DEVICE AMD METHOD FOR DETERMINING THE LOCATION OF A VASCULAR OPENING PRIOR TO APPLICATION OF HIFU ENERGY TO

SEAL THE OPENING

TECHNICAL FIELD

[0001] Methods and apparatuses fot sealing vascular praictuies and openings are disclosed Moie specifically, systems and methods ate disclosed to determine an accurate location of the vascular opening being treated so that energy delivered by a high intensity focused ultrasound (HIFU) device is accurately delivered to the opening with minimal damage to surrounding tissue and discomfort for the patient

BACKGROUND OFTHE RELATEDART

[0002] Various surgical procedures are performed by medical specialists such as cardiologists and radiologists, utilizing percutaneous entry into a blood vessel To facilitate cardiovascular ptoceduies, a small gauge needle is introduced through the skin and into a target blood vessel, often the femoral artery The needle forms a punctate through the blood vessel wall at the distal end of a tract that extends through the overlying tissue A guide wire is then introduced through the bore of the needle, and the needle is withdrawn over the guide wire An introducer sheath is next advanced over the guide wire The sheath and guide wire are left in place to provide access during subsequent procedures

[0003] The sheath facilitates passage of a variety of diagnostic and therapeutic instruments and devices into the vessel and its tributaries Such diagnostic procedures may include angiography, intravascular ultrasonic imaging, and the like Typical interventional procedures include angioplasty, atherectomy, stent and graft placement, embolization, and the like After a procedure is completed, the catheters, guide wire, and introducer sheath are removed, and it is necessary to close the vascular puncture to provide hemostasis and allow healing

[0004] The common technique for achieving hemostasis is to apply pressure, either manually or mechanically, on the patient's body in the region of the tissue tract and vascular puncture Initially, pressure is applied manually and subsequently is maintained through the use of mechanical clamps and other pressure-applying devices While

effective in most cases, the application of external pressure to the patient's skin presents a number of disadvantages For example, when applied manually, the procedure is time- consuming and lequires the presence of a medical professional for thirty minutes or more For both manual and mechanical piessuie application, the procedure is uncomfortable for the patient and frequently requires the administration of analgesics to be tolerable.

[0005] Moreover, complications from manual piessuie application are common The application of excessive pressute can occlude the undeilying aiteiy, iesulting in ischemia and/or thrombosis Even after hemostasis has apparently been achieved, the patient must remain immobile and under observation for hours to prevent dislodgment of the clot and to assure that bleeding from the puncture wound does not resume Renewed bleeding through the tissue tract is not uncommon which can result in hematoma, pseudoaneurisms, and arteriovenous fistulas Such complications may require blood transfusion, surgical intervention, or other corrective procedures The risk of these complications increases with the use of larger sheath sizes, which are frequently necessary in interventional procedures, and when the patient is anticoagulated with heparin or other drugs

[0006] As a result, several alternatives to the manual pressure hemostasis technique have been proposed to address the problem of sealing vessel wall opening following percutaneous transcatheter procedures For example, bioabsorbable, thrombogenic plugs comprising collagen and other materials have been used at the vessel wall opening to stop bleeding These large hemostasis plugs stimulate blood coagulation at the vessel opening, but they block the catheter entry tract, making catheter reentry difficult, if needed Other techniques provide for the use of small dissolvable disks or anchors that are placed in the vessel to block or clamp the opening However, these devices are problematic as any device remaining in the vessel lumen increases the risk of thrombus formation Such devices also can detach and cause occlusion in a distal section of the blood vessel, which would need to be surgically removed

[0007] Additional techniques use needles and sutures delivered through catheters are used to ligate the opening Obviously, this suturing procedure requires a high level of skill and suture material left in the vessel may cause tissue irritation that will prolong the

healing process Another technique involves the injection of a procoagulant into the opening with a balloon catheter blocking inside the vessel lumen However, it is possible for the clotting agent to leak past the balloon into the vessel lumen and cause stenosis Lasers and radio-frequency (RF) energy have also been used to thermally fuse or weld the punctured tissue together Other mote recent techniques involve the use of high frequency ultrasound (HIFU) energy

[0008] HIFU seals vascular openings by quickly increasing the temperature of surrounding tissue by 70-90°C in a matter of seconds The temperature rise mobilizes and denatures collagen, forming coagulum, which rapidly seals the opening

[0009] However, alternatives foi accurately delivering a HIFU dose is desirable. Two examples can be found in U S Patent No, 6,656,136 and U S Patent Application Publication Nos 2004/0106880 and 2005/0080334, all of which are incorporated herein by reference The methods and apparatuses disclosed herein aie further contributions to the art of accurately navigating and dosing HIFU energy at a vessel opening to seal the opening with minimal damage to suiiounding tissue oi discomfort for the patient.

SUMMARY OF THE DISCLOSURE

[0010] In satisfaction of the aforenoted needs, a medical system is disclosed that comprises a probe comprising a distal end, at least one transducer mounted on the distal end of the probe, and a high intensity focused ultrasound (HIFU) device comprising a therapeutic array, an imaging array, at least three transducers mounted around the therapeutic array, and related processing circuitry, The transducers on the probe and on the HIFU device generate acoustic energy that passes through the tissue The acoustic energy is converted to electrical signals by transceiver circuitry, and the electrical signals are used to produce time-of-flight (TOF) measurements, which, in turn, are used to generate a three-dimensional position of the end of the probe with respect to the HIFU device and the therapeutic array of the HIFU device

[0011] The transducer(s) on the end of the probe is preferably used as a transmitter and the transducers mounted on the HIFU device are preferably used as receivers so that multiple TOF measurements may be simultaneously made for each transducer on the HIFU device vis a vis the end of the probe The three dimensional position of the end of

the probe may be calculated from the IOF measurement data using a multi-dimensional scaling (MDS) algorithm or other suitable algorithm that will be appaient to those skilled in the art The processing circuitry may also calculate local coordinates of the distal end of the probe relative to the imaging and therapeutic arrays using a Procrustean similarity transform (PST) or other suitable algorithm that will be apparent to those skilled in the art

{0012] Using the imaging an ay and the acoustic data generated from the use of the transducers, the distal end of the probe can be guided into the vessel opening and the focus point of the HIFU device can be adjusted to match the thiee-dimensional position and the coordinates of the distal end of the probe so the operator is assured that the HTFU focus point is accurate and not out of plane With currently available technology, independent confirmation that the plane of the HIFU focus matches that of the vessel opening is not possible.

[0013] In a refinement, the transducer at the end of the piobe is a pressure transducer as well as an acoustic transducer or the probe tip may include separate acoustic and pressure ttansduceis In aielated refinement, one of the tiansduceis at the end of the probe is polyvinylidene difluoride (PVDF) piezo electric film transducer, a polyvinylidene fluoride (PVF) piezo electric transducer or a piezo electric copolymer transducer Copolymer piezo electric transducers are often copolymers of vinylidene fluoride, but the use of other copolymers are possible In such an embodiment, the use of an imaging an ay may be eliminated oi rendered superfluous as the vessel opening may be located using the pressure sensing capabilities of the probe tip In short, a pleasure change as the probe tip enters the vessel opening is detected

[0014] In another refinement, the at least three reference transducers fixedly mounted around the therapeutic array comprise four transducers. For more efficient TOF calculations, these four ttansduceis are used as receivers and the at least one transducer at the probe tip is used as a transmitter In a related refinement, the transducers may be of the ceramic type, the PVDF type or the piezo electric copolymer type

[0015] In another refinement, the MDS petfoimed by the control circuitry or software is performed multiple times for different sets of three transducers mounted around the

HIFU device In the event a large discrepancy is generated due to a noisy oi defective transducer, use of that noisy oi defective tiansducei infutuie calculations can be stopped In i elated refinement, the results of the MDS calculations are averaged

[0016] In another refinement, the controllei, processor oi control circuitry or software calculates a focal depth for HIFU theiapy based on the PST or use of a similar algorithm

[0017} In another refinement, the device generates an alarm if the -therapeutic an ay is displaced laterally oi longitudinally from the distal end of the probe by a distance greater than a predetermined threshold distance

[0018J A method for locating a vessel opening or puncture is also disclosed One disclosed method that utilizes pressure readings at the probe tip comprises: placing a HIFU device with at least three transducers mounted thereon on a patient's body above the vessel opening; inserting a probe through a skin puncture site and moving a distal end of the probe towards the vessel opening, the distal end of the probe being connected to at least one probe acoustic transducer and at least one pressure transducer oi at least one combination acoustic/pressure transducer; transmitting acoustic energy through the patient's tissue and between the probe transducer and at least three reference transducers mounted on the HIFU device; converting acoustic energy received at either the probe transducer or the transducers mounted on the HIFU device to electrical signals and generating TOF measurements from said electrical signals; generating three-dimensional position data for the end of the probe based on the TOF measurements; generating local coordinate data based on the three-dimensional position data; determining when the probe tip is at or near the opening in the vessel by changes in fluid pressure sensed by the pressure transducer;

calculating a final local coordinate position of the distal end of the probe with respect to the imaging and therapeutic arrays based on the TOF measurements and the three-dimensional position data; and calculating a focal point of the HIFU therapeutic array based on the final local coordinate position

10019] Another method foi locating a vessel opening or punctate that utilizes an imaging an ay comprises: placing a HIFU device with at least three transducers mounted thereon on a patient's body above the vessel opening; inserting a probe through a skin puncture site and moving a distal end of the piobe towards the vessel opening, the distal end of the piobe being connected to at least one piobe transducer; transmitting acoustic enetgy through the patient's tissue and between the piobe transducer and at least three iefeience transducer mounted on the HIFU device; converting acoustic energy received at either the probe tiansducei or the transducers mounted on the HIFU device to electrical signals and generating TOF measuiements fkom said electrical signals; generating three-dimensional position data fox the end of the piobe based on the TOF measuiements; generating local cooidinate data based on the three -dimensional position data; geneiating signals from an imaging array indicative of locations of the piobe and suiiounding tissue and geneiating video images of the distal end of the piobe and surrounding tissue based on the signals from the imaging array; manipulating the piobe and the HIFU device to place the distal end of the piobe at oi near the opening in the vessel while viewing the video images and confirming the distal end of the probe is in a common plane with the imaging array based on the three- dimensional position data and/or local coordinate data;

calculating a final local cooidinate position of the distal end of the probe with respect to the imaging and therapeutic aiiays based on the TOF measurements and the three-dimensional position data; and calculating a focal point of the HIPU theiapeutic aiiay based on the final local cooidinate position

[0020] In a refinement, the three-dimensional position data for the end of the probe is calculated using an MDS algorithm or other suitable algorithm

[0021] In a refinement, the local coordinates of the distal end of the probe are calculated using a PST algorithm or other suitable algorithm

[0022] In another refinement the method further comprises removing the probe and applying HlTU energy at the final local coordinates using a therapeutic array

[0023] In another refinement, the transducers are acoustic transducers and the at least three transducers on the HIFU comprise four reference transducers In a related refinement, the HIFU transducers are uses as receivers and the probe transducer is used at a transmitter

[0024] In another refinement, the method comprises performing an MDS multiple times for different sets of thiee of the four reference transducers mounted on the HIFU device In another related refinement, the method further comprises averaging the results of the multiple MDS calculations In another refinement, data from a noisy, defective or malfunctioning transducer is excluded from the calculations

[0025] Other advantages and features of the disclosed embodiments and methods will be best understood upon reference to the accompanying drawings and detailed description that follows

BRIEF DESCRIPTION OF THE DRAWINGS

[0026] The disclosed systems and methods will be described more or less diagrammatically in the accompanying drawings, wherein:

[0027] Fig, 1 is a sectional view of a portion of a body, illustrating a catheter and guide wire extending through a puncture that extends transdermally into an artery or vessel;

£0028] Fig 2 is aαothei sectional view the body as shown in Fig I ₅ illustrating the vessel and skin, openings or puncture sites;

[0029] Fig 3 is a cioss-sectional view of a portion of the body and an end view of a HIFϋ applicatot, schematically the application of HIFIJ eneigy to apunctuie in an aitery oi vessel;

[0030] Fig 4 is a bottom plan, view of the applicator shown in Fig 3 particularly illustrating two therapeutic arrays and an imaging array disposed therebetween and four reference transducer's mounted at fixed positions around the therapeutic arrays;

[0031] Fig 5 is a plan view of a probe adapted to be inserted into a puncture wound ovei a guide wire and that is equipped with a plurality of acoustic transducers at a distal end thereof;

[0032] Fig 6 is a cross-sectional view of a portion of a body like that shown in Figs 1 and 2, illustrating the probe of Fig 5 in use to determine a location of an opening or puncture in the vessel the applicator disposed above the puncture site and resting on the skin of the patient; and

[0033] Fig 7 is a flow diagram schematically illustrating the various calculations and process circuitry of the disclosed HIFU device and method of locating vessel openings

[0034] It should be understood that the drawings are not necessarily to scale and that the disclosed embodiments are illustrated using diagrammatic representations and fragmentary views In certain instances, details may have been omitted which are not necessary for an understanding of the disclosed embodiments or which render other details difficult to perceive It should be understood, of course, that the sample shaking apparatus is not necessarily limited to the particular embodiments disclosed herein

DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS

[0035] Ultrasound can be brought into a tight focus at relatively short distances from the source or origin If ultrasound with a sufficient energy is radiated into animal tissue, cells located within the focal volume or plane or rapidly heated while surrounding tissues are unaffected The surrounding tissues are unaffected primarily because ultrasound

energy outside of the focal volume is of a low density and theiefoie the heating of the surrounding tissues is minimal and low impact

[0036] High-intensity focused ultrasound (HIFU) applications utilize ultrasound intensities in excess of 1,000 watts/cm ² At a focal point, these intensities can result in large, controlled temperature rises within a matter of seconds These large, controlled temperature rises are useful in sealing holes oi punctures in blood vessels Specifically, when, accurately targeted on a vascular opening, HIFU has been shown to induce hemostasis in less a minute In addition to blood vessel punctures, HϊFU can be used in the treatment of other lacerations as well

[0037] The mechanism of the hemostasis induced by HIFU involves the denaturization of perivascular collagen, which results in the formation of coagulum and/or fibron that seals the hole or puncture HIFU has been observed to play an effective role in sealing vessel punctures of varying sizes

[0038] Turning to Fig 1, a catheter 11 has been inserted through a patient's skin 12 and a distal end 13 of the cathetei through a vessel puncture site 14 The vessel puncture site 14 and skin punctuie site 15 are better shown in Fig 2 The channel 16 left by the cathetei 11 and other related devices obviously presents a seiious bleeding problem, particularly when the vessel 17 is a major artery, such as the femoral artery Various epidermal and other tissue layers are indicated generally at 18

[0039] Turning to Fig 3, a typical HIFU applicator 20 is shown as applied to a patient's skin 12 The applicator 20 includes a lower surface 21 that, as shown in Fig 4, includes two separate arrays, including therapeutic arrays 22 separated by an imaging array 23 Essentially, the applicator 20 is an annular phase array ultiasound transducer with depth focusing The image array 23 is used to transmit data to a separate controller 30 or processing circuitry 30a disposed within the device 20 (or a combination thereof) which translates the data and generates visual images on a monitor 32 The circuitry 30, 30a and the related software may be distributed among the housing of the device 20 and a housing for the controller 30 The operator watches the monitor 32 to ensure that the applicator 20 is disposed on the outer skin in general lateral and longitudinal proximity to the vessel puncture 14

[0040] The clinical challenge is to position the applicatoi 20 ovei the vessel punctate 14 and apply the HIFU energy at the correct focal depth to seal the puncture 14 without damaging the surrounding tissue 1 S . This is clinically challenging because the vessel punctate site 14 is distinct from the skin puncture site 15 Thus, the lateral and longitudinal alignment of the applicator 20 with the vessel puncture site 14 is not straightfoiwaid

[0041] Theoretically, the image array 23 can be used to guide the device over the vessel puncture site 14 However, the interpi etation of exactly where the vessel puncture site 14 is relative to the applicator 20 can become complicated Therefore, use of a probe 34 that can be slid over a guidewiie 19 has proγen helpful The piobe 34, as shown in Fig 5, includes an outer sheath 35 with a distal end 36 that includes one or moie acoustic transducers 38 mounted to the distal end 36 of the probe 34 To assist in proper positioning, transducers 37a-37d aie fixed aiound the therapeutic ariay 22 of the applicator 20 as shown in Figs 4 and 6 and are used with the transducer 38 on the probe 34 as discussed in greater detail below

[0042) As shown in Fig 6, the transducers 37a- 37d and 38 generate and receive acoustic energy that passes through the patient's tissue 18 Preferably, the probe transducer 38 acts as a transmitter and the applicator transducers 37a-37d act as receivers oi reference transducers but a reverse orientation is possible It is preferred that the probe transducer 38 acts as a transmitter and the applicator transducers 37a~37d act as receivers because in this orientation the circuitry can process multiple time-of-fiight (TOF) calculations simultaneously

[0043] Still referring to Fig 6, the probe 34 is inserted into the channel 16 and is pushed down the channel 16 until the distal end 36 of the probe 34 is disposed at the vessel opening 14 During this process, the operator may use the imaging array 23 in combination with the local coordinate calculations that are based on the TOF measurements made possible by the one oi moie probe transducers 38 and the three or more applicator transducers 37a-37d ^" Use of the imaging ariay 23 and the images displayed on the video screen 32 enables the operator to watch the screen 32 as he/she manipulates the distal end 36 of the probe 34 to the desired location at or in the vessel

opening 14, After the desired position is achieved, through use of the imaging array 23 of the applicatoi 20, the position of the piobe 34 is held and the location of the distal end 36 of the probe 34 is determined by the acoustic energy exchanged by transducers 37, 38 as interpreted by the controller 30 or control circuitry 30a

[0044] In summary, referring to Fig 7, as the receiver transducers 37 receive acoustic energy created by the probe transducer 38, electrical signals are generated and transmitted to the transceiver circuitry at 52 which may reside in the applicator 20 (see 30a) or in a separate controller 30 or a combination of the two The transceiver circuitry performs TOF calculations at 53 to determine distances between the probe transducer 38 and any one of the applicatoi transducers 37a-37d. The control circuitry 30, 30a controls the timing of the transducer(s) 38 and is in communication with the imaging array subsystem 23, 32 The TOF measurements are used to generate three-dimensional position data at 54, which in turn is used to generate local coordinates at 55 The local coordinate calculations are used in combination with video images on the screen 32 or with pressure change signals generated at 56 to make sure that the piobe tip 36 is at the vessel opening and not out of plane. Using a "final" local cooidinate calculation, or the calculation performed by the circuitry or software after the operator is sure the probe tip 36 is at the vessel opening, a focal point calculation is performed at 57, Again, use of a pressure sensing transducer at the probe tip 36 may piove to be simpler and more straightforward that use of an imaging an array 23

[0045] If an imaging array 23 and video display 32 is used, the video data should be transmitted at a different frequency than acoustic eneigy transmitted by the transducers 38 or 37 to prevent acoustic crosstalk or interference between the TOF and imaging measurements

[0046] A prefeπed method of generating the three- dimensional position data involves the use of a MDS algorithm as explained below The local coordinates of the distal end 36 of the probe 34 aie calculated at 55, preferably using a PST algorithm The local cooidinates aie used in conjunction with image array data to confirm the location of the probe tip 36 with respect to the vessel opening 14 (see 56 in Fig, 7) and to confirm that the focal point determination at 57 is in the correct plane The above piocess is repeated

every time the applicator 20 and/oi piobe 34 is moved or manipulated as the operator moves the probe tip 36 into the position shown in Fig 6 and the applicator 20 to a position where the focal plane of the therapeutic arrays is coplanar with the vessel opening 14

[0047] The term "control circuitry" is intended to cover the software, circuitry, programmable memory, piocessors, miciopiocessoi chips, boaids or other processing means indicated schematically at 30, 30a in the drawings that (1) convert the signals from the transducers into TOF calculations, that (2) convert the TOF calculations into three- dimensional position data and that (3) conveit the three-dimensional position data into local coordinates The location of the devices and softwaie that perform these functions is unimportant They may reside in the applicator 20 housing itself, in a separate controller box or panel 30 or a combination thereof

[0048] More than one transducer 38 on the distal end 36 of the probe 34 can be utilized The imaging array 23 could be eliminated ot made redundant if the transducer 38 includes a pressure sensing capability ot if a separate pressure sensing transducer was added to the probe end A transducer 38 made from polyvinylidene difluoride (PVDF), polyvinylidene fluoride (PVF), PVDF piezo electric, PVF piezo electric or piezo electric copolymer materials can be utilized PVD film, PVDF film, PVF piezo electro film, PVDF piezo electric film, copolymer film and piezo electric copolymer film transducers ate known in the art U S Patent Nos 6,835,178, 6,504,289, 6485432, 6,387,051, and 6217,518 disclose such pressure sensing transducers Instead of relying on the imaging array, the pressure transducer can be used to determine when the probe top 36 enters the opening 14 of the vessel

[0049] In the example shown, four transducers 37a-37d are mounted directly on the applicator 20 as indicated in Figs 3 and 4 Since the transducers 37a-37d are mechanically fixed to the applicator 20, it is not necessary to measure acoustically the distance between the transducers 37a- 37d The distance is controlled at the time of manufacture and is therefore known,

[0050] Only three transducers 37 are required on the HIFU applicator 20 The use of four applicators 37 in this disclosure is an exemplary embodiment and allows for

redundant calculations to increase the confidence of the calculated thiee-dimensional position of the distal end 36 of the piobe 34 or the transducer 38 on the piobe 34 and piovide foi the possibility of rejection of noisy measurements or in the event one or more of the transducers 37a-37d malfunctions

[0051] The control circuitry 30, 30a utilizes a basic algorithm for determining if the three-dimensional position of the distal end 36 of the probe 34 with iespect to the applicator 20 That basic algorithm may be a multi-dimensional scaling (MDS) algorithm Given N reference transducers 37 mounted on the applicator 20 and one transducer 38 mounted on the probe tip 36, the input to the algorithm is aN + l xN -H matrix of input distances as follows where D _ij = the distance between the ith and jfh transducer and D _ij = 0 because the distance of a transducer to itself is 0 It will be noted that only the last column and iow of the matrix is actually calculated as the N x N sub matrix is deteimined by the mount location of the reference transducers 37

[0052] The MDS algorithm provides an output matrix P of positions, i e P _3xN+1 wherein in each column of P is the x, y, z coordinates of a single transducer 37 position In general, the output positions P have an arbitrary translation rotation and reflection. That is, there are an infinite number of output positions that match the input distances D The positions P can be transformed to a local coordinate system of the applicator 20 using the piocrastean similarity tiansfoim (PST) or other suitable algorithm. This algorithm matches the position of the two point sets fiom two different coordinate systems in a L ₂ norm sense. In this case, one would match the output positions of the N reference transducers 37 as provided by the MDS output coordinate system with the local coordinate system of the applicator 20 This would follow that registration of the applicator device 20 coordinates for both therapy and imaging with the three-dimensional position of the distal end 36 of the probe 34

[0053] Thus, using three or more fixed transducers 37 mounted on the applicator 20 and at least one transducer 38 disposed at the distal end 36 of the probe 34, a more accurate distance calculation between the arrays 22 of the applicator 20 and the distal end of the probe 36 and therefore the puncture site 14 are provided Therefore, a more accurate focal volume for the therapeutic arrays 22 can be calculated and the HIFU

eneigy can be moie accurately applied with minimal damage to surrounding tissue and organs

[0054] Utilizing font oi more refeience ttansduceis 37a-37d can provide a convenient redundancy Specifically, because only thiee iefeience transducers aie needed for an accurate calculation, the controller can peifomi the distance calculation multiple times and the results using a noisy oi defective transduce: can be ignoied Thus, the operator is assured that the calculation is accurate and not affected by transducer malfunction oi noise

[0055] While only ceitain embodiments have been set forth, alternative embodiments and various modifications will be apparent from the above description to those skilled in the art These and othei alternatives are considered equivalents and within the spirit and scope of this disclosure