described herein, method also comprises the signal detecting from radiating in patient body.

In any embodiment described herein, method also comprises and detects the signal radiating from equipment in the blood vessel in patient body.

In any embodiment described herein, focused ultrasound energy is passed the nerve being used for the treatment of in patient body.

In any embodiment described herein, neural round blood vessel, and focused ultrasound energy is delivered to nerve by target vascular therapy.

According to some embodiment, a kind ofly comprise comprising around the system of the Neural Area of blood vessel and be arranged to the electromagnetic field that applies in response to outside and the conduit of heated part for neural suppression therapy is delivered to, and be arranged to and apply that electromagnetic field makes its skin that passes patient and the part of conduit is heated to enough magnetic resonance equipments around the level of the Neural Area of blood vessel with treatment, and be arranged to the system for detecting temperature of restriction around the temperature of the Neural Area of blood vessel.

In any embodiment described herein, magnetic resonance equipment comprises system for detecting temperature.

In any embodiment described herein, within system for detecting temperature is positioned at conduit.

In any embodiment described herein, conduit the signal providing based on magnetic resonance system is at least partly provided and handles.

In any embodiment described herein, magnetic resonance system is arranged to shifts to blood vessel wall by conduit.

According to some embodiment, a kind of being used for the treatment of around the neural system of the blood vessel that leads to kidney comprises the focused ultrasound energy source being arranged in outside patient body, wherein this focused ultrasound energy source comprises ultrasound transducer array, programmable interface, be arranged to by switching on to control source of ultrasonic energy according to one or more phase places to one or more elements of array ultrasonic energy is delivered to around the region of blood vessel of leading to kidney, and comprise the magnetic resonance imaging system of permanent magnet, wherein this magnetic resonance imaging system is coupled to programmable interface by operation.

In any embodiment described herein, system also comprises the catheter in blood vessel equipment for inserting blood vessel.

In any embodiment described herein, system also comprises for being placed in patient's abdominal part radio-frequency coil around.

In any embodiment described herein, system also comprises for focused ultrasound energy being delivered to around the positioning equipment in region of blood vessel that leads to kidney.

In any embodiment described herein, source of ultrasonic energy is arranged to taking relative array center axle and with skew, focus supersonic is delivered to the tissue of the degree of depth as any value of 6cm～15cm at an angle.

According to some embodiment, a kind of being used for the treatment of around the neural system of the blood vessel that leads to kidney comprises the focused ultrasound energy source being arranged in outside patient body, wherein this focused ultrasound energy source comprises ultrasound transducer array, programmable interface, be arranged to by switching on to control source of ultrasonic energy according to one or more phase places to one or more elements of array ultrasonic energy is delivered to around the region of blood vessel of leading to kidney, and based on the focus supersonic time within certain preset distance from target of being arranged to is at least determined the processor of quality factor.

In any embodiment described herein, this preset distance is 500 microns.

In any embodiment described herein, this preset distance is 2mm.

In any embodiment described herein, processor is also arranged at least partly and operates source of ultrasonic energy based on this quality factor.

In any embodiment described herein, system also comprises the catheter in blood vessel for inserting blood vessel.

In any embodiment described herein, catheter in blood vessel is arranged to the signal that provides relevant to the movement in the region being treated, and processor is arranged at least partly and operates source of ultrasonic energy based on this signal.

In any embodiment described herein, system also comprises the motion tracking system that is coupled to processor.

According to some embodiment, a kind ofly comprise and be arranged to the transducer that focus supersonic is delivered to the blood vessel that leads to kidney for focus supersonic being put on to patient's equipment, wherein this transducer comprises the element of multiple phasings individually and for by the ultrasonic patient's of being coupled to barrier film, for the first mechanical mover of position transducer, wherein this first mechanical mover is arranged to the position that simultaneously operates the focus that changes transducer with element that can phasing, and for maintaining the second mechanical mover of the pressure between barrier film and the patient skin of transducer.

In any embodiment described herein, barrier film contains fluid, and the pressure and temperature of fluid is maintained at constant level.

In any embodiment described herein, equipment also comprises and can be used to the imaging system that is coupled to the first mechanical mover.

In any embodiment described herein, imaging system is MRI system.

In any embodiment described herein, imaging system is ultrasonic system.

In any embodiment described herein, imaging system is arranged to detection catheter in blood vessel.

In any embodiment described herein, imaging system is arranged to definite three-dimensional coordinate, and transducer is arranged at least partly and transmits ultrasonic based on determined three-dimensional coordinate.

According to some embodiment, a kind of for focused ultrasound energy being put on to patient's tremulous pulse neural system around, comprising: the piezoelectric-array that comprises multiple piezoelectric elements; Be arranged at least one in the described piezoelectric element that the subset of at least controlling described piezoelectric element makes described subset in signal emission mode, signal sensing pattern or both control units; The first platform and the second platform, described piezoelectric element is coupled on described the first platform, and wherein said the second platform is arranged at least a portion that supports described patient; Be configured to the generator of one or more element generation output in described piezoelectric element; And be arranged to the processor of processing by the signal of at least one sensing in described piezoelectric element.

According to said system embodiment, first in wherein said piezoelectric element is arranged to and generates described signal, and in described piezoelectric element second is arranged to after described signal is by the tissue reflection in described patient signal described in sensing.

According to said system embodiment, one of wherein said piezoelectric element is arranged to and both generates described signal, again signal described in sensing after described signal is by the reflection of described tissue.

According to said system embodiment, wherein said platform can be compatible with in magnetic field.

According to said system embodiment, wherein said magnetic field is the permanent magnetic field that magnetic field intensity is less than 1.0 teslas.

According to said system embodiment, at least one in wherein said piezoelectric element is optimized to the signal that reception is greater than 8cm from the described patient's of distance skin and is less than the degree of depth of 14cm.

According to said system embodiment, wherein said control unit is arranged at least partly based on described signal and controls at least some the phasing in described piezoelectric element; And wherein said generator is arranged to the described output generating enough to drive described one or more element of described piezoelectric element for the power of high intensity focused ultrasound.

According to said system embodiment, wherein said piezoelectric element is by described control unit control, so that treatment ultrasonic energy focuses in described patient the target that patient's skin described in distance is greater than 7cm, and wherein said signal comprises from arteriorenal flow signals.

According to said system embodiment, wherein said processor and described piezoelectric-array couple, and described processor is arranged to the direction of speed, the blood flow of determining blood or both.

According to said system embodiment, also comprise the mechanical movement actuator coupling with described the first platform, described mechanical movement actuator is arranged to and mechanically moves described piezoelectric-array to follow the motion of the tremulous pulse in described patient.

According to said system embodiment, wherein said the first platform is coupled to ball and cover connection mechanism.

According to said system embodiment, wherein said ball and cover connection mechanism comprise locking mechanism.

According to said system embodiment, at least one in wherein said piezoelectric element is arranged to the ultrasonic signal receiving from endovascular piezoelectric emitter.

According to said system embodiment, described processor is arranged at least partly determines parameters,acoustic based on described signal.

According to said system embodiment, wherein said the first platform is positioned at the position of described patient below.

According to said system embodiment, wherein after described signal is processed by described processor, described the first platform can automatically move with the motion based on tremulous pulse described in described signal trace.

According to said system embodiment, at least one in wherein said piezoelectric element is arranged to not only launches ultrasound wave but also receive ultrasound wave.

According to said system embodiment, wherein said generator be arranged to transmitting be enough to cause described piezoelectric element to the output of the phasing of the ultrasonic output of described neural transmitting focusing to suppress the function of described nerve.

According to said system embodiment, wherein said processor is arranged to processes described signal to determine temperature.

According to said system embodiment, wherein said processor is arranged to processes described signal to determine elastogram parameter.

According to said system embodiment, wherein said signal comprises that doppler flow moves signal.

According to said system embodiment, wherein said processor is arranged to based on the mobile signal of described Doppler determines the position focusing on from the energy of described piezoelectric-array.

According to said system embodiment, wherein said position is in vascular.

According to said system embodiment, wherein said signal comprises that doppler flow moves signal, and described the first platform is configured to mobile to follow the tracks of the mobile signal of described Doppler.

According to said system embodiment, wherein said signal comprises that doppler flow moves signal, and described control unit is arranged to and controls described piezoelectric element based on phasing pattern and make to be focused in different positions to surround at least in part described tremulous pulse from the energy of described piezoelectric element.

According to some embodiment, a kind of system for the circumvascular neurotransmission energy in patient, comprising: be arranged to across blood vessel and apply treatment energy to heat the first neural ultrasonic transducer on described blood vessel both sides; Be arranged to the receptor that receives the reflected energy producing from ultrasonic pulse; And be arranged at very first time point and receive the first data from described receptor, receive the second data at the second time point from described receptor, described the first data and described the second data are compared, and provide output signal to mover, to control the processor of position of described the first ultrasonic transducer.

According to said system embodiment, also comprise mover, wherein said mover within workbench, and described workbench be arranged to support patient, allow described the first ultrasonic transducer to be coupled to described patient simultaneously.

According to said system embodiment, also comprise mover, wherein said mover comprises ball and cover connection mechanism.

According to said system embodiment, wherein said ball and cover connection mechanism are lockable.

According to said system embodiment, wherein said ball and cover connection mechanism comprise vacuum lock mechanism.

According to said system embodiment, wherein whole ball and cover connected components can be along the planar movements that is arranged essentially parallel to described patient.

According to said system embodiment, wherein said ball and cover connection mechanism vacuum available mechanism lock along described plane.

According to some embodiment, a kind of for apply the system of focused ultrasound energy to patient, comprising: the piezoelectric-array that comprises multiple piezoelectric elements; Be arranged at least one in the piezoelectric element that the subset of at least controlling described piezoelectric element makes described subset in signal emission mode, signal sensing pattern or both control units; The first platform and the second platform, described piezoelectric element is coupled on described the first platform, and wherein said the second platform is arranged at least a portion that supports described patient; Be configured to the generator of one or more element generation output in described piezoelectric element; Be arranged to the processor of processing by the signal of described at least one sensing in described piezoelectric element; And the media of storage therapeutic scheme, wherein said therapeutic scheme is configured to process to cause that by described processor the blood vessel peripheral of the skin of described piezoelectric-array by described patient in described patient transmits ultrasonic energy, thereby one or more neural function of described blood vessel is surrounded in impact.

According to said system embodiment, wherein said blood vessel guiding kidney.

According to said system embodiment, in wherein said piezoelectric element described at least one be arranged to the described signal of sensing from inlying catheter.

According to said system embodiment, wherein said therapeutic scheme is configured to process to cause that by described processor described piezoelectric-array is transmitting described ultrasonic energy from about 7cm to the depth of about 14cm to described blood vessel to the variation output of described piezoelectric-array by utilizing from described generator.

According to said system embodiment, wherein said therapeutic scheme is configured to process to cause described piezoelectric-array described periphery transmission ultrasonic energy to described blood vessel on the blood vessel of about 1～2cm length by described processor.

According to said system embodiment, in wherein said piezoelectric element described at least one be arranged to and send ultrasonic pulse, and after the regional reflex of described blood vessel, received described ultrasonic pulse as described signal in described ultrasonic pulse.

According to said system embodiment, wherein said the second platform has the shape that is arranged to the back that allows the focus supersonic that undertaken by described piezoelectric-array to pass through described patient and arrives the described blood vessel of guiding kidney.

According to said system embodiment, also comprise the first mover, described the first mover be arranged to mobile described the first platform with the motion of following the tracks of described blood vessel to keep described circumvascular ultrasound focus.

According to said system embodiment, also comprise the second mover, described the second mover is arranged to along at least one direction that is arranged essentially parallel to described patient and moves described the first platform.

According to said system embodiment, first group in wherein said piezoelectric element is arranged to focus supersonic pulse is provided, and in described piezoelectric element second group is arranged to the reflection receiving from described focus supersonic pulse.

According to said system embodiment, wherein in the time that described the second platform supports described patient described in the first platform below described patient, described the second platform allows fluoroscopic examination machine to be positioned over around described patient.

By said system of the present utility model, patient has pain still less, complication still less, and the total cost of operation is lower.Visual being improved, thus the ability of carrying out with visual relevant task improved.

Particularly, this utility model allows the visual accurately of zone of ablation, makes operator can be sure of that correct region is melted and incorrect region is not melted.Because some embodiment need to not puncture on skin, so they are that aggressive is quite little, this is happier with safer In the view of patient.And abnormal dissection and atherosclerotic blood vessel can treat to have influence on respectively kidney sympathetic nerve and the nervus centripetalis from kidney with the external energy of triangularity on renal artery.

By reading the following detailed description about embodiment, other and more aspect and feature will become apparent.

Brief description of the drawings

Figure 1A-1B shows the focusing of energy source on autonomic nervous system.

Fig. 1 C shows the imaging system for helping guiding energy source.

Fig. 1 D shows system integration schematic diagram.

Fig. 1 E shows the block diagram of integrated system schematic diagram.

Fig. 2 shows by stomach and is delivered to the autonomic targeting at stomach rear and/or treats ultrasonic.

Fig. 3 A shows energy wave in the supraneural focusing of kidney.

Fig. 3 B shows the coordinate reference system being used for the treatment of.

Fig. 3 C shows and is arranged in the endovascular targeting conduit of any kidney or energy delivery conduit.

Fig. 3 D shows at the image detecting system that provisional benchmark is arranged in to the blood vessel in endovascular situation, and wherein this benchmark provides the positional information about referential.

Fig. 3 E shows the treatment normal form for hypertensive treatment and assessment.

Fig. 4 A shows applying around carotid autonomic energy.

Fig. 4 B shows through the energy of the blood vessel of the hilus renalis and applies.

Fig. 5 A-5B shows the autonomic ultrasonic energy of eye is applied.

Fig. 5 C shows the energy of other autonomic nervous system structure is applied.

Fig. 6 shows renal calices is applied to the contraction damage within the renal calices that is deep to kidney.

Fig. 7 A shows patient and in imaging system, accepts the treatment of carrying out with focus energy ripple.

Fig. 7 B shows the visual of the kidney that is treated.

Fig. 7 C shows the close up view of the kidney Neural Area of the kidney being treated.

Fig. 7 D shows for treating autonomic computational methods with MRI and transducer.

Fig. 7 E shows the geometric model obtaining from the cross-sectional image in the region of aorta and kidney along the angle that approaches blood vessel and kidney.

Fig. 7 F shows the close up view for the treatment of region.

Fig. 7 G shows the result from the measurement of a series of cross-sectional image reconstruct.

Fig. 7 H shows the result of the measurement of a series of cross-sectional images of the patient in comfortable more excellent position.

Fig. 7 I shows for the hilus renalis of kidney being applied to computational methods treatment and that kidney blood vessel is applied to energy.

Fig. 7 J shows the clinical algorithm for the blood vessel that leads to kidney being applied to energy.

Fig. 7 K shows the equipment of the suitable directivity for diagnosing the region for energy being put on to kidney.

Fig. 7 L shows for by applying hot cloud or the neural material of loosening melts tremulous pulse neural method around.

Fig. 7 M shows the clinical algorithm for apply energy along kidney blood vessel.

Fig. 7 N shows the neural hot cloud that leads to kidney for affecting.

Fig. 7 O shows neural feature hot cloud and that lead to kidney.

Fig. 7 P-7Q shows simulation and the emulation corresponding with dosage and motion control arithmetic according to some embodiment.

Fig. 8 A shows the autonomic percutaneous approach being used for the treatment of around kidney.

Fig. 8 B shows and is used for the treatment of or the autonomic intravascular method of targeting.

Fig. 8 C shows the renovascular percutaneous approach to the hilus renalis reaching with CT scan and probe.

Fig. 8 D shows the blood vessel inner detection technique for characterizing the path between blood vessel and skin.

Fig. 8 E-8F shows focus energy from rear to the cross-sectional image transmitting.

Fig. 8 G-I shows the result for the targeting experiment of the targeting beacon in localization of blood vessel.

Fig. 9 A-9C shows from aorta inside being used for the treatment of of aorta perimeter autonomic energy and applies.

Figure 10 shows and in monitor treatment process and motion, uses HIFU to treat the step of disease.

Figure 11 A shows the treatment of the brain pathology that uses cross section imaging.

Figure 11 B shows the image of the treatment of the brain region that demonstration is treated in indicator.

Figure 11 C shows another view of the brain injury that can may see on the imaging device of the treatment of auxiliary damage.

Figure 12 shows the treatment that uses the kidney Neural Area that peritoneoscope approach carries out.

Figure 13 shows the method in disorganize region for using imaging labelling monitor treatment process.

Figure 14 shows the part treatment of some part that uses the nerve tract that is converged to picture and treatment ripple.

Figure 15 A-15C shows as treating various spinal diseases (comprising treatment neural in spinal nerves or blood vessel) focus energy of spinal column is applied.

Figure 16 A shows the type of the damage (impact response) causing around renal artery.

Ultrasonic emulation around the blood vessel I that Figure 16 B shows at Figure 16 A supports.

Figure 16 C shows the data that put on respective change renovascular ultrasonic energy and noradrenaline levels.

Figure 16 D-16H shows along the emulation of multiple point of care of blood vessel.

Figure 16 I-16K shows the various therapeutic schemes at circumvascular focus energy.

Figure 16 L-16M shows the data of indicating the focus energy applying from outside can affect the sympathetic nerve supply to organ.

Figure 16 N shows the wherein result of the time-histories of the repressed experiment of sympathetic nerve.

Figure 17 A shows the application that is used for the treatment of multiple transducers that autonomic nervous system carries out in the region at hilus renalis place.

Figure 17 B-17C shows for guiding with imaging around method treatment and that show the damage form of predicting of the specific region of tremulous pulse.

Figure 17 D shows the method for locating HIFU transducer for relative doppler ultrasound signal.

Figure 17 E shows the layout of the relative target of transducer.

Figure 17 F shows the zone of ablation in the many focal areas in cross section.

Figure 18 show kidney inside for affect kidney inside regional level concrete function change energy apply.

Figure 19 A illustrates the direction of the energy wave propagation that is used for the treatment of the region of autonomic nervous system around hilus renalis district.

Figure 19 B show for provide with the HIFU access to the hilus renalis from the ultrasonic schematic diagram of determined direction Type B by experiment.

Figure 19 C-19D shows the foundation for renovascular treatment together with renovascular actual therapeutic.

Figure 19 E is the schematic algorithm for the therapeutic scheme of the treatment shown in Figure 19 C-D.

The ultrasound wave that passes through aorta wall that Figure 20 shows for apply treatment to autonomic nervous system applies.

Figure 21 A shows the focus energy of ciliary muscle is applied and the processing in eyeball proparea.

Figure 21 B shows applying of for example, for strengthening medicine or gene delivery or other treatment (, ionizing radiation) the non-ablation energy of focusing to eyeball rear portion.

Figure 22 shows the applying the neural focus energy at knee joint peripheral for affecting IA function of nervous system.

Figure 23 A-23B shows for making patient's sterillization oviducal energy is applied.

Figure 24 shows the algorithm of the effect of assessment to autonomic neuroregulation operation.After kidney nerve having been carried out to operation, by for example carry out the assessment of autonomic nerve response at one or more local emulation autonomic nervous system.

Figure 25 shows the optimum position for intrinsic nerve being applied to treatment.

Figure 26 A shows the patient location of the parameter for obtaining system design.

Figure 26 B shows the equipment design of the information based on recognizing from feasibility study.

Figure 27 shows the clinical normal form for treat autonomic kidney nerve based on feasibility study.

Figure 28 A-28C shows the treatment navigation system of the patient for having merged focused ultrasound system.

Figure 28 D-28I shows the system structure for treat the neural system in patient body with focus energy.

Figure 28 J has the partially or completely diagram of the back boxing for patient (underlining) of the element of inflation.

Figure 28 K is the structure being built in for the system of patient's workbench.

Figure 28 L shows the multidimensional mechanism for mobile ultrasonic transducer according to some embodiment.

Figure 28 M be wherein patient be lie on the back and transducer be placed in the patient interface structure of patient below.

Figure 28 N is the lie low feature of workbench thereon of patient.

Figure 29 A-D show research to apply focus energy around the nerve of tremulous pulse and for making nerve travel the result of the ultrasonic investigation of its visualization of blood vessels around.

Figure 29 E shows the result that is wherein quantized the design process of angle, length and surface area by CT scan.

Figure 30 A-30I shows for design the simulation result that arteriorenal region is applied to focus supersonic with prototype equipment based on emulation.

Figure 30 J shows customization for the treatment of the annular array of the dissection shown in kidney and kidney blood vessel for top and has highlighted annular array.

Figure 30 K shows the imaging part on summit.

Figure 30 L-N shows the various otch of ultrasound imaging probe.

Figure 30 O-P shows the projection of proposed transducer designs.

Figure 30 Q be produced by treatment transducer for focusing on the diagram of focal spot in single region.

Figure 30 R-30S shows the multicomponent array of Piza cheese, but has many rectangular member.

Figure 30 T-30U shows the emulation of the annular array that is exclusively used in the dissection around kidneys of patients to be treated.

Figure 30 V shows the shell of custom arrays.

Figure 30 W shows from custom arrays and focuses on along the energy of blood vessel.

Figure 31 A shows the eccentric focus from the alternative layout of annular array transducer.

The energy that Figure 31 B shows the alternative embodiment of the customization transducer array in the clinical example in conduit is arranged in patient body focuses on.

Figure 31 C is the diagram of the travel mechanism within patient table.

Figure 31 D is the general frame of the subsystem of system.

Detailed description of the invention

With reference to Figure 1A, people's kidney is dissected and is comprised that kidney structure comprises the kidney 100 of being supplied oxygenated blood and being connected to heart via ventral aorta 300 to it by renal artery 200.Deoxygenated blood is via renal veins (not shown) and then flow to heart via postcava (not shown) from kidney.Kidney is dissected and is comprised cortex, medullary substance and the hilus renalis.Blood is transported to cortex, and in cortex, it filters by glomerule and is then transported to medullary substance, and in medullary substance, it further filters by a series of absorptions again and filtration step in Heng Lishi (henle) ring and individual nephron; Ultrafiltrate then diafiltration to ureter acquisition system and be transported to ureter and bladder finally to excrete.

The hilus renalis is that main blood vessel (renal artery and renal veins) and neuropeptide 11 50(spreads out of sympathetic nerve, imports sensory nerve and parasympathetic nervous into) import and spread out of the region of kidney into.Kidney neuropeptide 11 50 contains for nervus centrifugalis after the joint of the sympathetic innervation of reply kidney.Import that sensory nerve leads to central nervous system by kidney into and be in central nervous system, to there is nervus centripetalis after the joint of neuron soma (nerve body).These nerves are delivered to central nervous system by sensory information and are considered to and flow out to a large amount of sympathetic nerve of all organs that comprise skin, heart, kidney, brain etc. for regulating from central nervous system.

In one approach, energy imports into from patient body, through skin, and to kidney nervus centripetalis and/or Renal efferent nerve.Perhaps can use microwave, light, vibration (for example, acoustics), ionizing radiation in many embodiment at some.

Transducer 500(Figure 1A) transfer energy to sympathetic ganglion 520 or joint metanephros neuropeptide 11 50 or lead to neural region of the adrenal gland 400 through skin.Energy generates outward at patient body, from multiple directions, and passes skin to the kidney nerve 624 around renal artery 620 or the region that holds neural sympathetic ganglion 622.Energy can be that focus on or non-focusing, but in a kind of preferred embodiment, energy focuses on high intensity focused ultrasound (HIFU) or low-strength focusing ultrasonic.

The focusing of low-strength focusing ultrasonic (LIFU) can also have a mind to or by mistake as HIFU(penumbra region) component and occurring.The neural mechanism suppressing is variable, depends on " height " or " low " of focus supersonic.Low-yieldly may comprise 25W/cm ²-200W/cm ²energy level.Higher intensity comprises 200W/cm ²-1MW/cm ²energy level.Focus on by from least two different angles, energy delivery being occurred in the mode of joining in focus through skin, wherein occurred the highest energy intensity and density in this focus.At this point, treatment is provided and this treatment can be that the neural interruption of subthreshold value (sub-threshold) (part melts), nerve melt (interruption completely), the controllable interrupters of nerve conduction device, part melts or target administration.Region can be heated to the temperature that is less than 60 degrees Celsius, for the treatment of non-ablative, or can be heated to and is greater than 60 degrees Celsius, for the destruction based on heat (melting).Melt nerve, even if the temperature in the scope of 40 degrees Celsius also can be used, and if the persistent period producing is greater than a few minutes, will cause melting.For the temperature of about 50 degrees Celsius, the time can be in one minute.Except heating, the vibrating effect that continues shorter time at the temperature of 60 degrees Celsius can cause neural part or benumbs completely or destroy.If temperature is increased to more than 50-60 degree Celsius, heat remarkable minimizing to affect the nerves via independent heating arrangements of required time.In certain embodiments, formation method is contained in system equally.Formation method can based on ultrasonic, based on MRI's or based on CT(X ray).Formation method can be used to targeting ablation region and determine the distance of target.

The energy transmitting can be ionization or non-ionized energy in certain embodiments.The form of unionized energy can comprise electromagnetic energy (for example, magnetic field, optical, electrical field), radio frequency energy and light base energy.The form of ionization energy comprises X ray, proton beam, gamma-rays, electron beam and alpha ray.In certain embodiments, ENERGY METHOD is combined.For example, carry out neural heating ablation and then ionizing radiation be delivered to this region to prevent neural regeneration.

As selection, first ionizing radiation applies as ablation method and later next heating of situation in tissue regeneration, because radiation may be impossible (supplementing or the use of multi-method energy) again.Ionizing radiation can prevent or be suppressed at the regeneration of circumvascular nervous tissue, although really there is the regeneration of nervous tissue.Therefore, the neural method of another kind for the treatment of is first to heat nerve and then apply ionizing radiation to prevent regeneration.

Other technology (for example, comprise photosensitizer and for activating the optical dynamic therapy of light source of photosensitizer) can be used as the mode of associated methods.Most of these photosensitizer are also to ultrasonic energy sensitivity, produce activated by light as it identical photoreaction thing.Photoreaction agent or photosensitizer are just introduced in target area before can be in device is introduced into blood vessel; For example,, by intravenous injection, subcutaneous injection etc.But, should be appreciated that if desired, device can optionally comprise for photoreaction agent is conveyed into the tube chamber in target area.The embodiment producing is likely particularly advantageous, and to be wherein absorbed in target tissue be comparatively faster in photoreaction agent, makes device need to not be distributed in target tissue and in by its absorption and remain in for a long time in blood vessel in photoreaction agent.

Array of source can comprise the light source of the optical wavelength or the optical band that provide more than one.Linear array of source is particularly useful to the prolongation of treated tissue.Array of source also comprises that reflecting element is to improve the light transmission in preferred orientations.For example, equipment can advantageously comprise expandable element (for example, inflatable sacculus), for block blood flow (blood flow can disturb the light transmission from light source to the target tissue of specifying) and make the device can be placed in the middle in blood vessel.Another kind of preferred embodiment has envisioned a kind of PDT method of percutaneous, and wherein photosensitizer induction system comprises the fat-body induction system being mainly made up of photosensitizer.Can make light source point to from the focus to EV position in blood vessel.Infrared, red, blue, green and ultraviolet light can use to affect EV nervous tissue in blood vessel.Light emitting diode can be introduced vein, tremulous pulse, aorta etc. via conduit.Introduced photoreaction agent (for example, via vein, subcutaneous, through tremulous pulse, through intravenous injection) afterwards, light is applied through blood vessel wall in the energy cloud of exciting light reactant.

For also having proposed another kind of embodiment for the method that uses sensitizer to carry out percutaneous ultrasonic therapeutic to the target damage in mammals main body.In this embodiment, biochemical compound is activated by the following method by ultrasonic:

1) impose treatment upper effectively ultrasonic sensitizer or ultrasonic sensitizer induction system or the prodrug of amount to main body, wherein ultrasonic sensitizer or ultrasonic sensitizer induction system or prodrug are optionally combined with the thick or thin new intima at position to be treated, neurocyte, nerve sheath, nucleus, artery plaque, vascular smooth muscle cell and/or abnormal extracellular matrix.Can also targeting neural part, for example, nerve sheath, myelin, S-100 protein.If this step is afterwards under the frequency that activates ultrasonic sensitizer or prodrug irradiates at least a portion main body by its prodrug product with ultrasonic energy, wherein ultrasonic energy is provided by ultrasonic energy emissions source.Optionally, the present embodiment also provided before irradiating ultrasonic therapeutic medicine has been cleared out of from the non-target tissue of main body.

Preferred embodiment has envisioned a kind of for target tissue being carried out to a method for percutaneous ultrasonic therapeutic, and wherein target tissue approaches blood vessel.Other preferred embodiment has envisioned outside the intact skin layer that ultrasonic energy emissions source is positioned at patient or within being inserted into patient's intact skin layer, but is positioned at outside blood vessel to be treated.Another kind of preferred embodiment provides ultrasonic sensitizer and ligand binding, and more preferably, wherein this part is selected from: target damage specific antibody; Target damage specific peptide and target damage specificity polymer.Other preferred embodiment has envisioned ultrasonic sensitizer and has been selected from: any other reagent that indocyanine-green (ICG), methylene blue, toluidine blue, amino-laevulic acid (ALA), chlorin compound, phthalocyanine, porphyrin, alizarinopurpurin, Dezhou porphyrin (texaphyrin) and absorbing wavelength are 500nm-1100nm.It is indocyanine-green (ICG) that a kind of preferred embodiment has envisioned photosensitizer.

Other embodiment proposes for the method for current disclosed percutaneous PDT, and wherein light source is located near main body target tissue and is selected from: LED light source, electroluminescent light source, incandescent source, cold-cathode fluorescent light source, organic polymer light source and inorganic light source.A kind of preferred embodiment comprises use LED light source.

Other embodiment of current disclosed method also proposes for using the light of certain wavelength, and this wavelength is about 500nm to about 1100nm, is preferably more than about 650nm and more preferably for being greater than about 700nm.A kind of preferred embodiment of this method cause for use photosensitizer Single Photon Absorption pattern light and propose.

Other embodiment comprises the composition of photosensitizer targeted system, and this photosensitizer targeted system comprises: photosensitizer and by receptors bind in the part having on specific target tissue.Preferably, the photosensitizer of targeted system with by receptors bind in the ligand binding having on specific target (nerve or vessel outer wall).More preferably, part comprises and the antibody of receptors bind.Most preferably, receptor is the antigen on thick or thin new intima, inner membrance, tunica adventitia of artery, artery plaque, vascular smooth muscle cell and/or the extracellular matrix at position to be treated.

Another preferred embodiment has envisioned photosensitizer and has been selected from: any other reagent that indocyanine-green (ICG), methylene blue, toluidine blue, amino-laevulic acid (ALA), chlorin compound, phthalocyanine, porphyrin, alizarinopurpurin, Dezhou porphyrin and absorbing wavelength are 500nm-1100nm.

Be known in the art with operable other photosensitizer of embodiment described herein, comprise phytochrome (photofrin), RTM, synthetic dimerization porphyrin (diporphyrin) and dimerization chlorin (dichlorin), tool is with or without the substituent phthalocyanine of metal, tool is with or without the chlorine aluminum phthalocyanine of different substituents, sulfonation chlorine aluminum phthalocyanine, adjacent to tetraphenylporphyrin, 3,1 meta-tetra-(the basic machine of mebenil) porphyrin, a yellow goldspink (verdins), alizarinopurpurin, the stannum of octaethyl alizarinopurpurin and zinc derivative, just alizarinopurpurin, hydrogenation porphyrin (hydroporphyrin), the Bacteriochlorin of four (hydroxyphenyl) porphyrin series, chlorin, chlorin e 6, single aspartoyl derivant of chlorin e 6, two aspartoyl derivants of chlorin e 6, chlorin e 6 stannum (IV), between tetrahydroxy phenyl chlorin, benzoporphyrin derivative, benzoporphyrin monoacid derivant, the 1,1,2,2-tetracyanoethene adduct of benzoporphyrin, the dimethyl butyn adduct of benzoporphyrin, Diels-Adler type adduct, monocyclic acids " a " derivant of benzoporphyrin, sulfonation aluminum PC, sulfonation AlPc, two sulfonated derivatives, four sulfonated derivatives, sulfonation aluminum naphthalene phthalocyanine, tool is with or without metal substituent and tool and is with or without the naphthalene phthalocyanine of the substituent of variation, zinc naphthalene phthalocyanine, anthraquinone, anthracene pyrazoles, amino anthraquinones, phenoxazine dyestuff, phenothiazine derivative, chalcogen pyrans (chalcogenapyrylium) dyestuff, cation selenium and tellurium pyrans (tellurapyrylium) derivant, cyclosubstituted cation PC, phoeophorbide derivant, phoeophorbide α and ether or esters derivative, pyropheophorbide and ether or esters derivative, the porphyrin of Nature creating, hemoporphyrin, hematoporphyrin derivative, hemoporphyrin ester or ether, protoporphyrin, the protoporphyrin IX of ALA induction, endogenous metabolism precursor, 5-ALA benzo naphthalene tetraazatetradecane porphyrin (benzonaphthoporphyrazine), cationic imines salt (imminium salt), tetracycline, Dezhou porphyrin lutecium, just alizarinopurpurin stannum, porphyrin alkene, benzo phenothiazine, five yuan of porphyrins (pentaphyrin), Dezhou porphyrin and hexa-atomic porphyrin (hexaphyrin), 5-ALA, hypericin, pseudohypericin, hypocrellin, three polythiophenes, aza porphyrin, azepine chlorin, rose bengal, phloxine B, erythrosine, the iodate of fluorescein or brominated derivative, merocyanine, Nile blue (nile blue) derivant, pheophytin and phyllins, Bacteriochlorin and bacteriochlorophll derivatives, porphacyanine (porphocyanine), benzo chlorin and oxygen benzo chlorin, thiophene quinoline (sapphyrin), oxa-thiophene quinoline (oxasapphyrin), cercosporin and relevant fungal metabolite and their combination.

Several photosensitizer known in the art is that FDA approves and can on market, buys.In a kind of preferred embodiment, photosensitizer is benzoporphyrin derivative (" BPD "), for example BPD-MA, on market also referred to as BPD Verteporfin (Verteporfin) or " BPD " (can buy from QLT).U.S. Patent No. 4,883,790 have described BPD compositions.BPD is second filial generation compound, and it does not have Photofrin long-term skin phototoxicity (Levy(1994) Semin Oncol 21:4-10).BPD has obtained all sidedly characterizing (the people such as Richter, (1987) JNCI 79:1327-1331), (people such as Aveline, (1994) Photochem Photobiol 59:328-35), and have been found that it is the effective photosensitizer of height for PDT.

In a kind of preferred embodiment, photosensitizer is just C.I. Natural Red 8 of stannum ethyl, and on market, being called purlytin(can buy from Miravant).

In certain embodiments, carry out wherein the low-energy ultrasonic Neural Area that is applied in to regulate neural outside neuroregulation.For example, having shown in the past that low intensive (for example, non-thermal) is ultrasonic can be with 30-500W/cm ²power affect the nerves, but HIFU(thermal conditioning) need to exceed 1000W/cm ²power level, wherein according to restriction, HIFU produces heat in focus.Depend on the environment including blood flow around and other structure to the actual power flux in region to be melted.With low intensive ultrasonic, energy not necessarily will so strictly focus on target, because it is non-ablative energy; Namely, vibration or mechanical pressure can be effect energy (effector energy) and target for effect can have different threshold values, depend on tissue.But, if if worry skin superheated or exist other suspicious structure and only want pinpoint area for treatment on path, even if low-energy ultrasonic also may needs focuses on.But the transducer 500 in Fig. 1 a provides and has applied the ability of a series of different energy and power level and the analog capability of targeting zones of different predicated response.

In Fig. 1 a, and in one embodiment,, MRI ultrasonic at imaging device 600(for example doppler ultrasound, infrared imaging, thermal imaging, Type B or CT scan) auxiliary under renal artery 640 is detected.With the image in region to be treated, can in a series of sections, measure to create the three dimensional representation of area-of-interest along multiple directions.By for example, detecting arteriorenal position by means of Doppler's triangulation () or other triangulation technique from multiple angles, can create the three-dimensional location drawing and renal artery can be mapped in coordinate reference system.In this respect, suppose that kidney nerve is round the kidney blood vessel in the hilus renalis, three-dimensional coordinate with reference in direction and the length of localization of blood vessel be the major part for these orthosympathetic operations of targeting.In three-dimensional referential, can be by (and whole being positioned at outside the patient body) equipment outside this proximity of being positioned at completely based on the understanding of coordinate reference system is put on to arteriorenal proximity by the energy of a certain pattern.

For example, once renal artery is arranged in the coordinate reference system taking energy delivery equipment as initial point, algorithm is used to the ultrasonic transmission of position of focusing facula, with external membrane and the sympathetic nerve that contains kidney with from the region heating around of the tremulous pulse of the nervus centripetalis of kidney or apply mechanical energy, reduce thus the sympathetic stimulation to kidney and reduce it and get back to autonomic input signal; Adjusting hypertension is inclined in impact on these targets, otherwise will there will be hypertension.Ultrasonic energy transmission can be by using to organize the distance obtaining with the formation method of path and measuring and predict that sound wave dissipates and simulates on mathematics.And, can be with determining quantitatively that such as such system of sound wave flight time from the treatment position transducer is to the distance in region of blood vessel of leading to kidney.This system allows to detect distance with ultrasonic pulse.Then the distance obtaining is like this used in treatment supersound process, because the tissue being asked and structure are identical, wherein treat and ultrasonicly will propagate through this tissue and structure, thereby substantially allow the automatic calibration for the treatment of ultrasonic pulse.

For example, Fig. 1 D shows and has integral duct 652 and the system at supravasal one or more transducers 654.Electric pulse sends to conduit 652 by generator 653 and to the transducer 654 that can be piezoquartz.Detector 650 detects apart from the distance 656 of piezoelectric transducer and the 3 D tropism of transducer 654 and accurate position.With the positional information in three dimensions, can make focused transducer 662 point to target under the guiding of motion controller/transducer 660.In certain embodiments, single transducer (inside) is detected.In other embodiments, multiple transducers 654 are detected.Using in the embodiment of multiple transducers, be available about the three-dimensional position of blood vessel and the more details of orientation, to allow the redundancy approach to position probing.Under any circumstance, by retracting endovascular conduit, the signal of telecommunication is applied to piezoquartz simultaneously the described signal of telecommunication can be detected outward at patient body, can shine upon and determine quantitatively the 3 D anatomical of blood vessel, thereby can treatment be put on to accurate position along blood vessel.In the method, seal wire is arranged in therapentic part and is then moved to for example, diverse location near therapentic part (, in blood vessel).During moving along blood vessel, the detector outside patient body shines upon this and moves and area for treatment.Then the mapping (for example) of blood vessel is used to carry out the treatment in the precise region of being planned with pinpoint accuracy due to the mapping in region.Signal generator 653 can produce has the frequency (or optional frequency value) within the scope of this of 0.5MHz～3MHz or for guaranteeing the signal of even wider frequency range of detection of orientation.

In a kind of embodiment of algorithm, identified by least two different directions and the direction of tremulous pulse is reconstructed and makes in three-dimensional space from the Doppler signal of tremulous pulse.In this example, can use the sound wave flight time by the doppler ultrasound of blood flow signal or by set piezoelectric transducer (inside) and receptor (outside) 650.With two points in space, create a line and in the situation that understanding blood vessel thickness, can create pipe or cylinder so that blood vessel is expressed as to dummy model.Treatment transducer outside pipe expression in time and the relative patient's of its coordinate in three dimensions skin is known.Can similarly apply treatment energy and can focus on (antetheca, central shaft or the rear wall of blood vessel) cylinder from multiple directions.With thirdly, the position of target can accurately be positioned in 3d space and by targeting with HIFU transducer 660.Detection algorithm 666 can be used to the position after the baseline position of conduit and a period of time to compare, and breathes and patient moves to detect.In one embodiment, the HIFU array 662 for the treatment of is used to send out the signal (diagnosis pulse) for imaging equally.For example, the element of any amount can both be activated by HIFU array, so that energy deposition is in tissue.Such energy deposition can be favourable, because it is focused in the region 664 that finally will treat according to restriction.Inverse signal is detected by the identical ultrasonic component that generates HIFU pulse equally, or can be detected by other imaging receptor.In this respect, according to restriction, the precise region for the treatment of can since inquire and this allows the imaging of the height specialty to area-of-interest from the focus supersonic pulse for the treatment of array 662.Therefore, in one embodiment, used wherein focus supersonic pulse before target treatment, first to put on the ultrasonic system of target.Focus supersonic pulse is that short and its reflection from target of persistent period is used to characterize target (for example, it can be used for determining the image property, tissue property, the degree of injury after treatment, the position in patient body, temperature, three-dimensional position of target etc.).Precise information with these about target, then can put on target to suppress neural from the treatment ultrasonic pulse for the treatment of transducer, melts nerve or vibration nerve etc.As selection, or additionally, can also delivering medicament.Parameter except imaging comprises Doppler's flow, tissue elasticity figure, stress-strain diagram, ultrasonic spectrum, and the targeting for the treatment of to region.Treatment array 662 can be used as receptor as the receptor of diagnostic signal or independent detector.In certain embodiments, conduit can be adapted to conduct drugs to region and help beam-focusing.Doppler's targeting algorithm can supplement the targeting based on conduit 652.Power supply is arranged to HIFU transducer and applies the blood vessel of suitable power with treatment depths in patient body.For example, can be that 150W, 200W, 500W, 750W or 1000W are to realize the output that is suitable for carrying out degree of depth treatment in patient body to the power input of HIFU transducer.Pulse frequency can be soon to 10Hz or 1KHz even.Piezoelectric signal can the multiple directions from patient body detect.One or more ultrasonic models can by with and detect from different direction outside patient's skin.In initial several microseconds of carrying in piezoelectricity pulse, can generate very large pulse.For example, in certain embodiments, 8W/cm ²can produce continue several delicate and then voltage can be reduced to rapidly zero until next cycle (<1% dutycycle).

Focus energy (for example, ultrasonic) can be put on to the center (within blood flow) of blood vessel, on the rear wall of blood vessel, between (for example,, when having back-to-back tremulous pulse adjacent one another are and vein) arteries and vein blood vessel etc.Mover 660 carrys out guiding ultrasonic focusing based on conduit 652 with respect to the position 666 of supersonic array 660.In certain embodiments, Doppler signal 670 makes with system combination together with system.

Imaging 600(Fig. 1 C of sympathetic nerve or sympathetic nerve district (target)) also used to assess direction and the orientation of transducer with respect to target 620; Target is internal reference, this internal reference is that kidney 610 and associated renal artery 620 can be located via their blood flow because of them in one embodiment, then around it, produce a model, and then they both can be as the target of energy.The continuous feedback of transducer 500,510 positions with respect to target 620 is provided by imaging system, and wherein position can be positioned at the coordinate space of for example imaging system.Imaging can be cross section imaging technique, for example CT or MRI, or it can be to produce the ultrasonic imaging technique of realtime imaging faster.In certain embodiments, imaging can be the combination of technology, for example MRI/CT and ultrasonic fusion.Imaging system can be taking scope as detect in real time the position of target from 1Hz to frequencies thousands of and tens thousand of images per second.

In the example merging, cross section imaging (for example, MRI/CT) is used to patient's health to be arranged in three-dimensional system of coordinate, and is then ultrasonicly connected to three-dimensional referential and is used for the health of following the tracks of in real time patient under cross section imaging ultrasonic being connected to.Deficiency by ultrasonic provided resolution is made up by cross section imaging, because be that several consistent anatomic landmarks need to make ultrasonoscopy be connected to MRI image.When health is in ultrasonic lower movement, new ultrasonoscopy be little by little attached to MRI image and therefore MRI " movement " MRI series can be visible under the frequency that cannot use in addition.

In one embodiment, ultrasonic is energy for suppressing the nerve conduction in sympathetic nerve.In one embodiment, from health, be for by transmitting ultrasound wave from the position of exterior and making this ultrasound wave focus on energy in patient body and suppress the sympathetic stimulation of kidney round the mode patient's arteriorenal sympathetic nerve through the focus supersonic (HIFU) of skin.MRI can be used for making area for treatment before ultrasonic applying, during or visual afterwards.MRI can also be used to heat the targeting conduit in sympathetic nerve district.For example, at the ferromagnetic element of catheter tip, absorption is present in to energy in magnetic field and to conducting self-heating, thereby heat can be put on round the nerve of blood vessel that leads to kidney.Heatable conduit can also configure (for example, shaping) and produce inductive circuit when being applied in its two ends in magnetic field.Shape comprises annular, taper, sharp turn, distortion etc.In the time that this shaping conduit is arranged in magnetic field, cause heating in conduit aspect.

Fig. 1 E shows the general view of the software subsystem 675 for safe treatment is provided to patient.Record, network that executive control system 677 contains operating system, systemic-function connect and other diagnostic device.Can complete by simulation and the empirical data that obtained before with communicating by letter of therapeutic dose scheme 681.Software in dosage allow with sound wave flight time transducer (ATOF) 679 and with for the diagnosis and treatment of the further of motion controller of array communicate by letter.Target location based on the sound wave flight time (ATOF) can provide the accurate and sane position sensing of target position with respect to treatment ultrasonic transducer.Can in the situation that not needing image interpretation, provide direct X, the Y of coordinate position of target and Z(, three-dimensional).Three-dimensional target has promoted the use at the user display interface of the action for guiding operator to information.ATOF and imaging technique compare patient dissect variation more insensitive.Compared with the complicated imaging system using with the technology that can select else, ATOF can complete with relatively simple and cheap system.In certain embodiments, can provide the Continuous Tracking to target mobile between target and outer transducer.In certain embodiments, ATOF allow with patient's contact area of utilizing major part produce treatment power (compared with having taken the possibility based on imaging in some space within the treatment transducer for diagnosing power) thus system architecture---reduced the power density that puts on patient skin.

In another kind of embodiment, the auxiliary path of determining that treatment is ultrasonic of ATOF sensor.For example, ultrasonic pulse can produce in blood vessel, and for example, is detected by the receptor outside patient body from one or more aspects (, path-length, quality, speed etc.) of the sound of transducer.One or more based in these parameters and variable, can determine that the path of HIFU makes the path of safe and effective rate be transferred to the target at blood vessel place.

As shown in Fig. 3 a-b, transducer 900 can be launched the kidney sympathetic nerve region of ultrasonic energy to the kidney base of a fruit 200 in the position outside patient body.As shown in Figure 1a, use the image of the renal artery 620 of ultrasonic, MRI or CT scan can be used to determine the position of kidney 610 and renal artery 620 targets.Doppler ultrasound can be used to determine from the position of the Doppler signal of tremulous pulse and direction and blood vessel is arranged in three-dimensional referential 950, thus make tremulous pulse 200 and thereby sympathetic nerve 220(Fig. 3 around tremulous pulse can be a) more obviously to process image and then accurately locate orthosympathetic position and treatment with focusing external energy.In the present embodiment, ultrasonic may be optimal imaging pattern.Ultrasonicly can refer to simple one dimension pulse echo (A type), or scanning area and pulse echo is integrated in to the equipment (being called Type B) in image.

Figure 1A also shows the transmission of the focus energy of the sympathetic trunk of advancing along spinal column and aorta 300 and neuroganglion 622; Renal artery nervus centrifugalis passes into these trunks and is formed into the ganglionic synapse in trunk.In another kind of embodiment, import kidney at T9-T11(neural current through wherein) neuroganglion or the aspect of Dorsal root nerve on Dorsal root will produce identical or similar ablation effect in arteriorenal aspect with front melt.

In another kind of embodiment, Figure 1B shows applying of ionizing energy to the sympathetic nerve region on renal artery 620 and/or renal veins.Generally speaking, linear accelerator or low-energy X-ray machine need to be greater than 20Gy(gray(Gy) (Gray)) energy level so that melt nervous tissue with ionizing energy; But, need lower energy to hit dizzy (stun), suppress nervous tissue, or prevent nervous tissue's regeneration; In a certain embodiment, the ionizing energy level that is low to moderate 2-5Gy or 5-10Gy or 10-15Gy is transmitted with the dosage of single or gradation.Ionizing energy can apply with the blood vessel internal X-ray irradiator of normal voltage x ray generator, linear accelerator, plesioradiotherapy and/or transmission electronics plesioradiotherapy.X ray (for example, from linear accelerator or from normal voltage x ray generator) can, from multiple directions transmission through skin, arrive the target nerve around blood vessel.In an example, blood vessel can be to have nerve to be arranged in its renal artery or renal veins around.By target vascular therapy, ionizing energy can be put on to the nerve around blood vessel.Can guide ionizing energy with ultrasonic, doppler imaging, angiography, fluoroscopy, CT scan, thermal imagery imaging and MRI.

Can use equally in the present embodiment the combination of the energy of ionizing energy and other form, to prevent nervous tissue's regeneration.For example, can prevent the regeneration in this nervous tissue after arteriorenal nervous tissue partially or completely melts with the combination of heating and/or vibration and/or coelosis and/or ionizing radiation.The combination of medicament can be each other or is combined to prevent or tentatively suppress the regeneration of nervous tissue and/or nervous tissue with equipment and physical method.For example, can steroid be put on via conduit or systematically to circumvascular region, then with ultrasonic this region of heating.Similarly, neurotoxin can be put on to this region, and then by the ultrasonic neural region being just treated (for example,, for interacting to activate it with neurotoxin, and/or for treating nerve in conjunction with neurotoxin) that puts on.

Fig. 2 illustrates in greater detail kidney dissection and dissection around, and wherein organ (for example, stomach 700) is shown on its anatomical position, is covered with ventral aorta 705 and renal artery 715.In the present embodiment, energy is passed through stomach to reach the region at stomach rear.In the present embodiment, stomach is used as entering ganglia coeliaca 710(otherwise will be difficult to the region arriving) pipeline.Aorta 705 is shown under stomach and ganglia coeliaca 710 is illustrated round superior mesenteric artery and aorta.The pipe 720 that direct oral cavity is inserted is arranged by esophagus and enters stomach.Pipe is positioned in ganglia coeliaca in the time being arranged in stomach, and therefore can be used to carry the sympatholytic equipment or the medicine that suppress or stimulate the autonomous ganglia coeliaca at stomach rear; These treatments will be transmitted through stomach via the ultrasonic or fluoroscopy-guided (for imaging) through abdominal part.Similarly can be delivered to inferior mesenteric ganglion, kidney by stomach or gastrointestinal other parts neural or along aortal sympathetic nerve in treatment.It is outer and can be used for increasing and be passed the treatment to ganglia coeliaca through stomach that energy delivery transducer 730 is shown in patient body.As selection, energy delivery transducer can be used in imaging area for treatment.For example, ultrasonic transducer can be used for imaging aorta and ganglia coeliaca and with after-applied ultrasonic energy to this region to suppress the nerve in this region.In some cases, melt and used, and in other cases, vibration is used to the function that suppresses neural.

In one embodiment, the region from patient body puts on energy in the region of ganglia coeliaca.In the present embodiment, fluid is placed in gastrointestinal system, for example, and in stomach or small intestinal.Then ultrasound-transmissive can be reached to the interested neuroganglion at stomach rear through gastrointestinal organ.

Provisional nerve stimulator can arrange by inserting in esophagus sick pipe in stomach equally, for example, may need therein during the ICU of the provisional obstruction of autonomic ganglion arranges.Provisional nerve stimulator can be used for exceeding the speed (over pace) of ganglia coeliaca nerve fiber and suppress their functions as nerve synapse.The inhibition of ganglia coeliaca can realize and melt or regulate the renal artery similar function of sympathetic nerve around.Namely, cause the reduction of patient's blood pressure by reducing the degree flowing out from the sympathetic nerve of SNE to the minimizing (now realizing with more approaching inhibition) of the sympathetic activity of kidney.In view of ganglia coeliaca is front neuroganglion and the more polyneural fiber with the region of more crossing than every kidney nerve in arrived region, thereby in ganglia coeliaca, the effect of Blood pressure drop is more far-reaching.Effect is also probably more lasting than the effect in rear neuroganglion nerve fiber.

Fig. 3 A more specifically shows kidney and dissects, within being wherein generally positioned at the outer layer segment of tremulous pulse along the kidney nerve 220 of renal artery 200 longitudinal extensions or just outside its adventitia.Tremulous pulse typically comprises three layers: ground floor is inner membrance, and the second layer is middle level, and the 3rd layer is adventitia.Outer (adventitia) is to contain blood vessel and neural fibrous tissue.Kidney nerve is generally sympathetic nerve after joint, although the neuroganglion that has some to be present in aortal tip of drawing branch (takeoff) makes to be actually Preganglionic along arteriorenal some nerve fiber.While arriving kidney to fiber, the major part of fiber is Postganglionic.On the other hand, nervus centripetalis pass-out and be Postganglionic outside kidney, until strata cerebrale.Even if there is regeneration, these fibers do not have efferent fiber to regenerate fast like that yet.

Power generator 900 transfers energy to and is accompanied by arteriorenal kidney nerve, and the target that makes energy be deposited on the neural complex of kidney from multiple directions suppresses.Power generator can be by ultrasonic energy, ionizing radiation, light (photon) treatment or microwave energy to region.In the case of the region of medicament targeting being waited melt or regulate, energy can be non-focusing.But preferably, energy is concentrated, the multiple angles from patient body apply to arrive the interested region sympathetic nerve of blood vessel (for example, around).Energy transducer 900 is arranged in X-Y-Z coordinate reference system 950, as the organ such as kidney.X-y-z coordinate system is real space coordinate system.For example, the real space meaning is that coordinate reference is discernible in physical world; As the GPS (global positioning system), can locate physical object with physical coordinates.Once be arranged in x-y-z coordinate reference system, just will use MRI, CT scan and/or ultrasonic cross section imaging to be used for internal anatomy to be coupled to transducer.These identical transducers can be used in determining of reference point and treatment.In the present embodiment, transducer 900 is focused on the region of the kidney nerve in kidney blood vessel, tremulous pulse and vein 200 aspects.Within the focus of beam can be positioned at tremulous pulse, within vein, on the adventitia of tremulous pulse or the adventitia of vein.

Ultrasonic energy being applied through skin when reaching renal artery district, in the area-of-interest of tunica adventitia, may need to exceed 1MW/cm ²energy density.But, typically, 100W/cm ²～3kW/cm ²power density will be expected for generation of suppressing these neural required heats (referring to the people's such as Foley Image-Guided HIFU Neurolysis of Peripheral Nerves To Treat Spasticity And Pain; Ultrasound in Med & Biol.Vol 30(9) p 1199-1207).Can pass skin in unfocused mode by pulse enable; But in order to apply heat, transducer must be focused, otherwise skin and lower-hierarchy will receive too much heat.In the situation that carrying out imaging with MRI, temperature can be measured with MRI image.When low-yield ultrasonic while being applied in region, the scope that can apply is 50mW/cm ²～500mW/cm ²energy (power) density.Low-yieldly ultrasonicly can be enough suppress kidney nerve to hit dizzy or part, particularly with pulse output and while depending on desired clinical effectiveness.In the situation that temperature is only raised several degrees, region is applied and high-intensityly ultrasonicly can have identical effect and this energy range can be 0.1kW/cm ²～500kW/cm ².Pulse train can be used for increasing the effect to nervous tissue equally.For example, the sequence of 100 short pulses, each short pulse is less than 1 second and applies 1W/cm ²～500kW/cm ²energy density.In certain embodiments, if temperature rise is considered to excessive so that can not accepts, can apply skin cooling.In certain embodiments, infrared thermal imagery is used to determine skin and hypodermic temperature, if or from inside more depths detect, from kidney and even from kidney blood vessel self.As selection, can make ultrasonic transducer generating pulse or this ultrasonic transducer can be replaced with another group transducer to propagate efficiently the surface of heat through skin.In certain embodiments, energy transmits to be further reduced in the risk of the intermediate structure between target and transducer with the form of pulse.Pulse can be closely to millisecond, as above, or reaches a few hours, a couple of days or several years.

In a kind of method of the physiological process that changes kidney sympathetic activation, region around renal artery use CT scan, MRI, thermal imaging, infrared imaging, optical coherence tomography (OCT), photoacoustic imaging, PET imaging, SPECT imaging or ultrasonic come imaging, and image is arranged in three-dimensional coordinate referential 950.Coordinate reference system 950 refers to the relation of knowing between anatomical structure, have two dimension with three-dimensional, structure be arranged in physical coordinates with reference within.Imaging device is determined coordinate system.Once coordinate system is established, just imaging and treatment transducer 900 can be coupled, make to be used for locating energy from the information of imaging system by treating transducer.Blood vessel can provide for the deposition of energy the referential of use, because they have unique imaging features.Ultrasonic pulse-echo can provide Doppler frequency shift feature, for identifying blood vessel from tissue around.At MRI, CT scan and even in ultrasonic examination, can identify the flow pattern that contributes to determine for the deposition of energy coordinate reference with intravenous injection contrast agent.The transducer 900 that can transmit ultrasonic, light, radiation, ionizing radiation or microwave energy is arranged in the three-dimensional referential identical with renal artery, processor (for example, using algorithm) can determine how to guide transducer to transfer energy to neural 910 region 220 at this moment.Algorithm comprises the targeting feature (plan features) that allows predicted position and leave the energy deposition of the energy of transducer 900.

Once three-dimensional coordinate reference system 950 is coupled or coupled, just can application plan and prediction algorithm energy beam is accurately positioned to the target in health.

Original formation method can be used to locate kidney sympathetic nerve region, and/or can be used to follow the tracks of the motion of this region during treating.For example, time zero place use imaging technique be counted as baseline scan and start at follow up scan and the t0(of time t1) baseline scan comparison.Renewal frequency can be every a few second single pass to Multiple-Scan per second.Ultrasonic, as imaging technique in the situation that, position may be according to being greater than 50Hz and upgrading up to the frame frequency of hundreds of Hz or several thousand Hz.At MRI, as formation method in the situation that, imaging refresh rate can be closer to 30Hz.In other embodiments, the inner benchmark of arranging sends positional information and this information with altofrequency and is used to make target and initial outside imaging device fusion.Internal reference can comprise one or more imageable elements, comprises region, rib, the kidney of Doppler signal, blood vessel and is different from blood vessel and the organ (for example, caval vein, adrenal gland, ureter) of target.These benchmark can be used to follow the tracks of the region being treated and/or be used for treating area for treatment and carry out triangulation.Benchmark can be arranged outside interior location or can be inherent benchmark, for example anatomical features and/or can imaging features.

(Fig. 3 C) in certain embodiments, provisional benchmark 960 is arranged in region, for example, in tremulous pulse 965, renal veins 975, aorta 945 and/or caval vein 985; The easily imaging from patient body of this type of benchmark.In one embodiment, provisional benchmark can Enhanced Imaging, such as can gas or the bubble sacculus of filling.In another kind of embodiment, provisional benchmark can be can via MRI or ultrasonic come the material of imaging.

Fig. 3 D shows in monitoring system 950 967 imageable transducer 960 in the blood vessel in coordinate reference 975.As selection, provisional benchmark 960 is further to improve the ability of imaging and tracing area so that the transducer for the treatment of to be provided.Transducer can be piezoquartz, and this piezoquartz is stimulated to launch the energy that can be detected to determine by one or more detectors three-dimensional position.In certain embodiments, receptor is arranged in outside patient body, and their geometry has been determined sensitivity and the position of the transducer in coordinate reference.Transducer can discharge radio-frequency (RF) energy, and this radio-frequency (RF) energy can be detected by one or more detectors, for accurately locating three-dimensional position.Transducer can be launched sound or the optical signalling that can hear.Provisional benchmark can be that mechanical, optics, dynamo-electric, RF radio emitter stage, ultrasonic generator, global location are followed the tracks of (GPS) equipment or ultrasonic response technology.Can be used for the auxiliary similar devices of carrying out treatment described herein can be at patent No.6, finds in 656,131 and 7,470,241, and at this patent No.6 in full, 656,131 and 7,470,241 to mention that mode is incorporated herein.

Can follow the tracks of equally internal reflection (for example, speckle).These speckles are the inherent characters with the tissue of ultra sonic imaging.They can be tracked and be merged in treatment plan algorithm, and then connect (link) to treating transducer.In certain embodiments, coelosis is detected, and wherein in this coelosis, detects steam bubble to determine temperature or degree of heat.

In certain embodiments, the test dose of energy can be put on to kidney sympathetic nerve district and then carry out this and test to determine whether to have produced effect.For example, a small amount of heat or vibrational energy can be delivered to orthosympathetic region and then can carry out the test of sympathetic activity, for example micro-neuronography (microneurography) (determine sympathetic activity around muscle and with the dirty associated nerve of pulsatile heart).The research in past and current clinical data show, affected by the terminal of kidney nervus centripetalis to the sympathetic nerve of peripheral muscle.The caused temperature rise degree of heating of little degree can be by determining with MRI thermometric or ultrasonic technique, and temperature rise can be determined or be limited to reversible size.

In another kind of embodiment, stimulate and be applied in the region such such as skin, and the downstream output from skin can be detected.For example, vibrational energy can be put on to skin and sympathetic nerve output (for example, heart rate) can be detected.In another kind of embodiment, can by heat or the cold skin that puts on, and can detect as output heart rate, blood pressure, vasoconstriction.These Input output Relationships can be affected by treatment described herein.In certain embodiments, treatment described herein can be indicated by Input output Relationship at least in part.

As selection, ultra sonic imaging can be used for determining that the approximate temperature of tissue regions rises.Hyperacoustic speed depends on temperature and therefore will depend on temperature from the relative velocity of the ultrasound-transmissive that is heated region, therefore provides measurable variable for monitoring.In certain embodiments, microvesicle is used to determine the rising of temperature.Microvesicle expands and then breaks in the time being exposed to cumulative temperature, makes them then can predict the temperature in heated region.Within microvesicle can be injected into patient's vein or tremulous pulse or within microvesicle can partly be injected aorta, renal artery, renal veins etc.Can use equally the technology that is called ultrasonic elastograph imaging.In the present embodiment, the elastic property of tissue depend on temperature and therefore elastogram can be used for following the tracks of the feature of variations in temperature.Microvesicle can also be used to increase the therapeutic effect that is treated region.For example, microvesicle can be used to discharge medicine while touching them ultrasonic.The medicine that can discharge comprises steroid, neurotoxin, neuroregulation medicament, nanoparticle, antibody, magnetic nano-particle, polymer nano-particle etc.As selection, microbubble structure can be used to strengthen the imaging of area for treatment, to improve targeting or the tracking to area for treatment.

In certain embodiments, only used temperature to determine.Namely, temperature sensing embodiment described herein and algorithm can be used for wherein will carrying out any operation of heating.For example, use therein in situation kidney Neural Area being heated by arteriorenal radio-frequency (RF) ablation, can when renal artery region is just via radio frequency method heating, carry out the imaging in this region in the position from patient body.Imaging can complete by MRI, ultrasonic, infrared or OCT method.Imaging can be used to determine in the region around blood vessel and/or supraneural temperature or temperature effect.For example, radiofrequency catheter can be used to apply energy and then can during treating or afterwards, apply ultra sonic imaging with radiofrequency catheter to blood vessel wall, can determine at this moment and have neural circumvascular temperature, curdled appearance and nerve injury.In addition or as selecting, MRI can be used for determining temperature or the mapping effect in the neuromechanism around blood vessel during to the radio frequency heating of blood vessel.

This therapeutic imaging can be assisted treatment is accurately directed to the peripheral region at blood vessel, and allows the heat of the safety to blood vessel wall to apply.For example, in one embodiment, energy is applied in blood vessel wall and this heat is detected during treating.In this embodiment, temperature can be defined in to specific level (for example, 55 degree, 60 degree, 65 degree) and reach specific duration (for example, 30 seconds, 60 seconds, 120 seconds).MRI or ultrasonic or both can be used in treatment and/or for measure.Can determine in the method near the location of heat blood vessel wall.

In another kind of embodiment, test can be carried out on the pressure receptor complex in the region of carotid artery fork.After the test dose of energy is put on to renal artery complex, pressure can be applied in carotid artery complex; Typically, with complete pressure receptor complex, system blood pressure will reduce after carotid artery is exerted pressure.But, for repressed kidney nervus centripetalis, pressure receptor to the variation of blood pressure by insensitive and therefore can determine the curative effect that the energy of kidney nerve is applied.Other test comprises the index that obtains autonomic nervous function, such as micro-neuronography, autonomic nervous function variation etc.

In another kind of embodiment, the stimulation of pressure receptor complex is completed non-invasively by the ultrasonic pulse that puts on carotid body region in outside.Ultrasonic pulse is enough to stimulate hole to affect blood pressure, and one will for example, in the time that nervus centripetalis (, kidney nervus centripetalis) is changed affected variation.

More specifically, this method is shown in Fig. 3 E.Ultrasonic pulse 980 is used to stimulation of carotid sinus, and this carotid sinus will make the instantaneous reduction by 982 of blood pressure by activation pressure sensor complex; The effect that the activation of carotid sinus 980 has stimulated blood pressure to increase, the compensatory outflow of parasympathetic activity that this blood pressure increase causes and the sympathetic nerve of reduction flow out, and reduce blood pressure subsequently.In this example, for example, in the time importing system (, from kidney) into and be suppressed, pressure cannot be revised rapidly, if need amendment.In this case, stimulate pressure receptor complex can not cause blood pressure 986 to reduce, this treatment is successful.Therefore this diagnostic techniques can be used to determine for example, therapeutic effect in system (, the neural complex of kidney).If treatment is successfully, ultrasonic pulse to the amendment effect of carotid sinus and blood pressure significantly and this treatment (treatment of nervus centripetalis) be successful; Therefore, treatment can temporarily or permanently be ended 988.If blood pressure along with pressure receptor stimulate and continue decline 982, the therapeutic effect of this treatment processing also do not reach and treat need to proceed 984 and/or raising dosage.Nearby to exert pressure with hands, compression balloon, electrostimulator etc. for stimulating other method of pressure receptor complex.

Technology described herein can also be by putting on another region and directly affect autonomic other region through the energy of tissue from a region and transmission.For example, Fig. 4 A shows a kind of system, and the energy in this system outside internal carotid artery is applied in an autonomic part, carotid body complex 1000, through internal jugular vein 1005, and to carotid body 1000 and/or vagus area 1022, and/or vertebral artery 1015.Ablation energy, vibration or electricity irritation energy can be used to have influence on these nerves and transmit from these neural signals.Transmission in this complex can for example, increase via energy (, ultrasonic, electricity irritation etc.), interrupts, suppress with overstimulation, or the combination of these effects.

In addition, or instead, in other embodiments, energy can be put on and be commonly referred to motorial nervus peripheralis, but this nervus peripheralis contains from principal fibers.This nerve comprises saphenous nerve, femoral nerve, lumbar nerves, median nerve, ulnar nerve and radial nerve.In certain embodiments, energy is applied in nerve and is specifically affected instead of other nerve fiber (for example motion or somesthesia fiber or spread out of or import autonomic nerve into) from principal fibers.In certain embodiments, the autonomic nerve fiber of other type is by being affected at energy inner or that apply in outside.For example, nerve around superior mesenteric artery, inferior mesenteric artery, femoral artery, pelvis tremulous pulse, portal vein, Hepatic artery, pulmonary artery, pulmonary vein, aorta, caval vein etc. can be affected in a particular manner by energy, to make changing from main response of blood vessel self or the organ relevant to blood vessel, this nerve through and lead to organ along blood vessel.

In another kind of embodiment, in Fig. 4 a, conduit 1010 advances in internal jugular vein 1005, and when time in place, stimulation or ablation energy 1020 are guided autonomic nerve into by the conduit being positioned in Venous system 1005, for example, and vagus nerve and carotid sinus/body 1000.

In a kind of embodiment 1100 of similar type, the treatment energy source 1110 based on conduit can be inserted within the region of renal artery or renal veins (Fig. 4 B), for from blood vessel (renal artery 1105 or renal veins 1106) internal stimulus or suppress kidney nerve.Energy is for example transmitted, through blood vessel (, renal veins) for example to arrive, at another root blood vessel (, renal artery) nerve around.For example, transmit and there is 50mW/cm ²～50kW/cm ²the conduit of not focused ultrasound energy of power can be arranged in renal artery within, and energy is radially transferred to nerve around around tremulous pulse or vein.As discussed below, 500mW-2500W/cm ²be suitable for causing specific delayed ischemic neurological deficits to affect the noradrenaline levels in kidney, a kind of being proved can cause substituting of function of nervous system that blood pressure reduces in time.Impulse type is ultrasonic, and for example, each persistent period is less than separately 100 pulse trains of 1 second and can be applied in this region.In another kind of embodiment, conduit comprises the Individual components being organized for generation of plane wave.This plane wave can be by mobile and/or focus on around conduit by alternation phasing mode, and this makes the ultrasonic circumference that is arranged in blood vessel (for example, tremulous pulse) around in different position.Vibration and heat are delivered to circumvascular nerve by the plane wave that produces ultrasound catheter.

In a kind of exemplary embodiment, tubular body 1105 is extended and is flexible, and comprises the oversheath being positioned on kernel.For example, being suitable for especially well in renovascular embodiment, oversheath 108 can comprise expanded politef (" PTFE "), polyether-ether-ketone (" PEEK "), polyethylene (" PE "), polyamide, woven (braided) polyamide and/or other similar material.In this type of embodiment, it is about 0.039 inch (0.039 inch ± 0.01 inch) and be the external diameter between about 0.033 inch (0.033 inch ± 0.01 inch) and about 0.039 inch (0.039 inch ± 0.01 inch) at its far-end that oversheath 108 has in its most proximal end.In this type of embodiment, oversheath 108 has the axial length of about 150 centimetres (150cm ± 20cm).In other embodiments, oversheath 108 can be formed by the woven pipe that comprises high density or low-density polyethylene, urethane, nylon etc.This structural reinforcing the flexibility of tubular body 1105.In other embodiments, oversheath can be included in the reinforcing element (not shown) of tubular body near-end.

Kernel has defined central lumen or " guidewire lumen " at least in part, and this central lumen or " guidewire lumen " preferably extend through the length of conduit.Central lumen has far-end and exits port and near-end entry port.In certain embodiments, the proximal part of conduit is defined by the treatment compound entrance on rear end hub (hub), and this treatment compound entrance is connected to near-end.In this exemplary embodiment, rear end hub is connected to control box adapter, and this control box adapter will be described in greater detail below.

In a kind of exemplary embodiment, central lumen is arranged to and receives the seal wire (not shown) with the diameter between about 0.010 inch (0.010 inch ± 0.005 inch) to about 0.012 inch (0.012 inch ± 0.005 inch).In a kind of exemplary embodiment, kernel by can optionally weave to improve the flexible polyimides of tubular body 1105 or similarly material form.

With reference now to the exemplary embodiment shown in Fig. 4 B,, the far-end of tubular body comprises ultrasonic radiation element 1110.In shown embodiment, ultrasonic radiation element 1110 comprises the ultrasonic transducer that for example electric energy is converted to ultrasonic energy.

Kernel extends through the ultrasonic radiation element being positioned on kernel.Ultrasonic radiation element can be fixed on kernel with suitable mode (for example,, with binding agent).Make kernel extend through element and advantageously provide strengthen cooling to ultrasonic radiation element.Treatment compound can be injected into by central lumen, thereby the heat producing for ultrasonic radiation element provides heat sink (heat sink).Treatment compound can strengthen ultrasonic in the supraneural effect around blood vessel.

The operation frequency that is applicable to ultrasonic radiation element includes, but are not limited to: from about 20kHz(20kHz ± 2kHz) to being less than about 20MHz(20MHz ± 2MHz).In one embodiment, frequency is in 500kHz and about 20MHz(20MHz ± 2MHz) between, and in another kind of embodiment, this frequency is in about 1MHz(1MHz ± 0.1MHz) and about 3MHz(3MHz ± 0.3MHz) between.In another embodiment, ultrasonic energy has about 3MHz(3MHz ± 0.3MHz) frequency.

In certain embodiments, unfocused ultrasonic edge is circumferentially passed blood and is passed blood vessel wall to affect the nerve of blood vessel outside towards the surrounding radiation of blood vessel.Neural can impact by whole in vibrational energy, heat energy, mechanical energy or these energy or the combination of some.Radio-frequency (RF) energy equally also can be simultaneously with in these energy any one, some or all applies.In one embodiment, sacculus is applied in renal artery blood vessel wall, and then can be by ultrasonic, radio frequency, light, heat, medicine, and their combination or they all put on blood vessel wall and through blood vessel wall.Sacculus can be half moon-shaped or other shape to allow blood flow to enter the center of sacculus.

In another kind of embodiment, light is applied through blood vessel by internal blood vessel.Infrared, red, indigo plant and near-infrared all can be used for affecting the function of circumvascular nerve.For example, within, light source is introduced into renal artery or renal veins 1105,1106 and light be transferred to circumvascular region.In a kind of preferred embodiment, photosensitizer is used to accelerate with this technology the inhibition to nerve tract or destruction.Photosensitizer can apply to infiltrate to general circumvascular region.Then light is applied to the neurological region outside blood vessel by internal blood vessel.Within light source is arranged in renal veins and then for example, light is transmitted through wall of vein, arrives tube wall adventitia district around, activates photosensitizer and injury or is suppressed at through the nerve in the adventitia of apoptosis (apoptosis) path.Light source can provide visible ray or black light.In another kind of embodiment, light is applied in the region that there is no photosensitizer.Light is created in tremulous pulse ambient heat by light absorption in region.Wavelength, for example those wavelength in red, near-infrared and ultrared, are absorbed and are caused the neural destruction in region by tissue.

In one embodiment, within a string light emitting diode (LED) is admitted to blood vessel and blood vessel irradiated from internal blood vessel by light.For near-infrared and infrared light have good blood and tissue penetration and can be used to heating or activate the medicine in the circumvascular region of leading to kidney.These optical frequency equipment and energy can be used for making inside and/or the exterior visual of blood vessel.Endovascular OCT can be used for making the damage of circumvascular nerve visual.

Treatment in Fig. 4 A-B can provide on acute basis, for example, disposes in (critical care setting) at ICU or critical illness monitoring.In this case, treatment will be urgent and discontinuity, source outside patient body and conduit in patient body, as shown in Fig. 4 a-b.Treatment is used during can be in the time that patient has pressure, thereby sympathetic nervous system is slowed down.After approaching end is in hospital in Intensive Care Therapy, can remove conduit and unit from patient.In one embodiment, having described a kind of wherein conduit is arranged in patient body to transfer energy to the region of health, enough for example, partially or even wholly to suppress the method for autonomic nerve complex during a certain state in deep layer sympathetic activity (, shock, sepsis, myocardial infarction, pancreatitis, postoperative).After the implantation acute stage being regulated at sympathetic nervous system, equipment is completely removed.

Fig. 5 A-B shows the detailed feature of eye, and wherein sympathetic nerve is around the rear of eyeball.Aspect eyes, glaucoma is worldwide great problem.Being used for the treatment of glaucomatous modal prescription drugs is timolol (timoptic), and wherein this timolol is that nonselective β 1 and β 2(are Adrenergic) antagonist.The compliance of this medicine is subject matter and limited it at the effectiveness preventing aspect glaucomatous complication, and wherein main complication is the progress of visual function disorder.

Ultrasonic, or other transducer 7000, can be applied to make energy the past side perimeter (for example, the distance from eye in external position) focus on the region on sympathetic nerve 2010 or parasympathetic ganglion at eye or eyeball 2500 rears, all these positions all will affect the reduction of intraocular pressure.Transducer 7000 puts on the energy of ablative ablative or near the adventitia of blood vessel.In certain embodiments, energy be not ablative but vibratory, its frequency (for example, 1-5MHz) and penetration depth (for example, 0.5mm-0.5cm) are enough to suppress to be responsible for the neural function of intraocular pressure.Lower energy (for example, sub-ablative) can be applied in eye carries or stimulates the tissue response of organization healing type with ancillary drug.

Fig. 5 B shows the neural dissection of leading to eyeball 2500 rears.In this diagram, make conduit 2000 tunnels arrive the sympathetic nerve district round ophthalmic artery 2010 through vascular, and be used to melt, hit dizzy or regulate and lead to spreading out of of eye and/or nervus centripetalis through blood vessel wall in addition.

Fig. 6 shows about renal artery, renal veins, gathering system and the blood vessel of the more far-end within excess of the kidney matter and total schematic diagram of gathering system conductor.Autonomic somatic nerves conventionally followed the vascular system of health and they and is being shown as immediately 3000 in renal artery, because this tremulous pulse just in time enters kidney 3100.The hilus renalis of kidney contains via leading to central nervous system from kidney and then affecting pressure transducer and the chemical sensor of the input that spreads out of sympathetic nervous system to the nervus centripetalis of efferent nervous system.Any one or more in these structures can both affect the function of kidney.Energy ablative or non-ablative can be applied in renal veins, renal artery, aorta, and/or caval vein, the hilus renalis, excess of the kidney matter, renal medulla, renal cortex etc.The example of non-ablative energy can be for example vibration from unfocused supersonic source.Another kind of non-ablative energy can be for example light through optical dynamic therapy.The non-ablative energy of another kind of type can be the electromagnetic energy being transmitted through patient, for example, have electric current and flow through large coil wherein.

In another kind of embodiment, optionally damage, constriction or implant (implant) 3200 is arranged in renal calices, for controlling or stoping blood to flow to the specific region of kidney.This damage or implant can be arranged on the tremulous pulse 3010 or venous side 3220 of kidney.In certain embodiments, damage/implant is caused to optionally stop orthosympathetic some part in kidney.Damage for example can be positioned, equally to melt the region that produces hormone (, feritin) in kidney, and wherein this feritin can be harmful to patient when excessive.Within implant or constriction can be arranged in aorta 3210 or renal veins 3230.Implant can be active implant, produces upper discrete multiple ablative of chronic stimulation energy or time or the dosage of inhibition.

In renal veins 3230, implant 3220,3200 can impel the pressure in kidney to increase (enter in kidney and increase pressure by allowing blood flow to fall back), this will prevent the spiral decline of above-described systolic heart failure, because kidney will work as it is just experiencing high-head (high pressure head).

Namely, once the pressure in kidney recovers by the vein pressure increasing or raises artificially, to no longer occur for the relevant kidney hypotension signaling that retains electrolyte and water, and kidney will " feel " to have expired and kidney sympathetic stimulation will be stopped.In one embodiment, cause narrow support conduit induction system to implant.In another kind of embodiment, narrow 3220 use are outside or produce at the heat of internal delivery.The outside heat transmitting is via transmitting or be transmitted through skin (for example,, to focus on the HIFU through skin) by means of the direct heating of percutaneous operation (region through skin to kidney).In one embodiment, implant is arranged between girota ' s fascia and the cortex of kidney.Implant can stimulate or suppress the circumvascular nerve of kidney, or even on long-term basis, in delivery system, discharges medicine.Any in use derived techniques, through patient's rib abdomen, this region easily enters.

Fig. 7 A shows the melting at least partly of the kidney sympathetic nerve 4400 to kidney that uses imaging system (for example, MRI machine or CT Scanner 4000).MRI/CT scanning can be attached to melting of focus supersonic (HIFU) machine sympathetic nerve 4400 around renal artery 4500 regions with execution.MRI/CT scanning is carried out imaging 4010 and data (for example, the three-dimensional representation in interested region) is transferred to ultrasonic controller, and then this ultrasonic controller guides ultrasonic with low intensity ultrasound (50-1000mW/cm ²), heat (>1000mW/cm ²), the combination of coelosis or these methods and/or comprise that introducing partly or capapie enhancement bioactivator carries (sound motivation therapy) to come the interested region of targeting.Optionally, doppler ultrasound or other 3D/4D are ultrasonic is performed and data are pushed into MRI system to help the location of pathology; As selection, ultrasound data is used to directly control and is used for guiding and the CT/MRI of energy of targeting physiological process and does not have obtained.Use this imaging and ablation system from the position outside patient body, many regions of kidney can both be treated, for example inner renal calices 4350, cortex 4300, medullary substance 4320, the hilus renalis 4330 and close aortal region 4340.Optionally, endovascular conduit can be introduced in patient body so that operation increases endovascular energy, temperature survey, acoustic energy detection, ionizing radiation detection etc.For example, conduit may arrive blood vessel wall by transmission of radio-frequency energy, or conduit can be heated in response to being applied in through patient's magnetic field.For example, sacculus or other catheter tip with metal coating are heated by exist in magnetic field in the situation that.This heat (normally unnecessary in the situation that there is catheter in blood vessel) can be used to suppress or melt the nerve (for example) that leads to kidney.MRI system also has advantages of can be measured temperature and/or check in the circumvascular tissue variation being treated, as described below.Similarly, endovascular conduit can be in response to ultrasonic and heat in the situation that conduit contains element.

More parameter its can be measured comprise that temperature is via thermography use MRI or ultrasonic temperature measurement/elastogram; Thermal imaging is the well-known feature of MRI scanner unit; Within being present in MRI scanning for the data of thermography and can be by more interested region before treating and afterwards or during be extrapolated in real time from recorded data.Temperature data covers the increase location visual and therefore heating that makes the operator of machine can make temperature on MRI scanning to guarantee its correct region and really melted and excessive energy is not applied in region.Having temperature data also allows the control of ablation areas so that apply correct temperature so that nerve is melted.For example, temperature in time can be determined and be fed back to operator or in automated system, be fed back to energy delivery devices self.And other spectrum parameter can be determined with MRI scanning, for example oxygenate, blood flow, checking, or other physiological and parameter function.In one embodiment, alternating magnetic field be used to stimulate and then overstimulation or suppress autonomic nerve (for example, to kidney or from kidney).

Elastogram is the technology that a kind of shearing that wherein detects ultrasonic beam involves reflectance.Because tissue is heated and tissue property changes, thereby tissue characteristics changes.Approximate temperature can be assigned to tissue based on elastogram and can monitor the progress of heating.

MRI scanner unit 4000 usually comprises magnet and RF coil.Magnet can be electromagnet or permanent magnet.Coil is generally the copper coil that produces radio-frequency field.In recent years, permanent magnet has been used to produce MRI scanner unit that can (for example, private working environment) used in any environment (setting) almost.In addition, supercool coil is developed out, and in this supercool coil, cryogen is circulated in wherein or around copper coil, is allowed for the higher electric current of imaging and larger sensitivity.This structure is favourable, because this structure has produced and had the image the same with the picture quality of the magnet from 1.5T with the magnet of 0.3T.Therefore, a kind of system being used for the treatment of comprises the MRI machine with permanent magnet and coil, and wherein this coil is supercool, and this MRI machine applies the target area in patient body together with focused ultrasound system by heat.MRI scanner unit based on office can be carried out quickly and easily imaging in doctor's office, and needs less magnetic force (being less than 0.5 tesla), and therefore, less shielding.The lower magnet of tesla also provides special advantage, such as the multiformity of imaging and the resolution of some feature.Importantly, permanent magnet MRI scanner unit is open scanner unit and does not seal patient in scan period.The low scanner unit of tesla can have field intensity and be low to moderate the magnet of 0.5T～0.1T.

In one embodiment, permanent magnet MRI is used to obtain the MRI image in interested region 4010.The ultrasonic interested region 4600 that is used to targeting use MRI identification of high-intensity focusing 4100.In one embodiment, MRI is used to detect for example, blood flow (only having pointed out subset) in one or more blood vessels (, renal artery, renal veins, superior mesenteric artery, vein, carotid artery and vein, aortic arch coronary artery, vein).In this embodiment, can be wound in patient's back or patient's rib abdomen for the designed coil of kidney blood vessel specially.In certain embodiments, coil is to be arranged in after one's death and the custom-designed surface coils of patient, for improving organum retroperitoneale's the sensitivity of imaging.

Image 4010 is by health care expert or can be monitored by health care expert, to guarantee that interested region is just treated, and if the region setting does not obtain medical treatment, can stop this treatment.As selection, imaging algorithm can be activated, region interested in this imaging algorithm (for example,, by image processing) identification and then follow-up image and the original area-of-interest of demarcating being compared by automatically.

May, the most important thing is, pass through MRI, can easily carry out imaging to the region around renal artery, vein, the hilus renalis, ureter, cortex, medullary substance, such as the equally easily imaging of any other region of eye, brain, prostate, mammary gland, liver, colon, spleen, aorta, hip, knee, spinal column, venous tree and pancreas.Especially, can be visualized in these intraorganic area vasculosas and by targeting with focus supersonic.The imaging of MRI can be used to ultrasonic beam accurately to focus on the interested region in other place of renal artery around or in health.By MRI, actual nerve to be modified or that regulate can be directly visual and by targeting with the energy through health by ultrasonic transducer transmission.An advantage of MRI can be frame collection (difficulty is tracking target) rate and MRI power traction is entered to treat the cost within normal form.In these areas, ultra sonic imaging provides more feasible solution.In certain embodiments, ultrasonic and advantage MRI is incorporated in individual system.In certain embodiments, endovascular conduit is also combined further to strengthen treatment with these two kinds of formation methods.In one embodiment, endovascular conduit has the ferromagnetic end that can be moved or be heated by MRI scanner unit (or both all can).This end can be manually or is operated by magnetic field (or both all can), blood vessel wall is exerted pressure and with this blood vessel wall of post-heating.In certain embodiments, end can be carried out above-mentioned functions in the temperature of measuring circumvascular region (Neural Area).In certain embodiments, can measure temperature with another kind of equipment.

Fig. 7 D shows the method for carrying out area for treatment with high intensity focused ultrasound (HIFU).Imaging is with MRI 4520 or ultrasonic 4510(or be preferably both) carry out.MRI can be used to directly or indirectly (for example, using functional MRI or wave spectrum) makes sympathetic nerve visual.Image T1 weighting or T2 weighting can obtain with MRI scanner unit.Except anatomy imaging, MRI scanner unit can also obtain about which part in the just heated degree of the temperature data of the effectiveness of zone of ablation and region and region just heated.Can add equally other spectrum parameter, for example, blood flow and even neural activity.Can edema, inflammation and necrosis be detected with MRI equally.Ultrasonic 4510 can be used to add blood flow (use doppler imaging) to image.Spectroscopic data can for example, be increased by imaging component (moiety) (particle), preparation or the particle that is coupled to preparation, and wherein this preparation is by vein or inject in patient body partly and near renal artery region; These imaging component can be visual in MRI, ultrasonic or CT scan.Ultrasonic can also be used for determine about heating information.Hyperacoustic reflectance changes along with the variation of tissue temperature.By the successive image after initial pictures and heating is compared, the temperature inversion occurring after heating is set up can be determined.And, in one embodiment, be incorporated to and treat in simulation about the time after t=0 during being determined and to be in the information of baseline heating the treatment of just carrying out.

In one embodiment, kidney for example, detects by cross section formation method (MRI, ultrasonic or CT scan).In use MRI image contrast agent or that do not use contrast agent, detect renal artery and vein.Then, imaging data is arranged in the three-dimensional coordinate system for example, connecting with one or more ultrasonic (, HIFU) transducer 4540, and wherein this ultrasonic transducer 4540 is by focus ultrasonic on the renal artery region in coordinate system 4530.Image with treatment transducer connect or couple by create anatomical model determine that the three-dimensional position of target completes.Transducer is arranged in relative three-dimensional system of coordinate equally.For example, during MRI or CT scan, can, by transducer arrangement in imaging area 4540, make cross-sectional image comprise transducer.Optionally, transducer contains motion sensor, for example electromagnetism, optics, inertia, MEMS and accelerometer, the one or more transducer positions that make in these motion sensors can be monitored, if for example health moves with respect to transducer or operator moves with respect to health.With motion sensor, can determine the position of transducer along with contingent movement during treating.Then the information of upgrading can be fed back to ultrasonic therapeutic apparatus, to readjust the position for the treatment of.

In one embodiment, describe a kind of system, in this system, the blood flow in renal artery is determined by detecting arterial wall or renal veins wall or the blood flow in renal artery or renal veins.Then the coordinate reference of blood vessel is transferred to treatment transducer, for example, and ultrasonic transducer.Use the information obtaining by image that treatment transducer is directed to kidney blood vessel.Blood flow and the neural blood vessel wall existing wherein of model (for example, Figure 16 M) the instruction blood vessel of blood vessel (comprising blood flow, movement etc.).Then energy is put on to the model of blood vessel to treat circumvascular nerve.

As selection, in another kind of embodiment, ultrasonic used and ultrasonoscopy 4510 can be directly related to the original image of imaging transducer.In certain embodiments, ultrasonic in two dimension, and in other embodiments, ultrasonic being present in three-dimensional.In certain embodiments, in the ultrasonic combination that is present in two and three dimensions.For example, two-dimensional transducer can rotate and picture integrated provides three-dimensional approximate rapidly by specific speed.Treatment transducer 4540 is identical with imaging transducer in certain embodiments, and therefore according to restriction, once the coordinate of imaging transducer is learned, treatment transducer is just coupled in coordinate reference 4540.If treatment transducer and imaging transducer are different equipment, they can couple by the relative position of knowing two equipment.Interested region (ROI) is highlighted in software algorithm; For example, renal artery, renal calices, medullary substance district, cortex, the hilus renalis, ganglia coeliaca, aorta or also have any vein in Venous system.In another kind of embodiment, adrenal gland, lead to adrenal blood vessel or lead to adrenal autonomic nerve by targeting with focus supersonic, and then adrenal gland or neural medullary substance or cortex and the tremulous pulse that leads to body of gland partially or even wholly melt with ultrasonic energy.

Ultrasonic target area or focus are the points of maximum intensity.In certain embodiments, targeting focus is arranged in the center of tremulous pulse, makes wall receive sizable energy or power in both sides and can heat more equably than the situation of a side of target vascular therapy wall.Blood vessel by some embodiment of targeting in, this blood vessel be tremulous pulse and this tremulous pulse have tightly around vein (for example, renal artery/pedicled with vein), the center of focus can be arranged in the boundary of vein and tremulous pulse.

Once to transducer energising 4550, organize with regard to heated 4560 and use such as MRI thermal imaging 4570 or the such technology of ultrasonic thermal imaging and determine tissue temperature after region is by targeting.Between the test period of temperature, then referenced to guarantee the accuracy of location from the anatomical data of MRI scanning or doppler ultrasound, and the degree of transducing is further measured so that the parameter of transducer 4550 to be set by simulation algorithm 4545 again.If exist target to move, may must close transducer and reorientate patient.As selection, transducer can be redirected the diverse location in coordinate reference system.

Melting the reagent (for example magnetic nanometer or Liposome nanaparticle) that can also use in response to the radio-frequency field being generated by magnet increases.These particles can optionally be heated by magnetic field.Particle can be enhanced equally and make them will use the concrete Organ and tissue of targeted constituent (such as antibody, polypeptide etc.) targeting.Except transferring heat, particle can also be activated medicine, bioactivator or preparation to be carried to the region (for example, renal artery) in needs effect.Particle can be introduced through blood vessel or percutaneous approach via intravenous route, subcutaneous route, direct injection approach.For example, magnetic nano-particle or microgranule produce heat in response to magnetic field (for example,, by MRI equipment) in the regional area around them.Similarly, liposome particles can have metallic therein, make magnetic particle heating liposome region around, but liposome allows accurate targeting and biocompatibility.

The interpolation of doppler ultrasound 4510 can be provided equally.Under the help that is with or without reference mark, use within renal artery (if the region around renal artery or tremulous pulse is target) is arranged in 3D coordinate reference system 4530 by software algorithm.Data are supplied to ultrasonic transducer 4540 and this transducer to be energized by thermal simulation algorithm 4545, thereby with suitable phase place and power, arteriorenal region are heated between 40 DEG C to 90 DEG C in the time span of a few minutes.Position in 3D coordinate reference is integrated in treatment algorithm equally, makes within ultrasonic transducer can be moved to suitable position.Ultrasonic transducer can have that 1 megahertz (MHz) is following, 1-20MHz or frequency more than 30MHz, or is about 750kHz, 500kHz or 250kHz.Transducer can adopt the form of annular, linearity or curved phased array, or transducer can mechanically be moved so as by focus ultrasonic in interested target.In addition, can also use MRI thermal imaging 4570 to obtain the actual temperature of heated tissue.These data can be slack-off or accelerate to make to melt 4560 processes via transducer 4550 by further feedthrough system.For example, in the case of temperature does not rise rapidly as planned, can improve energy level.On the other hand, in the case of temperature-rise ratio original scheme fast, can the decrease of power density.

Except focus supersonic, can also directly use ultrasound wave with the activation medicine in heating region or area-of-interest.There are several methods that strengthen drug conveying with focus supersonic.For example, particle can discharge medicine in the time that they are heated by magnetic field.Liposome can discharge payload in the time that they are activated with focus supersonic.If transducer is arranged near target and target contain such as biologically active drug or bioactive materials (for example, to the nanoparticle of sound wave sensitivity) such can activate constituent, ultrasound wave has the ability that nature focuses on.The example of the composition of ultrasonic power activation comprises some derivatives of porphyrin.

For the interested region of test and the potential physiological effect melting in this region, this region can be carried out local heat or vibrate to hit and swoon or partly melt nerve with focus supersonic.Then, physiological test (for example, test blood pressure or measure blood, kidney, pass into or the blood vessel of pass-out kidney in noradrenaline levels) can be performed to guarantee certain targeting the correct region for melting.The treatment that can also add, this depends on parameter.

Clinically, this technology can be called as treatment and separate, and it has emphasized a major advantage of this technology: external energy is put on to renal artery, instead of internal energy.Internal technology needs aggressive through skin and entering in renal artery tube chamber, and renal artery tube chamber is subject to the high and potentiality of cost and destroys.Patient will probably not accept repeatedly to treat, because they are Highly invasive and painful.Exterior technology makes the treatment that aggressive is lower be applied to multiple occasion, makes because low cost and the invasion and attack minimum of technology described herein become feasible.

In another kind of embodiment, benchmark is used to demarcate area-of-interest.Benchmark can be that inherent (for example a, part for dissection) or benchmark can be external (for example, being arranged in suitable position).For example, benchmark can be implanted benchmark, inherent benchmark, or is arranged in endovascular equipment, or by the equipment that conduit inserts or other operation is arranged through skin.Benchmark can be bone equally, for example rib, or another internal, for example, liver.In one embodiment, benchmark is beacon or the sacculus with the beacon that can arrive via ultrasound detection.In another kind of embodiment, benchmark is to implant renal artery, renal veins, caval vein or aortal support (stent).In the situation that needs apply treatment again, support can be by MRI or ultrasonic periodically heating.In one embodiment, the blood flow in renal artery detecting via doppler imaging or Type B imaging is benchmark, and its relative direction is determined via doppler analysis.Then, use internal reference by renal artery, and more specifically, within the region around renal artery is arranged in three-dimensional system of coordinate.The variable of overall situation location systems art can be used to follow the tracks of at benchmark endarterial or around tremulous pulse.In such an embodiment, by the puncture in groin, position sensor is arranged in to tremulous pulse or intravenous.The position of sensor is monitored because sensor be arranged in blood vessel within and therefore it in physical space, relatively patient's outside, relatively operator and the position of relatively treating transducer are known.Three-dimensional system of coordinate is transferred to treatment ultrasonic transducer and transducer and dissect and be coupled to identical coordinate system then.At the moment, HIFU is transmitted by transducer, and the position of transducer is calculated in the position according to target in referential.Benchmark can be active, and wherein electric current is transferred in benchmark by conduit or by being transmitted through the induction of the energy of skin.From conduit transmit through skin or transmit downwards and spread out of energy patient body along conduit and can be used to refer to the coordinate for the treatment of target, thereby exterior guiding energy can be put on to correct position.Internal reference can be used to follow the tracks of the motion in the region that is just being passed energy.In certain embodiments, in the blood vessel being treated, there are multiple benchmark.For example, within several benchmark are arranged in renal veins, thereby can determine direction and/or the shape of blood vessel.This information is important in the situation that blood vessel is tortuous.The precision that this redundancy can also be used to reduce error and increase targeting and track algorithm.

In one embodiment, virtual reference creates via imaging system.For example, for example, for blood vessel (, renal artery), can be with the ultrasonic blood-vessel image obtaining of Type B, this image is associated with the blood vessel of seeing in direct cross section (1705, Figure 17 F).In the time watching blood vessel with such visual angle, the center of blood vessel can be in alignment with supersonic array (for example, HIFU array 1600) center 1700 and transducer can be focused and put on blood vessel, hot injury 1680 is put on to blood vessel 1705 region around.Diverse location for transducer 1610 along circumference or hemisphere 1650, can produce different focus 1620,1630,1640.The directivity of transducer allows the damage 1620,1630,1640 of longitudinally advancing along blood vessel 1700.Thereby, can produce longitudinal damage 1620-1640 to guarantee the inhibition to function of nervous system's maximum along tremulous pulse.In certain embodiments, the center for the treatment of ultrasonic transducer is off-centered with respect to the center of blood vessel, thereby energy is put on to the both sides of blood vessel wall by a certain angle of relative blood vessel deflection.Transducer 1600 can also be aspheric, and relative its central shaft of the focusing of transducer is off-centered in this case.

In this Therapeutic Method, tremulous pulse (for example, renal artery) can be in cross section or close to seeing in cross section under ultrasonic guidance.In this position, blood vessel is arranged essentially parallel to the axle of sphere transducer to promote damage to produce.If tremulous pulse is in cross section 1680, the setting of ultrasonic transducer 1600 is by calibration in advance, for generation of the multiple focusing damages 1620,1630,1640 along tremulous pulse.

In one embodiment, benchmark is endovascular benchmark, the transmission equipment of for example sacculus or gas-tight seal.Sacculus can detect via the radio transmitter in sacculus, and this sacculus can be detected by external treatment transducer.Sacculus can have three transducers, and each transducer can both send its position, thereby sacculus can be arranged in three-dimensional coordinate reference.For example, for example, for example, once within sacculus is arranged in the coordinate system identical with outer transducer by use transmission beacon, energy conversion just can be delivered to energy (, focus supersonic) blood vessel (, renal artery) or circumvascular region (, kidney nerve).Sacculus and transmitter also provide the ability of following the tracks of clearly vascular (for example, renal artery) for mobile in the situation that.In another kind of embodiment, sacculus is measured temperature or for the conduit at the coolant applying to renal artery or between the neural period of heating.Multiple transducers can be arranged to patient body outer to detect from different directions the position (instead of three inner transducer, in the present embodiment, have three outer transducer for detection of the position of single or multiple internal reference) of internal reference.Again, this type of redundancy for target location is favourable, because the exact position of internal reference can be determined exactly.In another kind of embodiment, multiple internal reference are arranged in patient body, especially, and within blood vessel, for determining the 3 D tropism of blood vessel.

Treatment ultrasonic energy transmission to the tissue in health completes via ultrasonic transducer, and this ultrasonic transducer is directed for transferring energy to the target of coordinate system.

Once target is arranged in coordinate system and starts to carry out energy delivery, importantly maintains the targeting of position, particularly when target is during such as the such zonule of sympathetic nerve., the position of zone of ablation and its baseline position are compared for this reason, wherein zone of ablation and baseline thereof both all in three-dimensional coordinate referential.Ongoing monitoring position and information are fed into the algorithm for the new targeting direction of definite energy wave towards target.In one embodiment, if position cross far from home position away from (for example, patient moves), stop energy delivery and reorientate patient.If position far from home position be not too away from, can mechanically (for example, move) or electrically reorientate transducer by physics by phased array (for example,, by changing the relative phase of the ripple that sent by transducer).In another kind of embodiment, multiple transducers are arranged on the patient of diverse location, and each transducer is unlocked or cuts out to produce necessary energy delivery.By many transducer arrangement on patient in the situation that, can be to treat the ultrasonic larger scope that covers.Treatment position can also be with the image space that acts on inherent benchmark and/or external benchmark.

Except heat is transmitted, can also be with the ultrasonic cavitation measuring instrument energy (cavitating energy) that transmits, this cavitation measuring instrument energy can make drug conveying under some frequency, carry out.Cavitation measuring instrument energy can also cause melting at the tissue of focus area.The medicine of systematicness dosage can be transported to interested region and the region with ultrasonic energy targeting cavitation measuring instrument or other form.The treatment transmission method of other type comprises ultrasonic sensitive bubble or radiosensitive nanoparticle, and all these have strengthened the energy at interested target place.Therefore in one approach, ultrasonic sensitive bioactive materials is given patient, and focus on be ultrasonicly applied in skin by patient to the angiosomes that leads to kidney.To the ultrasonication in circumvascular region at material that will delivery of biologically active or in addition at circumvascular heating region.Within ultrasonic sensitive bioactive materials can be arranged in blood vessel, in this case, ultrasonic can being applied in by blood vessel wall with active material.

Fig. 7 E shows as the region 4600 of seeing from the rear of human patients, kidney 4620, renal artery 4630, and the dissection of bone structure 4610,4640.Fig. 7 E shows renal artery and arranges to the real world within the coordinate system of being summarized as Fig. 7 D.The cross section CT scan of actual human patients is integrated to produce the three-dimensional representation of renal artery, kidney and stage casing torso area.Plane 4623 is that to be parallel to the plane of transverse process and angle 4670 be that people must look up the angle of (towards patient's head) so that the renal artery of " seeing " rib below.This real world imaging and simulation have allowed the optimal system that will be developed out so that the risk that maximizes curative effect and minimize treatment.Therefore in the situation that considering these parameters, design and be used for the treatment of renal artery neural system around, wherein transducer can become the mode of negative angle to locate (for example, adjusting sight line) with respect to the line that connects spinous process.Multiple transducers can by use to allow with dissection or respiratory movement during the variation of the associated location of variation, wherein during treating, can follow the tracks of dissection.

Fig. 7 F shows the image that uses the renal artery of ultra sonic imaging and the region of kidney 4605.The hilus renalis that contains tremulous pulse and vein can come visual with this formation method.When from the direction shown in Fig. 7 E and angle kidney and renal artery, this image is typical.Importantly, with the angle 4607 in Fig. 7 E, on ultrasonic path, there is no rib and on this path, there is no other important structure yet.

Then carry out ultra sonic imaging test to detect obtainable window, to the ultrasonic rear area from patient for the treatment of is delivered to renal artery 4630 regions.It is found that, in the cross section of ultra sonic imaging ultrasonoscopy (Fig. 7 F) by shown in arrow 4600 and provide the optimum window for visual interested dissection (the kidney base of a fruit) by the window shown in arrow 4605.

Fig. 7 G contains some significant data from test 4700, and these data are in " normal place 4730 ".These data 4720 can be used to determine for the configuration to the clinical HIFU system of the hilus renalis by ultrasonic transmission.It is on average 7-17cm that renal artery 4635 is confirmed as apart from patient's skin.Rib abdomen is pointed out that be most appropriate to for imaging arteriorenal to the approach at rear portion, this approach typically passes the essence 4605 of the kidney shown in Fig. 7 F.The hilus renalis 4640 of kidney is approximately 4-8cm and approach 4637 apart from ultrasonic transducer and relatively spends by connecting two spinous process and being approximately-10 to-48 perpendicular to the angle (4607, Fig. 7 E) of the defined axle of line of spinal column.Should also be noted that through the rib abdomen approach of kidney be safest approach, because it has represented, other organ (for example, intestinal) is applied to ultrasonic minimum chance.

Therefore,, with these data, can design the system algorithm being used for the treatment of: b type is ultrasonic is used to make kidney visual in cross section; In the case of by means of doppler ultrasound using renal artery as the anatomical structure of identification, doppler ultrasound is used to identification and leads to the kidney base of a fruit 4640 of kidney; Determine the distance of the kidney base of a fruit via the imaging of b type.In the situation that kidney is positioned at b type image, safety can be achieved, because kidney has been confirmed as the good heat sink and absorber (, HIFU is very little on the impact of kidney) (referring to data in body below) of HIFU; Distance is fed into Processing Algorithm and by the position data feed-in HIFU transducer of HIFU transducer.For example, and little piezoquartz can be positioned (, along) treatment ultrasonic transducer, and can be used for determining the security path between supersonic source and the target vascular therapy of the crystal from ultrasonic transducer.Echo can send to target and can determine time of inverse signal from crystal.For example, with the information about inverse signal (, to the distance of target, return speed), can determine the safety in path.For example, if the inner intestines () with air are positioned on path, inverse signal will depart from desired signal, and then can reorientate transducer.Similarly, for example, if skeleton (, rib) is positioned on the path of ultrasonic beam, desired inverse signal will depart from desired time of return significantly, thereby indicates this path to use.In certain embodiments, treatment supersonic frequency can be reduced to below 1MHz, and this makes energy to reflect minimum in the situation that and to propagate through skeleton at ultrasound wave.For example, can use in certain embodiments the frequency that is low to moderate 100 kilo hertzs, 200 kilo hertzs or 300 kilo hertzs.

In the time of further experiment, find, by patient is located with ventricumbent position (upward, abdominal part is down at back), the structure 4750 that study, renal artery 4770 and 4780, the hilus renalis be even closer to skin, and the respiratory movement of tremulous pulse and kidney significantly reduces.Fig. 7 H shows these results 4750,4760, show renal artery 4770 at 6-10cm place and the angle of approach 4790 relative spinal columns 4607 more shallow, be-5 to-20 degree.In the situation that keeping flat sleeping and use chock or projection that they are supported, patient obtained similar result below shank.

Therefore,, with these clinical datas, in one embodiment, designed one and be used for the treatment of 4800(Fig. 7 I) method of patient's kidney nerve: the rib 4810 and the crista iliaca 4840 that 1) are identified in the patient on patient's left side and right side rib abdomen 4810; 2) with the ultrasonic kidney 4820 of identifying left side and right side; 3) identify the hilus renalis of kidney and the hilus renalis visible scope 4820 in surface along patient with imaging technique; 4) identify from one or more angles the blood vessel that leads to kidney, extract the scope 4860 of visibility along the surf zone at patient back; 5) determine the one or more distance 4850 in renal artery, renal veins, kidney and the hilus renalis; 6) optionally, make patient by location, ventricumbent position 4830, to optimize visibility with the entity positioning equipment under patient back or on patient's abdominal part; 7) optionally, determine required power by simulation, to obtain the therapeutic dose in the hilus renalis and the circumvascular region of kidney; 8) treatment energy is put on to kidney blood vessel; 9) optionally, follow the tracks of angiosomes to guarantee the continuous transferring energy in region to being planned in simulation; 10) optionally, in the case of outside the focus of energy is positioned at planned region, stop energy delivery; 11) optionally, carry out regulating system by the movement for the treatment of and the ultrasonic transducer of imaging, to be orientated ultrosonic applicator (applicator) about blood vessel target; 12) optionally, benchmark is arranged in one or more blood vessel, with the ability that further blood vessel was located and followed the tracks of to raising equipment; 13) the one or more algorithms that are identified for treatment in the distance based on to blood vessel, skin thickness, muscle thickness and kidney thickness (wherein ultrasonic through them); 14) carrying out application time with pulse, to be less than the treatment of 10s ultrasonic, to rise and to apply at least 100W/cm at least 1 second ²; 15) optionally, by becoming the angle (, pointing to head upward) of-5～-25 degree to guide treatment transducer with respect to the line that connects spinous process.

In another kind of embodiment, Fig. 7 J, clinical algorithm 4900 is illustrated, and is determined 4910 in the position of these clinical algorithm 4900 medium vesselses.For example, blood vessel may be adjacent to interested Neural Area (for example, renal artery and nerve, aorta and sympathetic nerve, cerebral arteries and nerve, carotid artery and nerve).A kind of test dose of energy is put on to the threshold value 4920 of patient's sensation.In the situation of kidney nerve, the threshold of feelings can be renal colic type sensation.At this sensory spots 4920, can reduce with cooling this dosage and then can apply other dosage according to the level under just below the threshold of feelings.This sequence 4900 can repeatedly repeat 4940, until obtain desired effect.The shut-in time of discontinuity allows cooling 4930 of this region.In Fig. 7 K, transducer 4950 is shown having diagnosis and two kinds of abilities for the treatment of.Ripple 4960 is diagnosis ripples, and this diagnosis ripple is disturbed by skeleton (rib) in this example.In certain embodiments, the treatment ripple of being launched by this region of transducer is in addition closed and is not produced treatment ripple.

At the opposite side of transducer, ripple 4956 has really allowed the accessible path of kidney blood vessel 4954 and treatment bundle really to be allowed by this region really.Diagnostic energy can be ultrasonic energy, radio-frequency (RF) energy, x ray energy or optical energy.For example, MRI, ultrasonic, CT scan or sound wave flying time technology can be used for determining whether to exist the accessible path of the hilus renalis.

In a word, in a kind of technology, diagnostic test energy is passed through skin and arrives kidney area vasculosa.Then, make the assessment of the visibility to the hilus renalis according to distance and accessible rate (clearance) and based on opening or close treatment transducer from the accessible rate that is routed to the hilus renalis through skin.This technology can continue to carry out or carry out before treatment in whole treatment.For example, can during treatment and processing, follow the tracks of such as the parameter of movement, distance, three-dimensional coordinate etc.

In conjunction with above data, Fig. 7 L shows a kind of for suppressing the neural general-purpose system 4975 round blood vessel.In the first step, generate the image 4964 of blood vessel; Then the length 4966 of vessel scanning; After this step, in three dimensions, determine the direction of blood vessel and blood vessel around edge circumferentially carry out the transmission of hot cloud, wherein hot cloud be generated with coverage distance blood vessel wall at least 5mm's and radially comprise blood vessel wall and at least region more than 5mm of length.This hot cloud is the region of diffusion heat, does not focus on hot spot.Heat from regional diffusion go out and can result from blood vessel within or outside blood vessel.Blood vessel self is by coming thermal convection current and heat abstraction by means of natural blood flow by blood vessel or by add other flow device is protected in blood vessel or near blood vessel.

Hot cloud can be generated by high strength supersonic, radio-frequency (RF) energy and/or optical energy (referring to simulation and data below).For example, can be by infrared energy transmission through blood vessel wall to heat circumvascular region.Heats can detect by MRI thermometric, infrared measurement of temperature, laser temperature-measuring etc.Infrared light can apply individually or in conjunction with photosensitiveness therapeutic agent.

In certain embodiments, do not generate hot cloud and still can be provided for the neural cloud in inhibition or ablation areas.This cloud can be gas (for example, carbon dioxide), liquid (hot water), photosensitiveness therapeutic agent, and gas toxin, for example ethanol, phenol and neurotoxin.

Compared with the heat of high order focusing being delivered to the conduction of tube wall and dependence blood vessel wall or the equipment of electric current decline, hot cloud or broad sense cloud have provided a option that may be safer: nerve melts composition and is spread in around blood vessel.

Fig. 7 M shows the example 4972 that hot cloud 4974 is delivered to blood vessel from external patient.Blood vessel is arranged in three-dimensional coordinate reference.Blood vessel during treating by targeting.Cloud surrounds the blood vessel and the whole hilus renalis that lead to kidney.

Fig. 7 N shows the neural diagram of leading to kidney.This picture is from the real anatomy of human corpse's blood vessel.As what can see, neural 4982 round the blood vessel that leads to kidney 4984.Hot cloud 4980 is shown as round the nerve 4982 that leads to kidney 4984.Importantly, the limitation of the approach based on conduit is that hot cloud cannot be generated by endovascular position around blood vessel in the past.This hot cloud effectively allow target area during treating by overscanning (overscan).

Figure 70 shows the cross section of the cloud 4984 around nerve 4986 and blood vessel 4988.Can find out, for example, may be difficult to affect most nerve for heat neural focal method (, by focusing on radio-frequency (RF) energy) through blood vessel wall, because nerve is to be so present in dispersedly in region in some cases.Therefore, in this embodiment, heat puts on to diffusibility circumvascular region in the form of cloud.Should " cloud " treat relevant to following described quality factor.For example, quality factor is lower, and cloud just becomes more greatly and more diffusion.When quality factor is 100%(or 1.0) time, cloud is a series of discrete thermal; When quality factor be about 90%(for example, 90% ± 10%) time, cloud is diffused into around blood vessel, as shown in Fig. 7 O.This hot cloud is most appropriate to treatment and defines so not good nerve 4986 regions, shown in Fig. 7 O.Therefore in one embodiment, quality factor can be confirmed as 70～90%(HIFU relative percentage of time outside target area within target area) any value.Within this quality factor scope, put relative hot cloud with individuality and be created in blood vessel around and neurological region.In other embodiments, quality factor can be about 50%(for example, 50% ± 10%), in other more embodiment, quality factor can be any value of 50%～90%.

Fig. 7 P shows the analog result 4990 with focus supersonic, blood vessel (for example, renal artery) being heated during movement for simulation.Simulation puts on that intra-arterial generates or that outside patient body, generate ultrasonic, and importantly, has considered the movement within 1mm4991 around proposed treatment region.Fig. 7 Q shows the proposed treatment normal form of having considered motion; In this case, consider closed loop mechanism mobile and pursuit movement and guiding ultrasonic beam by being used to, motion has reduced to 0mm4992.To describe in detail below for mechanism and equipment that motion is taken into account.

As what can see in simulation, motion is defined as in random direction from 1mm to close to 0mm, this has increased power and temperature within tissue 4994.Therefore, in one embodiment, the system with multiple transducers is used to treat circumvascular region, has wherein considered treatment plan and moving parameter is incorporated in treatment.In certain embodiments, 1mm is the movement setting.In other embodiments, 2mm is the movement setting.These move is that size is 1 or 1 or the 2mm in random direction of 2mm.In certain embodiments, directly follow the tracks of movement with ultrasonic, mechanical pick-up device, accelerometer, catheter in blood vessel or miscellaneous equipment.In one embodiment, providing wherein motion to obtain the treatment of following the tracks of, and when movement degree is while being high, the dosage of extended treatment or time.When movement degree is while being low, reduce dosage.These adjustment can also be carried out in real time in whole treatment.

Fig. 8 A shows percutaneous operation and equipment 5010, and the region in this operation around renal artery is directly approached through skin by external position.The combination that imaging and energy apply (for example, melting) can be performed to melt renal artery region around, is used for the treatment of hypertension, end stagerenaldisease, diabetes, sleep apnea and/or heart failure.Probe 5010 is positioned through skin and approaches kidney 5030.Probe endways 5020 places can comprise the sensor for detection of heat or temperature, or can make to treat energy delivery and can increase.One or more imaging devices (for example, CT equipment, ultrasonic device, MRI equipment) can be used to guarantee clog-free path, so that probe arrives hilus renalis region.These equipment can be used to detect the temperature of zone of ablation, and by simulation, the feedback that melts quality about renal artery district are offered to operator.Can use probe 5010 by ablative, ionizing energy, heat or light puts on this region to suppress renal artery sympathetic nerve around.Can be by ultrasonic, radio frequency, microwave, direct heating element heater and there is thermal source or the sacculus of energy source puts on sympathetic nerve district.Imaging can be contained in probe above or carry out individually when probe is put on to kidney area vasculosa.

In one embodiment, the operation of percutaneous in Fig. 8 A is carried out under MRI, CT or ultrasonic guiding, for obtaining location or the information about applied degree of heat.In one embodiment, ultrasonic being applied in, but be the dosage with sub-ablative.Namely, this energy level is enough for destroying or inhibition nerve, but temperature is to make nerve not by energy ablation but the temperature of paralysis or part inhibition.Particularly preferred embodiment performs the operation under the guiding of MRI scanner unit, because just heated region can be determined anatomically in real time via temperature map equally.As mentioned above, the image after heating can compare from those images of baseline and signal progressive comparison at different temperature.

In one embodiment, the selective area of kidney melts by percutaneous route of entry; For example, secrete to patient or the region to kidney or the harmful hormone of other organ.Use patient body provide through skin and the energy that applies from different angles outward targeting arbitrarily within kidney or on or along the region of kidney nerve or in the ability in the region of adrenal gland, aorta or sympathetic chain.This treat target area quantitative compared with large range by conjunction with outside imaging with become possibility from multiple angles through patient's skin the internal delivery that arrives the energy of target.Renal artery can be located in the arteriorenal aortal branch (takeoff) of drawing by targeting, synapse place in them in ganglia coeliaca, or in them along arteriorenal bifurcation point.

In another embodiment, probe 5010 can be used to temperature or the motion of surveyed area when ultrasonic transducer just applies energy to region.Motion sensor, position beacon or accelerometer can be used to provide feedback to HIFU transducer.In addition, optional temperature or formation method can be arranged on probe 5010.Probe 5010 can also be used to be positioned at the position in peritoneoscope region, melts to carry out.The dosage being transmitted by this probe is approximately uniform with the dosage transmitting by the equipment being arranged in outside patient body.

In Fig. 8 B, show energy from putting on equipment 5050,5055 in the blood vessel in renal artery 5065 region around in renal artery.Endovascular equipment can be used to radio frequency, electricity radiation and/or ultrasonic (focusing or unfocused) energy to put on renal artery or peripheral region.In the time that endovascular conduit is in place, can also determine the region of just heating by MRI or ultrasonic temperature measurement or direct temperature measurement.

In one embodiment, equipment 5050,5055(Fig. 8 B) not by heating, but mechanically, for example, stream in periodically pressure variation, radiation pressure, resisting medium or flow and the pressure (be restricted to the formation of hole in fluid media (medium)) relevant to coelosis applies the ultrasonic energy that suppresses function of nervous system.Enough these energy that optionally made an addition to of heat energy, instead of generation is melted neural temperature, the mechanism of promotion vibration and pressure thus.In such an embodiment, be not ultrasonicly focused, but from source to external radiation, substantially to produce the columnar ultrasound ripple crossing with blood vessel wall.The ultrasonic of this shape can produce the circumferential zone of ablation 5065 shown in Fig. 8 B.In work below, show, circumferential zone of ablation causes sympathetic nerve fully to reduce the effect of kidney.Boundary material between ultrasonic transducer and arterial wall can be provided, and makes ultrasonic effectively conversion through arterial wall, to reach tremulous pulse neurological region around.In another kind of embodiment, ultrasonicly directly enter blood and propagate through ultrasonic wall to affect the nerves.In certain embodiments, cooling being provided in around ultrasound catheter, the inside of this protection blood vessel, arrives the region outside renal artery but make ultrasonic penetration cross tube wall.This is ultrasonic can be that focus on or unfocused.For example, in certain embodiments, ultrasonic can not be HIFU, but unfocused low intensity ultrasound.Antihunt means for ultrasonic probe are also contained in this operation.Antihunt means can comprise stablizes the part adding to probe, and can comprise ultrasonic range finding element assembly, makes operator know where ultrasonic energy just puts on outside blood vessel wall.10W/cm for the neural energy range that effectively melts or suppress ²～500W/cm ².In certain embodiments, by ultrasonic this circumferential with neural drug conveying has been carried out to combination through blood vessel wall.

In another kind of embodiment, ultrasonic probe is applied directly to blood vessel wall, suppresses circumvascular nerve with heat and/or vibration.In this embodiment, the temperature at blood vessel wall place can directly be measured at catheter tip by laser temperature-measuring or critesistor.As selection, during ultrasonic applying, can also use MRI or infrared measurement of temperature.Similarly, ultrasonic can with for medicine being put on to blood vessel wall or combining use through the drug conveying of blood vessel wall.

In the present embodiment, imaging can be carried out in outside or in inside, within wherein conduit is arranged in renal artery.For example, can be used to make to change visual at the ultrasonic conditioning period to nerve tract with MRI or the ultrasonic outside imaging of carrying out.Really, these formation methods can be used to apply the energy of any type in arterial wall.The radio frequency transmission of for example, passing the energy of renal artery wall can be monitored by similar technology.Thereby the monitoring of successful surgery degree to this technology is independent of this technology in most cases.In one approach, radiofrequency catheter is put on to the temperature of blood vessel wall and measurement blood vessel peripheral region.In another kind of embodiment, the steam of heating is put on to angiosomes.In another kind of embodiment, the heating that the MRI of the conduit of metallicity end inducts detects with MRI thermometric.In another kind of embodiment, focus supersonic detects with MRI thermometric.MRI can be used to detect heat extraction variation in addition.For example, MRI can be used to detect edema to be changed, or nerve during treating is loosened.

As selection, in another, in embodiment, the energy (for example, ultrasonic) that equipment 5050,5055 can be used to outside to apply is directed to tremulous pulse accurate location around, transfers energy to this region as HIFU transducer.For example, endovascular probe 5050 can be used as the homing beacon (homing beacon) for transmit imaging/treatment technology of HIFU from outside.

Fig. 8 C shows for suppressing the orthosympathetic percutaneous operation of kidney.Probe 5010 is used to approach the hilus renalis 5060 regions from rear and renal artery 5065.With given below data, probe can be equipped with FIFU for making this region denervation.Given data have been indicated the feasibility of this method below, make the blood vessel can be fast and denervation easily until ultrasonic.In another kind of embodiment, thermal energy cloud (Fig. 7 O) for example, result near blood vessel with the gas that for example heated up, neurotoxin, gas (, titanium dioxide, known its is can paralysis under high concentration neural) etc. or around.

At Fig. 8 D, a kind of technology is shown, wherein ultrasonicly transmitted through blood vessel wall 5560 from conduit 5140 by piezoquartz 5120 at one end.Detector 5160 is arranged in outside patient's skin 5112, for detection of the signal of being launched by piezoelectrics.Many parameters 5170 can both in this way be determined/detect, and comprise position, temperature, acoustic power, radiation pressure and coelosis threshold value.Detection can or be carried out (in other embodiments) in catheter interior (in certain embodiments) on skin.For example, in one embodiment, hyperacoustic flight time of piezoelectric transducer of the one end by detecting comfortable conduit of the acoustic impedance from blood vessel to skin is determined.In another kind of embodiment, may stop that ultrasonic being passed transmits a signal to the structure that the mode of external detector detects and formed interior detectors.In another kind of embodiment, combination is transmitted in the outside of endovascular piezoelectrics and vibrational energy, to cause damage or to suppress circumvascular nerve.

Fig. 8 G shows the Proof of Concept for being arranged in inner ultrasonic beacon 5340.Fluoroscopic image 5300 is illustrated, and during the experimental verification of following the tracks of at beacon, conduit is in place.Show, beacon 5340 can be interior placed in the middle at blood vessel 5310, and this allows the symmetry treatment to blood vessel.Calibration is performed, to optimize the placed in the middle of beacon.Relatively the seal wire 5320 of rigidity is arranged through the end of beacon and this seal wire and is arranged in the blood vessel in kidney.In the situation that seal wire is fastened in internal blood vessel, beacon can be relatively stable ground and this beacon in angiocentric situation, move along seal wire.Beacon transmits by conduit 5315.Detector 5350 can detect with 50 times (50Hz) per second above repetition rate the position of beacon 5340, and precision reaches in 500 microns.Therefore, in certain embodiments, a kind of Therapeutic Method comprises: to fasten in the blood vessel in kidney and the other end enters aorta and the mode outside patient body of reaching is arranged in the seal wire of rigidity substantially in blood vessel in one end; The conduit with ultrasonic probe is led on seal wire and lead in the endovascular position of leading to kidney; Apply signal for activating the piezoquartz of ultrasonic probe; With piezoelectric detector or other ultrasonic detector array detection by the piezoelectric signal that probe was generated outside patient body; And will detect in input information algorithm, this algorithm allows to determine that ultrasonic probe is in position endovascular and in patient body.Subsequently, that focus on, relative focusing or unfocused energy can be put on to beacon region around.Again, importantly make beacon placed in the middle to allow the best (symmetry) targeting of blood vessel in blood vessel.Any embodiment of the technology providing at this can be used to make ultrasonic beacon placed in the middle.

Fig. 8 H shows endovascular and the resolution 5345 of the beacon of (Fig. 8 I) detected with transducer outside patient body 5350.In certain embodiments, resolution 5345 is 50～100 microns.Importantly, beacon is shown in blood vessel, is positioned at the center of blood vessel.One method is developed, and beacon is positioned at blood vessel center in the method, and this is important for the symmetry treatment in blood vessel outside.By seal wire is arranged by the center of beacon (the beacon part of conduit), seal wire makes within beacon is stable at blood vessel by fixing its near-end and far-end.In tremulous pulse in the wedged kidney of far-end, near-end fixes by entering aortal curve, and most proximal end is connected to the conduit hinge at operator place.These fixing points maintain conduit to put in place, and this is important to maintain treatment during treating to maintain the degree of accuracy that benchmark couples and treat between energy system.

Fig. 8 E and 8F show cross section 5200 images of abdominal part.Energy wave 5230 is shown as from rear through skin and leads to blood vessel 5210 regions of leading to kidney.Equipment 5240 can be arranged in outside patient body, and on patient's skin, ripple 5230 is transferred to circumvascular Neural Area by this equipment 5240.At the intra-operative for helping guide wave, can use CT or MRI imaging.In addition, or conduct selection, thermal imaging (for example,, with infrared light or laser) can be used.

In another kind of embodiment, the physiological process of arteriectasia (aneurysm) is by targeting.In Fig. 9 A, ultrasonic transducer 6005 is arranged near the outer wall of aneurysm 6030.Ultrasonic energy 6015 is applied in aneurysmal tumor wall 6030, to thicken tumor wall and to prevent that aneurysm from further expanding.In certain embodiments, the grumeleuse in aneurysm is equally by targeting, thereby smashes or dissolve this grumeleuse with ultrasonic energy.Once aneurysmal tumor wall is heated to the temperature of 40～70 degree by ultrasonic energy, collagen protein, elastin laminin and other extracellular matrix in tumor wall will harden in the time that it is cooling, thereby prevents that tumor wall from further expanding.

In another kind of embodiment, within material is arranged in aneurysmal sack and with focus supersonic or not focus supersonic make hardened material or lure that in addition the material in capsule clings the grumeleuse in aorta or aneurysm into, thereby and closure of aneurysms permanently.Therefore, in one embodiment, ultrasound catheter is arranged in aorta, is positioned at aneurysm wall region or the material close to aneurysm wall.Material can be the artificial material of being arranged by operator, or it can be the material (for example, thrombosis) being innately in aneurysm.Ultrasonic tumor wall or the material of being applied in, causes tumor wall or hardened material, strengthens aneurysm wall and prevents expansion.Energy can also be applied by the position from patient body or the energy delivery of locating by percutaneous conduit.

Fig. 9 b 6000 shows for example, grumeleuse prevention apparatus 6012(vena cava filter in blood vessel (, aorta or caval vein) 6010).Ultrasound catheter 6005 is applied in grumeleuse prevention apparatus (filter) 6012 to remove grumeleuse in slave unit or make equipment 6012 depart from blood vessel wall for equipment 6012 is removed from blood vessel 6000.

Fig. 9 C shows a kind of equipment and method, in the method from the heat energy of the ultrasonic energy 6005 vibrational energy melts or part heating near the solar plexus 6020 of aorta 6000, this ultrasonic energy 6005 can be to focus on or unfocused mode apply and focus on or unfocused ultrasound wave 6007 according to the frequency of 20kHZ～5MHz and with the energy more than from 1mW to 100kW.Solar plexus 6020 melt wholly or in part can via to kidney nerve is applied to the similar mechanism of ultrasonic energy and causes Blood pressure drop; Ablation catheter is focus supersonic conduit, but can be also that directly (not focusing) is ultrasonic, microwave transducer or stratie.Energy can also be from external position transmission through skin to aorta or solar plexus region.

Figure 10 shows for the method 6100 with high strength or low intensive focus supersonic (HIFU or LIFU) 6260 treatment patients.In the first step, CT and/or MRI scanning and/or thermal imaging and/or ultrasonic (1D, 2D, 3D) are performed 6110.Benchmark patient 6120 with it or in body or other labelling be optionally used for labelling and follow the tracks of 6140 patients.Benchmark can be can use CT/MRI/ ultrasonic device 6110 to its carry out imaging implanted benchmark, be arranged in patient body or patient's provisional benchmark with it, or benchmark (such as skeleton, blood vessel, arterial wall, speckle, Doppler signal etc.) in patient body.Benchmark can also be provisional benchmark, for example, be arranged in the conduit that patient's tremulous pulse or intravenous conduit or percutaneous are inserted temporarily.Plan step 6130 for HIFU treatment is performed, and position and the such baseline reading of temperature such as organ in this plan step 6130 are determined; Then HIFU treatment is planned, and use a model (for example, finite element model) predicts the pressure from the heat transmission of ultrasonic transducer 6130 or heat transmission.Plan step is incorporated to from the information of the tissue of imaging device 6110 or the position of target and allows dissection to be arranged in three-dimensional coordinate reference, and making to simulate 6130 can be carried out.

Plan step 6130 comprises the location of determining ultrasonic transducer, and the position of focus in patient.X, Y, Z, and nearly three angular coordinates are used to determine based on cross section imaging 6110 position of the ultrasound focus in patient body.HIFU transducer can have their built-in position sensor, thereby can assess the position with respect to target.As selection, HIFU transducer can be fixed on workbench rigidly, and wherein patient has a rest on this workbench, thereby can obtain easily the coordinate with respect to workbench and patient.In plan step 6130, also simulate heat flow, thus can be with the ultrasonic temperature of planning and predicting ad-hoc location.For example, arrive be modeled as this pressure wave penetrate tissue from the pressure wave of transducer in target.In most of the cases, tissue can be treated as the water having by the minimum loss due to interface.Analog data prediction is so really.Hyperacoustic relative power and phase place at target place can be coupled and be determined by the position between probe and target.The heat that convective heat transfer condition is added to simulate by due to blood flow is transmitted, particularly in arteriosomes.Conductive heat transfer condition is simulated equally in the equation (equation) of heat flow and temperature.

The other variable of considering in plan step is size and the site error thereof of damage.For example, in zonule in the melting of (, at circumvascular nerve), the temperature in region may need to increase to the temperature of 60～90 degrees Celsius with the nerve in ablation areas permanently.The temperature of 40～60 degree can temporarily suppress or block the nerve in these regions, and these temperature can be used to determine whether patient will be in response to specific treatment in the situation that permanently not melting Neural Area.Subsequently, can apply other treatment after a while to complete this work or may again suppress Neural Area.In certain embodiments, temperature only increases the several years or basic does not increase, and multiple pulse is passed, contrary with heating or hit nerve sheath and neuron soma by the fast-pulse of vibrational energy except heating.For example, can be 1W/cm in the power density at nerve place ²or 100W/cm ².The pulse of vibrational energy can be 0.1 per second, 1 is per second, 50 per second, 100 per second, 1000 frequencies per second, higher, or lower frequency.In certain embodiments, power can be low to moderate 100mw/cm ²or 50mw/cm ².Pulse train can reach 30 seconds, 60 seconds, 2～30 minutes, or middle any size.

In certain embodiments, endovascular temperature is measured and remain on the temperature that is less than 60 degrees Celsius or is less than 70 degrees Celsius, can stop in this case operation (for example,, in the time reaching desired temperature).

During the treatment of planning, also carry out error analysis in Figure 10.Each key element of temperature and position contains the error variance of propagating by the equation (equation) for the treatment of.Error simulated to obtain the virtual representation of the temperature that is mapped to position.This mapping is to relevant in the position of the ultrasonic transducer in the treatment of area-of-interest.

During the transmission for the treatment of 6260, patient can move, and benchmark 6120 is followed the tracks of this and moved and reanalyse the position of 6150 treatment regions in this case, and restarts this treatment or mechanically or electrically transducer is moved to new focal position.Therefore, in the present embodiment, the treatment automatically position based on target is moved ultrasound focus with phased array or mechanical motion system.If movement is greatly and outside target area, system closing, and reorientate patient.

In another kind of embodiment, cross section imaging technique is in conjunction with being used to produce pattern of fusion image such as ultrasonic such method.Cross section imaging is used to produce the 3-D data set of dissecting.Ultrasonic, two dimensional image is provided, connect with the three-dimensional imaging being provided by cross section machine by the benchmark coupling between ultrasonic and MRI.Because body part moves in ultrasonic field, thereby corresponding data are determined (being coupled to) cross section (for example, MRI image) and watch platform can be illustrated in the concentrated movement of three-dimensional data.Ultrasonicly real-time image is provided and has shown determined position in ultrasonic three-dimensional space with the coupling of MRI or other cross-sectional image.

Figure 11 shows the treatment 7410 of the another kind of disease in patient body, is the head patient specifically.Under dura mater and epidural hematoma because the angiorrbagia in die or the peridural space of brain, spinal column and scalp occurs.Figure 11 shows CT or MRI scanner unit 7300 and patient wherein 7400.Scan to obtain the image of brain 700 with CT or MRI.Image is used to treatment region 7100 to be coupled to the supersonic array for heating this region.In a kind of embodiment 7100, acute or chronic subdural hematoma are treated.In another kind of embodiment 7200, epidural hematoma is treated.In these two kinds of embodiment, the blood capillary of leakage and the region of blood vessel are heated bleeds to stop, or in the situation that chronic meninges hematochezia is swollen, stops the oozing out of blood capillary of inflammation.

Regulating in a kind of exemplary embodiment of physiological process, select to have under dura mater or the patient 7400 of epidural hematoma treats and obtain CT scan or the MRI 7300 for the treatment of region.Then produce the chronic district of 7010 hematoma under treatment plan and targeting epidural 7200 or dura mater to treat by focus supersonic 7100 transducer technology.Then interested target is arranged in the coordinate reference system at ultrasonic transducer place.Once together with target is coupled to ultrasonic transducer, just guarantee to treat 7100.Focus supersonic adds heat hematoma region, causes body fluid to accumulate on the leakage of brain 7420 blood capillary around to dissolve grumeleuse and/or prevention.This technology can be used for replacing boring (burr hole) or being added on boring, and this boring is to be arranged through scalp to evacuate the hole of this body fluid.

Figure 12 show renal artery district based on laparoscopically approach 8000, the sympathetic nerve 8210 in this renal artery district can be by ligation, be interrupted or be conditioned in addition.In laparoscopy, patient's abdominal part is introduced into the abdominal part of being blown by air blowing and laparoscopic instrument.Retroperitoneum can enter easily through the approach of rib abdomen or (taking second place) and pass through abdomen (peritoneum) approach.The laparoscopic instrument 8200 with end 8220 far away can put on the energy of heat energy or another kind of form in the region of sympathetic nerve 8210 or conduct drugs to the region of sympathetic nerve 8210.Laparoscopic instrument can also be used for melting or change the region of solar plexus 8300 and neuroganglion around.The radio frequency transducer that peritoneoscope can have attached ultrasonic transducer 8220, the temperature probe attaching, the microwave transducer attaching or attach.Peritoneoscope can be used to directly melt or hit dizzy circumvascular nerve (for example,, with lower frequency/energy) or can be used to melt or hit the dizzy neuroganglion passing through with vascular aid.For the percutaneous approach of kidney nerve, the same with the extrinsic pathways to kidney nerve, can use simulation and the imaging of similar type.In the case of having found that by zoopery (vide infra) the large-area neural single ultrasonic probe suppressing in the hard to bear single direction of energy affects (referring to above), Neural Area not necessarily will directly contact with probe, on the contrary can be along Neural Area and the ultrasonic general direction of transmitting guide probe.For example, probe can be arranged in a side of blood vessel and be activated for the ultrasonic transmission of focusing or semi-focusing to be greater than on the general region of tremulous pulse of 1cm to may not containing longitudinal length, but its effect is enough to suppress relevant function of nervous system completely.Ultrasonic can transmission through tremulous pulse from a side of tremulous pulse.This will illustrate below and describe, wherein by by ultrasonic two walls that through blood vessel, ultrasound focus are delivered to tremulous pulse from a direction transmission simultaneously.

Figure 13 shows with the algorithm 8400 for the treatment of interested region at a distance from the energy importing.MRI and/or CT can be used to demarcate interested region (for example, zone of ablation) in the situation that being with or without preparation 8410, and then can use above any method to melt 8420 in the execution around of the region of reagent place's mark.This algorithm is to can be applicable to any Therapeutic Method described above, comprise outside HIFU, laparoscopic instrument, catheter in blood vessel, percutaneous catheter and instrument, and any area for treatment, comprise kidney nerve, eye, kidney, tremulous pulse or any other nerve around peripheral tremulous pulse or vein.Can use in real time with CT, MRI, the imaging 8430 that ultrasonic or PET carries out, thus visual region of being melted.The destruction of damage is completed, can again carry out the imaging of for example, for example, carrying out with imaging (, molecular imaging agent or contrast agent, gadolinium) reagent 8410 at 8440 o'clock.Can also monitor the scope melting by temperature or the outward appearance of monitoring zone of ablation under formation method.Once damage is done 8440, operation has just completed.In certain embodiments, ultrasonic diagnosis technology (for example, elastogram) is used to determine the heating to region or the progress melting.

Figure 14 illustrates wherein and carrys out melting of the neurophilic specific nerve fiber of target by different thermogrades, power gradient or temperature 8500.For example, for example, if temperature by MRI thermometric or with another kind of technology (, ultrasonic temperature measurement, infrared measurement of temperature or thermocouple) determine, can make temperature be held in such temperature, at this temperature, only have some nerve fiber temperature by targeting for destroy or suppress.For example, with such technology, can targeting C fiber, or can targeting A fiber.C fiber be without marrow and in response to the nervus centripetalis communication from kidney to central nervous system, and can be the main nerve of being responsible for reducing blood pressure.These neural making it possible to more accurate of targeting especially, and may safer treatment put on kidney nerve.As selection, partly or entirely nerve can temporarily be disconnected, for then testing the neural downstream effect of disconnection.For example, the sympathetic nerve around renal artery can for example, disconnect and then can determine this effect with a small amount of heat energy or other energy (, vibrational energy).For example, can identify the noradrenaline levels in health blood, kidney or renal veins; As selection, can stop testing neural stimulating effect (for example,, cardiomotility fixed in response to dermoreaction, the unstable blood pressure of kidney nerve stimulation, lung activity, renal artery constriction) activity provisional.For example, in one embodiment, monitoring is intranueral sympathetic activity in periphery; Sympathetic activity typically shows as the spiking in nervus peripheralis electrographic recording.The quantity of spiking is relevant to the degree of sympathetic activity or over-activity.For example, in the time that activity is reduced (, by arteriorenal denervation), the density (concentration) of the spiking in peripheral nerve chain is lowered, and indicates sympathetic nerve or autonomic successfully treatment.The change frequency of vibration can be used to suppress specific nerve fiber, with respect to other nerve fiber.For example, in certain embodiments, efferent nerve fiber is suppressed, and in other embodiments, afferent nerve fiber is suppressed.In certain embodiments, the nerve fiber of two types all temporarily or is permanently suppressed.In certain embodiments, optionally block C fiber 8520 with the low heat energy level of the heat energy level than A nerve fiber.In other embodiments, B fiber is optionally treated or is blocked, and in certain embodiments, A fiber 8530 is preferentially blocked.In certain embodiments, suppress whole fibers by cutting off neural mode with ultrasonic 8510 of high dose.Based on experiment described above, can be about 100～800W/cm for the power density that realizes blocking-up completely ², or be about 500～2500W/cm for some nerve ².In certain embodiments, pulse train is 100 or multiple-pulse more, and each pulse persistance 1～2 second (for example) and transmitted power are about 50w/cm ²～500w/cm ².Really, existing document shows, for or be about 100w/cm ²energy be suitable for destroying or at least suppressing (the Lele of function of nervous system, PP.Effects of Focused Ultrasound Radiation on Peripheral Nerve, with Observations on Local Heating.Experimental Neurology 8,47-83 1963).Based on the data that obtain in Proof of Concept, owing to wherein existing by trunk, the characteristic in the region of a large amount of perfusions by renal veins, tremulous pulse, caval vein etc., rising to correct power is desirable in certain embodiments.Simulation points out, with make temperature in the time raising within several seconds compared with, the slow increase that power rises allows blood vessel to remove more substantial heat energy.Therefore, the more fast rise of the power to target area is desirable for heating near the structure of tremulous pulse.

Figure 15 a shows the treatment 8600 of vertebral body or intervertebral disc 8610, in this treatment 8600, with energy 8625 ripples come targeting within spinal column 8,630 8640 or around nerve.In one embodiment, the nerve around facet joint is by targeting.In another kind of embodiment, lead to the nerve of intervertebral disc or terminal plate of vertebral body by targeting.In another kind of embodiment, self carry out the nerve in this vertebra of targeting by heating vertebra 8630.Sensory nerve by the canalis spinalis 8635 in vertebra 8630 and can by heating vertebra 8630 suppress or melt.In a kind of Therapeutic Method, the position of focus supersonic from patient body applies and energy is drawn towards vertebra; This vertebra is heated by focus supersonic and nerve in this vertebra is damaged or benumbed by the heating in vertebra.In the case for the treatment of vertebral fracture in response to the pain of vertebral fracture for eliminating, the method can be used for the vertebra that hardens equally.

Figure 15 B shows the feature in the region of facet joint.Can suppress to relate to the nerve of back pain to the focus supersonic in this region, these nerves originate from Dorsal root nerve and lead to facet joint 8645.Melting or suppressing can limit or even treat the back pain by due to facet joint disease these nerves.Can the position from patient body focus supersonic be put on to the region of facet joint, for this facet joint, nerve is used to 100W/cm ²～2500W/cm ²power continue to reach the time of 1 second to 10 minutes.

Figure 16 A shows one group of type of impairment, size and dissection 8710a-f of causing the denervation of the different piece of the sympathetic nerve tree around renal artery.For example, damage can be annular, cigar-shaped, linear, annular and/or spherical; Damage can be arranged in around renal artery 8705, within kidney 8710, and/or around aorta 8700.For example, renal artery tree comprises a part, renal artery 8705 and the kidney 8715 of aorta 8700.Damage 8714 and 8716 is the dissimilar damages that produce around the vascular tree of aorta 8700 and kidney.Damage 8712 and 8718 is applied in from leading to the arteriorenal utmost point branch road (pole branch) of kidney and being suppressed at the nerve that the branch road of main renal artery works.These damages can also apply the position from patient body.Can damage be arranged to spiral type 8707 along the length of tremulous pulse equally.These damages can be with utilizing complete noninvasive approach produce from the outside energy coming that transmits of blood vessel, ultrasonicly in this approach is applied in through skin to area vasculosa or energy can transmit via percutaneous approach.Each transmission method can both be by above completing to entering approach after blood vessel of finding or describe.

Therefore, in one approach, ultrasonic energy can be by putting on by the heat energy of circular pattern and the ultrasonic mode that puts on blood vessel the blood vessel that leads to kidney.Energy is passed through skin (in one embodiment) or through tremulous pulse (in another kind of embodiment).As described below, ultrasonic by transmitting at a distance and being innately easier to apply with circular pattern, because it not only depends on conduction.

In the past, do not know not find that whether the annular as shown in Figure 16 a damaged enough to block the function of nervous system of circumvascular autonomic nerve yet.The application's applicant finds, melting of annular 8710 not only blocked function but also really blocked completely in renal artery and circumrenal function of nervous system, even and if the damage of tremulous pulse and vein self is had to also very little (Figure 16 C).In these experiments, focus supersonic is used to block nerves; Be 200～2500W/cm by level ²ultrasonicly (namely, only had a side of blood vessel) by top transmission through blood vessel with around blood vessel.Energy transmission is through mobile blood, to affect the offside of blood vessel.Simulation is shown in Figure 16 B and 16D and is below being described.Be used for determining that the noradrenaline levels in kidney 8780 of the neural degree suppressing is determined before energy applies and afterwards.Noradrenaline levels is lower, and nerve suppressed or that be affected is just more.In performed these experiment, noradrenaline levels and the high-caliber control of maintenance (same animal, relative kidney) 8784 is compared and is approached 0 8782.In fact, level is equal to or less than the blood vessel (peeling operation comprises performing the operation and directly denervates and apply phenol in blood vessel wall) that operation is peelled off.Importantly will point out, the tube wall of renal artery and vein keeps being without prejudice substantially; This is likely because artery blood flow has fast been removed from the fact of the heat of blood vessel wall and main renal artery because its large scale, high blood flow and thick tube wall are rich in the elastic fact; These find that the simulation of carrying out with shown in Figure 16 B and 16D is consistent.Generally speaking, ultrasonic (focusing with relative unfocused) be applied in a side of renal artery and Venous complex body.The neural labelling suppressing, the noradrenaline levels in kidney, be determined to be in to nerve from the applying of single direction, transmission of power through arterial wall to arrive after tremulous pulse circumference nerve around close to zero.Level is that zero norepinephrine 8782 is indicated substantially melting completely of function of nervous system, the damage that proves that in fact annular has produced as shown in Figure 16 A and simulated as Figure 16 B and 16D.Histology's result has confirmed the circular nature of the damage of being predicted as the simulation in Figure 16 B and limited consequential injury equally.

Therefore, in one embodiment, the position outside driven feeling pulse according to for around tremulous pulse, cause from start to finish annular or the heating at semi-circular edge apply ultrasonic in the mode that suppresses, melts or part melts autonomic nerve.The tube wall of tremulous pulse or blood flow can be used to make ultrasonic targeting nerve, if this nerve is not by directly visual visual by using a model, connect adnerval position with the position based on blood vessel.

Figure 16 B also supports physics described herein and physiology, shows physics described above and zooperal theoretical modeling 8750.Namely, focus supersonic in computer simulation 8750 by target vascular therapy.Renal artery 8755 is shown in the thermal treatment zone of focus supersonic place generation.Shown in the figure go out be at <1s 8760 with in the temperature of about 5s 8765 and longer time >10s 8767.Equally also show and flow to 8770.Larger ellipse represents higher temperature, central temperature >100 DEG C.Ultrasonic field is transmitted through tremulous pulse 8755, heat via temperature map 8765 shown in renal artery around accumulation.Importantly, this theoretical modeling has also disclosed ultrasonic current through tremulous pulse or blood vessel 8767 and affect the ability of two walls of blood vessel.These data are consistent with zoopery described above, produce unified physics and experimental data collection.In some cases, ultrasonic energy can be put on to blood vessel rapidly, to avoid heat to be removed by blood flow.In the situation that circumvascular ultrasonic rising is not applied rapidly, reach the heat that wherein applied and equal the steady statue of the heat dissipating, and may become the edge that is difficult to heat blood vessel.

Figure 16 C shows the result of experimental focused ultrasound therapy, and in this treatment, kidney is treated and another kidney is used as controlling with ultrasonic.Norepinephrine 8780 is that labelling and its concentration of the effect of sympathetic nerve inhibition is measured in the cortex of kidney.Experimental result 8782 is very low compared with 8784 levels of control, and instruction almost suppresses completely to the nerve that leads to kidney.The circumference effect of heat energy be provided for obtain this to leading to the remarkable effect of noradrenaline levels of kidney.

Figure 16 D is the diagram that multiple beams is put on to the simulation in the region of blood vessel wall.Ultrasonic can be scanned towards blood vessel or be positioned in addition point by point within treatment region.In one embodiment, be passed and make temperature and rise on 60 degree in 2s or in 5s or in 10s to the power of blood vessel.Subsequently, energy is closed and then after the time of 1,2,5 or 10 second, again applies.In certain embodiments, energy can be opened and continue the duration of one section of regulation, for example 1,2,5,10 second etc.In certain embodiments, be used to determine such as the technology of infrared therapeutic or laser-Doppler thermal imaging when skin and hypodermic temperature are safe to determine the energy delivery of additional dose to target area.This therapeutic scheme has produced the hot cloud of the inside that is centered at blood vessel wall.In other embodiments, energy can be opened and continue 30,60 or 90 seconds, but the power of shorter 1,2,5,10 seconds opening times of power ratio is low.

Similarly, other blood vessel that leads to other organ that relies on sympathetic nerve, parasympathetic nervous and general autonomic nerve domination can be treated by this technology equally.With reference to Fig. 5 C, lead to a 2105(carotid artery), the blood vessel of oral cavity (facial artery) and salivary gland 2107, heart 2109, bronchus 2110, stomach 2112, gallbladder 2114 and liver 2118, bladder 2114, adrenal gland 2116, pancreas can stimulate or suppress by the technology that this focus energy transmits target vascular therapy.In a kind of example, the pancreas of under-activity is treated by denervation, and this has caused the carbohydrate tolerance improving.In another kind of embodiment, liver carrys out denervation by what melted at periportal tremulous pulse or the Hepatic artery that leads to liver.Any above organ can with carry out denervation with reference to leading to technology like the described technology type of blood vessel of kidney.

Figure 16 D-H shows with for example another kind simulation of the multiple treatment that (up to 132s) carries out in time of the mode shown in Figure 16 D.Figure 16 H is the feature of Figure 16 D and shows blood vessel 8795(and have renal artery in human body and the flow of renal veins) and blood vessel wall 8796.In this simulation, focus energy applies in the mode that 10s opens or 6s closes, to allow heat round 8793 blood vessels 8795.There is shown transducer 8790, subcutaneous tissue 8792 and muscular wall 8794.This simulation discloses focus energy at blood vessel, and the blood vessel (for example, lead to kidney) particularly with high blood flow produces the ability of cloud around.

Figure 16 I, J, K illustrate some pattern that can put on blood vessel.In Figure 16 D, applying of the focus energy 8770 to blood vessel is shown in the pattern being produced by transducer mover.Figure 16 I shows have wider brush around the blood vessel pattern 8772 of another kind of type of (brush stroke).

Figure 16 I and Figure 16 J show in the cross section of blood vessel both sides pattern.Figure 16 K shows the vertical pattern 8774 along blood vessel.

Figure 16 L and 16M show the heat energy treatment with the source that applies from outside of the nerve that wherein leads to kidney, and the result of the experiment 8787 of neural suppressed generation norepinephrine.Figure 16 L shows HIFU8644 wherein and operation and controls the result of 8648 experiments that compare.HIFU be applied on blood vessel, make ultrasonic by blood and blood vessel to affect the both sides tube wall of blood vessel.As what can see in Figure 16 L, the HIFU applying from patient body is equally good with the denervation of carrying out with operation, has disclosed focus supersonic and really can remove, and suppresses or ablation vessels nerve around.Within being contained in blood vessel wall with regard to nerve, focus supersonic can be used to suppress or melt the nerve within the medium of blood vessel wall.

Figure 16 M shows focus supersonic wherein and is applied in through skin to the similar experiment of circumvascular nerve of leading to kidney.Post bar (bar) the 8788th, controlling kidney and post bar 8778 is treatment kidneys.The pattern of heat energy is applied in continuous vessel 2-3 minute above time, has produced the variation of viewed norepinephrine and has indicated in logical organotropic circumvascular orthosympathetic denervation.

As what can see, to control side 8788,8644,8646,8648 and demonstrated high noradrenaline levels and treat side 8778,8649 and demonstrated low noradrenaline levels, instruction treatment is successful.This experiment is used according to one of pattern shown in above energy is focused on and is supraneurally arranged in outside ultrasonic system and carries out.

Figure 16 N illustrates the low absolute dosages of another kind experiment 8797(with multiple time points), disclose noradrenaline levels at least several all 8798,8799,8796 after treatment and remain low.Importantly, in this experiment, with the dosage being used, any other organ is not all had to pathological effect, indicate neural nuisance threshold lower than to adjacent organs.Therefore, in a kind of Therapeutic Method, ultrasonic with transmission put on through the such mode of blood vessel the blood vessel that leads to kidney.Ultrasonicly continue across kidney and then arrive and lead to the blood vessel of kidney.In blood vessel aspect, after in-house decay, can be 10W/cm in the power density at blood vessel place ²～800W/cm ², and can be preferably 150～500W/cm ², continue several seconds until there is the heating of suitable size.In the present embodiment, the main mechanism of the nerve inhibition under responsible this dosage and injury is that vibration is instead of heat energy.Therefore, not necessarily need heating melt or block the nerve that leads to kidney, and can use the vibration of only having appropriate temperature rise in some cases.

Therefore,, based on animal and theoretical experiment, proved from the position outside blood vessel and from the ultrasonic renal artery neural feasibility around that suppresses fast and effectively for position outside patient's skin.

The pattern applying can be to be different from wherein to wish the system that is used for the treatment of tumor and other pathology for the treatment of 100% of region.In circumvascular Neural Area be scatter and not necessarily to suppress whole nerves and obtain the effect to blood pressure.Therefore, target is will apply in blood vessel both sides the energy of large brush to produce annulus, or at circumvascular hot cloud.After treatment for the first time, can apply treatment for the second time, nerve other in this is treated is for the second time affected.Treatment for the second time can occur several minutes, a few hours, a couple of days or several years after treatment, and may depend on the regeneration of physiological change or nerve.In some cases, the mobile degree of quality factor based on applicator calculated.Quality factor relates to applicator and in fact focuses on the degree of the time of identified target.Although the 100%th, desirable, it possibly cannot be realized sometimes.Therefore, in some cases, in the time that applicator focuses on target and reaches for 90% time, just can think that treatment is successful.In other embodiments, quality factor can be the time quantum in 90% scope of target area reality in target, for example, and within 500 microns of target, or within the 1mm of target, or within the 2mm of target etc.The detection of target is determined via imaging, internal reference and/or outside reference.

Use experimental simulation and zoopery described above, clinical instrumentation can and be designed out and in human patients, test.Figure 17 A along the tremulous pulse 1140(that leads to kidney 1130 for example shows, renal artery) apply the multi-transducer HIFU equipment 1100 of limited damage 1150.The shape of damage can be spherical, cigar shape 1150, annular 8710(Figure 16 A) or put shape; But in a kind of preferred embodiment, damage is advanced and has cigar shape 1150 along the length direction of tremulous pulse.In a kind of preferred embodiment, this damage is generated by supersonic array spherical or hemispherical type.Multiple cigar-shaped damage as shown in Figure 17 C causes the damage 1350 of annulus type.

Figure 17 B shows the imaging device display for monitor treatment.Damage 1150 is shown on imaging device as aorta 1160 and renal artery 1155.Image can illustrate heat, tissue, elastic graph, vibration, temperature, or simulation that can be based on damage 1150 position.MRI, CT, infrared thermal imaging, ultrasonic, LASER HEAT imaging or critesistor can be used to determine the temperature of organizing district.Figure 17 C shows another view for the treatment of monitoring, and renal artery is in cross section 1340.Damage 1350 is illustrated in the cross section of this image equally.In the embodiment that applies multiple damages, can think that damage 1350 is for drawing a circle to approve blood vessel 1340.

Figure 17 D illustrates the method 1500 of the transmission for analyzing and follow the tracks of the treatment focus supersonic to tremulous pulse district.Crucial step is first to locate 1510 patients to be most appropriate to imaging treatment region; Patient's imaging can comprise and use doppler imaging, M mode imaging, A sweep imaging, or even MRI, fluoroscopy or CT scan.Image-generating unit is used to obtain coordinate data 1530 from the Doppler frequency shift figure of tremulous pulse.Then, make focused ultrasonic transducer locate 1520 and can plan or apply treatment with respect to imaging treatment region 1510.

Figure 17 E shows the sound wave trajectory from the supersonic array 1600 of spherical or cylindrical shape type.In certain embodiments, transducer be spherical sharp focus is not existed but focus be in itself disperse or off-center axle.As selection, asphericity can allow the different path along focal axis.For example, can require one side of ultrasonic transducer to propagate 15cm, and require the another side of transducer only to propagate 10cm, may need in this case the combination of different frequency or angle.

Make the limit alignment of ultrasonic transducer 1610 along cylinder 1650, aim at and make them intersect at blood vessel (for example, renal artery) one or more focal spots 1620,1630,1640 around.Transducer 1610 for example, is located along spherical or spherical approximate (, aspheric) 1650 of cylinder, make certain several transducer closer to a focus or another focus, thereby produce some column distances 1620,1630,1640 of tremulous pulse.The center 1700 that patient and tremulous pulse are located so that them is location jointly with the center of supersonic array 1600.Once center is located jointly, HIFU energy just can be activated for depth and places different around tremulous pulse and produce along the damage of the length of arterial wall 1640,1620,1630.Naturally focusing on of transducer along the cylinder location in Figure 17 E is the damage of length direction, than thickness or highly large, this damage tremulous pulse 1340 during along the central shaft layout of cylinder by the length direction along tremulous pulse 1155.When watch (Figure 17 F) along cross-wise direction, nerve melts along circumvascular clock face 1680 locates.

In another kind of embodiment, used for the motor system of transducer, transducer is moved along the edge of their attached spherical or cylinders.Transducer can automatically or semi-automatically move based on imaging or based on external position labelling.Transducer is by electrically but mechanically coupled separately and control by rigid structure.

Importantly, during treating, treatment work station 1300(Figure 17 C) provide the multiple views 1350 about physical appearance and dissection for the treatment of region.Physical modeling is performed to predict lesion depths and the time for generation of damage; This information is fed back to ultrasonic transducer 1100.The position of damage in three-dimensional system of coordinate also constantly monitored and transducer more focuses on lesion center 1150 under news continuously in monitoring 1300.

In certain embodiments, motion tracking prevent damage or patient mobile too away from treatment region during melting.If patient has really moved to outside treatment region during treating, may stop treatment.Motion tracking can be carried out with ultrasonic transducer, follows the tracks of framework and position or carries out from multiple angles with transducer, produces the 3-D view with transducer.As selection, can follow the tracks of patient moving with video imaging system, as being positioned, patient's a series of accelerometers that are used to indicate motion with it can carry out.In some cases, this embodiment can comprise the quality factor for changing based on trending towards smearing the motion of transmitted dosage the dosage that passes to patient, as described herein.

Figure 18 shows the microtubular 8810 that can be arranged within renal calices 8820; This conduit allows operator to melt specially or stimulate the region of 8830 kidneys 8800.By other imaging capability being provided or by assisting for generation of or locate hyperacoustic motion tracking or the reflection of damage, conduit can being used for further allow targeting in renal artery and circumrenal region.Conduit or can transfer signals to outside patient body at catheter tip or near the equipment it, for guiding the energy delivery equipment through skin by energy delivery.Signal outside patient body can comprise energy, for example radio frequency transmission outside patient body or from the external radio frequency for the region around targeting conduit in body.Following patent and patent application have been described and have been used the ultrasonic transmission at endovascular targeting conduit, and are incorporated to herein to mention mode at this:

11/583569、12/762938、11/583656、12/247969、10/633726、09/721526、10/780405、09/747310、12/202195、11/619996、09/696076。

In a kind of system 8800, within microtubular 8810 is transported to renal artery and enters the arteriorenal branch in kidney 8820.Signal is generated by conduit, enters kidney and pass to patient body to arrive energy delivery system outward.Based on generated signal, the position of conduit in three-dimensional coordinate reference determined and the energy is activated that energy 8830 is delivered to the region indicated by microtubular 8810.

In a further embodiment, position keeps being used.Position keeps making operator can maintain for operator's movement or patient's movement the position of external energy transmission equipment.For instance, targeting can be realized relative to the tracking of moving of target by energy delivery system and to energy delivery system.In the time that energy delivery system leaves its original state, position keeps allowing focus to move with target in the time that target leaves its home position.This position remains on this and is described and is shown in Figure 19 C-D.Quality factor can be used to increase or reduce dosage according to mobile degree by equipment.Quality factor can be defined as the percentage ratio of the time that is positioned at predetermined target area.For example, if quality factor depart from desired value reach a certain size (for example, 10% or 10mm target area in 1mm), can increase or reduce dosage to adapt to this motion.

Microtubular can also be used for that current limiter is arranged in to kidney within (for example,, in renal veins) make it think that its internal pressure is higher than possible pressure with " deception " kidney.In the present embodiment, kidney is generated to central nervous system's signal, to be reduced to the sympathetic nerve output of target organ, attempts to reduce its perfusion pressure.

As selection, hormone secretion or the other factors of hypertension or other adverse effect to cardiovascular system may be responsible for causing in the specific region of kidney.That microtubular can generate is ultrasonic, radio frequency, microwave or X ray energy.Microtubular can be used to melt the region in renal veins or also have interior essence vein segment.In certain embodiments, do not need to melt, but the vibrational energy of being sent by probe is used to affect mechanoreceptor or the chemoreceptor of the hilus renalis that is positioned at kidney on permanent or provisional basis.

Figure 19 A shows and uses the energy in 8930,8931 pairs of renal artery 8910 of transducer of physical separation and the region of kidney 8920 to apply 8900.Although two transducers are shown, transducer can be the single transducer being connected along the whole length of external frame.Transducer (multiple transducer) can be spherical (sharp focus) or aspheric (dispersibility focus), and they can be coupled to imaging transducer directly or indirectly, and in this imaging transducer, image-generating unit can be from a distance.Compared with the transmission method of Figure 17, Figure 19 A shows horizontal in the arteriorenal instead of vertical ultrasonic transmission to tremulous pulse.The direction of energy delivery is patient's rear, because in the time propagating from skin direction forwards, renal artery is " seeing " first blood vessel, has promoted the transmission for the treatment of.In one embodiment, transducer 8930,8931 is arranged under patient's rib or below or between patient's rib; Then, transducer applies ultrasound wave makes it propagate and imaging is carried out in the region of renal artery and renal veins towards front stomach wall forward, makes them separated from one another.In certain embodiments, this transmission may be favourable, if longitudinal view of for example tremulous pulse is unavailable or treats faster normal form when being desirable.Transducer 8930,8931 communicates with one another and be connected to the computer model of the area-of-interest (ROI) of imaging, the MRI scanning of this ROI based on just in time carrying out before operation starts and in whole operation.Importantly, transducer is arranged in the rear in patient's cross section, enters more direct region, kidney district.Angle between imaging transducer can be little to 3 degree or greatly to 180 degree, depends on the optimal location in patient.

In another kind of embodiment, do not carry out MRI, but the ultrasonic all or part of cross sectional view of acquisition in Figure 19 A that be used to.For example, 8930 can contain imaging transducer and treatment energy source (for example, ionization energy, HIFU, mental retardation focus supersonic etc.).In certain embodiments, used CT scan, this CT scan can obtain two-dimentional image and export three-dimensional image.In other embodiments, can use fluoroscopy detecting unit.

Figure 19 B shows patient's ultrasonoscopy, shows the imaging in the region in the situation that patient like that suitably locates as described below.Be exactly that this interface can be processed with the HIFU of the image guiding to hilus renalis region.Make visual in cross section and the then transonic of kidney 8935 to renal artery 8973 and vein 8941.Distance can be taking the ultrasonic 8943(that accurately measures in this example as 8cm8943).This information is conducive to help simulation to renovascular energy delivery.Blood vessel (vein and/or tremulous pulse) is used as the benchmark for ultrasonic targeting, and kidney is used to verify whether blood vessel leads to correct organ really.Kidney is also used to ultrasonic conducting to blood vessel.In such an embodiment, kidney is used as targeting benchmark to indicate operator where energy is guided to.Once determine direction and the orientation of renal artery and kidney, treated the ultrasonic region that is just passed to the hilus renalis.Therefore, lead to the benchmark that the kidney of kidney and blood vessel are the expectation orientations of instruction treatment ultrasonic (for example, leading to the hilus renalis).

Figure 19 C-D shows the actual therapeutic of the hilus renalis 8945.There is shown target area 8946, wherein the movement of transducer and the hilus renalis is tracked and analyzed 8949 and 8948.Along with time interocclusal record show the precision of 8948 tracking.In the figure, show cooling cycle and treatment 8954 has been shown in Figure 19 D.In certain embodiments, energy transmits through kidney in mode described herein, and this kidney has been shown as being heat resilient.In some cases, the movement of the hilus renalis and transducer is by record in real time, and the treatment of blood vessel is illustrated in real time during treating.The success of following the tracks of can, and at the therapeutic advance in when treatment, can on screen, provide to be watched by user, as shown in the trackbar under ultrasonoscopy.Reach at least 90% the time of each treatment time within targeting is maintained at target circle 8647 time, can think successfully.This targeting precision is generally by the success owing to following described preclinical study.Motion tracking system is established within system to guarantee suitable dose delivered to the region of kidney nerve of leading to kidney.Motion tracking system makes three-dimensional coordinate be associated with treatment, and allows to determine the quality for the treatment of.Therefore, in one embodiment, focusing can be applied in the angiosomes that leads to kidney; Quantize the mobile degree between therapeutic equipment and treatment region with hardware and software; If quality factor is too low so that do not produce effective treatment, the using character factor confirms whether this treatment needs to increase the extra time.

Figure 19 C-D shows and arranges 8645 together with the kidney vascular treatment of the actual therapeutic 8654 of kidney blood vessel 8651.Window 8653 is the target windows that are used for the treatment of.Although show kidney blood vessel, being furnished with neural any blood vessel around can both be by targeting.The motion of the success factor 8648 based on target and/or operator.If treatment fails to remain on the duration that reaches setting within target 8647, fail indicator 8648 instead of successful designator are shown on screen 8646.

Figure 19 E shows the clinical method of the shown treatment of Figure 19 C-D based on above.The first step 8972 is to dream up for by the ultrasonic pipeline that is applied to circumvascular nerve.Next step be the ultrasonoscopy of formation zone 8960 and step be subsequently determine the distance 8962 of blood vessel and then make this scheme and HIFU transducer 8964 integrated.Based on above generated data, be identified for applying the parameter of pulse, be usually less than " unlatching " time of 10s, make the temperature in circumvascular region at least 2 seconds, rise to about 200W/cm ²8970.Then focus moves to opposite side from front to rear and/or from a side along tremulous pulse or blood vessel 8968.

Figure 20 shows a kind of for melting kidney neural 9015 or the method for selecting else, system 9000 and equipment in leading to of aorta-renal artery ostium place arteriorenal neural 9010.Within equipment 9020 is arranged in tremulous pulse 9050 in blood vessel and advance to the region of renal artery 9025.Energy applies and is focused 9040(in the situation of HIFU, LIFU, ionizing radiation by transducer 9020) in the starting area from aorta 9050 to renal artery 9025.9030 operations can guide with MRI and/or MRI thermometric in this blood vessel, or it can guide with fluoroscopy, ultrasonic or MRI.Because aorta is greater than renal artery, so within HIFU conduit directly can being inserted to aorta and can comprise psychrophore.In addition, in other embodiments, non-focused ultrasound can be put on to region around nephrostome or the region of aorta Nei Genggao.Non-focused ultrasound may need to carry out cooling probe tissue around with one or more coolants in certain embodiments, but in certain embodiments, aortal blood will replace coolant due to its high flow capacity; HIFU or focus supersonic can not need cooling, because ripple is focused on paraaortic region according to limiting from different angles.Caval vein and renal veins can be used as the conduit for focused transducer equally, to also transfer energy to region.In one embodiment, caval vein is entered and vibrational energy is passed the tube wall arrival renal artery through caval vein and renal veins, leads to kidney at this renal artery peripheral nerve.Having compared with the vein of thin pipe wall allows energy more easily to pass.

Figure 21 a-b shows eyeball 9100.The Suspensory ligament 9130(that also has eye illustrating equally controls the muscle of lens shapes) and ultrasonic transducer 9120.Focused ultrasound energy is put on Suspensory ligament region or Suspensory ligament itself around by transducer 9120, thereby make farsighted person can adapt to also visible object nearby to they are tightened up.Similarly, heat energy or vibration are applied in ciliary muscle, and the aqueous humor that then this ciliary muscle increases area-of-interest flows out, and makes the pressure of ophthalmic cannot be increased to high level.Ultrasonic transducer 9120 can also be used to Drug therapy to be transported to the regions such as crystalline lens 9150, corpus ciliare, Suspensory ligament, vitreous body interior wall, ante-chamber 9140, back cavity.

Some embodiment (Figure 21 b) in, treat the tissue of depths within the eye with multiple transducers 9160; Ultrasonic transducer 9170 is focused on the specific region of eyes from multiple directions, and making not to be subject to ultrasonic injury and focal area and active region 9180 along organizing of ultrasonic path is positions that ripple is joined within the eye.In one embodiment, transducer is conducted through the pars plana region of eye, the macula lutea (macula) 9180 with targeting at the rear utmost point 9175 places of eye.This structure can allow heating, vibratory stimulation, drug delivery, gene delivery, laser to increase (augmentation of laser) or ionizing radiation treatment etc.In certain embodiments, do not need focus supersonic and general vibration wave to pass eye with the frequency transmission of 20kHz～10MHz.This energy can be used to smash the grumeleuse in for example retinal vein or arterial occlusion, and this grumeleuse has caused the part ischemia within retina.This energy can use in conjunction with being specifically designed to the medicine that smashes the grumeleuse in retinal vein.

Figure 22 shows with heat energy and/or vibrates treatable periphery joint 9200.Ultrasonic transducer 9210 is launched ultrasound wave with just in time nerve 9260 under periosteum 92209250 or under cartilage of blocking-up towards knee joint.Although show knee joint, should be appreciated that many joints can treat, comprise little joint, articuli intervertebrales, hip joint, ankle joint, carpal joint and the shoulder joint of hand.Ultrasonic energy unfocused or that focus on can be put on to hinge area, for reversibly or irreversibly suppressing function of nervous system.This type of inhibition of function of nervous system can be used to treatment of arthritis, postoperative pain, tendinitis, relaxing tumor pain etc.In a kind of preferred embodiment, can use vibrational energy instead of heat energy.The vibrational energy that puts on articular nerve can suppress their function, thus inhibition of pain fiber.

Figure 23 a-b shows the closure of the fallopian tube 9300 that uses external ultrasonic 9310 uterus of carrying out 9320 that apply in order to prevent pregnancy.MRI or preferably, ultrasonic energy is enough in formation method.Thermal imaging can be used equally to check in real time real zone of ablation.Fallopian tube 9300 can come visual with ultrasonic, MRI, CT scan or peritoneoscope.Once fallopian tube is by targeting, outside energy 9310, for example, ultrasonic, just can be used to closed fallopian tube to prevent pregnancy.In the time that heat is applied in fallopian tube, the collagen protein in tube wall is heated and by swelling, then tube wall contacts with each other and closed fallopian tube, thereby prevents from ovulating completely and preventing pregnancy.Although in fallopian tube, there is no Doppler signal, for visual with treatment technology to be similar for the technology of tremulous pulse or other conduit.Namely, tube wall is identified and simulated, and then focus supersonic is applied in through skin and arrives fallopian tube, heat energy is put on to oviducal internal chamber wall.

In Figure 23 b, show a kind of method, in the method MRI, CT or ultrasonic next visual 9340 for fallopian tube.HIFU9350 is applying with under MRI or ultrasonic realization visual.In the time that fallopian tube is heated, the collagen protein in tube wall is heated until oviducal tube wall closure.At the moment, patient is by sterillization 9360.Within treatment time, how may need to determine the effect of ongoing heating.If need extra heating, the HIFU separately adding can be added into fallopian tube, until fallopian tube closure and patient are by sterillization 9360.This is one of advantage of extrinsic pathways, in this approach, multiple treatments can be put on to patient, and each treatment is all further closed fallopian tube, then after each treatment, all assesses successful degree.Then can apply further treatment 9370.

It is in other embodiments, ultrasonic that to be applied in uterus or fallopian tube conceived by improving sperm and/or ovum endometrial receptivity each other to help.This increase of being impregnated can be applied in sperm or the ovum outside uterus equally, and for example, outside palace, fertilization in the situation that is in test tube.

Figure 24 shows the feedback algorithm for the treatment of autonomic nerve.Importantly, there is the assessment to treating later response.Therefore,, in the first step, the adjusting of kidney nerve 9400 is completed by any one or more embodiment discussed above.Then assess 9410, the degree of the therapeutic effect producing has been determined in this assessment; If determined completely or gratifying response 9420, treated.For example, assessment 9410 may comprise by the determining of micro-neuronography, the assessment of the measured value of carotid sinus reaction (described above), heart rate variability, noradrenaline levels, inclining experiment, blood pressure, ambulatory blood pressure measurement etc.Gratifying, from main response in the situation that, further the degree of response may not be proceeded or be depended in treatment, and neural 9430 additional treatment may be proceeded.

Figure 25 show according to the Skin observing from seeing through patient 9500 to patient's the reconstruction of CT scan image of the position that kidney 9520 is shown.Rib 9510 parts are covered with kidney, but have really demonstrated the window at the lower utmost point 9530 places of kidney 9520.Caused wherein on patient, having identified rib 9510, pelvis 9420 and vertebra 9440 about the analysis of many these reconstructions, kidney is identified and clinical normal form that then renal artery is identified via doppler ultrasound via ultrasonic.Relevant clinical window can have the angle that enters of 40～60 degree.

As shown in Figure 26 a, once identify rib and vertebra with doppler ultrasound, just exterior source of energy 9600 can be put on to region.Particularly, once identify these structures, just focus supersonic (HIFU or LIFU) can be put on to region and damage be put on to the blood vessel (renal artery and kidney nerve) 9620 that leads to kidney 9610.As the described herein, the position of ultrasonic transducer 9600 is optimized at patient's rear shown in Figure 26 A.Namely, vertebra, rib and crista iliaca are adjacent to ultrasonic be applied to region.

Data based on above and especially the CT scan anatomic information in Figure 26 A, Figure 26 B shows the equipment and the system 9650 that design into this region (blood vessel in the hilus renalis of kidney) in treatment patient body.Otch or the attachment location of the ultra sonic imaging transducer 9675 that this system contains 0.5～3MHz of the heart therein and the ultrasonic pottery (for example, PZT) arranged for diagnostic ultrasound.This system is also containing being useful on the motion 9660 of controlling treatment transducer 9670.Diagnostic ultrasound equipment 9675 is good according to defining, and known relation is coupled to therapeutic equipment.This relation can by rigidity or semirigid couple to define or it can pass through electric coupling (for example, passing through infrared ray), optical-mechanical couples and/or electromechanics couples to define.Along the border of the outer rim of equipment, can arrange less transducer 9670, this transducer 9670 identifies transonic haply by tissue wherein.For example, can use the transducer of simple and cheap one dimension or two dimension, ultrasonicly organize whether can be used to targeting and safety at it to what pass on the path of target to determine.From the angle of safety, these type of data are that important making ultrasonicly do not hit skeleton or intestines and transducer is suitably arranged with the circumvascular region of targeting kidney.Be contained in equally in system is for being transferred to the cooling system of the fluid 9662 that spreads all over this system from the heat of transducer.Via the cooling permission cooling ultrasonic transducers of this mechanism and the skin of system below.Another feature of system is to be coupled to system 9650 recording system 9650 sensor mechanism 9665 with respect to the movement of baseline or near coordinate.In one embodiment, used wherein sensor can determine the Magnetic Sensor of system with respect to the orientation of the Magnetic Sensor in system.Sensor 9665 and travel mechanism 9660 and imaging transducer 9675 rigid couplings.Except magnetic, sensor for example can also be, based on photoelectricity, acoustics, imaging (, camera) or radio frequency.

And the front 9672 of transducer 9670 is shaped as and makes within it is suitable for the bone region shown in described and Figure 26 A.For example, in certain embodiments, shape can be oval-shaped or aspheric; In other embodiments, shape can be triangle or cheese.In addition, in certain embodiments, ultra sonic imaging engine may not be located immediately at the center of equipment and in fact may be on center and the upper limb in more approaching front and more approach rib, and wherein renal artery is visual better by imaging probe 9675.

Given clinical data and designed technology (for example, Figure 26 A-B) described above, Figure 27 shows for energy being put on to renal artery neural new therapeutic scheme 9700 around, and the position of energy outside patient body transmits.

In one embodiment, patient is stablized and/or is located so that renal artery and kidney located 9710 best.Diagnostic ultrasound 9730 is applied in region and optionally, ultrasonicly applies from second direction 9715.The position 9720 that allows to set up renal artery, the hilus renalis and vein is handled in location and imaging.The test dose for the treatment of energy 9740 can be applied in hilus renalis region.In certain embodiments, can measure temperature 9735.This test dose can be considered to full dosage, if treatment is actually effective by one or more measurements.These measurements can be blood pressures 9770, the minimizing (being measured by micro-neuronography 9765) that sympathetic nerve flows out, the increase that parasympathetic nervous flows out, the variation of blood vessel 9755 calibers, or at peripheral nervous (for example, peroneal nerve) minimizing of 9765 the micro-neuronography spontaneous spiking quantity in analyzing, or demonstrate MRI or the CT scan of the variation of neuro anatomy 9760.In certain embodiments, the index in kidney is used to feedback.For example, resistance coefficient, the vasoconstrictive degree in kidney of being measured by doppler ultrasound relates to the neururgic useful index of kidney; For example, in the time there is larger autonomic activities, resistance coefficient increases, and vice versa.

Having treated 9745 may occur in the time that blood pressure reaches desired value 9770.In fact, this may never can occur or its only generation after several years for the treatment of.Blood pressure may continue too high and repeatedly treat and can within the several years, apply---the concept that dosage is cut apart.Cutting apart is the major advantage that applies energy from the region outside the renal artery peripheral region in patient body, because for example, for example, compare with aggressive treatment (, stimulus object is implanted) and intervene operation (, arteriorenal conduit inserts), it is more convenient and expense is lower.

Another pith is the location of renal artery, renal veins and the hilus renalis and the foundation of position of kidney 9720.As discussed above, the use of doppler ultrasound signal allows the neural location that is easy to approach, and makes ultrasonicly can put on neural general area.In Figure 29 A-D, can see neural region.Figure 29 A-C is the sketch from actual Histological section.0.3mm～10mm can be seen and be generally to distance from arterial wall on different positions.But these images are from actual renal artery and neural and used to develop the therapeutic scheme for this system.For example, once use Doppler or other ultrasonic signal to locate arterial wall 9730, the model of neural position just can be established and then can make this region of energy targeting to suppress neural activity 9720.Note, the treatment that many these nerves indicate from the distance of blood vessel wall the tube wall that radio frequency is applied to blood vessel from internal blood vessel is probably difficult to arrive the major part nerve around blood vessel wall.

For example, Figure 29 D shows the ultrasonic schematic diagram of living person.As seen, transonic, through skin, through subcutaneous fat, passes muscle and passes at least in part kidney 8935 to reach the hilus renalis 8941 and the kidney blood vessel 8937 of kidney.This direction is not optimized by clinical experiment to do not comprise and is tended to the ultrasonic structure of scattering (for example, skeleton and lung).Experiment has caused this position for imaging and the treatment of kidney nerve.Ultrasonic position is between above and following described patient palp bone mark behind.Vertebra is in centre, rib up and crista iliaca below.Importantly, the distance of these structures 8942 is about 8-12cm and prohibitive from the angle right and wrong of technology.Therefore, these are consistent from ultrasonic image with the result of the CT scan from above same description.

Figure 29 E shows the available surface area 8760 of ultrasonic transducer from two patients of clinical research.Patient is fat and another one is thinner.The quantification of these surface areas 8762 obtains by the following method: 1) obtain CT scan; 2) border of labelling organ (for example, vertebra, crista iliaca and rib); 3) draw the line from kidney blood vessel to the point along bone edges; 4) draw the vertical line from rib bone to skin surface; 5) collection of the point that mapping obtains along bone border.Surface area is that surface area and the maximum gauge between point is the ultimate range between bone border.The ultrasonic transducer available area of patient behind for the region of visual or treatment focal spot defined in the collection of the point in this way obtaining.By the research to a series of patients, the scope of surface area is determined to assist to meet the design of Most patients.The transducer of simulating in Figure 30 has just in time about 11 × 8cm or the 88cm within the surf zone 8762 shown in Figure 29 E ²surface area, this has represented patient's series.And the length from renal artery to skin or distance quantize with the shortest ray 8764 and long shot line 8766.Together with above given angle-data, these data make the design of suitable transducer can realize blood pressure from main regulation and and control.

In one is independently studied, show ultrasonic inhibition that these nerves can apply with outside.The nerve that pathological analysis has disclosed around tremulous pulse is suppressed completely or is degenerated, and has confirmed the ability for suppressing these neural and final treatment such as therapeutic schemes of the such disease of hypertension.And, use these parameters, ultrasonic through kidney and arrive in the path of the hilus renalis and can not cause any infringement.

Importantly, also find by means of clinical trial, when ultrasonic while being used as the energy that outside applies, thereby making diagnostic ultrasound probe make between two parties the cross section of kidney visual and make visualization of blood vessels, is the pith that treatment is passed to correct position along blood vessel.A step in the first step of algorithm 9700 is that patient is stable in patient's stabilising arrangement of customization, to transfer energy to arteriorenal region.After having stablized patient, diagnostic ultrasound is put on to the scope that put to set up rib, vertebra, the basin position of bone in region 9730.Palpation bone mark also allows to demarcate interested treatment region.Then external ultrasound system is arranged in these regions, to avoid skeleton.Then, cross kidney (for example, with ultrasonic next visual) by guaranteeing that a part of external energy is passed, the probability of hitting intestines has nearly all been eliminated.Ultrasonoscopy in Figure 29 D shows from patient body the soft tissue path of the hilus renalis in patient body.Distance is about 8～16cm.Once patient has been positioned, liner 9815 is arranged under patient.In one embodiment, liner 9815 is the mode at a kind of patient of supporting back.In another kind of embodiment, patient 9815 is expandable devices, and wherein the expansion of this equipment can be adjusted for individual patient.Expandable part 9815 allows compression retroperitoneums (position at kidney place) to slow down or the motion of damping kidney and maintain its position for energy source or ultrasonic treatment.In another kind of embodiment, adjust and automatically carried out, the wherein such variable of sensor sensing such as pressure on each expandable part, and equipment based on felt side to variable automatically carry out adjustment (for example,, in the time that pressure exceedes or be less than predetermined threshold value).

The test dose 9740 of energy can according to the hilus renalis or arteriorenal region and temperature imaging 9735, Vasoconstriction 9755, CT scan 9760, micro-neural Figure 97 65 diaphragms (patch) or electrode and even blood pressure 9770 provide.Afterwards, can complete this treatment 9745.May betide several minutes completely, after a few hours, a couple of days or several years, depend on measured parameter.

By experiment, determine, under the local application of force below rib and in the region above renal pelvis in to abdominal part, the region of the hilus renalis and body can utilize gravity to stablize.For example, Figure 28 A-C shows the example that is intended to patient's localizer for the treatment of renovascular region.

Figure 28 A is the example that patient locates, and ultrasonic diagnosis in this example and treatment 9820 are arranged under patient.Localizer 9810 adopts the form of tiltable bed.Being arranged in patient's lifter 9815 under patient promotes the hilus renalis and makes its more close skin and can promote forward by this way; As determined in clinical trial, renal artery in such layout from surface also want close to about 2～3cm, in the patient who studies in clinical trial, distance is about 7～15cm.Patient's weight makes the respiratory movement that can occur in addition obtain certain stablizing; Patient's lifter can be positioned a side or opposite side, depends on region to be treated.The approach (in the situation that doctor wants to make patient be maintained at bed flat position) that can select else is that positioning equipment is arranged under patient's shank and maintains upper trunk is flat substantially.

Figure 28 B shows the more detailed structure of embedded ultra sonic imaging and treatment engine 9820.Patient interface 9815 is used to produce superly to be propagated through skin and arrives the seamlessly transitting of sound wave of the kidney being used for the treatment of.Interface is adjustable, makes it can be patient customized for every.For example, fill with the ultrasonic fluid easily passing (, the water of deionized and defat) conventionally at interface.In certain embodiments, fluid management system is used to be controlled at one or more parameters of the fluid in the barrier film that is coupled to patient.For example, the pressure of the fluid in barrier film can be controlled by pressure transducer and closed loop feedback system, to maintain the pressure of predetermining to patient skin.The temperature of the fluid in barrier film can be controlled in 10 degrees Celsius, 15 degrees Celsius, 20 degrees Celsius or 25 degrees Celsius, so that cooling transducer and/or skin.

Figure 28 C shows the another kind of embodiment of positioning equipment 9850, means that specifically patient will face down.In such an embodiment, patient is located with ventricumbent position, be positioned on patient's lifter 9815.Again, by clinical experiment, determined, the ventricumbent position of localizer below patient pushed the hilus renalis to rear and is renal artery and vein spread apart, allows them higher and be accessibility for the energy deposition in this region for ultrasonic visibility.Localizer below patient provides the big or small controllability that puts on the pressure below patient.Thereby localizer can also have expandable 9825 and the open kidney blood vessel of expandable front compression institute that patient's back can be pushed to localizer with allow energy device more top layer and the backboard (back side) that more easily applies.These data can find at Fig. 7 G and 7H, and wherein renal artery is more close to skin (being down to 6～10cm from 7～17cm).In Figure 28 C, illustrated for patient left side 9827 and for the location of the energy device on patient right side 9828.Rib 9829 has defined the upper limit region of apparatus arrangement and crista iliaca 9831 and has defined the lower limit region of apparatus arrangement.Medial side (medial edge) and region 9828 therebetween that spinous process 9832 has defined region that can advancing equipment are positions that treatment transducer is arranged.

Figure 28 D-28E shows a kind of system implementation described above.Be with 9853 to be fixed in transducer 9855.Air bag 9857 is cavitys adaptable and that can fill, and air bag 9857 can be used for helping to stablize patient's rib abdomen region by behind skin being pressed to band and transducer 9855.Transducer is incorporated in many embodiment described herein.For example, in shown embodiment, transducer carrys out Design and manufacture according to following specification: it applies the energy that points to renal artery and neural region.Can make transducer form the shape as pizza with ring-shaped work pieces, or multiple element form spherical, as pizza (as the described herein).Transducer can also be provided as picture and motion tracking ability, for example, with pulse echo detection system or with overall ultra sonic imaging.Imaging assistor can detect indwelling vessel catheter or implant.But imaging assistor can either detect target also can follow the tracks of its motion.The focus supersonic that generated frequency is 0.5MHz～3MHZ can be carried out according to desired ad hoc structure or pattern in the treatment aspect of transducer 9855.Monitor 9862 is used to the progress of monitor treatment in whole therapeutic scheme.

Thereby, in a kind of embodiment of this system, as shown in Figure 28 D and 28E, this system comprises the band for limiting patient, and for example air bag (optionally) is put on to patient's a side, to limit abdomen organ's skew and to stablize at least partly abdomen organ, kidney.In addition, imaging and tracking can be used to maintain the location for the treatment of energy focus.Then the focus energy system of stabilisation can be guided (for example, by processor) to follow the tracks of and to follow blood vessel and to carry out treatment according to therapeutic scheme automatically, for example, is used for the treatment of and is leading to the circumvascular tissue (nerve) of kidney.Air bag can automatically be filled.In some cases, motion air can be used to treatment energy focus to guide to the region hilus renalis or that approaches kidney therein.

Figure 28 F-G shows the more complete picture of transducer at the back that will put on the patient in 9853.Figure 28 F show have orientable arm with and be matched with the motions of 6 dimensions of transducer platform within system structure 9860.6 degree of freedom can be used for motion, and this motion comprises selection and the translation of transducer.Platform can move and bottom mover allows transducer to be pressed towards patient's skin with 6 degree of freedom.

Figure 28 H shows patient treatment system 9800, and in this therapy system 9800, conduit 9805 is inserted in patient's 9810 bodies and system 9820 is arranged in patient behind.Couple applicator 9815 and be pressed towards patient, contact for the coupling maintaining between therapy system 9820 and patient.Conduit 9805 can be used to auxiliary target to the blood vessel of being treated by therapy system and nerve.Make therapy system 9820 be maintained at patient after one's death, allow patient's weight to be used to coupling between the system that maintains 9820 and patient 9810.Conduit 9805 is preferably the form of one of above embodiment, and can be used to targeting or guiding external treatment.As selection, conduit 9805 can be used as the primary treatment in conjunction with outside imaging (diagnosis).System 9820 is arranged in patient behind and optionally comprises multicomponent ultrasound transducer array, together with the mechanism system for locating this array.

Figure 28 I is the feature of transducer 9820.Element 9809 is shown having different directional patterns and cartesian coordinate position, to join at intersection point 9807 places.Element 9809 can also translation or selection within transducer, allows multi-method treatment.In the inside of transducer 9820, treatment piezoelectric-array can be circular ring type, bowl type or multicomponent phased (2D) array.For any array, this array and arbitrary element thereof can communicate by letter to characterize tissue treatment path, location and the targeting of ultrasonic energy with conduit.

Figure 28 J shows the part 9865 in the specific anatomical district for pressure being put on to patient.Individual air bag 9860 can be inflated 9860 or venting 9863, depends on the patient's who is applied in pressure region.This system help makes applicator conform to patient.In Figure 28 K, show the another kind of structure for treatment energy being put on to the system in hilus renalis region.Transducer 9875 is illustrated and is arranged in workbench and is located in the part under patient to be treated.Angiogram 9874 is visible in the situation that conduit is used to targeting.Therefore, in one embodiment, described a kind ofly for energy being put on to the system in renal artery district, it is ultrasonic that in this system, typical OR or cardiac catheter laboratory table are transformed treatment for below patient.The motion that treatment supersonic array comprises the contact skin for maintaining array and patient, wherein this mechanism can move to patient's left side or patient's right side.Motion can operate (for example, tracking target) by the image (for example, doppler image) based on blood vessel.

Figure 28 K shows the motion 9875 in the workbench 9870 that is used for the treatment of the patient who is positioned as dorsal position.Workbench raises in patient's front, upwards pushes the hilus renalis or kidney to.The head of workbench can be lowered or be raised to allow specifically to determine bit position.Raised portion can contain a side of the trunk that controllably pressure is put on to patient or the inflatable structure of opposite side, head or basin bone.One or more chocks can be arranged in to patient's knee below to launch lower back, so that kidney and the blood vessel that leads to kidney expose with associated kidney nerve.Monitor 9874 and 9875 can be used for the position of visualization catheter by doctor.Bed compatibility has CT scan or fluoroscopy, makes to determine for angiosomes to be treated the position of conduit.

Figure 28 L shows and on strategy, is arranged in the feature of the transducer mover of (for example,, in sick bed inside) below patient and detailed mechanism.Shell 9884 allows inner shell 9885 to rotate therein, allows towards patient's multiple directions axle and thereby for example has, towards the many different angle of interested target the kidney nerve around renal artery of junction ().Workbench 9886 has for the recess of transducer 9887 and cover (ball in socket) the mover mechanism 9885 of receiving.Should " cover is received (ball in socket) " shell allow transducer 9887 to be positioned on patient's back.This mechanism can with respect to upright position and through the centrage of its axle 9883-30(and up to-50 degree) with+30 degree (and up to+50 degree) rotate.The motion of ball 9885 and ball cover 9884 can be automatic or manual.For example, electronic frame and pinion type layout can be attached to ball and ball cover motion.In shown example, the transducer 9887 when axle 9882 shows at relative its center at an angle.In another kind of embodiment, transducer 9887 moves along line 9882, pressure is put on to patient according to the angle being locked by ball and ball cover mover mechanism 9884.Movement along axle 9882 can be carried out automatically by controlled feedback system, to maintain contacting of pressure to transducer and maintenance and patient on workbench 9886.The top of transducer assemblies can be mounted with on the top of bed of this assembly 4 inches thereon to 13 inches of places of as many as.Thereby another component of this transducer motion mechanism is it moves along its basal surface whole ball and the engaging mechanism ability along the plane surface translation on bed for example that makes.

Figure 28 M shows a kind of embodiment, and in this embodiment, two dimensional phased array 9952 is arranged on the patient 9960 on workbench 9985.Flexible phased array 9962 in band is arranged on patient 9960 and within being fixed on banding pattern layout.This light section (low profile) focused ultrasound system can be arranged on conduit insertion or MRI/CT scan table, fluoroscopy table or operating-table.As selection, the recess that it can be positioned in bed lies on transducer patient.The design of the present embodiment results from industrial design and clinical research, and the angle to the approach in renal artery district in this research is analyzed for determining whether kidney blood vessel and neural rear approach are for melting these nerves to treat hypertensive optimum way.

Figure 28 N shows for heating and is leading to the another kind of embodiment of two-dimensional array of circumvascular autonomic nerve of kidney.Water pillow 9974 is shown as the ingredient of workbench 9956.Two-dimensional array 9970 is built in workbench, under water pillow 9974.Then patient is placed on workbench and on water pillow.Then, apply immediately and make it pass water pillow 9974 from array 9970 ultrasonic to arrive and leading to the circumvascular autonomic nerve of kidney.

Figure 29 A-C shows the anatomic basis 9900 of targeting approach described herein.These figure directly obtain from tissue slice.Position around renal artery 9920 and vein 9922 can see neural 9910.The scope of the radial distance of tremulous pulse is to arrive greatly 2mm and arrive even greatly 10mm.Associatedly with the dissection of the simulation in Figure 16 B disclose the feasibility of targeting and verified this approach based on actual pathology; Namely, by the adventitia of targeting tremulous pulse, kidney nerve is applied the approach for the treatment of, and use for example, pipeline and benchmark as focus energy (, focused ultrasound energy) of kidney.This is important, is a kind of detection from the Doppler signal of tremulous pulse the method for targeting Doppler signal blood vessel wall around then because be used for the neurophilic method of target.Can see that neural 9910 round renal artery 9920, this renal artery 9920 makes their squarelys and enters the temperature field shown in Figure 16 B, has pointed out the feasibility of the targeting approach summarized in Figure 27 and the damaged structure in Figure 16 A.Further experiment (using the pathology of similar type and the noradrenaline levels in kidney) has disclosed, and for the variation that affects the nerves for the required ultraphonic agent amount in region is: melt for neural part, magnitude is 100W/cm ², and to nerve melt completely and downright bad, magnitude is 1-2kW/cm ².The degree that these dosage or the dosage between them can suppress according to the desired nerve of therapeutic scheme is selected.Importantly, also find by experiment, passed the sound plane of blood vessel enough partially or completely to suppress the nerve in this region.That is to say, blood vessel vertically the plane by wherein enough to melt the nerve around the tremulous pulse shown in Figure 16 B.Before this experiment, also not evidence suggests ultrasonic can be by plane ultrasonic be applied through blood vessel and melts the nerve around tremulous pulse.Really, verified, plane ultrasonic can circumferentially suppress circumvascular nerve substantially in the situation that not having case to affect on blood vessel wall itself.

Figure 29 D shows the treatment in conjunction with technical factor described herein.The ultrasonoscopy obtaining with Doppler is shown having the blood vessel 8941 that leads to kidney 8935.Carry out taking three dimensions the pipeline that target vascular therapy (Doppler signal and image) 8937 and kidney 8935 are used as focus energy (in this example as ultrasonic) to conduct to blood vessel.Kidney is also used as benchmark, this benchmark direction indication and indicate the correct blood vessel of certain targeting.Produce one and treat normal form, be generated for moving the focal plane around target along three dimensions at this treatment normal form Program.The data that produce aspect two in theory and in preclinical model have disclosed, and kidney really can be as the pipeline of conduction HIFU energy, because due to the high blood flow of kidney, thereby kidney is given prominence to not have the in the situation that of heating to transmit ultrasonic ability.Therefore, a kind of preferred embodiment is that kidney is used as guided focused ultrasonic benchmark, also allows the blood vessel of transmission through kidney.In the present embodiment, kidney be positioned and then the position 8935 of its hilus renalis be positioned equally.Then, plan step determined, in this step, the ultrasonic degree of depth 8943 can be determined, and focus on or not focus supersonic be then passed to the tremulous pulse 8941 or the vein 8937 that lead to kidney.In certain embodiments, the plan of this treatment can be carried out in the observable situation of kidney.

Figure 30 A-I shows the three-dimensional simulation from one group of CT scan to the patient's model shown in Figure 26 A.Numerical simulation is dissected and is carried out in three-dimensional for the actual human body from CT scan.Being used for producing Fig. 7 E, 19 and 25 same CT scan is used to considering the theory on treatment in situation Imitating renal artery district of dissection of actual patient.Use in conjunction with the dosage shown in the anthropotomical above experiment (Figure 29 A-D) of CT scan, these simulations show, have the ability that the ultrasonic position from patient body for the treatment of is put on to the hilus renalis.In conjunction with Figure 29, wherein Figure 29 shows in the position of circumvascular nerve and the position of the blood vessel in ultrasonic as discussed, Figure 30 A-I shows the feasibility of ultrasonic transducer, and this ultrasonic transducer is arranged to the hilus renalis that required energy is put on to kidney in the situation that not injuring intermediate structure.In fact these simulations have confirmed the Proof of Concept of this treatment and have been incorporated to the knowledge obtaining from pathology, human body CT scan, human body ultrasonic scanning and the system design that provides hereinbefore before.

In one embodiment, Figure 30 A, in the case of being the design of transducer 10000 of 750MHz, the maximum intensity reaching in focus 10010 is about 186W/cm ²; Ultrasonic transducer is about 11 × 8cm, and core 10050 is for ultra sonic imaging engine.The input wattage of transducer is about 120W～150W, depends on that specific patient dissects.Input voltage can be up to 1000W, depends on desired focus peak strength.For example,, for 2kW/cm ²peak strength, may preferably there is the input wattage of about 600～800W.

Figure 30 B and 30C show the depth of about 9～11cm and for two-dimentional area for sound,focal 10020,10030.Importantly, near the region (tissue of (10040 and 10041) focus 10020,10030, for example kidney, ureter, skin, muscle) absorb without any significant acoustical power, instruction treatment can be passed those organization securitys described above and be put on renal artery district.Importantly, intermediate structure does not come to harm in this simulation, has indicated the feasibility of this treatment normal form.

Figure 30 D-F shows the simulation that the transducer 10055 of the frequency with about 1MHz carries out.Under this frequency, compared with shown in Figure 30 A-C, the size of focal spot 10070,10040,10050 is a little less (being about 2cm × 0.5cm), and peak power is higher at focus place, is about 400W/cm ².In human body simulation, this has specified design parameter close to optimum response and for the equipment of disposed outside.Transducer in this design is the design (having scabbled the spherical of limit) of rectangle type, to optimize the work space between patient's aft rib and the upper section of patient's crista iliaca.It is of a size of about 11cm × 8cm, this size as above and below described just in time within the interval between the bone mark at patient back.

Figure 30 G-I shows the simulation with the similar ultrasonic variable of seeing in Figure 30 D-F.Difference is, transducer 10090 is left has the spherical of center cut, instead of has the rectangle of center cut.The surface area that spherical transducer arranges 10090 increases due to vibrational energy makes there is more macro-energy closeness in focus 1075.Really, the ceiling capacity of this transducer (Figure 30 G) is about 744W/cm ², but for the transducer in Figure 30 d, maximum intensity is about 370W/cm ².Plane and Figure 30 I that Figure 30 H shows model show another plane.Focus 10080,10085 is illustrated, and zone line 10082 and 10083 does not have acoustical power and delivery in hot weather life, is similar to Figure 30 A-F.

These simulations have for example confirmed, in the situation that does not hurt intermediate structure or structure (, skeleton, intestinal and lung) feasibility to the orthosympathetic treatment processing of kidney from outside.Hypertension is a kind of clinical practice of this treatment.The transducer that inside has image-generating unit is used to focus supersonic to put on renal artery kidney nerve around.Nervus centripetalis and nervus centrifugalis are affected by this treatment both.

Other transducer architecture is possible.Although single treatment transducer has been shown in Figure 30 A-I, be possible such as the such structure of phased array treatment transducer (the treatment transducers of multiple independent controls).This type of transducer allows to carry out cutting more specifically for individual patient.For example, larger transducer can use with together with more than 2,3,4 or 4 transducer.Individual transducer can open or cut out according to patient's dissection.For example, the transducer that has covered rib in individual patient can cut out during treating.

Although the intracardiac central space that shows in the transducer of Figure 30 A-I, imaging transducer can be arranged in this place Anywhere, if its relatively position for the treatment of transducer be well-known.For example, the in the situation that of being coupled to imaging transducer at the transducer being used for the treatment of and always knowing this relation in three dimensions on space, imaging transducer can be positioned in the arbitrary orientation with respect to treatment transducer.

Another kind of embodiment about customization transducer 11030 has been shown in Figure 30 J-30K.Importantly, this transducer is above for the dissection shown in kidney dissection for adapting to by specialized designs.Pizza shape 11000 is the specific dissections of wherein having considered rib, spinal column and basin bone that are used for the treatment of.Sensor 11040 is along the edge location of transducer and allow imaging or in addition for propagating through patient to the direction that detects ultrasonic system in its target ultrasonic.At the end 11050 of system, include ultrasound imaging probe, wherein this probe couples with treatment supersonic array 11030 and 11020.The quantity of element 11030 has determined that the spatial resolution of array and focus can be with electronically controlled degree.

Sensor around side 11010 can be little 1D imaging transducer or contain single plane.As selection, they can be sound wave time-of-flight sensors distance or that combine these two kinds of different technologies for measuring target.

Figure 30 L-N shows the other view of transducer, within this transducer, imaging part is positioned at the otch 11075 of center 11070, side and is cutting cheese shape 11085.Pizza shape not necessarily will be shaped as section, and can be larger array, and the shape of cutting into slices in this array produces by opening or close many transducers.That transducer in this embodiment can have is square, the element of annular or rectangle, and each element has the controller of himself, for imaging or therapeutic use.

Figure 30 O-Q shows has the transducer that is arranged in the several elements within fixed-focus 11130.These 6 elements 11150 are each can both be conditioned to focus on a speckle, a given focal length apart from transducer.Pizza shape can be suitable for the region between rib and spinal column and basin bone, thereby blood vessel (for example renal artery or renal veins) is applied to treatment.Figure 30 Q shows the discrete mover (discreet mover) 11141,11143,11145 having specified at the overlapping degree of focus 11147.

Figure 30 R-S shows the transducer 11200 with many elements 11230.Again, although it is sliced 11220 to be configured as cake, this shape can produce by the transducer of opening in larger otch.Cross section 11210 has been illustrated (Figure 30 R) equally, and having demonstrated can be for several mm be to the thickness of the array of several cm.Section is produced, and makes within transducer can be adapted to match the acoustic window of the human patients with dissection described herein.

Figure 30 V is the enlarged drawing of transducer 11300, and in this transducer 11300, discrete bowl is matched being similar to the larger bowl 11310 of simulation together.In this layout, individual bowl 11324,11324,11326 provides a slice of the curved surface (curvature) compared with jorum separately, is otherwise very difficult manufacture.

Figure 30 W shows the assembly of the structure 11350 of the bowl with combination, and this assembly produces single focus 11355 in the time being powered.By mobile each a little individual bowl, just can make focus elongate or change circle.

Figure 30 T-U shows the simulation of the annular array transducer shown in Figure 30 J-K.This simulation has disclosed, and focus can be with Electronic Control in the distance 11510 that is less than 10cm to being greater than between 14cm 11500.These distances are be suitable for the blood vessel of image kidney and discharged from the envelope of the window on the rear part at patient's back.

Figure 30 V shows the exploded view of the assembly of transducer 1130.Substrate 11310 can be containing the kinetic control system that is useful on x-y-z motion, and optionally, for the pivot of the rotation of transducer array.Array 11322 comprises the one or more ultrasound emitting crystals 11324 that have for the different curvature 11326,11320 of focus energy.Shell 11330 can be containing being useful on the nose cone (nosecone) or other directive construction that ultrasonic energy are guided to focus.Shade (covering) the 11340th, has the structure that couples for making integrated diaphragm that ultrasonic energy and patient couple.Transducer 11322 can provide for its operation the combination of phasing and mechanical movement.

Figure 31 A shows for the perspective view of transducing devices of dissection customization of blood vessel that leads to kidney.This design is based on above special dissection, biology and the technical problem for finding and describe at the clinical treatment of circumvascular nerve that leads to kidney.Transducer 11650 has multiple elements and can rotate and translation.The Individual components of this array can be by phased, thereby the focal length 11600,11610 that can obtain different depth is treated blood vessel 11620 region around.Imaging transducer 11710 is attached to, or is integrated in, equipment 11700.Although ultra sonic imaging transducer is described, in other embodiments, MRI, CT or fluoroscopy imaging can be attached to system 11700 equally.This equipment also contains element described above, for example, for the mover that whole equipment is moved as full unit, the motion tracking of the global motion for tracking equipment in three dimensions, and for the temperature of skin and transducer being maintained to the water circulation system of acceptable level.

It is important that angle 11652 aligns the dissection being treated.Its representative is treated the envelope of beam and is merged in the design of system.It is shown in a plane in this figure and in this figure, comprises about 40～70 degree, and this has allowed the treatment that the degree of depth is 6cm～15cm.For minor face (entering the direction of figure), angle (not shown) is 35～65 degree.The treatment degree of depth can be adjusted on demand according to the out of phase from transducer; But the shape of focus is substantially unaffected.Position at X and Y place can be adjusted with mechanically actuated, but also can adjust by phasing element.Therefore, in one embodiment, ultrasonic transducer is described, in this ultrasonic transducer, arrange multicomponent array, this transducer is designed to allow focus supersonic beam to carry out electrofocusing with the angle 11652 of the central shaft about transducer, so as to make beam focus along perpendicular to the plane of transducer but move with the central shaft of transducer direction at an angle.This angular pin customizes the dissection being treated.For example, when treatment is when leading to the renal artery of kidney and neural such region, in the time that transducer is arranged in rib, crista iliaca and spinal column, blood vessel be positioned as with the plane of skin at an angle (for example, referring to Figure 31 A, angle 11652, transducer is arranged on the skin under rib, horizontal to spinal column and on crista iliaca).Can also provide and make transducer in the plane of transducer and perpendicular to the mover of the central shaft motion of transducer.

Figure 31 B shows and is designed for the another kind of embodiment that focus supersonic is specifically delivered to the region of kidney and the transducer 11700 of associated blood vessel 11770.Transducer has the multiple little bowl-type transducer 11720 being combined together for ultrasonic dark focus 11740.Less bowl-type transducer 11720 can move respectively with mechanically actuated device, has different big or small focal lengths to be created in target place.Have equally water cooling system 11730, this water cooling system guarantees to make skin and transducer to be maintained at predetermined temperature.The variation of focal length comprises elongation, spiral and annular, and every kind of variation has the different degree of depth 11740.In the present embodiment, imaging is the part of transducer 11720.The ATOF(sound wave flight time) receptor 11710 can optionally receive the signal from the transducer 11750 on indwelling catheter in blood vessel 11760, and this indwelling catheter in blood vessel 11760 contains the piezoelectric transducer that information transmission can be arrived to receptor 11710 through patient.

Figure 31 C shows to be had for shell being provided to transducer layout and maintaining two part mover mechanisms (being called upper mover and lower mover) 11820 of patient's patient table 11800.On the skin of patient within the responsible otch 11830 that transducer 11840 is placed in to workbench of mover 11850; Clinical research has shown the pressure of 50 pounds to be applied by lower transducer on patient's skin and has coupled to maintain.The same upper transducer 11840 of reduction of being responsible for of mover 11850.Upper transducer 11840 is according to treating such as locating in neural such required angle and the position, region of the circumvascular kidney of kidney.Electrofocusing can be used to some component of system, comprise as the vertical direction through the central shaft of transducer and refer generally to the z direction that enters and come from the patient's who is treated direction.By electron focusing, distance can automatically be determined and calibrate with respect to transducer.In certain embodiments, X and Y motion change with the various phasing patterns that produce by transducer on electronics.In certain embodiments, the combination of electronics phasing and mechanical movement is used to suitable focusing and the location of the system that realizes on patient.Being used to transducer that the energy of the treatment to patient applies can also be used to detect and can be used in the ultrasonic signal that imaging detects.Independent imaging transducer can be used to increase treatment transducer.For example, the sound wave flight time can be used or Type B or doppler imaging can be used.Therefore, in one embodiment, transducer locates to reach kidney blood vessel according to suitable angle.

Figure 31 D shows a kind of system of structure and the synoptic chart of subsystem.Transducer band 12010 can be applied in patient, and wherein band comprises that the applicator 12020 with transducer, this transducer comprise diaphragm assembly, encapsulation, temperature sensor and for being coupled to patient's the coupled connection mechanism of skin.Is the otch for imaging engine 12180 within transducer assemblies, this imaging engine 12180 can be with the annular array for imaging in the identical encapsulation for the treatment of transducer, or it can be the array 12040 of the tuning separation of different frequency for being exclusively used in imaging.Is the mover for applicator within transducer band, for example, can be in x-y-z translation and rotate to transmit the mover 12030 of ultrasound focus to any position in circumvascular space around pivot.As selection, in another kind of embodiment, phased array transducers can be used to treatment, imaging or both.Cooling subsystem 12060 is ingredients of system, and wherein cooling subsystem is arranged to the temperature of transducer and barrier film is maintained to predetermined level.Optional targeting conduit 12170 is contained in system, and wherein targeting conduit can be used to characterize the energy being transmitted by focus supersonic, and for assisting and verify the targeting precision of the coupling of imaging and imaging and motor control 12030.Targeting conduit can also comprise for during treating, before or after determine energy size, blood vessel that blood vessel is applied and around the sensor of temperature, acoustical power flux and angiokinetic degree.Also comprise user interface, this user interface comprises tracking ball, mouse, touch screen or the keyboard for allowing user and system interaction.Come to system power supply with power 12150, this power supply 12150 can be switching regulator switching regulator or non-, depends at any which subsystem of given time and is just activated.

Figure 30 R and 30S show the active shape of transducer, and 30T and 30U show the simulation of focus supersonic in the treatment degree of depth.The perspective view of focus 11600 is shown in Figure 31 A, and has shown equally for by the ultrasonic Annular Transducer 11650 that puts on blood vessel 11620 and peripheral nerve 11610.Imaging array 11710 is contained in system 11700 equally.The shape of transducer is optimized for and is transported to renal artery kidney neurological region around.Namely, cake section shape allows focus energy to be transferred to the region at renal artery place.The annular array structure of transducer allows the different degree of depth to carry out electronics phasing.

Claims

1. one kind is used for the treatment of and leads to the perineural system of renal blood vessels and comprise:

Ultra sonic imaging transducer;

Treatment transducer, wherein said treatment transducer is coupled to imaging transducer according to defining good relationship;

Travel mechanism, its be suitable for control treatment transducer with aiming circle the region around renal blood vessels.

2. according to the system of claim 1, wherein, described in define good relationship and define by electric coupling.

3. according to the system of claim 2, wherein, described electric coupling comprises infrared coupling, and optical-mechanical couples, and/or electromagnetism couples.

4. according to the system of claim 1, also comprise the cooling system that spreads all over described system, this cooling system is transferred to from described treatment transducer the fluid that spreads all over described system by heat.

5. according to the system of claim 1, also comprise sensor.

6. according to the system of claim 5, wherein, system is with respect to the movement of baseline or near coordinate described in described sensor record.

7. according to the system of claim 1, wherein, the front of described treatment transducer be shaped as make its be applicable to being arranged in patient behind by rib up, vertebra centre and crista iliaca below the bone region of limited boundary.

8. according to claim 1 system, wherein said treatment transducer is arranged in patient below, and system also comprises the patient's lifter that is arranged in patient below, and this patient's lifter promotes the hilus renalis and make its more close patient's skin.

9. also comprise patient interface according to the system of claim 1, this patient interface is suitable for producing and seamlessly transitting for propagating through skin and arriving ultrasound wave that kidney is used for the treatment of.

10. according to the system of claim 9, wherein, described patient interface also comprises the barrier film that makes this interface can be full of fluid.

11. according to the system of claim 10, and wherein, the fluid in described interface is maintained at the pressure of predetermining to patient.

12. according to the system of claim 11, and wherein, the fluid temperature (F.T.) in described barrier film can be monitored.

13. according to the system of claim 1, and wherein, described imaging transducer or described treatment transducer have motion tracking ability.

14. according to the system of claim 1, also comprises imaging assistor, and this imaging assistor can be surveyed the conduit of indwelling blood vessel.

15. according to the system of claim 1, and wherein said treatment transducer produces 0.5MHz to the focus supersonic between 3.0MHz.

16. according to the system of claim 1, and wherein, imaging and tracking are used to the location of the treatment energy focusing that maintains described treatment transducer.

17. according to the system of claim 16, wherein, described in the treatment energy that is maintained focus on by guiding automatically to follow the tracks of and to follow blood vessel.

18. according to the system of claim 17, and the treatment energy that wherein said motion controller is used to guiding treatment transducer focuses on.

19. according to the system of claim 1, also comprises sextuple motion.

20. according to the system of claim 1, and wherein said system also comprises the conduit that is used to be arranged in blood vessel.

21. according to the system of claim 1, and wherein said treatment transducer comprises the element with different phasing patterns, and these phasing patterns intersect at a point.

22. according to the system of claim 21, and wherein, described element can translation or rotation in treatment transducer.

23. according to the system of claim 1, and wherein said treatment transducer comprises circular ring type, bowl type or two-dimensional array.

24. according to the system of claim 1, also comprises: be transformed into the typical catheter laboratory table with the treatment ultrasound machine that is positioned at below; With, can insert patient's conduit, this conduit can operate to allow to aim at described blood vessel.

25. according to the system of claim 1, also comprises the mechanism that can move described treatment transducer, and it comprises shell and inner shell, and wherein said inner shell can rotate in described shell, so that the multiple axles towards patient's orientation treatment to be provided.

26. according to the system of claim 25, and the movement of wherein said inner shell is automatization.

27. according to the system of claim 1, and wherein said treatment transducer is the focused ultrasound system that comprises ultrasonic component phased array.

28. according to the system of claim 1, and wherein said treatment transducer is two-dimensional array built-in in the workbench of patient.

29. according to the system of claim 28, and wherein patient can dorsal position be positioned on workbench, is provided with water pillow in workbench, is placed in this patient below, and can operates that treatment ultrasound wave is passed to circumvascular autonomic nerve thereby make to treat transducer.

30. according to the system of claim 1, and wherein said treatment transducer is suitable for applying and is approximately 100W/cm ²to 1-2kW/cm ²energy be used for suppressing described nerve.

31. according to the system of claim 1, and wherein said treatment transducer is suitable for applying the sound plane through blood vessel, partially or completely to suppress described nerve.

32. according to the system of claim 1, also comprises that treatment plan is with guiding travel mechanism.

33. according to the system of claim 32, and described treatment plan is suitable for mobile focussing plane.

34. according to the system of claim 32, and wherein said treatment plan detects Doppler signal and aims at Doppler signal blood vessel wall around.

35. according to the system of claim 1, and wherein said treatment transducer is the treatment ultrasonic transducer that comprises multiple ultrasonic components.

36. according to the system of claim 35, within wherein said treatment ultrasonic transducer can be suitable for matching patient's acoustic window.

37. according to the system of claim 35, and the focusing of wherein said treatment ultrasonic transducer is that electronics is controlled.

38. according to the system of claim 37, and the focusing of wherein said treatment ultrasonic transducer is that machinery is controlled and electronics is controlled.

39. according to the system of claim 1 or claim 35, and wherein becoming image converter is one of in supersonic imaging apparatus, MRI equipment, CT scan equipment or fluoroscopy equipment.

40. according to the system of claim 1, and the moving method of wherein said travel mechanism is the phasing based on ultrasonic component.

41. according to the system of claim 1, wherein, described in define good relationship and defined by rigid coupling.

42. according to the system of claim 1, wherein, described in define good relationship and defined by semi-rigid coupling.

43. according to the system of claim 5, and wherein, described sensor is the photoelectric sensor that uses camera.

44. according to the system of claim 1, and wherein, described treatment transducer is multicomponent phased array, and phasing, rotation or the translation of each element of the motion utilization treatment transducer for the treatment of transducer.