Patent Application: US-25701705-A

Abstract:
disclosed herein is a minimally invasive , radio - frequency device and a method for local and regional vascular therapy , more particularly for passivation of atherosclerotic , inflammatory , and / or vulnerable plaque in blood vessels . radio - frequency devices of the type described herein constitute an important , inexpensive , disposable , minimally invasive approach for passivation or removal of plaques in various parts of the human body , and , as such , have cardiological applications , such as the treatment of coronary atherosclerosis , as well as other applications , such as the treatment occluded blood vessels in the legs and extremities .

Description:
unless otherwise defined , all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs . in case of conflict , the present specification , including definitions , will control . the words “ a ”, “ an ”, and “ the ” as used herein mean “ at least one ” unless otherwise specifically indicated . the present invention makes reference to “ atherosclerotic ”, “ inflammatory ”, and “ vulnerable ” plaque . atherosclerosis is commonly referred to as a “ hardening ” or “ furring ” of blood vessels , but this is an oversimplification . vascular lesions , known as atheromas , develop in the vessel wall and , in late stages , may suddenly rupture ( e . g ., a vulnerable plaque or acute inflammatory plaque ) and reduce or totally stop blood flow in the lumen ( i . e ., stenosis ), leading to damage of the tissue downstream which has lost needed blood flow ( i . e ., ischemia ). in the context of the present invention , a vulnerable plaque is an unstable inflammatory plaque which is particularly prone to rupture and then to either embolize or to occlude the artery it occupies , thereby producing sudden acute events , such as heart attack or stroke . importantly , it is vascular biology and not the degree of stenosis that determines plaque stability . in general , the process of plaque destabilization begins with endothelial dysfunction against a background of inflammation . the vulnerable plaque typically has three hallmark histologic features : ( i ) a large , highly thrombogenic , lipid core occupying more than 40 % of the plaque volume ; ( ii ) an abundance of inflammatory cells ; and ( iii ) a thin fibrous cap that lacks proper collagen and smooth muscle cell support . the acute clinical event is precipitated by the formation of an intimal , platelet - rich thrombus followed in some cases by a fibrin - red cell intraluminal thrombus . established risk factors of plaque vulnerability include : increased lipid content (& gt ; 40 %) reduced collagen content in a thinned fibrous cap increased inflammatory cell infiltration , commonly macrophages increased expression of matrix degrading metalloproteinases ( mmp ) reduced expression of tissue inhibitor of mmp ( timp ) increased concentrations of macrophage colony stimulating factor ( m - csf ) haemodynamic shear stress . treatment of these risk factors may reduce the probability of plaque erosion or rupture and subsequent thrombus formation and acute coronary syndrome ( acs ). the present invention is primarily directed to plaque stabilization and passivation , as distinguished from plaque ablation and removal . in the context of the present invention , plaque stabilization is defined by any intervention or interaction which , by causing a change in either the structure , content or function of an atherosclerotic plaque and / or the overlying endothelium , will either prevent or reduce the severity of erosion or rupture . plaque passivation is defined as any intervention that decreases the thrombogenicity of the endoluminal oriented vascular surface . in the context of the present invention , selective heating of the vascular plaque , through local application of low power radio - frequency energy , results in a modification of the plaque structure and / or content ( e . g ., a transformation of the inflamed tissue into fibrotic lesions and / or a selective reduction of the lipid core and / or macrophages , each of which translate into an increase in plaque density , mechanical stability and / or rigidity ). the upshot of passivation is a reduction in the risk of subsequent rupture and thrombosis , which , in turn , correspond to a reduction in the risk of acute events such as myocardial infarction . the radio - frequency devices of the present invention have both medical and veterinary applications . accordingly , the term “ subject ” as used herein refers to both humans and animals , more preferably mammals . hereinafter , reference is made to the accompanying drawings which depict , by way of illustration , specific embodiments of the invention and its practice . these embodiments are described in sufficient detail to enable those skilled in the art to practice the invention , and is to be understood that other embodiments may be utilized , and that structural , logical and electrical changes may be made without departing from the spirit and the scope of the present invention . in the drawings , like elements are designated by like reference numerals when appropriate . the words exposed electrode , probe tip , distal tip , and active electrode are used interchangeably to describe the exposed , non - insulated , electrically conductive area of the device which is in contact with the blood , plaque and / or tissue . activating , or energizing , the active tip , from an external radio - frequency control unit , will lead to current flow in the vicinity of the active tip and surrounding region , and passivation of vascular plaque , which together generate a clinically beneficial effect for the patient . the heat produced by radio - frequency device of the present invention is localized and focused in close vicinity to the active element ( s ), mounted at the distal end of the catheter . the degree of heat focusing depends on the geometry of the active element ( s ) and on the electrical properties of the blood , tissue and plaque in its vicinity , as well as the degree of heat losses from the area ( due to blood flow and conduction of heat ). by properly positioning the active element in the blood vessel , and by properly choosing the radio - frequency exposure time and power , the apparatus will have no deleterious effects on the surrounding patient tissue , and the plaque can be selectively heated and passivated by selectively reducing the lipid core and / or macrophages , converting the plaque into mechanically stable fibrotic lesions that are less prone to rupture . it is envisioned that moving , or repositioning , the catheter during the procedure could enhance the passivation and will also allow the medical personnel to effectively and quickly treat large regions . in addition , by properly choosing other exposure time and power settings , the plaque can be evaporated and / or removed . as noted above , devices based on the principles of this invention can be both monopolar or bipolar . referring now to the drawings : fig1 shows a schematic diagram of a catheter based radio - frequency system 1 for use in the context of local and regional vascular therapy , more particularly for passivation of vascular plaque . the system is composed of a radio - frequency control unit 3 , a radio - frequency catheter or probe 5 , a hand switch 7 , a foot switch for activation 9 . also shown is a catheter electrical cable 11 , a return electrode 13 ( also known as a dispersive pad ), an electrical cable 15 connecting the return electrode 13 to the radio - frequency control unit 3 and an imaging system 17 to monitor the position of the catheter in the patient body ( not shown ). the radio - frequency device of the present invention can be either monopolar , as shown in this figure , or bipolar . in the case of bipolar devices , no return pad is needed . fig2 ( a ) shows schematically a human body 2 with some of the blood vessels labeled . one possible way to deliver the device of the present invention to the desired position within the vasculature is through a small opening in a main blood vessel . the schematic diagram of fig2 ( a ) shows the delivery system 20 ( labeled as guiding catheter ) being inserted into the patient &# 39 ; s blood vessel , while its position is carefully monitored by a well known imaging system , such as fluoroscopy ( not shown ), available from various vendors like phillips and others . an expanded view of the region marked by a dashed line 22 in fig2 ( a ) is shown in fig2 ( b ). it shows schematically the area around the tip ( i . e ., the active area ) 24 of an embodiment of the radio - frequency device for passivation of vascular plaque and wire 29 connecting the active area 24 to the external radio - frequency control unit ( 3 in fig1 ). the active area 24 of the radio - frequency system 1 for passivation of vascular plaque is delivered by the medical personnel to the vicinity of the area inside the blood vessel 28 where the plaque 26 is located , with the help of an imaging system ( not shown ). fig3 shows a schematic diagram of the active area ( tip ) of an embodiment of the radio - frequency device of the present invention , for use in the context of local or regional vascular therapy , more particularly for passivation of vascular plaque . the exposed active area 31 of the device is navigated through the blood vessel 28 while being monitored by an imaging system 17 and brought to the vicinity of the plaque area 26 inside a blood vessel 28 . the active area 31 is connected to the radio - frequency control unit 3 via an electrical conductor 33 which is coated with an insulator 34 made of a flexible dielectric . the exposed active area 31 as well as the electrical insulation 34 of the electrical connector 33 are all immersed in the blood 32 flowing in the blood vessel 28 . the schematic diagram in fig3 is shown for illustration purpose only . it will be used as an example for the purpose of numerical modeling , the results of which are shown in fig4 and 5 , in order to demonstrate the principle of selective heating of the plaque . an example of a numerical three - dimensional , azimuthally symmetric calculation showing the lines of constant electric field / current density in the vicinity of the exposed tip 31 of the device is shown in fig4 . the figure is symmetric around the centerline , and shows only half of the plane around the centerline . the calculation shows concentration of radio - frequency energy in the vicinity of the active element 31 and in the plaque region 26 during activation . the dimensions provided in fig4 are given in millimeters and are for illustrative purposes only . fig5 further demonstrates , through a numerical example , the principle of selective heating . the figure shows the temperature rise 50 as a function of the distance away from the center of the blood vessel . the temperature distribution is shown in a cross section inside and outside a blood vessel partially blocked with plaque after 0 . 5 sec of rf activation , with a blood flow rate of 1 cm per second . because of symmetry , only half of the plane around the centerline is shown . from the figure , one can see that the highest temperature rise is achieved in the plaque region , which then leads to plaque passivation . this process is referred to as selective heating , wherein the radio - frequency energy is concentrated mostly in the plaque region , as desired . the degree of heating in the blood vessel wall 28 and in the tissue around it 51 is minimal . fig6 show eight exemplary embodiments of the front active area ( tip ) of the radio - frequency device of the present invention , based on a monopolar , azimuthally symmetric design . note that activating , or energizing , the device tip will lead to heating and passivation of vascular plaque , and thereby generate the clinically beneficial effect for the patient . fig6 ( a ) and ( b ) show an active , exposed electrode 31 , an electrical insulator 34 and an electrical conductor ( e . g ., a wire or metal catheter ) 33 connecting the electrode to the radio - frequency control unit . the electrode 31 can slightly protrude beyond the front end of the insulator 34 , as shown in fig6 ( a ), or , alternatively , may be flush with the insulator . it can also extend well beyond the front surface of the insulator 34 , in order to be able to treat long sections inflicted with plaque . fig6 ( c ) shows yet another embodiment where the active electrode 31 is connected at its distal end to a second insulator 35 . yet another embodiment is shown in fig6 ( d ), wherein the active electrode 31 has a diameter larger than that of the conducting wire 33 . the embodiment shown in fig6 ( e ) is similar to that of fig6 ( c ), wherein the active electrode 31 extends to a second insulator 35 ; however , in the depicted embodiment , the active tip 31 has an outside diameter slightly less than that of the insulators 34 and 35 . fig6 ( f ), ( g ) and ( h ) are variations of the designs shown in ( a ) through ( e ), with the exception that the exposed active electrode can extend radially beyond the outside diameter of the insulators 34 and 35 . note that the any embodiment of a devices of the present invention may be equipped with a front guide coil 36 , as shown in ( f ) and ( g ), that can be used to help navigate the device inside the patients blood vessels , under the guidance of the imaging system . accordingly , the front guide coil may be made of a material that will be clearly visible under the imaging system . for example , the front guide coil can be made of stainless steel , platinum , or the like so as to allow it to be visualized using an imaging system such as a fluoroscope . fig7 ( a ), ( b ) and ( c ) depict additional illustrative embodiments of the active element of the present invention , based on a monopolar , non - symmetric design . more particularly , the embodiments of fig7 ( a )-( c ) depict an electrical insulator 34 having a non - symmetrical distal end . for example , in fig7 ( a ), a portion of the distal tip of the electrical insulator 34 is beveled , chamfered , or cut away so as to control the direction of rf energy applied , for example , to one side of the vessel or the other . similarly , fig7 ( b ) and ( c ) depict an electrical insulator 34 having at least one lateral opening through which rf energy may focused . the active electrode may be contained within the insulator or , alternatively , may be provided with a lateral projection that protrudes through the opening . as with the embodiments of fig6 , in the context of the embodiments of fig7 , the electrode 31 can slightly protrude beyond the insulator , or , alternatively , may be flush with the insulator . it can also extend well beyond the front surface of the insulator in order to be able to treat long sections inflicted with plaque . these devices will be especially useful for treating regions in blood vessels where plaque has accumulated on only one side of the vessel ( i . e ., an asymmetric plaque ). the active electrode 31 and the electrical insulator 34 may be non - cylindrically symmetric , allowing for plaque passivation in preferred regions . the active electrode is energized by radio - frequency energy supplied by a radio - frequency control unit ( not shown ), via the electrical connection 33 . note that all the devices based on the principles of this invention can also be equipped with a front guide coil as shown in fig6 ( f ) and ( g ). fig8 ( a ) to ( d ) show four exemplary coaxial embodiments of the distal active element of the present invention , based on a bipolar , azimuthaly symmetric design . for bipolar devices , according to the principles of the present invention , the device is equipped with at least one active electrode 31 , at least one passive return electrode 80 electrically insulated from each other using a first insulator 82 and a second insulator 84 . when the device is activated , radio - frequency current flows between the active electrode and the return electrode . an additional embodiment is shown in fig8 ( d ), wherein the active electrode 31 includes another electrical insulator 86 . note , the roles played by the active electrode 31 and the return electrode 80 may be easily reversed . connection to the external radio - frequency unit ( i . e ., element 3 shown in fig1 ) is made via the electrical connection 33 connected to the active element 31 , and an additional electrical connection ( not shown ) connected to the return electrode 80 . no dispersive pad is needed for the bipolar devices . additional bipolar , coaxial embodiments are shown in fig9 ( a ) to ( d ), all based on azimuthally symmetric designs . note that the devices based on the principles of the present invention can also be of non - azimuthally symmetric designs , and equipped with a front guide coil of the type shown schematically in fig6 ( f ) ( g ). the embodiments of fig9 include three or four different zones of insulation . for example , 82 is the insulation around the active electrode 31 , and between the active electrode 31 and the return electrode 80 . a third zone of insulation 90 partially covers the return electrode 80 . yet another zone of insulator 86 is attached to active electrode 31 . note that non - azimuthally symmetric embodiments are also contemplated , and that the devices based on the principles of this invention can also be equipped with a front guide coil 36 as shown in fig6 ( f ) and ( g ). fig1 ( a ) to ( c ) show still further embodiments of the present invention , based on bipolar or multi - polar electrode designs . in the embodiment depicted in fig1 ( a ), the number of electrodes is n = 4 ; however , it can be any even number , i . e ., n = 2 , 4 , 6 , 8 , . . . etc . fig1 ( a ) shows an embodiment incorporating four electrodes 100 , 101 , 102 , 103 , insulated by insulator 110 . fig1 ( b ) shows embodiments with n = 2 , equipped with a front insulator 35 . fig1 ( c ) shows an embodiment similar to ( b ) with the addition of a leading coil 36 . the devices based on the principles of this invention can also be non - azimuthally symmetric and accordingly equipped with either an even or odd number of electrodes n . fig1 ( a ) schematically shows yet another embodiment of the device of the present invention , in which the active electrode 31 is equipped with an aspiration and or / irrigation port 310 . it can be used , for example , to aspirate out debris from the active area or for introducing a cooling agent so as to reduce the local temperature in the active area . both bipolar and monopolar devices aspiration / irrigation versions are contemplated herein . fig1 ( b ) schematically shows an active electrode 31 based on the principles of this invention , equipped with a temperature - sensing element 140 . both monopolar and bipolar devices of this type are contemplated . fig1 shows still further embodiments of the device of the present invention . the active electrode 204 in fig1 ( a ) is monopolar and includes multiple exposed protrusions or projections 200 , 201 , 202 , and 203 . the active electrode 204 is electrically connected to the external radio - frequency control unit ( element 3 shown in fig1 ) via an electrical connection 33 . in fig1 ( b ), the active electrode 31 is inserted into an insulator sleeve 210 which has one or more openings , symmetric on non - symmetric . the insulator 210 can be moved along and rotated around the electrode 31 , thus exposing different segments depending on its relative position with respect to the electrode 31 depending on the specific needs of the patient . fig1 ( c ) shows yet another monopolar embodiment equipped with three independent electrodes 220 , 221 and 222 , connected to an external radio - frequency unit with wires 230 , 231 and 232 . the independent electrodes can be activated simultaneously , sequentially or independently depending of the desired clinical effect . both monopolar and bipolar devices of this type are possible based on the principles of this invention . fig1 ( d ) is an example of a device equipped with one or more electrically detached electrodes 250 ( i . e ., electrodes not connected to an external source of electric energy ). the detached electrode 250 is insulated from the active electrode 31 with an insulator 240 . note that the devices can also be of non - azimuthally symmetric designs , and equipped with a front guide coil . other variations according to the principles of this invention are possible . fig1 illustrates exemplary methods for guiding the radio - frequency device of the present invention for passivation of vascular plaque inside blood vessels . in fig1 ( a ), the device is equipped with a front insulator 35 and a guide coil 36 . in fig1 ( b ), the active electrode 31 is disposed inside a flexible , non - conducting tube 300 which is then inserted into the blood vessel 28 to be treated , and in this case a front guide coil is not needed . both monopolar and bipolar devices of this type are contemplated , as are azimuthally symmetric and non - symmetric designs , with and without guide coils . in fig1 ( c ), the active electrode 31 glides along a guide wire 400 with the aid of a sliding fixture 410 , made of an insulating , flexible material , attached to the front end of active electrode 31 . the device in fig1 ( d ) is similar to the one shown in fig1 ( c ), with the exception that the active electrode 31 glides along a guide wire 400 with the aid of a sliding fixture 420 , made of an insulating material , attached to the side or front end of 31 . the disclosure of each publication , patent or patent application mentioned in this specification is specifically incorporated by reference herein in its entirety . 1 . murray c j l , lopez a d . the global burden of disease . global burden of disease and injury series . boston , mass . : harvard school of public health / harvard university press , 1996 : 1 - 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3 , 1987 . 22 . sigel b , dunn m r . the mechanism of blood vessel closure by high frequency electrocoagulation . surg gynecol obstet . 121 : 823 - 31 , 1965 . while the invention has been described with reference to specific examples and preferred embodiments , it will be appreciated that the description is illustrative of the invention and , therefore , should not be constructed as limiting thereof . it should also be understood that the invention is intended not to be limited by the foregoing description , but to be defined by the appended claims and their equivalents . various modifications and applications may occur to those who are skilled in the art , without departing from the spirit and the scope of the invention , as described by the appended claims .